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Woo Y, Choi HJ, Lee SH, Choi Y, Park SE, Hong TH, You YK. Perioperative outcomes of sinusoidal obstruction syndrome in patients undergoing liver resection for colorectal metastases after neoadjuvant chemotherapy: a retrospective cohort research. Ann Surg Treat Res 2024; 107:346-353. [PMID: 39669389 PMCID: PMC11634394 DOI: 10.4174/astr.2024.107.6.346] [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: 08/05/2024] [Revised: 09/19/2024] [Accepted: 10/31/2024] [Indexed: 12/14/2024] Open
Abstract
Purpose We investigated the factors that affect the occurrence of sinusoidal obstruction syndrome (SOS) and the effect of SOS on the patient's perioperative outcomes through histological review of liver resection specimens from patients who underwent chemotherapy. Methods From December 2007 to December 2020, liver specimens from patients who underwent liver resection for colorectal liver metastasis after neoadjuvant chemotherapy were analyzed regarding liver damage in the nontumorous lesion. Through pathological review, patients with grade 1-3 sinusoidal dilatation were categorized into the SOS (+) group, compared to a control group (grade 0, SOS [-]). Results Of 286 patients, 175 were included. Preoperative factors were similar between the groups. Although not statistically significant, the SOS (+) group had a shorter chemotherapy-free interval before resection (7.96 weeks vs. 10.0 weeks, P = 0.069). The SOS (+) group had higher intraoperative blood loss (889.1 ± 1,126.6 mL vs. 555.3 ± 566.7 mL, P = 0.012) and transfusion rates (46.6% vs. 25.3%, P = 0.003). SOS correlated with increased liver surgery-specific complications (40.9% vs. 26.4, P = 0.043). Patients with SOS experienced adverse effects on intrahepatic recurrent-free survival and overall survival (5-year survival, 46.0% vs. 33.9%; P = 0.014). Conclusion SOS development during liver surgery is associated with increased intraoperative blood loss, transfusion volume, and liver surgery-specific complications and has a higher risk of early recurrence and decreased overall survival. Thus, it is crucial to exercise caution during liver surgery in these patients.
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Affiliation(s)
- Yoonkyung Woo
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sung Hak Lee
- Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yoonyoung Choi
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sung Eun Park
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Tae Ho Hong
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Young Kyoung You
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Russolillo N, Zingaretti CC, Langella S, Fontana AP, Lo Tesoriere R, Ferrero A. GAME-SCORE predicts pathological and radiological response to chemotherapy in patients with colorectal liver metastases. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108529. [PMID: 39216236 DOI: 10.1016/j.ejso.2024.108529] [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: 04/12/2024] [Revised: 06/28/2024] [Accepted: 06/30/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Genetic And Morphological Evaluation (GAME) score is the newest prognostic model for patient with colorectal liver metastases (CRLMs). Pathological and radiological responses to neoadjuvant chemotherapy (NAC) are key factors for prognostic stratification of these patients. The present study aims to evaluate the GAME-score's ability to predict pathological and radiologic responses to NAC. METHODS CRLM patients who underwent liver resection after NAC from January 2010 to December 2021 were categorized by GAME scores: low risk (LR, 0-1), moderate risk (MR, 2-3), and high risk (HR, ≥4). Correlations between groups and radiological/pathological features were analyzed. Poor pathological response was defined as Tumor Regression Grade 4-5. RESULTS Of 1054 liver resections for CRLMs, 448 were included. GAME scores were LR: 80 (18 %), MR: 228 (51 %), and HR: 140 (31 %). In this cohort, HR-GAME scores were associated with lower pathological response (LR: 67.1 %, MR: 74.9 %, HR: 82.6 %; p = 0.010). Radiologic progression occurred in 10 % of HR patients, significantly more than in LR (3.8 %) and MR (3.5 %) groups (p = 0.011). Multivariable analysis for independent predictors of pathological response confirmed HR-GAME (RR 1.843, p=0.025) along with age higher than 70 years (RR 2.111, p=0.022) and irinotecan-based NAC (RR 3.066, p < 0.001). For radiological progression disease after NAC, the HR-GAME score (RR 2.77, p=0.016) was the only independent predictor. HR-GAME scores were also associated with higher rates of mucinous differentiation (p = 0.021), satellitosis (p = 0.001), vascular invasion (p = 0.011), and perineural invasion (p = 0.010). CONCLUSIONS GAME score category should be considered into planning of therapeutic strategy of patients with CRLMs.
