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Aberle MR, Coolsen MME, Wenmaekers G, Volmer L, Brecheisen R, van Dijk D, Wee L, Van Dam RM, de Vos-Geelen J, Rensen SS, Damink SWMO. Skeletal muscle is independently associated with grade 3-4 toxicity in advanced stage pancreatic ductal adenocarcinoma patients receiving chemotherapy. Clin Nutr ESPEN 2025; 65:134-143. [PMID: 39577693 DOI: 10.1016/j.clnesp.2024.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 11/06/2024] [Accepted: 11/09/2024] [Indexed: 11/24/2024]
Abstract
BACKGROUND Patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) are regularly treated with FOLFIRINOX, a chemotherapy regimen based on 5-fluorouracil, irinotecan and oxaliplatin, which is associated with high toxicity. Dosing of FOLFIRINOX is based on body surface area, risking under- or overdosing caused by altered pharmacokinetics due to interindividual differences in body composition. This study aimed to investigate the relationship between body composition and treatment toxicity in advanced stage PDAC patients treated with FOLFIRINOX. METHODS Data from patients treated at the Maastricht University Medical Centre + between 2012 and 2020 were collected retrospectively (n = 65). Skeletal muscle-, visceral adipose tissue, subcutaneous adipose tissue-, (SM-Index, VAT-Index, SAT-Index resp.) and Skeletal Muscle Radiation Attenuation (SM-RA) were calculated after segmentation of computed tomography (CT) images at the third lumbar level using a validated deep learning method. Lean body mass (LBM) was estimated using SM-Index. Toxicities were scored and grade 3-4 adverse events were considered dose-limiting toxicities (DLTs). RESULTS Sixty-seven DLTs were reported during the median follow-up of 51.4 (95%CI 39.2-63.7) weeks. Patients who experienced at least one DLT had significantly higher dose intensity per LBM for all separate cytotoxics of FOLFIRINOX. Independent prognostic factors for the number of DLTs per cycle were: sarcopenia (β = 0.292; 95%CI 0.013 to 0.065; p = 0.013), SM-Index change (% per 30 days, β = -0.045; 95%CI -0.079 to -0.011; p = 0.011), VAT-Index change (% per 30 days, β = -0.006; 95%CI -0.012 to 0.000; p = 0.040) between diagnosis and the first follow-up CT scan, and cumulative relative dose intensity >80 % (β = -0.315; 95 % CI -0.543 to -0.087; p = 0.008). CONCLUSION Sarcopenia and early muscle and fat wasting during FOLFIRINOX treatment were associated with treatment-related toxicity, warranting exploration of body composition guided personalized dosing of chemotherapeutics to limit DLTs.
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Affiliation(s)
- Merel R Aberle
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Mariëlle M E Coolsen
- Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of General, Visceral- and Transplantation Surgery, RWTH Aachen University, Germany
| | - Gilles Wenmaekers
- Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Leroy Volmer
- GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Radiotherapy (MAASTRO), Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Ralph Brecheisen
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - David van Dijk
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Leonard Wee
- GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Radiotherapy (MAASTRO), Maastricht University Medical Centre+, Maastricht, the Netherlands; Clinical Data Science, Maastricht University, Maastricht, the Netherlands
| | - Ronald M Van Dam
- Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of General, Visceral- and Transplantation Surgery, RWTH Aachen University, Germany
| | - Judith de Vos-Geelen
- GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Medical Oncology, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Sander S Rensen
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
| | - Steven W M Olde Damink
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of General, Visceral- and Transplantation Surgery, RWTH Aachen University, Germany
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S D, D S, P VK, K S. Enhancing pancreatic cancer classification through dynamic weighted ensemble: a game theory approach. Comput Methods Biomech Biomed Engin 2025; 28:145-169. [PMID: 37982236 DOI: 10.1080/10255842.2023.2281277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 10/27/2023] [Accepted: 11/02/2023] [Indexed: 11/21/2023]
Abstract
The significant research carried out on medical healthcare networks is giving computing innovations lots of space to produce the most recent innovations. Pancreatic cancer, which ranks among of the most common tumors that are thought to be fatal and unsuspected since it is positioned in the region of the abdomen beyond the stomach and can't be adequately treated once diagnosed. In radiological imaging, such as MRI and CT, computer-aided diagnosis (CAD), quantitative evaluations, and automated pancreatic cancer classification approaches are routinely provided. This study provides a dynamic weighted ensemble framework for pancreatic cancer classification inspired by game theory. Grey Level Co-occurrence Matrix (GLCM) is utilized for feature extraction, together with Gaussian kernel-based fuzzy rough sets theory (GKFRST) for feature reduction and the Random Forest (RF) classifier for categorization. The ResNet50 and VGG16 are used in the transfer learning (TL) paradigm. The combination of the outcomes from the TL paradigm and the RF classifier paradigm is suggested using an innovative ensemble classifier that relies on the game theory method. When compared with the current models, the ensemble technique considerably increases the pancreatic cancer classification accuracy and yields exceptional performance. The study improves the categorization of pancreatic cancer by using game theory, a mathematical paradigm that simulates strategic interactions. Because game theory has been not frequently used in the discipline of cancer categorization, this research is distinctive in its methodology.
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Affiliation(s)
- Dhanasekaran S
- Department of Electronics and Communication Engineering, Sri Eshwar College of Engineering, Coimbatore, Tamil Nadu, India
| | - Silambarasan D
- Department of Electronics and Communication Engineering, Sri Venkateswara College of Engineering, Tamil Nadu, India
| | - Vivek Karthick P
- Department of Electronics and Communication Engineering, Sona College of Technology, Salem, Tamil Nadu, India
| | - Sudhakar K
- Department of Electronics and Communication Engineering, M. Kumarasamy College of Engineering, Karur, Tamil Nadu, India
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Davis MP, Bader N, Basting J, Vanenkevort E, Koppenhaver N, Patel A, Gupta M, Lagerman B, Wojtowicz M. Are Muscle and Fat Loss Predictive of Clinical Events in Pancreatic Cancer? The Importance of Precision Metrics. J Pain Symptom Manage 2025; 69:141-151. [PMID: 39461674 DOI: 10.1016/j.jpainsymman.2024.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 10/07/2024] [Accepted: 10/08/2024] [Indexed: 10/29/2024]
Abstract
CONTEXT Muscle and fat loss from cancer may have prognostic significance. Skeletal muscle and fat areas measured at L3 on a CT scan correlate with body muscle and fat mass. We wished to know if reduced skeletal muscle area or fat on diagnostic CT scans or changes from initial CT scans in patients with pancreatic cancer who died in 2018 and 2019 predicted mortality. METHOD Electronic records of 112 patients with locally advanced or metastatic pancreatic cancer were used to extract stage, age, gender, comorbidities, weight, and height at the time of the first CT scan. Survival (in days) was defined from the first CT scan to the death date. Patients had at least one CT scan of the abdomen. I. Two trained medical students read scans independently using TeraRecon software (Durham, NC). Results were averaged, and the differences determined precision. Interclass correlation coefficient (ICC), coefficient of variation, and least significant change determined the precision between readers. Independent prognostic modeling included age and BMI. RESULTS An evaluable sample of 104 with an average age of 67, 56 were male. Nearly half had a TNM Stage of IV (45%). The average Charlson Comorbidity index is 7.2. In those undergoing repeat scans, most were in the timeframe of 60-120 days. Changes in visceral fat in men in the unadjusted Cox proportional hazard model and reduced skeletal muscle area in the age-adjusted model of men predicted mortality. In contrast, myosteatosis in women marginally predicted improved survival. ICC's precision between readers was adequate but by least significant change would have missed subtle, clinically important changes. DISCUSSION Muscle loss during chemotherapy in men predicted mortality in men but not women. Precision is an important metric when measuring body composition. CONCLUSION Muscle loss in men during chemotherapy of pancreatic cancer predicts mortality.
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Affiliation(s)
- Mellar P Davis
- Geisinger Health System (M.P.D., N.K., A.P., M.G., B.L.), Danville, PA.
| | - Nada Bader
- Geisinger Commonwealth School of Medicine (N.B., J.B.), Scranton, PA
| | - James Basting
- Geisinger Commonwealth School of Medicine (N.B., J.B.), Scranton, PA
| | - Erin Vanenkevort
- Geisinger Health System (M.P.D., N.K., A.P., M.G., B.L.), Danville, PA
| | | | - Aalpen Patel
- Geisinger Health System (M.P.D., N.K., A.P., M.G., B.L.), Danville, PA
| | - Mudit Gupta
- Geisinger Health System (M.P.D., N.K., A.P., M.G., B.L.), Danville, PA
| | - Braxton Lagerman
- Geisinger Health System (M.P.D., N.K., A.P., M.G., B.L.), Danville, PA
| | - Mark Wojtowicz
- Geisinger Health System (M.P.D., N.K., A.P., M.G., B.L.), Danville, PA
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Terayama M, Ohashi M, Yamaguchi K, Takahari D, Makuuchi R, Hayami M, Ida S, Kumagai K, Sano T, Nunobe S. Feasibility and predictive factors on the completion of docetaxel plus S-1 adjuvant chemotherapy in pathological stage III gastric cancer. Ann Gastroenterol Surg 2025; 9:60-68. [PMID: 39759998 PMCID: PMC11693541 DOI: 10.1002/ags3.12840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 06/12/2024] [Accepted: 06/18/2024] [Indexed: 01/07/2025] Open
Abstract
Background The standard adjuvant chemotherapy regimen for stage III gastric cancer is docetaxel plus S-1 (DS) based on the results of the START-II trials. However, in clinical practice some patients could not continue this intensive doublet chemotherapy because of limited tolerability. This study aimed to assess the practical feasibility of DS and elucidate the predictive factors for the completion of adjuvant DS therapy. Methods Data from consecutive patients who underwent radical gastrectomy between 2018 and 2021 and were diagnosed with histopathologically confirmed stage III gastric cancer were retrospectively collected. First, the completion rate and adverse effects of DS were assessed. Second, the association between DS incompletion and patient backgrounds including body weight, skeletal muscle index (SMI), and intramuscular adipose content (IMAC) were examined. Results Of 87 patients, 59 patients (67.8%) completed DS and dose reduction was required in 18 patients (20.6%). Neutropenia of grade 3 or higher was the most common hematological toxicity observed (17.2%). The most frequent nonhematological toxicity of grade 3 or higher was fatigue (6.9%), followed by diarrhea (5.7%), nausea (4.5%), and anorexia (4.5%). In a multivariate analysis, low SMI (p = 0.005) and high IMAC (p = 0.004) were significant risk factors for DS incompletion. Conclusions DS adjuvant chemotherapy after radical gastrectomy for pathological stage III gastric cancer is acceptable, even in clinical practice, with respect to completion and toxicity. Additionally, the body composition factors such as SMI and IMAC might be useful in predicting incompletion of DS. These findings will help us to preoperatively select patients for DS.
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Affiliation(s)
- Masayoshi Terayama
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan
| | - Manabu Ohashi
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan
| | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, Gastroenterological CenterCancer Institute Hospital, Japanese Foundation for Cancer ResearchTokyoJapan
| | - Daisuke Takahari
- Department of Gastroenterological Chemotherapy, Gastroenterological CenterCancer Institute Hospital, Japanese Foundation for Cancer ResearchTokyoJapan
| | - Rie Makuuchi
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan
| | - Masaru Hayami
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan
| | - Satoshi Ida
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan
| | - Koshi Kumagai
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan
| | - Takeshi Sano
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan
| | - Souya Nunobe
- Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan
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Zhang X, Wei L, Li J, Deng Y, Xu W, Chen D, Li X. Influence of myosteatosis on survival of patients with pancreatic cancer: A systematic review and meta-analysis. iScience 2024; 27:111343. [PMID: 39640579 PMCID: PMC11617386 DOI: 10.1016/j.isci.2024.111343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 08/28/2024] [Accepted: 11/05/2024] [Indexed: 12/07/2024] Open
Abstract
The present meta-analysis aims to evaluate the impact of myosteatosis on overall survival (OS) and progression-free survival (PFS) in patients with pancreatic cancer (PC). A comprehensive literature search was conducted in the Medline, Web of Science, and Embase databases. The hazard ratio (HR) and corresponding 95% confidence interval (CI) for the association between myosteatosis and survival outcomes were pooled using a random-effects model. A total of 14 studies were included. The pooled analysis demonstrated that myosteatosis was significantly associated to poorer OS (HR: 1.50, 95% CI: 1.35-1.67, p < 0.001; I 2 = 0%). The subgroup analysis revealed consistent results across various study characteristics, including geographic regions, cancer stages, follow-up durations, and study quality. In addition, myosteatosis was associated to worse PFS (HR: 1.34, 95% CI: 1.15-1.57, p < 0.001; I 2 = 34%). The present meta-analysis indicates that myosteatosis is associated to significantly worse OS and PFS in patients with PC.
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Affiliation(s)
- Xin Zhang
- Department of Gastroenterology, The Fourth Hospital of Changsha, Changsha City, Hunan Province 410006, P.R. China
| | - Licheng Wei
- Department of Gastroenterology, The Fourth Hospital of Changsha, Changsha City, Hunan Province 410006, P.R. China
| | - Jiangguo Li
- Department of Gastroenterology, The Fourth Hospital of Changsha, Changsha City, Hunan Province 410006, P.R. China
| | - Yuexia Deng
- Department of Gastroenterology, The Fourth Hospital of Changsha, Changsha City, Hunan Province 410006, P.R. China
| | - Wei Xu
- Department of Gastroenterology, The Fourth Hospital of Changsha, Changsha City, Hunan Province 410006, P.R. China
| | - Dongkui Chen
- Department of Gastroenterology, The Fourth Hospital of Changsha, Changsha City, Hunan Province 410006, P.R. China
| | - Xing Li
- Department of Critical Care Medicine, Changsha Hospital of Traditional Chinese Medicine (Changsha No. 8 Hospital), Changsha City, Hunan Province 410100, P.R. China
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Chen HB, Miao Q, Liu YS, Lou XY, Zhang LD, Tan XD, Liang KK. The prognostic value of myosteatosis in pancreatic cancer: A systematic review and meta-analysis. Clin Nutr 2024; 43:116-123. [PMID: 39442392 DOI: 10.1016/j.clnu.2024.10.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 10/07/2024] [Accepted: 10/08/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND AND AIMS The phenomenon of myosteatosis, characterized by the accumulation of ectopic fat within and surrounding skeletal muscle, has been identified as a potential adverse factor in the prognosis of individuals with cancer. This systematic review and meta-analysis sought to examine the association between myosteatosis and survival rates as well as postoperative complications in patients diagnosed with pancreatic cancer (PC). METHODS A systematic search was conducted on Web of Science, Embase, and Pubmed until March 25, 2024, to identify pertinent articles assessing the prognostic significance of myosteatosis in patients with PC, utilizing the search terms: myosteatosis, PC, and prognosis. The selected studies were utilized to investigate the prognostic impact of myosteatosis on the survival of PC patients. Forest plots and pooled effects models were employed to present the findings of this meta-analysis. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). A total of 565 studies were initially identified from the three databases, with 14 retrospective cohort studies ultimately included in the final quantitative analysis. RESULTS The meta-analysis revealed a significant association between myosteatosis and both overall survival (OS) [Hazard Ratio (HR): 1.55, 95 % Confidence Interval (CI): 1.40-1.72, P < 0.001, I2 = 0.0 %] and recurrence-free survival (RFS) (HR 1.48, 95 % CI: 1.17-1.86, P = 0.001, I2 = 0.0 %) in patients diagnosed with PC. Subgroup analyses revealed that myosteatosis continued to be a negative prognostic factor in PC across various treatment modalities, patient populations, and myosteatosis assessment methods. Additionally, myosteatosis was identified as a risk factor for postoperative complications, with a pooled odds ratio of 2.20 (95 % CI: 1.45-3.35, P < 0.001, I2 = 37.5 %). All included studies achieved NOS scores of 6 or higher, indicating a relatively high level of methodological quality. CONCLUSION These results suggest that myosteatosis is significantly associated with both survival outcomes and postoperative complications in patients with PC.
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Affiliation(s)
- Hong-Bo Chen
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Qi Miao
- Department of Radiology, The First Hospital of China Medical University, Shenyang 110002, China
| | - Ya-Shu Liu
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Xin-Yu Lou
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Lu-Dan Zhang
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Xiao-Dong Tan
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
| | - Ke-Ke Liang
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
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Tsukagoshi M, Araki K, Shirabe K. Pancreatic cancer and sarcopenia: a narrative review of the current status. Int J Clin Oncol 2024; 29:1055-1066. [PMID: 38954075 DOI: 10.1007/s10147-024-02576-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 06/19/2024] [Indexed: 07/04/2024]
Abstract
Pancreatic cancer is still a difficult disease to treat, despite recent advances in surgical techniques and chemotherapeutic drugs. Its incidence continues to rise, as does the number of older patients. Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass and strength. Sarcopenia is present in approximately 40% in patients with pancreatic cancer. Sarcopenia is primarily diagnosed through imaging, and progress is being made in the development of automated methods and artificial intelligence, as well as biomarker research. Sarcopenia has been linked to a poor prognosis in pancreatic cancer patients. However, some studies suggest that sarcopenia is not always associated with a poor prognosis, depending on the resectability of pancreatic cancer and the nature of treatment, such as surgery or chemotherapy. Recent meta-analyses have found that sarcopenia is not linked to postoperative complications. It is still debated whether there is a link between sarcopenia and drug toxicity during chemotherapy. The relationship between sarcopenia and immunity has been investigated, but the mechanism is still unknown.
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Affiliation(s)
- Mariko Tsukagoshi
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi Gunma, 371-8511, Japan
| | - Kenichiro Araki
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi Gunma, 371-8511, Japan
| | - Ken Shirabe
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi Gunma, 371-8511, Japan.
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Barbosa S, Pedrosa MB, Ferreira R, Moreira-Gonçalves D, Santos LL. The impact of chemotherapy on adipose tissue remodeling: The molecular players involved in this tissue wasting. Biochimie 2024; 223:1-12. [PMID: 38537739 DOI: 10.1016/j.biochi.2024.03.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 03/21/2024] [Accepted: 03/23/2024] [Indexed: 04/05/2024]
Abstract
The depletion of visceral and subcutaneous adipose tissue (AT) during chemotherapy significantly correlates with diminished overall survival and progression-free survival. Despite its clinical significance, the intricate molecular mechanisms governing this AT loss and its chemotherapy-triggered initiation remain poorly understood. Notably, the evaluation of AT remodeling in most clinical trials has predominantly relied on computerized tomography scans or bioimpedance, with molecular studies often conducted using animal or in vitro models. To address this knowledge gap, a comprehensive narrative review was conducted. The findings underscore that chemotherapy serves as a key factor in inducing AT loss, exacerbating cachexia, a paraneoplastic syndrome that significantly compromises patient quality of life and survival. The mechanism driving AT loss appears intricately linked to alterations in AT metabolic remodeling, marked by heightened lipolysis and fatty acid oxidation, coupled with diminished lipogenesis. However, adipocyte stem cells' lost ability to divide due to chemotherapy also appears to be at the root of the loss of AT. Notably, chemotherapy seems to deactivate the mitochondrial antioxidant system by reducing key regulatory enzymes responsible for neutralizing reactive oxygen species (ROS), thereby impeding lipogenesis. Despite FDG-PET evidence of AT browning, no molecular evidence of thermogenesis was reported. Prospective investigations unraveling the molecular mechanisms modulated in AT by chemotherapy, along with therapeutic strategies aimed at preventing AT loss, promise to refine treatment paradigms and enhance patient outcomes.
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Affiliation(s)
- Samuel Barbosa
- Research Centre in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto, 4200-450, Porto, Portugal; Experimental Pathology and Therapeutics Group, Research Center (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center (P.CCC), 4200-072, Porto, Portugal.
| | - Mafalda Barbosa Pedrosa
- Research Centre in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto, 4200-450, Porto, Portugal; Experimental Pathology and Therapeutics Group, Research Center (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center (P.CCC), 4200-072, Porto, Portugal; Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV-REQUIMTE), Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal
| | - Rita Ferreira
- Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV-REQUIMTE), Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal
| | - Daniel Moreira-Gonçalves
- Research Centre in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto, 4200-450, Porto, Portugal; Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600, Porto, Portugal
| | - Lúcio Lara Santos
- Experimental Pathology and Therapeutics Group, Research Center (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center (P.CCC), 4200-072, Porto, Portugal
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Turner K, Kim DW, Gonzalez BD, Gore LR, Gurd E, Milano J, Riccardi D, Byrne M, Al-Jumayli M, de Castria TB, Laber DA, Hoffe S, Costello J, Robinson E, Chadha JS, Rajasekhara S, Hume E, Hagen R, Nguyen OT, Nardella N, Parker N, Carson TL, Tabriz AA, Hodul P. Support Through Remote Observation and Nutrition Guidance (STRONG), a digital health intervention to reduce malnutrition among pancreatic cancer patients: A study protocol for a pilot randomized controlled trial. Contemp Clin Trials Commun 2024; 38:101271. [PMID: 38440777 PMCID: PMC10910065 DOI: 10.1016/j.conctc.2024.101271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 01/19/2024] [Accepted: 02/13/2024] [Indexed: 03/06/2024] Open
Abstract
Background Malnutrition is a common and distressing condition among pancreatic cancer patients. Fewer than a quarter of pancreatic cancer patients receive medical nutrition therapy (MNT), important for improving nutritional status, weight maintenance, quality of life and survival. System, provider, and patient level barriers limit access to MNT. We propose to examine the feasibility of a 12-week multi-level, digital health intervention designed to expand MNT access among pancreatic cancer patients. Methods Individuals with advanced pancreatic cancer starting chemotherapy (N = 80) will be 1:1 randomized to the intervention or usual care. The Support Through Remote Observation and Nutrition Guidance (STRONG) intervention includes system-level (e.g., routine malnutrition and screening), provider-level (e.g., dietitian training and web-based dashboard), and patient-level strategies (e.g., individualized nutrition plan, self-monitoring of dietary intake via Fitbit, ongoing goal monitoring and feedback). Individuals receiving usual care will be referred to dietitians based on their oncologists' discretion. Study assessments will be completed at baseline, 4-, 8-, 12-, and 16-weeks. Results Primary outcomes will be feasibility (e.g., recruitment, retention, assessment completion) and acceptability. We will collect additional implementation outcomes, such as intervention adherence, perceived usability, and feedback on intervention quality via an exit interview. We will collect preliminary data on outcomes that may be associated with the intervention including malnutrition, quality of life, treatment outcomes, and survival. Conclusion This study will advance our knowledge on the feasibility of a digital health intervention to reduce malnutrition among individuals with advanced pancreatic cancer. Trial registration: NCT05675059, registered on December 9, 2022.
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Affiliation(s)
- Kea Turner
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, USA
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, USA
- Department of Oncological Sciences, University of South Florida, USA
| | - Dae Won Kim
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, USA
- Department of Oncological Sciences, University of South Florida, USA
| | - Brian D. Gonzalez
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, USA
- Department of Oncological Sciences, University of South Florida, USA
| | - Laurence R. Gore
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, USA
| | - Erin Gurd
- Department of Nutrition Therapy, Moffitt Cancer Center, USA
| | - Jeanine Milano
- Department of Nutrition Therapy, Moffitt Cancer Center, USA
| | - Diane Riccardi
- Department of Nutrition Therapy, Moffitt Cancer Center, USA
| | - Margaret Byrne
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, USA
- Department of Oncological Sciences, University of South Florida, USA
| | | | - Tiago Biachi de Castria
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, USA
- Department of Oncological Sciences, University of South Florida, USA
| | - Damian A. Laber
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, USA
- Department of Oncological Sciences, University of South Florida, USA
| | - Sarah Hoffe
- Department of Radiation Oncology, Moffitt Cancer Center, USA
| | - James Costello
- Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, USA
| | - Edmondo Robinson
- Department of Oncological Sciences, University of South Florida, USA
- Department of Internal and Hospital Medicine, Moffitt Cancer Center, USA
- Center for Digital Health, Moffitt Cancer Center, USA
| | | | | | - Emma Hume
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, USA
| | - Ryan Hagen
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, USA
| | - Oliver T. Nguyen
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, USA
| | - Nicole Nardella
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, USA
| | - Nathan Parker
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, USA
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, USA
- Department of Oncological Sciences, University of South Florida, USA
| | - Tiffany L. Carson
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, USA
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, USA
- Department of Oncological Sciences, University of South Florida, USA
| | - Amir Alishahi Tabriz
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, USA
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, USA
- Department of Oncological Sciences, University of South Florida, USA
| | - Pamela Hodul
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, USA
- Department of Oncological Sciences, University of South Florida, USA
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10
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Karuppannan M, Muthanna FMS, Mohd Fauzi F. Breaking Down Cachexia: A Narrative Review on the Prevalence of Cachexia in Cancer Patients and Its Associated Risk Factors. Nutr Cancer 2024; 76:404-418. [PMID: 38546174 DOI: 10.1080/01635581.2024.2321654] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 02/16/2024] [Indexed: 10/01/2024]
Abstract
Cachexia is an irreversible condition that involves a significant loss of body weight, muscle mass, and adipose tissue. It is a complex condition that involves a variety of metabolic, hormonal, and immune-related factors, with the precise mechanisms not yet fully understood. In this review, the prevalence of cachexia in different types of cancer as well as the potential risk factors was evaluated from literature retrieved from databases such as ScienceDirect, PubMed and Scopus. Potential risk factors evaluated here include tumor-related factors such as location, and stage of the cancer, as well as patient-related factors such as age, gender, and comorbidities. Several findings were observed where cachexia is more prevalent in male cancer patients than females, with higher incidences of weight loss and poorer outcomes. This may be due to the different muscle compositions between gender. Additionally, cachexia is more prevalent at the later stages, which may be brought about by the late-stage diagnosis of certain cancers. The anatomical location of certain cancers such as the pancreas and stomach may play a significant factor in their high prevalence of cachexia. These are sites of the synthesis of digestive enzymes and hormones regulating appetite. Cachexia is an issue faced by cancer patients which could affect their recovery. However, it is poorly understood, which limit therapeutic options. Hence, understanding this disease from different perspectives (clinical and pre-clinical), and bridging those findings could further improve our comprehension and consequently improve therapeutic options.
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Affiliation(s)
- Mahmathi Karuppannan
- Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Bandar Puncak Alam, Malaysia
- Cardiology Therapeutics Research Initiative Group, Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Bandar Puncak Alam, Malaysia
| | - Fares M S Muthanna
- Pharmacy Department, Faculty of Medicine and Health Sciences, University of Science and Technology, Aden, Yemen
| | - Fazlin Mohd Fauzi
- Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Bandar Puncak Alam, Malaysia
- Centre for Drug Discovery Research, Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Bandar Puncak Alam, Malaysia
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11
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Sohal DPS, Boutin RD, Lenchik L, Kim J, Beg MS, Wang-Gillam A, Wade JL, Guthrie KA, Chiorean EG, Ahmad SA, Lowy AM, Philip PA, Chang VTS. Body composition measurements and clinical outcomes in patients with resectable pancreatic adenocarcinoma - analysis from SWOG S1505. J Gastrointest Surg 2024; 28:232-235. [PMID: 38445914 DOI: 10.1016/j.gassur.2023.12.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 12/08/2023] [Accepted: 12/16/2023] [Indexed: 03/07/2024]
Abstract
BACKGROUND Sarcopenic obesity and muscle attenuation have been associated with survival in patients with borderline resectable and advanced pancreatic ductal adenocarcinoma (PDA); however, these relationships are unknown for patients with resectable PDA. This study examined the associations between skeletal muscle and adipose tissue as measured on baseline computed tomography (CT) and the overall survival (OS) of participants with resectable PDA in a secondary analysis of the Southwest Oncology Group S1505 clinical trial (identifier: NCT02562716). METHODS The S1505 phase II clinical trial enrolled patients with resectable PDA who were randomized to receive modified FOLFIRINOX or gemcitabine and nab-paclitaxel as perioperative chemotherapy, followed by surgical resection. Baseline axial CT images at the L3 level were analyzed with externally validated software, and measurements were recorded for skeletal muscle area and skeletal muscle density, visceral adipose tissue area (VATA) and density, and subcutaneous adipose tissue area and density. The relationships between CT metrics and OS were analyzed using Cox regression models, with adjustment for baseline participant characteristics. RESULTS Of 98 eligible participants with available baseline abdominal CT, 8 were excluded because of imaging quality (eg, orthopedic hardware), resulting in 90 evaluable cases: 51 men (57.0%; mean age, 63.2 years [SD, 8.5]; mean body mass index [BMI], 29.3 kg/m2 [SD, 6.4]), 80 White (89.0%), 6 Black (7.0%), and 4 unknown race (4.0%). Sarcopenia was present in 32 participants (35.9%), and sarcopenic obesity was present in 10 participants (11.2%). Univariable analyses for the 6 variables of interest indicated that the standardized mean difference (hazard ratio [HR], 0.75; 95% CI, 0.57-0.98; P = .04) was statistically significantly associated with OS. In models adjusted for sex, race, age, BMI, performance score, contrast use, sarcopenia, and sarcopenic obesity, VATA was statistically significantly associated with OS (HR, 1.58; 95% CI, 1.00-2.51; P = .05). No difference was observed in OS between participants according to sarcopenic obesity or sarcopenia categories. The median OS estimates were 25.1 months for participants without sarcopenic obesity, 18.6 months for participants with sarcopenic obesity, 23.6 months for participants without sarcopenia, and 27.9 months for participants with sarcopenia. CONCLUSION This was the first study to systematically evaluate body composition parameters in a prospective multicenter trial of patients with resectable PDA who received perioperative chemotherapy. Visceral adipose tissue was associated with survival; however, there was no association between OS and sarcopenia or sarcopenic obesity. Further studies should evaluate these findings in more detail.
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Affiliation(s)
| | - Robert D Boutin
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington State, United States
| | - Leon Lenchik
- Stanford University, Stanford, California, United States
| | - Jiyoon Kim
- Wake Forest University, Winston-Salem, North Carolina, United States
| | - M Shaalan Beg
- University of Texas Southwestern Medical Center, Dallas, Texas, United States
| | - Andrea Wang-Gillam
- Washington University School of Medicine in St. Louis, St. Louis, Missouri, United States
| | - James Lloyd Wade
- Heartland Cancer Research National Cancer Institute Community Oncology Research Program, Decatur, Illinois, United States
| | - Katherine A Guthrie
- Southwest Oncology Group Statistics and Data Management Center, Seattle, Washington State, United States
| | - E Gabriela Chiorean
- University of Washington, Fred Hutchinson Cancer Research Center, Seattle, Washington State, United States
| | - Syed A Ahmad
- University of Cincinnati, Cincinnati, Ohio, United States
| | - Andrew M Lowy
- University of California San Diego Moores Cancer Center, La Jolla, California, United States
| | | | - Victor Tsu-Shih Chang
- Section of Hematology/Oncology, Veterans Administration New Jersey Health Care System, East Orange, New Jersey, United States
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12
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Stoop TF, Theijse RT, Seelen LWF, Groot Koerkamp B, van Eijck CHJ, Wolfgang CL, van Tienhoven G, van Santvoort HC, Molenaar IQ, Wilmink JW, Del Chiaro M, Katz MHG, Hackert T, Besselink MG. Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer. Nat Rev Gastroenterol Hepatol 2024; 21:101-124. [PMID: 38036745 DOI: 10.1038/s41575-023-00856-2] [Citation(s) in RCA: 51] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/05/2023] [Indexed: 12/02/2023]
Abstract
Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda.