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Affiliation(s)
- Nadia Russolillo
- Department of Oncological and General Surgery, Mauriziano Umberto I Hospital, Largo Turati 62, 10128, Turin, Italy.
| | - Caterina C Zingaretti
- Department of Oncological and General Surgery, Mauriziano Umberto I Hospital, Largo Turati 62, 10128, Turin, Italy
| | - Serena Langella
- Department of Oncological and General Surgery, Mauriziano Umberto I Hospital, Largo Turati 62, 10128, Turin, Italy
| | - Andrea P Fontana
- Department of Oncological and General Surgery, Mauriziano Umberto I Hospital, Largo Turati 62, 10128, Turin, Italy
| | - Roberto Lo Tesoriere
- Department of Oncological and General Surgery, Mauriziano Umberto I Hospital, Largo Turati 62, 10128, Turin, Italy
| | - Alessandro Ferrero
- Department of Oncological and General Surgery, Mauriziano Umberto I Hospital, Largo Turati 62, 10128, Turin, Italy
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Hayashi K, Ono Y, Oba A, Ito H, Sato T, Inoue Y, Saiura A, Takahashi Y. Posthepatectomy Liver Failure in Patients with Splenomegaly Induced by Induction Chemotherapy for Colorectal Liver Metastases. J Gastrointest Cancer 2024; 56:13. [PMID: 39480572 DOI: 10.1007/s12029-024-01130-7] [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] [Accepted: 10/23/2024] [Indexed: 11/02/2024]
Abstract
PURPOSE With advances in chemotherapy, conversion surgery is often performed for initially unresectable colorectal cancer liver metastasis (CLM). However, unexpected posthepatectomy liver failure (PHLF) is sometimes associated with chemotherapy-associated liver injuries following long-term chemotherapy. We aimed to identify predictive factors for PHLF after conversion surgery for initially unresectable CLM. METHODS We retrospectively identified 774 consecutive patients who underwent initial liver resections for histologically confirmed CLMs between 2010 and 2019 at our institute. We enrolled 107 patients with initially unresectable CLMs. Clinicopathological characteristics were evaluated to determine their association with PHLF. Logistic regression analysis was performed to analyze the predictors of PHLF. RESULTS Among the 107 patients, PHLF occurred in 15 cases (14%). Multivariate analysis revealed that splenomegaly during preoperative chemotherapy (> 135%) was an independent risk factor for PHLF (P = 0.002; odds ratio 14.30; 95% confidence interval 2.69-76.08). In the analysis limited to the splenomegaly group, lower platelet counts, increased blood loss and operative times, and large liver resection areas (> 100 cm2) were significant risk factors for PHLF (P = 0.018, 0.043, 0.020, and 0.024, respectively). Among them, a liver resection area > 100 cm2 can be calculated preoperatively and correlate with a complex hepatectomy. CONCLUSION These findings could help predict PHLF after conversion surgery and induction chemotherapy for initially unresectable CLMs. Careful decisions, including detailed procedures and timing of hepatectomy, should be made before conversion hepatectomy in patients who develop splenomegaly after induction chemotherapy and require complex hepatectomies with a large liver resection area.
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Affiliation(s)
- Koki Hayashi
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan
| | - Yoshihiro Ono
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan.
| | - Atsushi Oba
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan
| | - Hiromichi Ito
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan
| | - Takafumi Sato
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan
| | - Yosuke Inoue
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan
| | - Akio Saiura
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Hospital, Bunkyo, Japan
| | - Yu Takahashi
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan.