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Affiliation(s)
- Thomas F Stoop
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Rutger T Theijse
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands
- Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Leonard W F Seelen
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, Netherlands
| | - Casper H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, Netherlands
| | - Christopher L Wolfgang
- Division of Surgical Oncology, Department of Surgery, New York University Medical Center, New York City, NY, USA
| | - Geertjan van Tienhoven
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Radiation Oncology, Amsterdam, Netherlands
| | - Hjalmar C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - Johanna W Wilmink
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Medical Oncology, Amsterdam, Netherlands
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Marc G Besselink
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands.
- Cancer Center Amsterdam, Amsterdam, Netherlands.
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13
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Damm M, Efremov L, Jalal M, Nadeem N, Dober J, Michl P, Wohlgemuth WA, Wadsley J, Hopper AD, Krug S, Rosendahl J. Body composition parameters predict survival in pancreatic cancer-A retrospective multicenter analysis. United European Gastroenterol J 2023; 11:998-1009. [PMID: 37987099 PMCID: PMC10720684 DOI: 10.1002/ueg2.12489] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 07/31/2023] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND Parameters to adapt individual treatment strategies for patients with pancreatic ductal adenocarcinoma (PDAC) are urgently needed. The present study aimed to evaluate body composition parameters as predictors of overall survival (OS) in PDAC patients. METHODS Measurements of body composition parameters were performed on computed tomography scans at diagnosis. Height-standardized and Body Mass Index- and sex-adjusted regression formulas deriving cut-offs from a healthy population were used. The Kaplan-Meier method with the log-rank test was performed for survival analysis. Independent prognostic factors were identified with uni- and multivariable Cox regression analyses. RESULTS In total, 354 patients were analyzed. In a multivariable Cox model, besides tumor stage and resection status, only myosteatosis (HR 1.53; 95% CI 1.10-2.14, p = 0.01) was an independent prognostic factor of OS among body composition parameters. Subgroup analyses revealed that the prognostic impact of myosteatosis was higher in patients ≤68 years of age, with advanced tumor stages and patients without curative intended resection. CONCLUSIONS The analysis of one of the largest Caucasian cohorts to date, demonstrated myosteatosis to be an independent prognostic factor of OS in PDAC. To improve outcomes, prospective trials aiming to investigate the utility of an early assessment of myosteatosis with subsequent intervention by dieticians, sports medicine physicians, and physiotherapists are warranted.
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Affiliation(s)
- Marko Damm
- Department of Internal Medicine I, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
| | - Ljupcho Efremov
- Institute for Medical Epidemiology, Biometrics and Informatics (IMEBI), Interdisciplinary Center for Health Sciences, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
- Department of Radiation Oncology, Martin-Luther-University, Halle (Saale), Germany
| | - Mustafa Jalal
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Nabeegh Nadeem
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Johannes Dober
- Department of Radiology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
| | - Patrick Michl
- Department of Internal Medicine I, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
| | - Walter A Wohlgemuth
- Department of Radiology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
| | | | - Andrew D Hopper
- Department of Infection and Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Sebastian Krug
- Department of Internal Medicine I, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
| | - Jonas Rosendahl
- Department of Internal Medicine I, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
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14
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Wu HY, Liu T, Zhong T, Zheng SY, Zhai QL, Du CJ, Wu TZ, Li JZ. Research trends and hotspots of neoadjuvant therapy in pancreatic cancer: a bibliometric analysis based on the Web of Science Core Collection. Clin Exp Med 2023; 23:2473-2485. [PMID: 36773211 DOI: 10.1007/s10238-023-01013-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 01/26/2023] [Indexed: 02/12/2023]
Abstract
Neoadjuvant therapy (NAT) for pancreatic cancer (PC) has achieved certain results. This article was aimed to analyze the trends in NAT in PC over the past 20 years using bibliometric analysis and visualization tools to guide researchers in exploring future research hotspots. Articles related to NAT for PC were retrieved from the Web of Science Core Collection for the period 2002-2021. The information was analyzed and visualized using VOSviewer, Citespace, Microsoft Excel and R software. The number of articles per year has continued to increase over the past 20 years. Of the 1,598 eligible articles, the highest number was from the United States (760), and an analysis of institutions indicated that the University of Texas System (150) had the highest number of articles. Matthew H. G. Katz had the highest number of citations and the highest H-index. "Pancreatic cancer" (981), "Resection" (623), "Cancer" (553), "Neoadjuvant therapy" (509) and "Survival" (484) were the top five ranked keywords. Combined with the keywords-cluster analysis and citation burst analysis, current research hotspots were the optimal NAT regimen, NAT response assessment, NAT for resectable PC and management of complications. NAT has received increasing attention in the field of PC over the past 20 years, but greater collaboration between countries and additional multicenter randomized clinical trials are needed. Overall, we have revealed current research hotspots and provided valuable information for the choice of future research directions.
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Affiliation(s)
- Hong-Yu Wu
- Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Chongqing, 400010, Yuzhong District, People's Republic of China
| | - Tao Liu
- Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Chongqing, 400010, Yuzhong District, People's Republic of China
| | - Tao Zhong
- Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Chongqing, 400010, Yuzhong District, People's Republic of China
| | - Si-Yuan Zheng
- Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Chongqing, 400010, Yuzhong District, People's Republic of China
| | - Qi-Long Zhai
- Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Chongqing, 400010, Yuzhong District, People's Republic of China
| | - Chang-Jie Du
- Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Chongqing, 400010, Yuzhong District, People's Republic of China
| | - Tian-Zhu Wu
- Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Chongqing, 400010, Yuzhong District, People's Republic of China
| | - Jin-Zheng Li
- Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Chongqing, 400010, Yuzhong District, People's Republic of China.
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15
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Klassen PN, Baracos V, Ghosh S, Martin L, Sawyer MB, Mazurak VC. Muscle and Adipose Wasting despite Disease Control: Unaddressed Side Effects of Palliative Chemotherapy for Pancreatic Cancer. Cancers (Basel) 2023; 15:4368. [PMID: 37686641 PMCID: PMC10486774 DOI: 10.3390/cancers15174368] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 08/21/2023] [Accepted: 08/29/2023] [Indexed: 09/10/2023] Open
Abstract
Muscle and adipose wasting during chemotherapy for advanced pancreatic cancer (aPC) are associated with poor outcomes. We aimed to quantify the contributions of chemotherapy regimen and tumour progression to muscle and adipose wasting and evaluate the prognostic value of each tissue loss. Of all patients treated for aPC from 2013-2019 in Alberta, Canada (n = 504), computed-tomography (CT)-defined muscle and adipose tissue index changes (∆SMI, ∆ATI, cm2/m2) were measured for patients with CT images available both prior to and 12 ± 4 weeks after chemotherapy initiation (n = 210). Contributions of regimen and tumour response to tissue change were assessed with multivariable linear regression. Survival impacts were assessed with multivariable Cox's proportional hazards models. Tissue changes varied widely (∆SMI: -17.8 to +7.3 cm2/m2, ∆ATI: -106.1 to +37.7 cm2/m2) over 116 (27) days. Tumour progression contributed to both muscle and adipose loss (-3.2 cm2/m2, p < 0.001; -12.4 cm2/m2, p = 0.001). FOLFIRINOX was associated with greater muscle loss (-1.6 cm2/m2, p = 0.013) and GEM/NAB with greater adipose loss (-11.2 cm2/m2, p = 0.002). The greatest muscle and adipose losses were independently associated with reduced survival (muscle: HR 1.72, p = 0.007; adipose: HR 1.73, p = 0.012; tertile 1 versus tertile 3). Muscle and adipose losses are adverse effects of chemotherapy and may require regimen-specific management strategies.
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Affiliation(s)
- Pamela N. Klassen
- Department of Agricultural, Food & Nutritional Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Vickie Baracos
- Department of Oncology, University of Alberta, Edmonton, AB T6G 2P5, Canada
| | - Sunita Ghosh
- Department of Oncology, University of Alberta, Edmonton, AB T6G 2P5, Canada
| | - Lisa Martin
- Nutrition Services, Alberta Health Services, Edmonton, AB T5J 3E4, Canada
| | - Michael B. Sawyer
- Department of Oncology, University of Alberta, Edmonton, AB T6G 2P5, Canada
| | - Vera C. Mazurak
- Department of Agricultural, Food & Nutritional Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada
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16
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Hanna L, Sellahewa R, Huggins CE, Lundy J, Croagh D. Relationship between circulating tumour DNA and skeletal muscle stores at diagnosis of pancreatic ductal adenocarcinoma: a cross-sectional study. Sci Rep 2023; 13:9663. [PMID: 37316578 DOI: 10.1038/s41598-023-36643-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 06/07/2023] [Indexed: 06/16/2023] Open
Abstract
Low skeletal muscle index (SMI) and low skeletal muscle radiodensity (SMD) are associated with reduced survival time in pancreatic ductal adenocarcinoma (PDAC). The negative prognostic impact of low SMI and low SMD is often reported as independent of cancer stage when using traditional clinical staging tools. Therefore, this study sought to explore the relationship between a novel marker of tumour burden (circulating tumour DNA) and skeletal muscle abnormalities at diagnosis of PDAC. A retrospective cross-sectional study was conducted in patients who had plasma and tumour tissue samples stored in the Victorian Pancreatic Cancer Biobank (VPCB) at diagnosis of PDAC, between 2015 and 2020. Circulating tumour DNA (ctDNA) of patients with G12 and G13 KRAS mutations was detected and quantified. Pre-treatment SMI and SMD derived from analysis of diagnostic computed tomography imaging was tested for its association to presence and concentration of ctDNA, as well as conventional staging, and demographic variables. The study included 66 patients at PDAC diagnosis; 53% female, mean age 68.7 years (SD ± 10.9). Low SMI and low SMD were present in 69.7% and 62.1% of patients, respectively. Female gender was an independent risk factor for low SMI (OR 4.38, 95% CI 1.23-15.55, p = 0.022), and older age an independent risk factor for low SMD (OR 1.066, 95% CI 1.002-1.135, p = 0.044). No association between skeletal muscle stores and concentration of ctDNA (SMI r = - 0.163, p = 0.192; SMD r = 0.097, p = 0.438) or stage of disease according to conventional clinical staging [SMI F(3, 62) = 0.886, p = 0.453; SMD F(3, 62) = 0.717, p = 0.545] was observed. These results demonstrate that low SMI and low SMD are highly prevalent at diagnosis of PDAC, and suggest they are comorbidities of cancer rather than related to the clinical stage of disease. Future studies are needed to identify the mechanisms and risk factors for low SMI and low SMD at diagnosis of PDAC to aid screening and intervention development.
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Affiliation(s)
- Lauren Hanna
- Department of Nutrition, Dietetics and Food, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
- Department of Nutrition and Dietetics, Monash Health, Clayton, VIC, Australia.
| | - Rav Sellahewa
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Monash University, Clayton, VIC, Australia
- Department of Surgery, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
- Department of Upper Gastrointestinal Surgery, Monash Health, Clayton, VIC, Australia
| | - Catherine E Huggins
- Department of Nutrition, Dietetics and Food, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
- Global Obesity Centre (GLOBE), Institute for Health Transformation, School of Health and Social Development, Deakin University, Burwood, VIC, Australia
| | - Joanne Lundy
- Department of Surgery, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
- Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia
| | - Daniel Croagh
- Department of Surgery, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
- Department of Upper Gastrointestinal Surgery, Monash Health, Clayton, VIC, Australia
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17
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Yang L, Liao X, Xie Z, Li H. Prognostic value of pretreatment skeletal muscle index in pancreatic carcinoma patients: A meta-analysis. Medicine (Baltimore) 2023; 102:e33663. [PMID: 37171343 PMCID: PMC10174348 DOI: 10.1097/md.0000000000033663] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 04/07/2023] [Accepted: 04/10/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND The association between pretreatment skeletal muscle index (SMI) and long-term survival of pancreatic carcinoma patients remains unclear up to now. METHODS The PubMed, Web of Science and EMBASE databases were searched up to March 1, 2022 for relevant studies. The primary and secondary outcomes were overall survival and progression-free survival, respectively. The hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to assess the relationship between pretreatment SMI and prognosis of pancreatic carcinoma patients. All statistical analysis was conducted by STATA 15.0 software. RESULTS Twenty retrospective studies involving 3765 patients were included. The pooled results demonstrated that lower pretreatment SMI was significantly related to poorer overall survival (HR = 1.42, 95% CI: 1.25-1.62, P < .001) and progression-free survival (HR = 1.41, 95% CI: 1.08-1.84, P = .012). Besides subgroup analysis based on the treatment (non-surgery vs surgery) and tumor stage (advanced vs early stage) showed similar results. CONCLUSION Pretreatment SMI could serve as a promising and reliable prognostic factor for pancreatic carcinoma patients and lower pretreatment SMI predicted worse prognosis.
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Affiliation(s)
- Li Yang
- Department of Digestive Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, P.R. China
| | - Xianghui Liao
- Department of Digestive Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, P.R. China
| | - Zhong Xie
- Department of Digestive Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, P.R. China
| | - Haiwen Li
- Department of Head and Neck Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, P.R. China
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18
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Takaichi S, Tomimaru Y, Kobayashi S, Toya K, Sasaki K, Iwagami Y, Yamada D, Noda T, Takahashi H, Asaoka T, Tanemura M, Doki Y, Eguchi H. Change Impact of Body Composition During Neoadjuvant Chemoradiotherapy in Patients with Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma Undergoing Pancreatectomy. Ann Surg Oncol 2023; 30:2458-2468. [PMID: 36575288 DOI: 10.1245/s10434-022-12985-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 12/06/2022] [Indexed: 12/28/2022]
Abstract
BACKGROUND The change impact of body composition during neoadjuvant therapy on clinical outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. The aim of this study was to investigate the association between changes in body composition during neoadjuvant chemoradiotherapy (NACRT) and postoperative outcomes in patients with PDAC undergoing pancreatectomy, using three-dimensional images. METHODS We reviewed 66 consecutive patients with resectable/borderline resectable PDAC receiving gemcitabine and S-1 with radiotherapy between April 2010 and June 2016. Body compositions were evaluated pre- and post-NACRT. All patients were hospitalized and supplied with regulated diet during NACRT treatment. RESULTS Psoas major muscle volume index (PMI), abdominal fat volume index, and visceral fat volume index decreased significantly after NACRT (P < 0.0001, P < 0.0001, P < 0.0001, respectively). The post-NACRT CA19-9 level decreased significantly in the small-PMI-decrease group compared with the large-PMI-decrease group (P = 0.046). Recurrence-free survival (RFS) and overall survival (OS) of the large-PMI-decrease group were significantly poorer than those of the small-PMI-decrease group (P = 0.002, P = 0.006, respectively). On the other hand, there were no significant differences in RFS and OS between groups with high and low PMI, at the point of either pre-NACRT (P = 0.117, P = 0.123, respectively) or post-NACRT (P = 0.065, P = 0.064, respectively). Multivariate analysis identified a large percentage decrease in PMI as an independent risk factor for recurrence and death (P = 0.003, P = 0.002, respectively). CONCLUSIONS Loss of skeletal muscle mass during NACRT was an independent risk factor for survival in patients with PDAC.
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Affiliation(s)
- Shohei Takaichi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
| | - Keisuke Toya
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
- Department of Surgery, Osaka Police Hospital, Osaka, Japan
| | - Masahiro Tanemura
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
- Department of Surgery, Rinku General Medical Center, Izumisano, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
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Pedrosa MB, Barbosa S, Vitorino R, Ferreira R, Moreira-Gonçalves D, Santos LL. Chemotherapy-Induced Molecular Changes in Skeletal Muscle. Biomedicines 2023; 11:biomedicines11030905. [PMID: 36979884 PMCID: PMC10045751 DOI: 10.3390/biomedicines11030905] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/10/2023] [Accepted: 03/13/2023] [Indexed: 03/17/2023] Open
Abstract
Paraneoplastic conditions such as cancer cachexia are often exacerbated by chemotherapy, which affects the patient’s quality of life as well as the response to therapy. The aim of this narrative review was to overview the body-composition-related changes and molecular effects of different chemotherapy agents used in cancer treatment on skeletal-muscle remodeling. A literature search was performed using the Web of Science, Scopus, and Science Direct databases and a total of 77 papers was retrieved. In general, the literature survey showed that the molecular changes induced by chemotherapy in skeletal muscle have been studied mainly in animal models and mostly in non-tumor-bearing rodents, whereas clinical studies have essentially assessed changes in body composition by computerized tomography. Data from preclinical studies showed that chemotherapy modulates several molecular pathways in skeletal muscle, including the ubiquitin–proteasome pathway, autophagy, IGF-1/PI3K/Akt/mTOR, IL-6/JAK/STAT, and NF-κB pathway; however, the newest chemotherapy agents are underexplored. In conclusion, chemotherapy exacerbates skeletal-muscle wasting in cancer patients; however, the incomplete characterization of the chemotherapy-related molecular effects on skeletal muscle makes the development of new preventive anti-wasting strategies difficult. Therefore, further investigation on molecular mechanisms and clinical studies are necessary.
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Affiliation(s)
- Mafalda Barbosa Pedrosa
- Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV-REQUIMTE), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
- Research Centre in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal
- Experimental Pathology and Therapeutics Group, Research Center (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center (P.CCC), 4200-072 Porto, Portugal
- Correspondence: (M.B.P.); (L.L.S.)
| | - Samuel Barbosa
- Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV-REQUIMTE), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
- Research Centre in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal
- Experimental Pathology and Therapeutics Group, Research Center (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center (P.CCC), 4200-072 Porto, Portugal
| | - Rui Vitorino
- Department of Medical Sciences, Institute of Biomedicine—iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Rita Ferreira
- Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV-REQUIMTE), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Daniel Moreira-Gonçalves
- Research Centre in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal
| | - Lúcio Lara Santos
- Experimental Pathology and Therapeutics Group, Research Center (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center (P.CCC), 4200-072 Porto, Portugal
- Correspondence: (M.B.P.); (L.L.S.)
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20
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Nakajima H, Yamaguchi J, Takami H, Hayashi M, Kodera Y, Nishida Y, Watanabe N, Onoe S, Mizuno T, Yokoyama Y, Ebata T. Impact of skeletal muscle mass on the prognosis of patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer. Int J Clin Oncol 2023; 28:688-697. [PMID: 36872415 DOI: 10.1007/s10147-023-02321-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Accepted: 02/21/2023] [Indexed: 03/07/2023]
Abstract
BACKGROUND Neoadjuvant chemotherapy is a common therapeutic procedure for patients with pancreatic cancer. This study aimed to investigate the association between the total psoas area (TPA) and prognosis in patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer. STUDY DESIGN This retrospective study included patients who underwent neoadjuvant chemotherapy for pancreatic cancer. TPA was measured at the level of the L3 vertebra using computed tomography. The patients were divided into low-TPA and normal-TPA groups. These dichotomizations were separately performed in patients with resectable and those with borderline resectable pancreatic cancer. RESULTS In total, 44 patients had resectable pancreatic cancer and 71 patients had borderline resectable pancreatic cancer. Overall survival among patients with resectable pancreatic cancer did not differ between the normal- and low-TPA groups (median, 19.8 vs. 21.8 months, p = 0.447), whereas among patients with borderline resectable pancreatic cancer, the low-TPA group had shorter overall survival than the normal-TPA group (median, 21.8 vs. 32.9 months, p = 0.006). Among patients with borderline resectable pancreatic cancer, the low-TPA group was predictive of poor overall survival (adjusted hazard ratio, 2.57, p = 0.037). CONCLUSION Low TPA is a risk factor of poor survival in patients undergoing neoadjuvant chemotherapy for borderline resectable pancreatic cancer. TPA evaluation could potentially suggest the treatment strategy in this disease.
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Affiliation(s)
- Hiroki Nakajima
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showaku, Nagoya, Aichi, 466-8550, Japan
- Department of Rehabilitation, Nagoya University Hospital, Nagoya, Japan
| | - Junpei Yamaguchi
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showaku, Nagoya, Aichi, 466-8550, Japan
| | - Hideki Takami
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Hospital, Nagoya, Japan
| | - Masamichi Hayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Hospital, Nagoya, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Hospital, Nagoya, Japan
| | - Yoshihiro Nishida
- Department of Rehabilitation, Nagoya University Hospital, Nagoya, Japan
| | - Nobuyuki Watanabe
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showaku, Nagoya, Aichi, 466-8550, Japan
| | - Shunsuke Onoe
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showaku, Nagoya, Aichi, 466-8550, Japan
| | - Takashi Mizuno
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showaku, Nagoya, Aichi, 466-8550, Japan
| | - Yukihiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showaku, Nagoya, Aichi, 466-8550, Japan.
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showaku, Nagoya, Aichi, 466-8550, Japan
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21
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Suzuki Y, Saito K, Nakai Y, Oyama H, Kanai S, Suzuki T, Sato T, Hakuta R, Ishigaki K, Saito T, Hamada T, Takahara N, Tateishi R, Fujishiro M. Early skeletal muscle mass decline is a prognostic factor in patients receiving gemcitabine plus nab-paclitaxel for unresectable pancreatic cancer: a retrospective observational study. Support Care Cancer 2023; 31:197. [PMID: 36862196 PMCID: PMC9981495 DOI: 10.1007/s00520-023-07659-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 02/22/2023] [Indexed: 03/03/2023]
Abstract
PURPOSE Patients with pancreatic cancer often have cancer cachexia at diagnosis. Recent studies suggested that loss of skeletal muscle mass was related to cancer cachexia, which hindered continuance of chemotherapy and could be one of prognostic factors in pancreatic cancer, however the association remains unclear in patients receiving gemcitabine and nab-paclitaxel (GnP). METHODS We retrospectively studied 138 patients with unresectable pancreatic cancer receiving first-line GnP at the University of Tokyo from January 2015 to September 2020. We calculated body composition in CT images before chemotherapy and at initial evaluation, and evaluated the association of both body composition before chemotherapy and its changes at initial evaluation. RESULTS Compared by skeletal muscle mass index (SMI) change rate between pre-chemotherapy and initial evaluation, there were statistically significantly differences in the median OS: 16.3 months (95%CI 12.3-22.7) and 10.3 months (95%CI 8.3-18.1) between SMI change rate ≥ -3.5% and < -3.5% groups (P = 0.01). By multivariate analysis for OS, CA19-9 (HR 3.34, 95%CI 2.00-5.57, P < 0.01), PLR (HR 1.68, 95%CI 1.01-2.78, P = 0.04), mGPS (HR 2.32, 95%CI 1.47-3.65, P < 0.01) and relative dose intensity (HR 2.21, 95%CI 1.42-3.46, P < 0.01) were significantly poor prognostic factors. SMI change rate (HR 1.47, 95%CI 0.95-2.28, P = 0.08) showed a trend to poor prognosis. Sarcopenia before chemotherapy was not significantly associated with PFS or OS. CONCLUSION Early skeletal muscle mass decline was associated with poor OS. Further investigation is warranted whether the maintenance of skeletal muscle mass by nutritional support would improve prognosis.
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Affiliation(s)
- Yukari Suzuki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kei Saito
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Yousuke Nakai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- Department of Endoscopy and Endoscopic Surgery, The University of Tokyo Hospital, 7-3-1 Hongo Bunkyo-Ku, Tokyo, 113-8655, Japan.
| | - Hiroki Oyama
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Sachiko Kanai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsunori Suzuki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsuya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryunosuke Hakuta
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazunaga Ishigaki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Outpatient Chemotherapy, The University of Tokyo Hospital, Tokyo, Japan
| | - Tomotaka Saito
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tsuyoshi Hamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Naminatsu Takahara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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22
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De Luca R, Gianotti L, Pedrazzoli P, Brunetti O, Rizzo A, Sandini M, Paiella S, Pecorelli N, Pugliese L, Pietrabissa A, Zerbi A, Salvia R, Boggi U, Casirati A, Falconi M, Caccialanza R. Immunonutrition and prehabilitation in pancreatic cancer surgery: A new concept in the era of ERAS® and neoadjuvant treatment. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:542-549. [PMID: 36577556 DOI: 10.1016/j.ejso.2022.12.006] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/21/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022]
Abstract
Pancreatic cancer (PC) is an aggressive disease, with a growing incidence, and a poor prognosis. Neoadjuvant treatments in PC are highly recommended in borderline resectable and recently in upfront resectable PC. PC is characterized by exocrine insufficiency and nutritional imbalance, leading to malnutrition/sarcopenia. The concept of malnutrition in PC is multifaceted, as the cancer-related alterations create an interplay with adverse effects of anticancer treatments. All these critical factors have a negative impact on the postoperative and oncological outcomes. A series of actions and programs can be implemented to improve resectable and borderline resectable PC in terms of postoperative complications, oncological outcomes and patients' quality of life. A timely nutritional evaluation and the implementation of appropriate evidence-based nutritional interventions in onco-surgical patients should be considered of importance to improve preoperative physical fitness. Unfortunately, nutritional care and its optimization are often neglected in real-world clinical practice. Currently available studies and ERAS® guidelines mostly support the use of pre- or perioperative medical nutrition, including immunonutrition, in order to decrease the rate of postoperative infections and length of hospital stay. Further data also suggest that medical nutrition should be considered proactively in PC patients, to possibly prevent severe malnutrition and its consequences on disease and treatment outcomes. This narrative review summarizes the most recent data related to the role of prehabilitation, ERAS® program, medical nutrition, and the timing of intervention on clinical outcomes of upfront resectable and borderline PC, and their potential implementation within the timeframe of neoadjuvant treatments.
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Affiliation(s)
- Raffaele De Luca
- Department of Surgical Oncology, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - Luca Gianotti
- School of Medicine and Surgery, University of Milano-Bicocca, HPB Unit, San Gerardo Hospital, Monza, Italy.
| | - Paolo Pedrazzoli
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo and Department of Internal Medicine, University of Pavia, Pavia, Italy
| | - Oronzo Brunetti
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - Alessandro Rizzo
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - Marta Sandini
- Surgical Oncology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Salvatore Paiella
- General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Nicolò Pecorelli
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Luigi Pugliese
- Department of Surgery, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Andrea Pietrabissa
- Department of Surgery, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS and Humanitas University - Department of Biomedical Sciences Rozzano, Milan, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Ugo Boggi
- Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy
| | - Amanda Casirati
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Riccardo Caccialanza
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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23
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Couderc AL, Liuu E, Boudou-Rouquette P, Poisson J, Frelaut M, Montégut C, Mebarki S, Geiss R, ap Thomas Z, Noret A, Pierro M, Baldini C, Paillaud E, Pamoukdjian F. Pre-Therapeutic Sarcopenia among Cancer Patients: An Up-to-Date Meta-Analysis of Prevalence and Predictive Value during Cancer Treatment. Nutrients 2023; 15:nu15051193. [PMID: 36904192 PMCID: PMC10005339 DOI: 10.3390/nu15051193] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 02/18/2023] [Accepted: 02/21/2023] [Indexed: 03/08/2023] Open
Abstract
This study will address the prevalence of pre-therapeutic sarcopenia (PS) and its clinical impact during cancer treatment among adult cancer patients ≥ 18 years of age. A meta-analysis (MA) with random-effect models was performed via a MEDLINE systematic review, according to the PRISMA statement, focusing on articles published before February 2022 that reported observational studies and clinical trials on the prevalence of PS and the following outcomes: overall survival (OS), progression-free survival (PFS), post-operative complications (POC), toxicities (TOX), and nosocomial infections (NI). A total of 65,936 patients (mean age: 45.7-85 y) with various cancer sites and extensions and various treatment modes were included. Mainly defined by CT scan-based loss of muscle mass only, the pooled prevalence of PS was 38.0%. The pooled relative risks were 1.97, 1.76, 2.70, 1.47, and 1.76 for OS, PFS, POC, TOX, and NI, respectively (moderate-to-high heterogeneity, I2: 58-85%). Consensus-based algorithm definitions of sarcopenia, integrating low muscle mass and low levels of muscular strength and/or physical performance, lowered the prevalence (22%) and heterogeneity (I2 < 50%). They also increased the predictive values with RRs ranging from 2.31 (OS) to 3.52 (POC). PS among cancer patients is prevalent and strongly associated with poor outcomes during cancer treatment, especially when considering a consensus-based algorithm approach.