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Fan L, Stewart F, Ruiz K, Devani D, Fusco N, Gill M, Amber V, Su W, Gangi A, Hanvesakul R. Burden of illness of non-hematopoietic stem cell transplant-related hepatic sinusoidal obstruction syndrome: A systematic review. Heliyon 2024; 10:e36883. [PMID: 39640784 PMCID: PMC11619986 DOI: 10.1016/j.heliyon.2024.e36883] [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: 04/11/2024] [Revised: 07/17/2024] [Accepted: 08/23/2024] [Indexed: 12/07/2024] Open
Abstract
Background Sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD) is generally associated with hematopoietic cell transplant (HCT), but little is known about this condition outside the HCT setting. This systematic review examines the burden of illness and current management approaches in non-HCT SOS/VOD. Methods We searched Embase, Medline, and grey literature sources for non-HCT SOS/VOD studies published 2002-2023. Inclusion criteria were studies of any design reporting incidence, diagnosis, underlying disease and any ongoing treatment at the time of SOS/VOD onset, management of non-HCT SOS/VOD, clinical burden, health-related quality of life, healthcare resource use, costs, and patients' unmet needs. Studies investigating pulmonary VOD or SOS/VOD related to the ingestion of pyrrolizidine alkaloids were excluded.Two authors independently screened results, extracted data, and assessed the methodological quality of studies using the Motheral scale for retrospective studies, Newcastle-Ottawa scale for prospective studies and case control studies, the Cochrane risk of bias tool for randomized controlled trials, and the Joanna Briggs Institute critical appraisal tool for case series. Results were synthesized narratively. Results Ninety-two studies were included; 57 % were retrospective cohort studies and 70 % were conducted in the US or Europe. The study populations included hematological and solid tumor cancers, various indications for liver transplant, Wilms' tumor, and transfusion-dependent beta thalassemia. Non-HCT SOS/VOD occurs most frequently in people with colorectal liver metastases (CRLM), acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). Approximately 35 % of oxaliplatin-treated CRLM patients and 5 % of ALL and AML patients have non-HCT SOS/VOD. Diagnosis varies according to initial disease setting. Defibrotide is the most frequently reported treatment. Most studies did not clearly report their data sources or methods of outcome assessment. Conclusion Non-HCT SOS/VOD occurs in diverse disease conditions, therefore guidelines on diagnosis and treatment are needed to optimize management in clinical practice.
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Affiliation(s)
- Lin Fan
- Jazz Pharmaceuticals, Philadelphia, PA, USA
| | | | | | | | | | | | | | - Wayne Su
- Jazz Pharmaceuticals, Philadelphia, PA, USA
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Cheng X, Zhu C, Chen Y, Li M, Li G, Zu Y, Gao Q, Shang T, Liu D, Zhang C, Ren X. Huaier relieves oxaliplatin-induced hepatotoxicity through activation of the PI3K/AKT/Nrf2 signaling pathway in C57BL/6 mice. Heliyon 2024; 10:e37010. [PMID: 39286172 PMCID: PMC11402744 DOI: 10.1016/j.heliyon.2024.e37010] [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: 01/23/2024] [Revised: 08/25/2024] [Accepted: 08/26/2024] [Indexed: 09/19/2024] Open
Abstract
Hepatotoxicity caused by the anticancer medication oxaliplatin (OXA) significantly restricts its clinical use and raises the risk of liver damage. Huaier, a fungus found in China, has been demonstrated to have various beneficial effects in adjuvant therapy for cancer. However, the preventive impact of Huaier against OXA-induced hepatotoxicity is still unknown. The potential molecular pathways behind the hepatoprotective activity of Huaier against OXA-induced hepatotoxicity were investigated in the current study Mice were intraperitoneally injected with 10 mg/kg of OXA once a week for six consecutive weeks to establish a liver injury model. Huaier (2 g/kg, 4 g/kg, and 8 g/kg) was administered weekly to mice by gavage for six weeks. Commercial kits were used to determine the contents of glutathione, catalase, superoxide dismutase, and malondialdehyde. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to assess the impact of Huaier therapy on the expression of the PI3K pathway. Huaier exhibited a good protective effect on OXA-induced hepatotoxicity in a dose-dependent manner, which was connected to the suppression of oxidative stress, according to the results of biochemical index detection and histological staining analysis. In addition, Huaier could counteract the OXA-induced suppression of the PI3K/AKT signaling pathway. Moreover, the hepatoprotective effect and PI3K activation of Huaier were eradicated by LY294002. These findings imply that by decreasing oxidative stress, Huaier can minimize OXA-induced liver injury, establishing the groundwork for Huaier to lessen chemotherapy-induced hepatotoxicity in clinical practice.