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Affiliation(s)
- Anne-Laure Couderc
- Internal Medicine Geriatrics and Therapeutic Unit, APHM, 13009 Marseille, France
- CNRS, EFS, ADES, Aix-Marseille University, 13015 Marseille, France
| | - Evelyne Liuu
- Department of Geriatrics, CHU Poitiers, 86000 Poitiers, France
- CIC1402 INSERM Unit, Poitiers University Hospital, 86000 Poitiers, France
| | - Pascaline Boudou-Rouquette
- Ariane Program, Department of Medical Oncology, Cochin Hospital, Paris Cancer Institute CARPEM, APHP, 75014 Paris, France
- INSERM U1016-CNRS UMR8104, Cochin Institute, Paris Cancer Institute CARPEM, Paris Cité University, 75015 Paris, France
| | - Johanne Poisson
- Department of Geriatrics, Georges Pompidou European Hospital, Paris Cancer Institute CARPEM, APHP, 75015 Paris, France
- Faculty of Health, Paris Cité University, 75006 Paris, France
| | - Maxime Frelaut
- Department of Medical Oncology, Gustave Roussy Institute, 94805 Villejuif, France
| | - Coline Montégut
- Internal Medicine Geriatrics and Therapeutic Unit, APHM, 13009 Marseille, France
- Coordination Unit for Geriatric Oncology (UCOG), PACA West, 13009 Marseille, France
| | - Soraya Mebarki
- Department of Geriatrics, Georges Pompidou European Hospital, Paris Cancer Institute CARPEM, APHP, 75015 Paris, France
| | - Romain Geiss
- Department of Medical Oncology, Curie Institute, 92210 Saint-Cloud, France
| | - Zoé ap Thomas
- Department of Cancer Medicine, Gustave Roussy Institute, 94805 Villejuif, France
| | - Aurélien Noret
- Department of Geriatrics, Georges Pompidou European Hospital, Paris Cancer Institute CARPEM, APHP, 75015 Paris, France
| | - Monica Pierro
- Department of Geriatrics, Georges Pompidou European Hospital, Paris Cancer Institute CARPEM, APHP, 75015 Paris, France
| | - Capucine Baldini
- Drug Development Department, Gustave Roussy Institute, 94805 Villejuif, France
| | - Elena Paillaud
- Department of Geriatrics, Georges Pompidou European Hospital, Paris Cancer Institute CARPEM, APHP, 75015 Paris, France
- INSERM, IMRB, Clinical, Epidemiology and Ageing, Université Paris-Est Creteil, 94010 Creteil, France
| | - Frédéric Pamoukdjian
- Department of Geriatrics, Avicenne Hospital, APHP, 93000 Bobigny, France
- INSERM UMR_S942 Cardiovascular Markers in Stressed Conditions MASCOT, Sorbonne Paris Nord University, 93000 Bobigny, France
- Correspondence:
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24
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Paiella S, Azzolina D, Trestini I, Malleo G, Nappo G, Ricci C, Ingaldi C, Vacca PG, De Pastena M, Secchettin E, Zamboni G, Maggino L, Corciulo MA, Sandini M, Cereda M, Capretti G, Casadei R, Bassi C, Mansueto G, Gregori D, Milella M, Zerbi A, Gianotti L, Salvia R. Body composition parameters, immunonutritional indexes, and surgical outcome of pancreatic cancer patients resected after neoadjuvant therapy: A retrospective, multicenter analysis. Front Nutr 2023; 10:1065294. [PMID: 36860690 PMCID: PMC9968808 DOI: 10.3389/fnut.2023.1065294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 01/23/2023] [Indexed: 02/17/2023] Open
Abstract
BACKGROUND AND AIMS Body composition parameters and immunonutritional indexes provide useful information on the nutritional and inflammatory status of patients. We sought to investigate whether they predict the postoperative outcome in patients with pancreatic cancer (PC) who received neoadjuvant therapy (NAT) and then pancreaticoduodenectomy. METHODS Data from locally advanced PC patients who underwent NAT followed by pancreaticoduodenectomy between January 2012 and December 2019 in four high-volume institutions were collected retrospectively. Only patients with two available CT scans (before and after NAT) and immunonutritional indexes (before surgery) available were included. Body composition was assessed and immunonutritional indexes collected were: VAT, SAT, SMI, SMA, PLR, NLR, LMR, and PNI. The postoperative outcomes evaluated were overall morbidity (any complication occurring), major complications (Clavien-Dindo ≥ 3), and length of stay. RESULTS One hundred twenty-one patients met the inclusion criteria and constituted the study population. The median age at the diagnosis was 64 years (IQR16), and the median BMI was 24 kg/m2 (IQR 4.1). The median time between the two CT-scan examined was 188 days (IQR 48). Skeletal muscle index (SMI) decreased after NAT, with a median delta of -7.8 cm2/m2 (p < 0.05). Major complications occurred more frequently in patients with a lower pre-NAT SMI (p = 0.035) and in those who gained in subcutaneous adipose tissue (SAT) compartment during NAT (p = 0.043). Patients with a gain in SMI experienced fewer major postoperative complications (p = 0.002). The presence of Low muscle mass after NAT was associated with a longer hospital stay [Beta 5.1, 95%CI (1.5, 8.7), p = 0.006]. An increase in SMI from 35 to 40 cm2/m2 was a protective factor with respect to overall postoperative complications [OR 0.43, 95% (CI 0.21, 0.86), p < 0.001]. None of the immunonutritional indexes investigated predicted the postoperative outcome. CONCLUSION Body composition changes during NAT are associated with surgical outcome in PC patients who receive pancreaticoduodenectomy after NAT. An increase in SMI during NAT should be favored to ameliorate the postoperative outcome. Immunonutritional indexes did not show to be capable of predicting the surgical outcome.
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Affiliation(s)
- Salvatore Paiella
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Danila Azzolina
- Department of Environmental and Preventive Science, University of Ferrara, Ferrara, Italy
| | - Ilaria Trestini
- Dietetics Services, Hospital Medical Direction, University Hospital Trust of Verona, Verona, Italy
| | - Giuseppe Malleo
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Gennaro Nappo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Claudio Ricci
- Pancreatic Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
- Department of Internal Medicine and Surgery (DIMEC), S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Carlo Ingaldi
- Pancreatic Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
- Department of Internal Medicine and Surgery (DIMEC), S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Pier Giuseppe Vacca
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Matteo De Pastena
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Erica Secchettin
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Giulia Zamboni
- Radiology Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Laura Maggino
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Maria Assunta Corciulo
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Marta Sandini
- General Surgery Unit, University of Siena, Siena, Italy
| | - Marco Cereda
- School of Medicine and Surgery, University of Milano-Bicocca and HPB Unit, San Gerardo Hospital Monza, Monza, Italy
| | - Giovanni Capretti
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Riccardo Casadei
- Pancreatic Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
- Department of Internal Medicine and Surgery (DIMEC), S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Claudio Bassi
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | | | - Dario Gregori
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Michele Milella
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, Verona, Italy
| | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Luca Gianotti
- School of Medicine and Surgery, University of Milano-Bicocca and HPB Unit, San Gerardo Hospital Monza, Monza, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
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Choi MH, Yoon SB. Sarcopenia in pancreatic cancer: Effect on patient outcomes. World J Gastrointest Oncol 2022; 14:2302-2312. [PMID: 36568942 PMCID: PMC9782618 DOI: 10.4251/wjgo.v14.i12.2302] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 10/29/2022] [Accepted: 11/28/2022] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cancer is a challenging disease with an increasing incidence and extremely poor prognosis. The clinical outcomes of pancreatic cancer depend on tumor biology, responses to treatments, and malnutrition or cachexia. Sarcopenia represents a severe catabolic condition defined by the age-related loss of muscle mass and strength and affects as much as 70% of malnourished pancreatic cancer patients. The lumbar skeletal muscle index, defined as the total abdominal muscle area at the L3 vertebral level adjusted by the square of the height, is widely used for assessing sarcopenia in patients with pancreatic cancer. Several studies have suggested that sarcopenia may be a risk factor for perioperative complications and decreased recurrence-free or overall survival in patients with pancreatic cancer undergoing surgery. Sarcopenia could also intensify chemotherapy-induced toxicities and worsen the quality of life and survival in the neoadjuvant or palliative chemotherapy setting. Sarcopenia, not only at the time of diagnosis but also during treatment, decreases survival in patients with pancreatic cancer. Theoretically, multimodal interventions may improve sarcopenia and clinical outcomes; however, no study has reported positive results. Further prospective studies are needed to confirm the prognostic role of sarcopenia and the effects of multimodal interventions in patients with pancreatic cancer.
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Affiliation(s)
- Moon Hyung Choi
- Department of Radiology, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, South Korea
| | - Seung Bae Yoon
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 03312, South Korea
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Hashimoto D, Satoi S, Yamamoto T, Yamaki S, Ishida M, Hirooka S, Shibata N, Boku S, Ikeura T, Sekimoto M. Long-term outcomes of patients with multifocal intraductal papillary mucinous neoplasm following pancreatectomy. Pancreatology 2022; 22:1046-1053. [PMID: 35871123 DOI: 10.1016/j.pan.2022.07.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 06/29/2022] [Accepted: 07/11/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND The decision to perform surgery is complicated by the presence of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs), which are characterized by two or more cysts located in different areas of the pancreas. OBJECTIVES We aimed to establish a suitable treatment strategy and surgical indications in patients with MF-IPMNs. METHODS This single-center retrospective study included patients with IPMNs who underwent pancreatic resection from 2006 to 2020. Patients with distant metastasis and patients with IPMNs of the main pancreatic duct were excluded from the analysis. RESULTS After excluding 22 patients, 194 patients were included. One hundred thirteen patients (58.2%) had unifocal IPMNs, while 81 patients (41.8%) had MF-IPMNs. There were no significant differences in the 5-year disease-specific survival (DSS) rate (92.3% vs. 92.4%, p = 0.976) and the 5-year disease-free survival rate (88.6% vs. 86.5%, p = 0.461). The multivariate analysis identified high-risk stigmata, invasive carcinoma, and lymph node metastasis as independent predictors of DSS. The presence of cystic lesions in the pancreatic remnant was not a predictor of survival. Even in the MF-IPMN group, there were no significant differences in DSS when stratified by procedure (total pancreatectomy vs. segmental pancreatectomy, p = 0.268) or presence of cystic lesions in the pancreatic remnant (p = 0.476). The multivariate analysis identified lymph node metastasis as an independent predictor of DSS in the MF-IPMN group. CONCLUSIONS In patients with MF-IPMNs, each cyst should be evaluated individually for the presence of features associated with malignancy.
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Affiliation(s)
- Daisuke Hashimoto
- Department of Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
| | - Sohei Satoi
- Department of Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan; Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
| | - Tomohisa Yamamoto
- Department of Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
| | - So Yamaki
- Department of Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
| | - Mitsuaki Ishida
- Department of Pathology, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
| | - Satoshi Hirooka
- Department of Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
| | - Nobuhiro Shibata
- Cancer Treatment Center, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
| | - Shogen Boku
- Cancer Treatment Center, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
| | - Tsukasa Ikeura
- Third Department of Internal Medicine, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
| | - Mitsugu Sekimoto
- Department of Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
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Scopel Poltronieri T, de Paula NS, Chaves GV. Skeletal muscle radiodensity and cancer outcomes: A scoping review of the literature. Nutr Clin Pract 2022; 37:1117-1141. [PMID: 34752653 DOI: 10.1002/ncp.10794] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Patients with cancer are more prone to experience myosteatosis than healthy individuals. The aim of this review was to summarize the methodologies applied for low skeletal muscle radiodensity (SMD) assessment in oncology patients, as well as to describe the major findings related to SMD and cancer outcomes. This scoping review included studies that were published until November 2020 in English, Portuguese, or Spanish; were performed in humans diagnosed with cancer, adult and/or elderly, of both sexes; investigated SMD through computed tomography of the region between the third and fifth lumbar vertebrae, considering at least two muscular groups; and evaluated clinical and/or surgical outcomes. Eighty-eight studies met the inclusion criteria (n = 37,583 patients). Survival was the most evaluated outcome. Most studies reported a significant association between low SMD and unfavorable outcomes. However, this relationship was not clear for survival, antineoplastic treatment, and surgical complications, potentially because of the unstandardized approaches for the assessment of SMD and inadequate study design. Future studies should address these issues to provide an in-depth understanding of the clinical relevance of SMD in cancer outcomes as well as how SMD is influenced by individuals and tumor-related characteristics in patients with cancer.
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Affiliation(s)
- Taiara Scopel Poltronieri
- Department of Nutrition, Cancer Hospital II, National Cancer Institute José Alencar Gomes da Silva (INCA), Rio de Janeiro, Rio de Janeiro, Brazil
- Postgraduate Program in Medical Sciences, Endocrinology, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Nathália Silva de Paula
- Department of Nutrition, Cancer Hospital II, National Cancer Institute José Alencar Gomes da Silva (INCA), Rio de Janeiro, Rio de Janeiro, Brazil
| | - Gabriela Villaça Chaves
- Department of Nutrition, Cancer Hospital II, National Cancer Institute José Alencar Gomes da Silva (INCA), Rio de Janeiro, Rio de Janeiro, Brazil
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28
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Gong J, Thomassian S, Kim S, Gresham G, Moshayedi N, Ye JY, Yang JC, Jacobs JP, Lo S, Nissen N, Gaddam S, Tighiouart M, Osipov A, Hendifar A. Phase I trial of Bermekimab with nanoliposomal irinotecan and 5-fluorouracil/folinic acid in advanced pancreatic ductal adenocarcinoma. Sci Rep 2022; 12:15013. [PMID: 36056179 PMCID: PMC9440135 DOI: 10.1038/s41598-022-19401-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 08/29/2022] [Indexed: 11/09/2022] Open
Abstract
In this phase I dose-escalation trial, we assess the maximum tolerated dose (MTD) of Bermekimab in combination with Nanoliposomal Irinotecan (Nal-Iri) and 5-Fluorouracil/Folinic Acid (5-FU/FA). Secondarily, we investigate effects on weight, lean body mass, quality-of-life, the gut microbiome composition, inflammatory biomarkers, progression-free survival, and overall survival. This was a single-arm, open-label adaptive Bayesian dose-escalation study of Bermekimab combined with Nal-Iri and 5FU/FA in patients with advanced or locally advanced PDAC who failed gemcitabine-based chemotherapy. 22 patients enrolled between 2017 and 2019. 3 of 21 patients experienced dose-limiting toxicities attributable to the chemotherapy backbone. 58% (10/17) of patients exhibited weight stability. Physical performance status was preserved among all subjects. Patients reported improvements in quality-of-life metrics via QLQ-PAN26 questioner (-3.6, p = 0.18) and functional well-being (1.78, p = 0.02). Subjects exhibited a decrease in inflammatory cytokines, notably, vascular endothelial growth factor (-0.86, p = 0.017) with Bermekimab. Bermekimab treatment was associated with an increased abundance of gut health-promoting bacterial genera Akkermansia, with 3.82 Log2-fold change from baseline. In sum, Bermekimab is safe to be used in conjunction with Nal-Iri and 5-FU/FA chemotherapy. This benign toxicological profile warrants further Phase I/II investigation of Bermekimab in combinatorial strategies, and the impact of anti-IL-1α antibodies on the gut microbiome.Clinical trials registration: NCT03207724 05/07/2017.
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Affiliation(s)
- Jun Gong
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Shant Thomassian
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Sungjin Kim
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Gillian Gresham
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Natalie Moshayedi
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Jason Y Ye
- The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA
| | - Julianne C Yang
- The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA
| | - Jonathan P Jacobs
- The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA
| | - Simon Lo
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Nick Nissen
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Srinivas Gaddam
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Mourad Tighiouart
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Arsen Osipov
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Andrew Hendifar
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
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Xu T, Li ZH, Liu T, Jiang CH, Zhang YJ, Li H, Jiang Y, Zhao J, Guo WJ, Guo JY, Wang L, Li JX, Shen J, Jin GW, Zhang ZW, Li QF. Progress in Research on Antitumor Drugs and Dynamic Changes in Skeletal Muscles. Front Pharmacol 2022; 13:893333. [PMID: 35873591 PMCID: PMC9298970 DOI: 10.3389/fphar.2022.893333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 06/08/2022] [Indexed: 11/24/2022] Open
Abstract
Objective: To review the research progress of reltionship between antitumor drugs and the dynamic changes of the skeletal muscles during treatment phase. Background: Sarcopenia is a common disease in patients with tumors, and it has been agreed that patients with tumors and sarcopenia experience more serious adverse reactions and have a shorter long-term survival after antitumor therapy than patients without sarcopenia. Antitumor drugs whilst beneficial for tumor regression, interferes and synergizes with cancer-induced muscle wasting/sarcopenia, induced myodemia or intramuscular fat and the two conditions often overlap making it difficult to drive conclusions. In recent years, increasing attention has been paid to the dynamic changes in skeletal muscles during antitumor drug therapy. Dynamic changes refer not only measurement skeletal muscle quantity at baseline level, but give more emphasis on the increasing or decreasing level during or end of the whole treatment course. Methods: We retrievaled published English-language original research articles via pubmed, those studies mainly focused on repeated measurements of skeletal muscle index using computed tomography (CT) in cancer patients who received antitumor drug treatment but not received interventions that produced muscle mass change (such as exercise and nutritional interventions). Conclusion: This article will summarize the research progress to date. Most of antineoplastic drug cause skeletal muscle loss during the treatment course, loss of L3 skeletal muscle index is always associated with poor clinical outcomes.
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Affiliation(s)
- Ting Xu
- Ordos Clinical College, Inner Mongolia Medical University, Ordos, China
| | - Zhen-Hao Li
- School of Public Health and Management, Wenzhou Medical University, Wenzhou, China
| | - Ting Liu
- Department of Medical Oncology, Ordos Central Hospital, Ordos, China
| | - Cai-Hong Jiang
- Department of Medical Oncology, Ordos Central Hospital, Ordos, China
| | - Ya-Juan Zhang
- Department of Medical Oncology, Ordos Central Hospital, Ordos, China
| | - Hui Li
- Department of Medical Oncology, Ordos Central Hospital, Ordos, China
| | - Ying Jiang
- Department of Medical Oncology, Ordos Central Hospital, Ordos, China
| | - Juan Zhao
- Department of Medical Oncology, Ordos Central Hospital, Ordos, China
| | - Wen-Jing Guo
- Department of Medical Oncology, Ordos Central Hospital, Ordos, China
| | - Jia-Yuan Guo
- Ordos Clinical College, Inner Mongolia Medical University, Ordos, China
| | - Lu Wang
- Ordos Clinical College, Inner Mongolia Medical University, Ordos, China
| | - Jia-Xuan Li
- Ordos Clinical College, Inner Mongolia Medical University, Ordos, China
| | - Jing Shen
- Ordos Clinical College, Baotou Medical College, Ordos, China
| | - Gao-Wa Jin
- Department of Medical Oncology, Ordos Central Hospital, Ordos, China
| | - Ze-Wei Zhang
- State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Quan-Fu Li
- Department of Medical Oncology, Ordos Central Hospital, Ordos, China
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30
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Gastrointestinal Cancer Patient Nutritional Management: From Specific Needs to Novel Epigenetic Dietary Approaches. Nutrients 2022; 14:nu14081542. [PMID: 35458104 PMCID: PMC9024975 DOI: 10.3390/nu14081542] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/28/2022] [Accepted: 04/05/2022] [Indexed: 02/06/2023] Open
Abstract
Nutritional habits impinge on the health of the gastrointestinal (GI) tract, contributing to GI disorder progression. GI cancer is a widespread and aggressive tumor sensitive to nutritional changes. Indeed, specific nutritional expedients can be adopted to prevent GI cancer onset and to slow down disease activity. Moreover, the patient’s nutritional status impacts prognosis, quality of life, and chemotherapy tolerance. These patients encounter the highest frequency of malnourishment risk, a condition that can progressively evolve into cachexia. Clinical studies dealing with this topic stressed the importance of nutritional counseling and put under the spotlight nutrient delivery, the type of nutrient supplementation, and timing for the start of nutritional management. A medical practitioner well-prepared on the topic of nutrition and cancer should operate in the clinical team dedicated to these oncological patients. This specific expertise needs to be implemented as soon as possible to adopt nutritional interventions and establish a proper patient-tailored dietary regimen. The nutritional gap closure should be prompt during anticancer treatment to stabilize weight loss, improve treatment tolerability, and ameliorate survival rate. Recently, novel nutritional approaches were investigated to target the bidirectional link between epigenetics and metabolism, whose alteration supports the onset, progression, and therapeutic response of GI cancer patients.
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31
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Capurso G, Pecorelli N, Burini A, Orsi G, Palumbo D, Macchini M, Mele R, de Cobelli F, Falconi M, Arcidiacono PG, Reni M. The impact of nutritional status on pancreatic cancer therapy. Expert Rev Anticancer Ther 2022; 22:155-167. [PMID: 34989653 DOI: 10.1080/14737140.2022.2026771] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 01/05/2022] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive disease with poor outcomes. One of the reasons for the dismal prognosis resides in its impressive ability to alter the nutritional status of patients who develop malnutrition, cachexia, anorexia, and sarcopenia in most cases. The ideal way to measure such changes in PDAC patients, in order to readily identify them and avoid complications or discontinuations of treatment is a relatively unexplored area. In addition, most PDAC patients experience pancreatic exocrine insufficiency (PEI) that contributes to the complex puzzle of malnutrition and that can be treated with Pancreatic Enzyme Replacement Therapy (PERT). AREAS COVERED We review current knowledge on the impact of nutritional status on both surgical and medical treatments for PDAC, reporting available data on the causes of malnutrition, characteristics, and advantages of different tools to investigate nutritional status and possible strategies to improve patient outcomes. EXPERT OPINION All PDAC patients should receive a careful nutritional assessment at diagnosis, and this should be repeated alongside their treatment path. Screening tools and biochemical variables or scores are associated with prognosis, but bioimpedance vector analysis (BIVA) and radiological assessment of body composition seem more accurate in predicting clinical outcomes and postoperative complications.
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Affiliation(s)
- Gabriele Capurso
- Pancreas Translational & Clinical Research Center, Pancreato-Biliary Endoscopy & Endosonography Division, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Nicolò Pecorelli
- Pancreas Translational & Clinical Research Center, Division of Pancreatic Surgery, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Alice Burini
- Nutrition Service, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Giulia Orsi
- Pancreas Translational & Clinical Research Center, Oncology Department, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Diego Palumbo
- Pancreas Translational & Clinical Research Center, Department of Radiology & Center for Experimental Imaging, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Marina Macchini
- Pancreas Translational & Clinical Research Center, Oncology Department, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Roberto Mele
- Nutrition Service, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Francesco de Cobelli
- Pancreas Translational & Clinical Research Center, Department of Radiology & Center for Experimental Imaging, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Massimo Falconi
- Pancreas Translational & Clinical Research Center, Division of Pancreatic Surgery, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- Pancreas Translational & Clinical Research Center, Pancreato-Biliary Endoscopy & Endosonography Division, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Michele Reni
- Pancreas Translational & Clinical Research Center, Oncology Department, San Raffaele Scientific Institute IRCCS, Milan, Italy
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Chi MY, Zhang H, Wang YX, Sun XP, Yang QJ, Guo C. Silibinin Alleviates Muscle Atrophy Caused by Oxidative Stress Induced by Cisplatin through ERK/FoxO and JNK/FoxO Pathways. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:5694223. [PMID: 35096269 PMCID: PMC8794676 DOI: 10.1155/2022/5694223] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 12/17/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023]
Abstract
Cisplatin (DDP), a widely used chemotherapeutic drug in cancer treatment, causes oxidative stress, resulting in cancer cachexia and skeletal muscle atrophy. This study investigated the effects and activity of silibinin (SLI) in reducing DDP-induced oxidative stress and skeletal muscle atrophy in vivo and in vitro. SLI alleviated weight loss, food intake, muscle wasting, adipose tissue depletion, and organ weight reduction induced by DDP and improved the reduction of grip force caused by DDP. SLI can attenuated the increase in reactive oxygen species (ROS) levels, the decrease in Nrf2 expression, the decrease in the fiber cross-sectional area, and changes in fiber type induced by DDP. SLI regulated the ERK/FoxO and JNK/FoxO pathways by downregulating the abnormal increase in ROS and Nrf2 expression in DDP-treated skeletal muscle and C2C12 myotube cells. Further, SLI inhibited the upregulation of MAFbx and Mstn, the downregulation of MyHC and MyoG, the increase in protein degradation, and the decrease of protein synthesis. The protective effects of SLI were reversed by cotreatment with JNK agonists and ERK inhibitors. These results suggest that SLI can reduce DDP-induced skeletal muscle atrophy by reducing oxidative stress and regulating ERK/FoxO and JNK/FoxO pathways.
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Affiliation(s)
- Meng-yi Chi
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China
| | - Hong Zhang
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China
- School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Ya-xian Wang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China
| | - Xi-peng Sun
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China
| | - Quan-jun Yang
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China
| | - Cheng Guo
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China
- School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
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Petzel MQB, Ebrus CS. Nutrition in Pancreatic Cancer. PANCREATIC CANCER: A MULTIDISCIPLINARY APPROACH 2022:317-341. [DOI: 10.1007/978-3-031-05724-3_26] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Rovesti G, Valoriani F, Rimini M, Bardasi C, Ballarin R, Di Benedetto F, Menozzi R, Dominici M, Spallanzani A. Clinical Implications of Malnutrition in the Management of Patients with Pancreatic Cancer: Introducing the Concept of the Nutritional Oncology Board. Nutrients 2021; 13:3522. [PMID: 34684523 PMCID: PMC8537095 DOI: 10.3390/nu13103522] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 10/04/2021] [Accepted: 10/05/2021] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cancer represents a very challenging disease, with an increasing incidence and an extremely poor prognosis. Peculiar features of this tumor entity are represented by pancreatic exocrine insufficiency and an early and intense nutritional imbalance, leading to the highly prevalent and multifactorial syndrome known as cancer cachexia. Recently, also the concept of sarcopenic obesity has emerged, making the concept of pancreatic cancer malnutrition even more multifaceted and complex. Overall, these nutritional derangements play a pivotal role in contributing to the dismal course of this malignancy. However, their relevance is often underrated and their assessment is rarely applied in clinical daily practice with relevant negative impact for patients' outcome in neoadjuvant, surgical, and metastatic settings. The proper detection and management of pancreatic cancer-related malnutrition syndromes are of primary importance and deserve a specific and multidisciplinary (clinical nutrition, oncology, etc.) approach to improve survival, but also the quality of life. In this context, the introduction of a "Nutritional Oncology Board" in routine daily practice, aimed at assessing an early systematic screening of patients and at implementing nutritional support from the time of disease diagnosis onward seems to be the right path to take.
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Affiliation(s)
- Giulia Rovesti
- Division of Oncology, Department of Medical and Surgical Sciences of Children and Adults, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (M.R.); (C.B.); (M.D.)
| | - Filippo Valoriani
- Division of Metabolic Diseases and Clinical Nutrition, Department of Specialistic Medicines, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (F.V.); (R.M.)
| | - Margherita Rimini
- Division of Oncology, Department of Medical and Surgical Sciences of Children and Adults, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (M.R.); (C.B.); (M.D.)
| | - Camilla Bardasi
- Division of Oncology, Department of Medical and Surgical Sciences of Children and Adults, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (M.R.); (C.B.); (M.D.)
| | - Roberto Ballarin
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of General Surgery, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (R.B.); (F.D.B.)
| | - Fabrizio Di Benedetto
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of General Surgery, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (R.B.); (F.D.B.)
| | - Renata Menozzi
- Division of Metabolic Diseases and Clinical Nutrition, Department of Specialistic Medicines, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (F.V.); (R.M.)
| | - Massimo Dominici
- Division of Oncology, Department of Medical and Surgical Sciences of Children and Adults, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (M.R.); (C.B.); (M.D.)
| | - Andrea Spallanzani
- Division of Oncology, Department of Medical and Surgical Sciences of Children and Adults, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (M.R.); (C.B.); (M.D.)
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Trestini I, Cintoni M, Rinninella E, Grassi F, Paiella S, Salvia R, Bria E, Pozzo C, Alfieri S, Gasbarrini A, Tortora G, Milella M, Mele MC. Neoadjuvant treatment: A window of opportunity for nutritional prehabilitation in patients with pancreatic ductal adenocarcinoma. World J Gastrointest Surg 2021; 13:885-903. [PMID: 34621468 PMCID: PMC8462076 DOI: 10.4240/wjgs.v13.i9.885] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 05/28/2021] [Accepted: 07/20/2021] [Indexed: 02/06/2023] Open
Abstract
Patients affected by pancreatic ductal adenocarcinoma (PDAC) frequently present with advanced disease at the time of diagnosis, limiting an upfront surgical approach. Neoadjuvant treatment (NAT) has become the standard of care to downstage non-metastatic locally advanced PDAC. However, this treatment increases the risk of a nutritional status decline, which in turn, may impact therapeutic tolerance, postoperative outcomes, or even prevent the possibility of surgery. Literature on prehabilitation programs on surgical PDAC patients show a reduction of postoperative complications, length of hospital stay, and readmission rate, while data on prehabilitation in NAT patients are scarce and randomized controlled trials are still missing. Particularly, appropriate nutritional management represents an important therapeutic strategy to promote tissue healing and to enhance patient recovery after surgical trauma. In this regard, NAT may represent a new interesting window of opportunity to implement a nutritional prehabilitation program, aiming to increase the PDAC patient's capacity to complete the planned therapy and potentially improve clinical and survival outcomes. Given these perspectives, this review attempts to provide an in-depth view of the nutritional derangements during NAT and nutritional prehabilitation program as well as their impact on PDAC patient outcomes.
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Affiliation(s)
- Ilaria Trestini
- Section of Oncology, Department of Medicine, Pancreas Institute, University of Verona Hospital Trust, Verona 37126, Italy
| | - Marco Cintoni
- Scuola di Specializzazione in Scienza dell’Alimentazione, Università di Roma Tor Vergata, Roma 00133, Italy
| | - Emanuele Rinninella
- UOC Nutrizione Clinica, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli IRCCS, Roma 00168, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma 00168, Italy
| | - Futura Grassi
- UOC Nutrizione Clinica, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli IRCCS, Roma 00168, Italy
| | - Salvatore Paiella
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, Verona 37126, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, Verona 37126, Italy
| | - Emilio Bria
- Oncologia Medica Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Roma 00167, Italy
- Oncologia Medica Unit, Università Cattolica del Sacro Cuore, Roma 00168, Italy
| | - Carmelo Pozzo
- Oncologia Medica Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Roma 00167, Italy
- Oncologia Medica Unit, Università Cattolica del Sacro Cuore, Roma 00168, Italy
| | - Sergio Alfieri
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma 00168, Italy
- Digestive Surgery Unit and Pancreatic Surgery Gemelli Center Director, Fondazione Policlinico Universitario A Gemelli IRCCS, Roma 00167, Italy
| | - Antonio Gasbarrini
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A Gemelli IRCCS, Roma 00167, Italy
| | - Giampaolo Tortora
- Oncologia Medica Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Roma 00167, Italy
- Oncologia Medica Unit, Università Cattolica del Sacro Cuore, Roma 00168, Italy
| | - Michele Milella
- Section of Oncology, Department of Medicine, Pancreas Institute, University of Verona Hospital Trust, Verona 37126, Italy
| | - Maria Cristina Mele
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma 00168, Italy
- UOSD Nutrizione Avanzata in Oncologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A Gemelli IRCCS, Roma 00167, Italy
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Jalal M, Campbell JA, Wadsley J, Hopper AD. Computed Tomographic Sarcopenia in Pancreatic Cancer: Further Utilization to Plan Patient Management. J Gastrointest Cancer 2021; 52:1183-1187. [PMID: 34292498 PMCID: PMC8376713 DOI: 10.1007/s12029-021-00672-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/13/2021] [Indexed: 11/30/2022]
Abstract
Purpose The presence of a sarcopenia adversely affects the prognosis of patients with pancreatic cancer. There is an emerging role for using computed tomography (CT) to calculate skeletal muscle index (SMI) and the presence of sarcopenia. The aim of this study was to assess if detecting ‘computed tomographic sarcopenia’ is feasible and can contribute to the management of patients with locally advanced pancreatic cancer (LAPC). Methods Patients diagnosed with LAPC referred for endoscopic ultrasound-guided biopsy (EUS-B) by our regional cancer network were identified. Age, body mass index (BMI), and Eastern Cooperative Oncology Group performance status (ECOG-PS) were noted. CT images were analysed for SMI and the presence of sarcopenia. Decision outcomes on receiving chemotherapy or not were collected from the regional oncology database. Results In total, 51/204 (25%) patients with LAPC who underwent EUS-B were not given chemotherapy and received best supportive care (BSC) only. The prevalence of sarcopenia (p = 0.0003), age ≥ 75 years old (p = 0.03), and ECOG-PS 2–3 (p = 0.01) were significantly higher in the patients receiving BSC only. Logistic regression analysis demonstrated that SMI was the only independent associated factor identifying patients with LAPC who were treated with BSC only and not chemotherapy after adjusting for age and ECOG-PS. Conclusion Our study has shown that computed tomographic skeletal muscle analysis at the time of a diagnostic CT for patients with pancreatic cancer is feasible and can detect sarcopenia and malnourished patients who are much less likely to take up chemotherapy. These patients could be triaged to oncology assessment prior to EUS-B to avoid unnecessary investigations.