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Affiliation(s)
- Xinwei Cheng
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chen Zhu
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yunzhou Chen
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Min Li
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Guodong Li
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yue Zu
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qianyan Gao
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tianze Shang
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dong Liu
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chengliang Zhang
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiuhua Ren
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Bi X, Zhao H, Zhao H, Li G, Wang X, Chen B, Zhang W, Che X, Huang Z, Han Y, Jiang L, Sun Y, Yang Z, Zhou J, Zhang Y, Zhu Z, Chen M, Cheng S, Cai J. Consensus of Chinese Experts on Neoadjuvant and Conversion Therapies for Hepatocellular Carcinoma: 2023 Update. Liver Cancer 2024:1-16. [DOI: 10.1159/000541249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy in China, with high recurrence rate and low resection rate among patients first diagnosed. Preoperative treatments including neoadjuvant and conversion therapy have the potential to overcome these challenges. In December 2021, Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma was published. With the emersion of new evidence regarding the neoadjuvant and conversion therapies for HCC, the cooperative group brought together multidisciplinary researchers and scholars with experience in related fields to update the new edition (2023 Edition) for reference in China, including principle of the treatment strategies, the potential populations selection, treatment methods, multidisciplinary team, and future research for preoperative treatments. The new consensus aims to provide guidance for clinical application. Through the use of neoadjuvant therapy and conversion therapy, we can enhance the resection rate and reduce the recurrence of intermediate-to-advanced HCC patients, thereby improving survival outcomes.
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Chen YY, Yang L, Li J, Rao SX, Ding Y, Zeng MS. Gadoxetic acid-enhanced magnetic resonance imaging in the assessment of hepatic sinusoidal obstruction syndrome in a mouse model. World J Hepatol 2024; 16:1167-1176. [PMID: 39221094 PMCID: PMC11362905 DOI: 10.4254/wjh.v16.i8.1167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 07/13/2024] [Accepted: 08/02/2024] [Indexed: 08/21/2024] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy can cause hepatic sinusoidal obstruction syndrome (SOS) in patients with colorectal cancer liver metastases and increases postoperative morbidity and mortality. AIM To evaluate T1 mapping based on gadoxetic acid-enhanced magnetic resonance imaging (MRI) for diagnosis of hepatic SOS induced by monocrotaline. METHODS Twenty-four mice were divided into control (n = 10) and experimental (n = 14) groups. The experimental groups were injected with monocrotaline 2 or 6 days before MRI. MRI parameters were: T1 relaxation time before enhancement; T1 relaxation time 20 minutes after enhancement (T1post); a reduction in T1 relaxation time (△T1%); and first enhancement slope percentage of the liver parenchyma (ESP). Albumin and bilirubin score was determined. Histological results served as a reference. Liver parenchyma samples from the control and experimental groups were analyzed by western blotting, and organic anion transporter polypeptide 1 (OATP1) was measured. RESULTS T1post, △T1%, and ESP of the liver parenchyma were significantly different between two groups (all P < 0.001) and significantly correlated with the total histological score of hepatic SOS (r = -0.70, 0.68 and 0.79; P < 0.001). △T1% and ESP were positively correlated with OATP1 levels (r = 0.82, 0.85; P < 0.001), whereas T1post had a negative correlation with OATP1 levels (r = -0.83; P < 0.001). CONCLUSION T1 mapping based on gadoxetic acid-enhanced MRI may be useful for diagnosis of hepatic SOS, and MRI parameters were associated with OATP1 levels.