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Affiliation(s)
- Mustafa Jalal
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK.
| | - Jennifer A Campbell
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK
| | - Jonathan Wadsley
- Department of Oncology, Weston Park Hospital, Whitham Road, Sheffield, S10 2SJ, UK
| | - Andrew D Hopper
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK
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Grant C, Loman B, Bailey M, Pyter L. Manipulations of the gut microbiome alter chemotherapy-induced inflammation and behavioral side effects in female mice. Brain Behav Immun 2021; 95:401-412. [PMID: 33895287 PMCID: PMC8461613 DOI: 10.1016/j.bbi.2021.04.014] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 04/06/2021] [Accepted: 04/13/2021] [Indexed: 12/27/2022] Open
Abstract
Chemotherapy treatment is associated with acute behavioral side effects (fatigue, anorexia) that significantly reduce patient quality of life and are dose-limiting, thereby increasing mortality (Kidwell et al., 2014). Disruptions to gut homeostasis (diarrhea, constipation, microbial dysbiosis) are also observed in patients receiving chemotherapy. In non-oncological patients, facets of mental health (fatigue, anxiety, depression) correlate with alterations in the gut microbiome, suggestive of a contribution of the gut in CNS disease etiology. The potential gut-to-brain pathway is poorly understood in patients receiving chemotherapy. Our prior studies have demonstrated a correlation between chemotherapy treatment, gut changes, peripheral and central inflammation, and behavioral symptoms in mice. Here we aimed to determine the extent to which chemotherapy-associated gut manipulations modulate the behavioral and biological consequences of chemotherapy. We measured sickness behaviors, peripheral and central inflammatory mediators, and anxiety in conventional or germ-free female mice: 1) cohabitating with mice of the opposite treatment group, 2) pre-treated with broad-spectrum antibiotics, or 3) given an intra-gastric gavage of gut content from chemotherapy-treated mice. In cohabitation studies, presumed coprophagia promoted body mass recovery, however strong associations with inflammation and behavior were not observed. Reduction of gut microbial alpha diversity via antibiotics did not prevent chemotherapy-associated side effects, however the relative abundances of the genera Tyzzerella, Romboutsia, and Turicibacter correlated with circulating inflammatory (IL-1β) and behavioral outcomes (lethargy, anxiety-like behavior). A gut microbiota transplant from chemotherapy-treated mice decreased central locomotion in open field testing, increased circulating CXCL1, and increased hippocampal Il6 and Tnfa in germ-free mice compared to germ-free mice that received a transplant from vehicle-treated mice. Taken together, these data provide further evidence that the gut microbiota likely contributes to the development of chemotherapy-associated side effects. This work has significant implications in the future treatment of anxiety in patients, and warrants future studies using microbe-based treatment options.
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Affiliation(s)
- C.V. Grant
- Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA
| | - B.R. Loman
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA
| | - M.T. Bailey
- Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA.,Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA.,Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA
| | - L.M. Pyter
- Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio, USA.,Department of Psychiatry and Behavioral Health, Ohio State University, Columbus, Ohio, USA.,Department of Neuroscience, The Ohio State University, Columbus, Ohio, USA
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Conceição MS, Derchain S, Vechin FC, Telles G, Maginador GF, Sarian LO, Libardi CA, Ugrinowitsch C. Maintenance of Muscle Mass and Cardiorespiratory Fitness to Cancer Patients During COVID-19 Era and After SARS-CoV-2 Vaccine. Front Physiol 2021; 12:655955. [PMID: 34248658 PMCID: PMC8267586 DOI: 10.3389/fphys.2021.655955] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 05/06/2021] [Indexed: 01/22/2023] Open
Abstract
There is emerging evidence that decreased muscle mass and cardiorespiratory fitness (CRF) are associated with increased risk of cancer-related mortality. This paper aimed to present recommendations to prescribe effective and safe exercise protocols to minimize losses, maintain or even improve muscle mass, strength, and CRF of the cancer patients who are undergoing or beyond treatment during the COVID-19 era. Overall, we recommend performing exercises with bodyweight, elastic bands, or suspension bands to voluntary interruption (i.e., interrupt the exercise set voluntarily, according to their perception of fatigue, before concentric muscular failure) to maintain or increase muscle strength and mass and CRF during COVID-19 physical distancing. Additionally, rest intervals between sets and exercises (i.e., long or short) should favor maintaining exercise intensities between 50 and 80% of maxHR and/or RPE of 12. In an exercise program with these characteristics, the progression of the stimulus must be carried out by increasing exercise complexity, number of sets, and weekly frequency. With feasible exercises attainable anywhere, modulating only the work-to-rest ratio and using voluntary interruption, it is possible to prescribe exercise for a wide range of patients with cancer as well as training goals. Exercise must be encouraged; however, exercise professionals must be aware of the patient's health condition even at a physical distance to provide a safe and efficient exercise program. Exercise professionals should adjust the exercise prescription throughout home confinement whenever necessary, keeping in mind that minimal exercise stimuli are beneficial to patients in poor physical condition.
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Affiliation(s)
- Miguel S Conceição
- School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.,Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil
| | - Sophie Derchain
- Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil
| | | | - Guilherme Telles
- School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil
| | - Guilherme Fiori Maginador
- Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil
| | - Luís Otávio Sarian
- Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil
| | - Cleiton Augusto Libardi
- MUSCULAB-Laboratory of Neuromuscular Adaptations to Resistance Training, Department of Physical Education, Federal University of São Carlos, São Carlos, Brazil
| | - Carlos Ugrinowitsch
- School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil
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Ruby L, Sanabria SJ, Saltybaeva N, Frauenfelder T, Alkadhi H, Rominger MB. Comparison of ultrasound speed-of-sound of the lower extremity and lumbar muscle assessed with computed tomography for muscle loss assessment. Medicine (Baltimore) 2021; 100:e25947. [PMID: 34032704 PMCID: PMC8154376 DOI: 10.1097/md.0000000000025947] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 04/23/2021] [Indexed: 01/04/2023] Open
Abstract
To compare the speed of propagation of ultrasound (US) waves (SoS) of the lower leg with the clinical reference standard computed tomography (CT) at the level of lumbar vertebra 3 (L3) for muscle loss assessment. Both calf muscles of 50 patients scheduled for an abdominal CT were prospectively examined with ultrasound. A plexiglas-reflector located on the opposite side of the probe with the calf in between was used as a timing reference for SoS (m/s). CT measurements were performed at the level of L3 and included area (cm2) and attenuation (HU) of the psoas muscle, abdominal muscles, subcutaneous fat, visceral fat and abdominal area. Correlations between SoS, body mass index (BMI) and CT were determined using Pearson's correlation coefficient. Based on reported CT sarcopenia threshold values, receiver operating characteristic (ROC) analysis was performed for SoS. Inter-examiner agreement was assessed with the median difference, inter-quartile range (IQR) and intraclass correlation coefficients. SoS of the calf correlated moderately with abdominal muscle attenuation (r = 0.48; P < .001), psoas muscle attenuation (r = 0.40; P < .01), abdominal area (r = -0.44; P < .01) and weakly with subcutaneous fat area (r = -0.37; P < .01). BMI correlated weakly with psoas attenuation (r = -0.28; P < .05) and non-significantly with abdominal muscle attenuation. Normalization with abdominal area resulted in moderate correlations with abdominal muscle area for SoS (r = 0.43; P < .01) and BMI (r = -0.46; P < .001). Based on sarcopenia threshold values for skeletal muscle attenuation (SMRA), area under curve (AUC) for SoS was 0.724. Median difference between both examiners was -3.4 m/s with IQR = 15.1 m/s and intraclass correlation coefficient = 0.794. SoS measurements of the calf are moderately accurate based on CT sarcopenia threshold values, thus showing potential for muscle loss quantification.
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Affiliation(s)
- Lisa Ruby
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zürich, Switzerland
| | - Sergio J. Sanabria
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zürich, Switzerland
- Deusto Institute of Technology, University of Deusto/IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
| | - Natalia Saltybaeva
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zürich, Switzerland
| | - Thomas Frauenfelder
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zürich, Switzerland
| | - Hatem Alkadhi
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zürich, Switzerland
| | - Marga B. Rominger
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zürich, Switzerland
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Nakano O, Kawai H, Kobayashi T, Kohisa J, Ikarashi S, Hayashi K, Yokoyama J, Terai S. Rapid decline in visceral adipose tissue over 1 month is associated with poor prognosis in patients with unresectable pancreatic cancer. Cancer Med 2021; 10:4291-4301. [PMID: 33993635 PMCID: PMC8267120 DOI: 10.1002/cam4.3964] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 04/12/2021] [Accepted: 04/15/2021] [Indexed: 01/06/2023] Open
Abstract
Background Involuntary weight loss related to cachexia is common in patients with advanced cancer, but the association between body composition changes and survival is still unclear in pancreatic cancer. Methods We retrospectively reviewed the clinical outcomes of 55 patients with advanced pancreatic cancer undergoing palliative therapy or best supportive care (BSC). The skeletal muscle index (SMI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue area ratio (VSR) were calculated based on the cross‐sectional area on two sets of computed tomography images obtained at cancer diagnosis and 1 month later before treatment. The prognostic value of body composition indexes at diagnosis and the changes in those indexes over 1 month was then evaluated. Results In total, 45 patients (81.8%) received chemotherapy, chemoradiation, or radiation therapy, whereas the remaining patients underwent BSC. There were 27 patients (49.1%) who had low SMI at cancer diagnosis. Univariate analysis showed no significant associations between the baseline body composition indexes including SMI, VATI, SATI, and VSR and survival. Meanwhile, male sex (HR, 2.79; 95% CI, 1.16–6.71, p = 0.022) and higher decrease in VATI over 1 month (HR, 2.41; 95% CI, 1.13–5.13, p = 0.023) were identified as independent risk factors for mortality in multivariate analysis. Conclusion Rapid decline in VAT over 1 month is closely associated with poorer survival in unresectable advanced pancreatic cancer. A short‐term assessment of body composition changes may be a rational approach to predict prognosis in these patients.
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Affiliation(s)
- Oki Nakano
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.,Department of Internal Medicine, Nagaoka Chuo General Hospital, Nagaoka, Japan
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.,Department of Internal Medicine, Niigata Prefectural Shibata Hospital, Shibata, Japan
| | - Takamasa Kobayashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.,Department of Gastroenterology, Nagaoka Red Cross Hospital, Nagaoka, Japan
| | - Junji Kohisa
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.,Department of Gastroenterology, Nagaoka Red Cross Hospital, Nagaoka, Japan
| | - Satoshi Ikarashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Kazunao Hayashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Junji Yokoyama
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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Salinas-Miranda E, Deniffel D, Dong X, Healy GM, Khalvati F, O'Kane GM, Knox J, Bathe OF, Baracos VE, Gallinger S, Haider MA. Prognostic value of early changes in CT-measured body composition in patients receiving chemotherapy for unresectable pancreatic cancer. Eur Radiol 2021; 31:8662-8670. [PMID: 33934171 DOI: 10.1007/s00330-021-07899-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 01/27/2021] [Accepted: 03/16/2021] [Indexed: 12/14/2022]
Abstract
OBJECTIVES Skeletal muscle mass is a prognostic factor in pancreatic ductal adenocarcinoma (PDAC). However, it remains unclear whether changes in body composition provide an incremental prognostic value to established risk factors, especially the Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1). The aim of this study was to determine the prognostic value of CT-quantified body composition changes in patients with unresectable PDAC starting chemotherapy. METHODS We retrospectively evaluated 105 patients with unresectable (locally advanced or metastatic) PDAC treated with FOLFIRINOX (n = 64) or gemcitabine-based (n = 41) first-line chemotherapy within a multicenter prospective trial. Changes (Δ) in skeletal muscle index (SMI), subcutaneous (SATI), and visceral adipose tissue index (VATI) between pre-chemotherapy and first follow-up CT were assessed. Cox regression models and covariate-adjusted survival curves were used to identify predictors of overall survival (OS). RESULTS At multivariable analysis, adjusting for RECISTv1.1-response at first follow-up, ΔSMI was prognostic for OS with a hazard ratio (HR) of 1.2 (95% CI: 1.08-1.33, p = 0.001). No significant association with OS was observed for ΔSATI (HR: 1, 95% CI: 0.97-1.04, p = 0.88) and ΔVATI (HR: 1.01, 95% CI: 0.99-1.04, p = 0.33). At an optimal cutoff of 2.8 cm2/m2 per 30 days, the median survival of patients with high versus low ΔSMI was 143 versus 233 days (p < 0.001). CONCLUSIONS Patients with a lower rate of skeletal muscle loss at first follow-up demonstrated improved survival for unresectable PDAC, regardless of their RECISTv1.1-category. Assessing ΔSMI at the first follow-up CT may be useful for prognostication, in addition to routine radiological assessment. KEY POINTS • In patients with unresectable pancreatic ductal adenocarcinoma, change of skeletal muscle index (ΔSMI) in the early phase of chemotherapy is prognostic for overall survival, even after adjusting for Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1) assessment at first follow-up. • Changes in adipose tissue compartments at first follow-up demonstrated no significant association with overall survival. • Integrating ΔSMI into routine radiological assessment may improve prognostic stratification and impact treatment decision-making at the first follow-up.
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Affiliation(s)
- Emmanuel Salinas-Miranda
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.,Joint Department of Medical Imaging, University Health Network, Sinai Health System and University of Toronto, Toronto, ON, Canada
| | - Dominik Deniffel
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.,Joint Department of Medical Imaging, University Health Network, Sinai Health System and University of Toronto, Toronto, ON, Canada.,Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Xin Dong
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada
| | - Gerard M Healy
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.,Joint Department of Medical Imaging, University Health Network, Sinai Health System and University of Toronto, Toronto, ON, Canada
| | - Farzad Khalvati
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.,Joint Department of Medical Imaging, University Health Network, Sinai Health System and University of Toronto, Toronto, ON, Canada
| | - Grainne M O'Kane
- Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Ontario Institute for Cancer Research, Toronto, ON, Canada
| | - Jennifer Knox
- Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Ontario Institute for Cancer Research, Toronto, ON, Canada
| | - Oliver F Bathe
- Departments of Surgery and Oncology, University of Calgary, Calgary, AB, Canada
| | - Vickie E Baracos
- Department of Oncology, University of Alberta, Edmonton, AB, Canada
| | - Steven Gallinger
- Ontario Institute for Cancer Research, Toronto, ON, Canada.,Hepatobiliary Pancreatic Surgical Oncology Program, University Health Network, Toronto, ON, Canada
| | - Masoom A Haider
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada. .,Joint Department of Medical Imaging, University Health Network, Sinai Health System and University of Toronto, Toronto, ON, Canada. .,Ontario Institute for Cancer Research, Toronto, ON, Canada.
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Abstract
ABSTRACT Diet and exercise interventions may help reverse malnutrition and muscle wasting common in pancreatic cancer. We performed a scoping review to identify the knowledge gaps surrounding diet and exercise interventions. We searched PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature, Embase, ProQuest Theses and Dissertations, and Google Scholar using the umbrella terms of "pancreatic cancer," "diet/nutrition," and "exercise." Included were articles reporting on ambulatory adults with diagnosed pancreatic cancer. Excluded were studies examining prevention and/or risk, animal, or cell lines. Of the 15,708 articles identified, only 62 met the final inclusion criteria. Almost half of the articles were randomized controlled studies (n = 27). Most studies were from the United States (n = 20). The majority examined dietary interventions (n = 41), with 20 assessing the use of omega-3 fatty acids. Exercise interventions were reported in 13 studies, with 8 examining a diet and exercise intervention. Most studies were small and varied greatly in terms of study design, intervention, and outcomes. We identified 7 research gaps that should be addressed in future studies. This scoping review highlights the limited research examining the effect of diet and exercise interventions in ambulatory patients with pancreatic cancer.