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Affiliation(s)
- Yuan-Yuan Chen
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Li Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jun Li
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Sheng-Xiang Rao
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Ying Ding
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
| | - Meng-Su Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Yabushita Y, Park JS, Yoon YS, Ohtsuka M, Kwon W, Choi GH, Imamura M, Matsumoto I, Mizuno S, Matsuyama R, Sakata J, Hayashi H, Takeda Y, Katagiri S, Sugawara T, Kobayashi S, Kawasaki Y, Nagano H, Murase K, Kim HS, Nah YW, Jang JY, Yamaue H, Yoon DS, Yamamoto M, Choi D, Nakamura M, Kim KH, Endo I. Conversion surgery for initially unresectable locally advanced biliary tract cancer: A multicenter collaborative study conducted in Japan and Korea. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2024; 31:481-491. [PMID: 38822227 DOI: 10.1002/jhbp.1437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 03/11/2024] [Accepted: 04/12/2024] [Indexed: 06/02/2024]
Abstract
BACKGROUND Although surgical resection is the only curative treatment for biliary tract cancer, in some cases, the disease is diagnosed as unresectable at initial presentation. There are few reports of conversion surgery after the initial treatment for unresectable locally advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of conversion surgery in patients with initially unresectable locally advanced biliary tract cancer. METHODS We retrospectively collected clinical data from groups of patients in multiple centers belonging to the Japanese Society of Hepato-Biliary-Pancreatic Surgery and Korean Association of Hepato-Biliary-Pancreatic Surgery. We analyzed two groups of prognostic factors (pretreatment and surgical factors) and their relation to the treatment outcomes. RESULTS A total of 56 patients with initially unresectable locally advanced biliary tract cancer were enrolled in this study of which 55 (98.2%) patients received chemotherapy, and 16 (28.6%) patients received additional radiation therapy. The median time from the start of the initial treatment to resection was 6.4 months. Severe postoperative complications of Clavien-Dindo grade III or higher occurred in 34 patients (60.7%), and postoperative mortality occurred in five patients (8.9%). Postoperative histological results revealed CR in eight patients (14.3%). The median survival time from the start of the initial treatment in all 56 patients who underwent conversion surgery was 37.7 months, the 3-year survival rate was 53.9%, and the 5-year survival rate was 39.1%. CONCLUSIONS Conversion surgery for initially unresectable locally advanced biliary tract cancer may lead to longer survival in selected patients. However, more precise preoperative safety evaluation and careful postoperative management are required.
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Affiliation(s)
- Yasuhiro Yabushita
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Joon Seong Park
- Pancreatobiliary Cancer Clinic, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
- Department of Surgery and Cancer Research Institute, Seoul National College of Medicine, Seoul, South Korea
| | - Yoo-Seok Yoon
- Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, South Korea
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Wooil Kwon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Gi Hong Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Masafumi Imamura
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan
| | - Ippei Matsumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan
| | - Shugo Mizuno
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Jun Sakata
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan
| | - Yutaka Takeda
- Department of Gastrointestinal Surgery, Kansai Rosai Hospital, Amagasaki, Japan
| | - Satoshi Katagiri
- Department of Surgery, Division of Gastroenterological Surgery, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan
| | - Toshitaka Sugawara
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yota Kawasaki
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Katsutoshi Murase
- Department of Gastroenterological Surgery, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Hyung Sun Kim
- Pancreatobiliary Cancer Clinic, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Jin-Young Jang
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
- Korean Association of Hepato-Biliary-Pancreatic Surgery (KAHBPS), Seoul, South Korea
| | - Hiroki Yamaue
- Department of Cancer Immunology, Wakayama Medical University, Wakayama, Japan
- Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS), Tokyo, Japan
| | - Dong Sup Yoon
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
- Korean Association of Hepato-Biliary-Pancreatic Surgery (KAHBPS), Seoul, South Korea
| | - Masakazu Yamamoto
- Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS), Tokyo, Japan
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Dongho Choi
- Korean Association of Hepato-Biliary-Pancreatic Surgery (KAHBPS), Seoul, South Korea
- Department of Surgery, College of Medicine, Hanyang University, Seoul, South Korea
| | - Masafumi Nakamura
- Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS), Tokyo, Japan
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ki-Hun Kim
- Korean Association of Hepato-Biliary-Pancreatic Surgery (KAHBPS), Seoul, South Korea
- Division of HB Surgery and Liver Transplant, Department of Surgery, Asan Medical Center and University of Ulsan, Seoul, South Korea
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
- Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS), Tokyo, Japan
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Tatsumi K, Wada H, Hasegawa S, Asukai K, Nagata S, Ekawa T, Akazawa T, Mizote Y, Okumura S, Okamura R, Ohue M, Obama K, Tahara H. Prediction for oxaliplatin-induced liver injury using patient-derived liver organoids. Cancer Med 2024; 13:e7042. [PMID: 38400666 PMCID: PMC10891453 DOI: 10.1002/cam4.7042] [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: 07/04/2023] [Revised: 01/22/2024] [Accepted: 02/09/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Liver injury associated with oxaliplatin (L-OHP)-based chemotherapy can significantly impact the treatment outcomes of patients with colorectal cancer liver metastases, especially when combined with surgery. To date, no definitive biomarker that can predict the risk of liver injury has been identified. This study aimed to investigate whether organoids can be used as tools to predict the risk of liver injury. METHODS We examined the relationship between the clinical signs of L-OHP-induced liver injury and the responses of patient-derived liver organoids in vitro. Organoids were established from noncancerous liver tissues obtained from 10 patients who underwent L-OHP-based chemotherapy and hepatectomy for colorectal cancer. RESULTS Organoids cultured in a galactose differentiation medium, which can activate the mitochondria of organoids, showed sensitivity to L-OHP cytotoxicity, which was significantly related to clinical liver toxicity induced by L-OHP treatment. Organoids from patients who presented with a high-grade liver injury to the L-OHP regimen showed an obvious increase in mitochondrial superoxide levels and a significant decrease in mitochondrial membrane potential with L-OHP exposure. L-OHP-induced mitochondrial oxidative stress was not observed in the organoids from patients with low-grade liver injury. CONCLUSIONS These results suggested that L-OHP-induced liver injury may be caused by mitochondrial oxidative damage. Furthermore, patient-derived liver organoids may be used to assess susceptibility to L-OHP-induced liver injury in individual patients.