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Zhang H, Chi M, Chen L, Sun X, Wan L, Yang Q, Guo C. Daidzein alleviates cisplatin-induced muscle atrophy by regulating Glut4/AMPK/FoxO pathway. Phytother Res 2021; 35:4363-4376. [PMID: 33876509 DOI: 10.1002/ptr.7132] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/22/2021] [Accepted: 04/06/2021] [Indexed: 12/19/2022]
Abstract
Cisplatin (DDP) is widely used in cancer treatment, but DDP can cause skeletal muscle atrophy and cachexia. This study explored the effect and mechanism of daidzein (DAI) in reducing DDP-induced skeletal muscle atrophy and cachexia in vivo and in vitro. DAI alleviated the weight, food intake, muscle, adipose tissue, kidney weight and forelimb grip of LLC tumour-bearing mice after DDP treatment, and did not affect the antitumour effect of DDP. DAI can reduce the decrease of the cross-sectional area of skeletal muscle fibre-induced by DDP and prevent the change of fibre type proportion. In skeletal muscle, it can inhibit Glut4/AMPK/FoxO pathway, down-regulate the expression of atrogin1 and MuRF1, and inhibit skeletal muscle protein degradation. In DDP treated C2C12 myotubes, DAI could inhibit Glut4/AMPK/FoxO pathway to reduce myotubes atrophy, while AMPK agonist MK-3903 could reverse the protective effect of DAI. These results suggest that DAI can alleviate DDP-induced skeletal muscle atrophy by downregulating the expression of Atrogin1 and MuRF1 through the regulation of Glut4/AMPK/FoxO pathway.
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Affiliation(s)
- Hong Zhang
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.,School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Mengyi Chi
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.,School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Linlin Chen
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.,School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xipeng Sun
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China
| | - Lili Wan
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China
| | - Quanjun Yang
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China
| | - Cheng Guo
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.,School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Takeda T, Sasaki T, Mie T, Furukawa T, Yamada Y, Kasuga A, Matsuyama M, Ozaka M, Sasahira N. The impact of body composition on short-term outcomes of neoadjuvant chemotherapy with gemcitabine plus S-1 in patients with resectable pancreatic cancer. Jpn J Clin Oncol 2021; 51:604-611. [PMID: 33479765 DOI: 10.1093/jjco/hyaa247] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 11/20/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Although the efficacy of neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC GS) has recently been reported in resectable pancreatic cancer, severe adverse events were frequently observed. Sarcopenia has been reported to be associated with reduced antitumor response and chemotherapy toxicity in several malignancies. The aim of this study is to evaluate the impact of body composition on short-term outcomes of NAC GS in resectable pancreatic cancer patients. METHODS Clinicopathological data of consecutive patients treated with NAC GS at our institution from February 2019 to April 2020 were retrospectively reviewed. Anthropometric variables were calculated at the third lumbar vertebra using pretreatment computed tomography images. We investigated the association between body composition variables, and antitumor response and chemotherapy toxicity. RESULTS Among 62 patients included in this study, 25 patients (40%) were sarcopenic at diagnosis. Sixty-one patients received surgery at our institution and 57 patients received pancreatic resection (R0/R1 resection 56/1). Fifty-six patients completed two cycles of NAC GS and severe adverse events (≥grade 3) occurred in 42 patients (hematologic toxicity 41 patients [66%]; non-hematologic toxicity 3 patients). Body mass index and total adipose tissue index were significantly lower in sarcopenic patients compared to non-sarcopenic patients. Completion rate of NAC, rate of treatment delay/interruption, relative dose intensity of gemcitabine and S-1, radiological and pathological tumor response after NAC were not different between sarcopenic and non-sarcopenic patients. Furthermore, there was no significant association between body composition, and severe adverse events and intolerance. CONCLUSIONS In our experience, NAC GS was similarly tolerable and effective in resectable pancreatic cancer patients regardless of the presence of sarcopenia.
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Affiliation(s)
- Tsuyoshi Takeda
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Sasaki
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takafumi Mie
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takaaki Furukawa
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yuto Yamada
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akiyoshi Kasuga
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masato Matsuyama
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masato Ozaka
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoki Sasahira
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
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45
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Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform. Cancers (Basel) 2020; 12:cancers12123787. [PMID: 33334063 PMCID: PMC7765482 DOI: 10.3390/cancers12123787] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 11/20/2020] [Accepted: 12/11/2020] [Indexed: 12/20/2022] Open
Abstract
Simple Summary Patients with pancreatic cancer and other advanced cancers suffer from progressive weight loss that reduces treatment response and quality of life and increases treatment toxicity and mortality. Effective interventions to prevent such weight loss, known as cachexia, require molecular markers to diagnose, stage, and monitor cachexia. No such markers are currently validated or in clinical use. This study used a discovery platform to measure changes in plasma proteins in patients with pancreatic cancer compared with normal controls. We found proteins specific to pancreatic cancer and cancer stage, as well as proteins that correlate with cachexia. These include some previously known proteins along with novel ones and implicates both well-known and new molecular mechanisms. Thus, this study provides novel insights into the molecular processes underpinning cancer and cachexia and affords a basis for future validation studies in larger numbers of patients with pancreatic cancer and cachexia. Abstract Patients with pancreatic ductal adenocarcinoma (PDAC) suffer debilitating and deadly weight loss, known as cachexia. Development of therapies requires biomarkers to diagnose, and monitor cachexia; however, no such markers are in use. Via Somascan, we measured ~1300 plasma proteins in 30 patients with PDAC vs. 11 controls. We found 60 proteins specific to local PDAC, 46 to metastatic, and 67 to presence of >5% cancer weight loss (FC ≥ |1.5|, p ≤ 0.05). Six were common for cancer stage (Up: GDF15, TIMP1, IL1RL1; Down: CCL22, APP, CLEC1B). Four were common for local/cachexia (C1R, PRKCG, ELANE, SOST: all oppositely regulated) and four for metastatic/cachexia (SERPINA6, PDGFRA, PRSS2, PRSS1: all consistently changed), suggesting that stage and cachexia status might be molecularly separable. We found 71 proteins that correlated with cachexia severity via weight loss grade, weight loss, skeletal muscle index and radiodensity (r ≥ |0.50|, p ≤ 0.05), including some known cachexia mediators/markers (LEP, MSTN, ALB) as well as novel proteins (e.g., LYVE1, C7, F2). Pathway, correlation, and upstream regulator analyses identified known (e.g., IL6, proteosome, mitochondrial dysfunction) and novel (e.g., Wnt signaling, NK cells) mechanisms. Overall, this study affords a basis for validation and provides insights into the processes underpinning cancer cachexia.
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46
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Zhang H, Chi M, Chen L, Sun X, Wan L, Yang Q, Guo C. Linalool Prevents Cisplatin Induced Muscle Atrophy by Regulating IGF-1/Akt/FoxO Pathway. Front Pharmacol 2020; 11:598166. [PMID: 33390985 PMCID: PMC7774296 DOI: 10.3389/fphar.2020.598166] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 11/10/2020] [Indexed: 12/14/2022] Open
Abstract
Skeletal muscle atrophy is an important feature of cancer cachexia, which can be induced by chemotherapy, and affects the survival and quality of life of cancer patients seriously. No specific drugs for cancer cachexia have been applied in clinical practice. This study explored the therapeutic effect of linalool (LIN) on cisplatin (DDP) induced skeletal muscle atrophy. In vivo, LIN can improve skeletal muscle weight loss, anorexia, muscle strength decline and other cachexia symptoms caused by cisplatin treatment in a Lewis lung cancer tumor bearing mouse model, and cause no adverse effects on the anti-tumour effect. LIN treatment decreased the expression of muscle RING-finger protein-1 (MuRF1) and Atrogin1(MAFbx) in muscle, and the activation of insulin-like growth factor-1 (IGF-1)/protein kinase B (Akt)/forkhead box O (FoxO) pathway was observed. In vitro, LIN alleviated DDP induced C2C12 myotube atrophy, and IGF-1 receptor inhibitor Picropodophyllin (PIC), which had no adverse effect on C2C12 myotube cells, could reverse the protective effect of LIN. These results indicate that LIN down-regulates the expression of Atrogin1 and MuRF1 through the IGF-1/Akt/FoxO pathway, alleviating DDP-induced muscle atrophy and improving cachexia symptoms. LIN has the potential to be developed as a drug against cancer cachexia.
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Affiliation(s)
- Hong Zhang
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.,School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Mengyi Chi
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.,School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Linlin Chen
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.,School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xipeng Sun
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China
| | - Lili Wan
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China
| | - Quanjun Yang
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China
| | - Cheng Guo
- Department of Pharmacy, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.,School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Baimas-George M, Watson M, Thompson K, Shastry V, Iannitti D, Martinie JB, Baker E, Parala-Metz A, Vrochides D. Prehabilitation for Hepatopancreatobiliary Surgical Patients: Interim Analysis Demonstrates a Protective Effect From Neoadjuvant Chemotherapy and Improvement in the Frailty Phenotype. Am Surg 2020; 87:714-724. [PMID: 33170023 DOI: 10.1177/0003134820952378] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Prehabilitation encompasses multidisciplinary interventions to improve health and lessen incidence of surgical deterioration by reducing physiologic stress and functional decline. This study presents an interim analysis to demonstrate prehabilitation for hepatopancreatobiliary (HPB) surgical patients. METHODS In 2018, a structured prehabilitation pilot program was implemented. Eligibility required HPB malignancy, neoadjuvant chemotherapy, and residence within hour drive. Patients were enrolled into the 4-month program. The fitness component was composed of timed up and go test and grip strength with exercise recommendations. Nutrition involved evaluation of sarcopenic obesity, glucose management, and smoking and alcohol counseling. Psychological services included psychosocial assessments and advanced care planning, with social work referrals. Component were evaluated monthly by a physician using laboratory results, nutritional data and questionnaires, psychological assessments, and validated fitness tests. Nurse navigators spoke with patients weekly to monitor compliance. RESULTS At 12 months, nineteen patients were enrolled. Ten completed prehabilitation, neoadjuvant chemotherapy and underwent their surgical procedure. There were no differences found after prehabilitation in functional status, physical performance, psychosocial assessments, or nutrition. Frailty, as assessed by Fried frailty criteria, improved significantly after prehabilitation (P < .0001). Symptom severity and laboratory values did not change. Length of stay was 6.5 days and all patients were discharged to home. There was 1 readmission for transient ischemic attack and 90-day mortality rate was 0%. DISCUSSION Prehabilitation to improve recovery is a promising concept encompassing a wide array of multidisciplinary assessments and interventions. It may demonstrate a protective effect on physiologic decline from chemotherapy and may reverse frailty phenotypes.
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Affiliation(s)
- Maria Baimas-George
- Division of Hepatobiliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
| | - Michael Watson
- Division of Hepatobiliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
| | - Kyle Thompson
- Division of Hepatobiliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
| | - Vivek Shastry
- Division of Hepatobiliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
| | - David Iannitti
- Division of Hepatobiliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
| | - John B Martinie
- Division of Hepatobiliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
| | - Erin Baker
- Division of Hepatobiliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
| | - Armida Parala-Metz
- Department of Supportive Oncology, Levine Cancer Institute, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
| | - Dionisios Vrochides
- Division of Hepatobiliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
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Valan CD, Halvorsen TO, Slaaen M, Grønberg BH. Changes in muscle measures during chemoradiotherapy in patients with limited stage small cell lung cancer. JCSM CLINICAL REPORTS 2020. [DOI: 10.1002/crt2.31] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Affiliation(s)
- Christine Damgaard Valan
- Department of Clinical and Molecular Medicine NTNU, Norwegian University of Science and Technology Trondheim Norway
- The Cancer Clinic St. Olav's Hospital, Trondheim University Hospital Trondheim Norway
| | - Tarje Onsøien Halvorsen
- Department of Clinical and Molecular Medicine NTNU, Norwegian University of Science and Technology Trondheim Norway
- The Cancer Clinic St. Olav's Hospital, Trondheim University Hospital Trondheim Norway
| | - Marit Slaaen
- Department of Internal Medicine Innlandet Hospital Trust Hamar Norway
- Institute of Clinical Medicine, Faculty of Medicine University of Oslo Oslo Norway
| | - Bjørn Henning Grønberg
- Department of Clinical and Molecular Medicine NTNU, Norwegian University of Science and Technology Trondheim Norway
- The Cancer Clinic St. Olav's Hospital, Trondheim University Hospital Trondheim Norway
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49
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Zhao X, Cao D, Ren Z, Liu Z, Lv S, Zhu J, Li L, Lang R, He Q. Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma. Biosci Rep 2020; 40:BSR20200214. [PMID: 32701143 PMCID: PMC7396423 DOI: 10.1042/bsr20200214] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 07/07/2020] [Accepted: 07/21/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Hypermethylation of gene promoters plays an important role in tumorigenesis. The present study aimed to identify and validate promoter methylation-driven genes (PMDGs) for pancreatic ductal adenocarcinoma (PDAC). METHODS Based on GSE49149 and the PDAC cohort of The Cancer Genome Atlas (TCGA), differential analyses of promoter methylation, correlation analysis, and Cox regression analysis were performed to identify PMDGs. The promoter methylation level was assessed by bisulfite sequencing polymerase chain reaction (BSP) in paired tumor and normal tissues of 72 PDAC patients. Kaplan-Meier survival analyses were performed to evaluate the clinical value of PMDGs. RESULTS In GSE49149, the β-value of the dipeptidyl peptidase like 6 (DPP6) promoter was significantly higher in tumor compared with normal samples (0.50 vs. 0.24, P<0.001). In the PDAC cohort of TCGA, the methylation level of the DPP6 promoter was negatively correlated with mRNA expression (r = -0.54, P<0.001). In a multivariate Cox regression analysis, hypermethylation of the DPP6 promoter was an independent risk factor for PDAC (hazard ratio (HR) = 543.91, P=0.002). The results of BSP revealed that the number of methylated CG sites in the DPP6 promoter was greater in tumor samples than in normal samples (7.43 vs. 2.78, P<0.001). The methylation level of the DPP6 promoter was moderately effective at distinguishing tumor from normal samples (area under ROC curve (AUC) = 0.74, P<0.001). Hypermethylation of the DPP6 promoter was associated with poor overall (HR = 3.61, P<0.001) and disease-free (HR = 2.01, P=0.016) survivals for PDAC patients. CONCLUSION These results indicate that DPP6 promoter methylation is a potential prognostic biomarker for PDAC.
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MESH Headings
- Biomarkers, Tumor/genetics
- Carcinoma, Pancreatic Ductal/genetics
- Carcinoma, Pancreatic Ductal/mortality
- Carcinoma, Pancreatic Ductal/pathology
- Carcinoma, Pancreatic Ductal/therapy
- Chemotherapy, Adjuvant
- CpG Islands/genetics
- DNA Methylation
- Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics
- Disease-Free Survival
- Epigenesis, Genetic
- Follow-Up Studies
- Gene Expression Regulation, Neoplastic
- Humans
- Kaplan-Meier Estimate
- Middle Aged
- Nerve Tissue Proteins/genetics
- Pancreas/pathology
- Pancreas/surgery
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/mortality
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/therapy
- Pancreaticoduodenectomy
- Potassium Channels/genetics
- Prognosis
- Promoter Regions, Genetic/genetics
- Radiotherapy, Adjuvant
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Affiliation(s)
- Xin Zhao
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China
| | - Di Cao
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China
| | - Zhangyong Ren
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China
| | - Zhe Liu
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China
| | - Shaocheng Lv
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China
| | - Jiqiao Zhu
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China
| | - Lixin Li
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China
| | - Ren Lang
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China
| | - Qiang He
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China
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50
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The impact of sarcopenia on patients undergoing treatment for pancreatic ductal adenocarcinoma. JOURNAL OF PANCREATOLOGY 2020. [DOI: 10.1097/jp9.0000000000000046] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
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