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Affiliation(s)
- Kumiko Tatsumi
- Department of Cancer Drug Discovery and Development, Research CenterOsaka International Cancer InstituteOsakaJapan
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Hiroshi Wada
- Department of Gastroenterological SurgeryOsaka International Cancer InstituteOsakaJapan
| | - Shinichiro Hasegawa
- Department of Gastroenterological SurgeryOsaka International Cancer InstituteOsakaJapan
| | - Kei Asukai
- Department of Gastroenterological SurgeryOsaka International Cancer InstituteOsakaJapan
| | - Shigenori Nagata
- Department of Diagnostic Pathology and CytologyOsaka International Cancer InstituteOsakaJapan
| | - Tomoya Ekawa
- Department of Cancer Drug Discovery and Development, Research CenterOsaka International Cancer InstituteOsakaJapan
| | - Takashi Akazawa
- Department of Cancer Drug Discovery and Development, Research CenterOsaka International Cancer InstituteOsakaJapan
| | - Yu Mizote
- Department of Cancer Drug Discovery and Development, Research CenterOsaka International Cancer InstituteOsakaJapan
| | - Shintaro Okumura
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Ryosuke Okamura
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Masayuki Ohue
- Department of Gastroenterological SurgeryOsaka International Cancer InstituteOsakaJapan
| | - Kazutaka Obama
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Hideaki Tahara
- Department of Cancer Drug Discovery and Development, Research CenterOsaka International Cancer InstituteOsakaJapan
- Project Division of Cancer Biomolecular TherapyThe Institute of Medical Science, The University of TokyoTokyoJapan
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10
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Huang R, Cai Y, He Y, Yu Z, Zhao L, Wang T, Shangguan X, Zhao Y, Chen Z, Chen Y, Zhang C. Predictive Model of Oxaliplatin-induced Liver Injury Based on Artificial Neural Network and Logistic Regression. J Clin Transl Hepatol 2023; 11:1455-1464. [PMID: 38161498 PMCID: PMC10752815 DOI: 10.14218/jcth.2023.00399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 10/08/2023] [Accepted: 10/24/2023] [Indexed: 01/03/2024] Open
Abstract
Background and Aims Identifying potential high-risk groups of oxaliplatin-induced liver injury (OILI) is valuable, but tools are lacking. So artificial neural network (ANN) and logistic regression (LR) models will be developed to predict the risk of OILI. Methods The medical information of patients treated with oxaliplatin between May and November 2016 at 10 hospitals was collected prospectively. We used the updated Roussel Uclaf causality assessment method (RUCAM) to identify cases of OILI and summarized the patient and medication characteristics. Furthermore, the ANN and LR models for predicting the risk of OILI were developed and evaluated. Results The incidence of OILI was 3.65%. The median RUCAM score with interquartile range was 6 (4, 9). The ANN model performed similarly to the LR model in sensitivity, specificity, and accuracy. In discrimination, the area under the curve of the ANN model was larger (0.920>0.833, p=0.019). In calibration, the ANN model was slightly improved. The important predictors of both models overlapped partially, including age, chemotherapy regimens and cycles, single and total dose of OXA, glucocorticoid drugs, and antihistamine drugs. Conclusions When the discriminative and calibration ability was given priority, the ANN model outperformed the LR model in predicting the risk of OILI. Other chemotherapy drugs in oxaliplatin-based chemotherapy regimens could have different degrees of impact on OILI. We suspected that OILI may be idiosyncratic, and chemotherapy dose factors may be weakly correlated. Decision making on prophylactic medications needs to be carefully considered, and the actual preventive effect needed to be supported by more evidence.
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Affiliation(s)
- Rui Huang
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuanxuan Cai
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yisheng He
- Ciechanover Institute of Precision and Regenerative Medicine, School of Medicine, The Chinese University of Hong Kong-Shenzhen, Shenzhen, Guangdong, China
| | - Zaoqin Yu
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Li Zhao
- Hubei Center for Adverse Drug Reaction/Adverse Drug Event Monitoring, Wuhan, Hubei, China
| | - Tao Wang
- National Center for Adverse Drug Reaction Monitoring, Beijing, China
| | - Xiaofang Shangguan
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuhang Zhao
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zherui Chen
- School of Statistics and Mathematics, Zhongnan University of Economics and Law, Wuhan, Hubei, China
| | - Yunzhou Chen
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Chengliang Zhang
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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11
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Chouari T, Merali N, La Costa F, Santol J, Chapman S, Horton A, Aroori S, Connell J, Rockall TA, Mole D, Starlinger P, Welsh F, Rees M, Frampton AE. The Role of the Multiparametric MRI LiverMultiScan TM in the Quantitative Assessment of the Liver and Its Predicted Clinical Applications in Patients Undergoing Major Hepatic Resection for Colorectal Liver Metastasis. Cancers (Basel) 2023; 15:4863. [PMID: 37835557 PMCID: PMC10571783 DOI: 10.3390/cancers15194863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 08/05/2023] [Accepted: 10/02/2023] [Indexed: 10/15/2023] Open
Abstract
Liver biopsy remains the gold standard for the histological assessment of the liver. With clear disadvantages and the rise in the incidences of liver disease, the role of neoadjuvant chemotherapy in colorectal liver metastasis (CRLM) and an explosion of surgical management options available, non-invasive serological and imaging markers of liver histopathology have never been more pertinent in order to assess liver health and stratify patients considered for surgical intervention. Liver MRI is a leading modality in the assessment of hepatic malignancy. Recent technological advancements in multiparametric MRI software such as the LiverMultiScanTM offers an attractive non-invasive assay of anatomy and histopathology in the pre-operative setting, especially in the context of CRLM. This narrative review examines the evidence for the LiverMultiScanTM in the assessment of hepatic fibrosis, steatosis/steatohepatitis, and potential applications for chemotherapy-associated hepatic changes. We postulate its future role and the hurdles it must surpass in order to be implemented in the pre-operative management of patients undergoing hepatic resection for colorectal liver metastasis. Such a role likely extends to other hepatic malignancies planned for resection.
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Affiliation(s)
- Tarak Chouari
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
| | - Nabeel Merali
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
| | - Francesca La Costa
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Jonas Santol
- Department of Surgery, HPB Center, Vienna Health Network, Clinic Favoriten and Sigmund Freud Private University, 1090 Vienna, Austria
- Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria
| | - Shelley Chapman
- Department of Radiology, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Alex Horton
- Department of Radiology, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Somaiah Aroori
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery and Transplant Surgery, Derriford Hospital, Plymouth PL6 8DH, UK
| | | | - Timothy A. Rockall
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
| | - Damian Mole
- Clinical Surgery, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh EH10 5HF, UK
- Centre for Inflammation Research, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh EH105HF, UK
| | - Patrick Starlinger
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN 55902, USA
- Center of Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria
- Department of Surgery, Medical University of Vienna, General Hospital, 1090 Vienna, Austria
| | - Fenella Welsh
- Hepato-Biliary Unit, Hampshire Hospitals Foundation Trust, Basingstoke, Hampshire RG24 9NA, UK
| | - Myrddin Rees
- Hepato-Biliary Unit, Hampshire Hospitals Foundation Trust, Basingstoke, Hampshire RG24 9NA, UK
| | - Adam E. Frampton
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
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12
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Starlinger P, Brunnthaler L, Watkins R, Pereyra D, Stift J, Finsterbusch M, Santol J, Gruenberger T, Assinger A, Smoot R. Tyrosine phosphorylation of YAP-1 in biliary epithelial cells mediates posthepatectomy liver regeneration and is affected by serotonin. J Cell Biochem 2023; 124:687-700. [PMID: 36946436 PMCID: PMC10200759 DOI: 10.1002/jcb.30398] [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: 12/12/2022] [Revised: 02/26/2023] [Accepted: 03/01/2023] [Indexed: 03/23/2023]
Abstract
Experimental data suggested activation of yes-associated protein (YAP-1) as a critical regulator of liver regeneration (LR). Serotonin (5-HT) promotes LR in rodent models and has been proposed to act via YAP-1. How 5-HT affects LR is incompletely understood. A possible mechanism how 5-HT affects human LR was explored. Sixty-one patients were included. Tissue samples prior and 2 h after induction of LR were collected. Circulating levels of 5-HT and osteopontin (OPN) were assessed. YAP-1, its phosphorylation states, cytokeratin 19 (CK-19) and OPN were assessed using immunofluorescence. A mouse model of biliary epithelial cells (BECs) specific deletion of YAP/TAZ was developed. YAP-1 increased as early as 2 h after induction of LR (p = 0.025) predominantly in BECs. BEC specific deletion of YAP/TAZ reduced LR after 70% partial hepatectomy in mice (Ki67%, p < 0.001). SSRI treatment, depleting intra-platelet 5-HT, abolished YAP-1 and OPN induction upon LR. Portal vein 5-HT levels correlated with intrahepatic YAP-1 expression upon LR (R = 0.703, p = 0.035). OPN colocalized with YAP-1 in BECs and its circulating levels increased in the liver vein 2 h after induction of LR (p = 0.017). In the context of LR tyrosine-phosphorylated YAP-1 significantly increased (p = 0.042). Stimulating BECs with 5-HT resulted in increased YAP-1 activation via tyrosine-phosphorylation and subsequently increased OPN expression. BECs YAP-1 appears to be critical for LR in mice and humans. Our evidence suggests that 5-HT, at least in part, exerts its pro-regenerative effects via YAP-1 tyrosine-phosphorylation in BECs and subsequent OPN-dependent paracrine immunomodulation.
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Affiliation(s)
- Patrick Starlinger
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria
| | - Laura Brunnthaler
- Center of Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria
| | - Ryan Watkins
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
| | - David Pereyra
- Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria
| | - Judith Stift
- Clinical Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria
| | - Michaela Finsterbusch
- Center of Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria
| | - Jonas Santol
- Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria
| | - Thomas Gruenberger
- Department of Surgery, HPB Center, Viennese Health Network, Clinic Favoriten and Sigmund Freud Private University, Vienna, Austria
| | - Alice Assinger
- Center of Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria
| | - Rory Smoot
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
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13
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Extracellular Volume Fraction Calculated Using Contrast-Enhanced Computed Tomography as a Biomarker of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome: A Preliminary Histopathological Analysis. JOURNAL OF ONCOLOGY 2023; 2023:1440257. [PMID: 36824665 PMCID: PMC9943597 DOI: 10.1155/2023/1440257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 01/31/2023] [Accepted: 02/02/2023] [Indexed: 02/18/2023]
Abstract
Background Oxaliplatin (OX)-based chemotherapy induces sinusoidal obstruction syndrome (SOS) in the nontumorous liver parenchyma, which can increase the risk of liver resection due to colorectal liver metastasis (CRLM). The extracellular volume (ECV) calculated from contrast-enhanced computed tomography (CT) has been reported to reflect the morphological change of hepatic fibrosis. The present retrospective study aimed to evaluate the ECV fraction as a predictive factor for OX-induced SOS. Methods Our study included 26 patients who underwent liver resection for CRLM after OX-based chemotherapy with a preoperative dynamic CT of appropriate quality. We investigated the relationship between the pathological SOS grade and the ECV fraction. Results Overall, 26 specimens from the patients were graded with the SOS classification of Rubbia-Brandt et al. as follows: grade 0, n = 17 (65.4%); grade 1, n = 4 (15.4%); and grade 2, n = 5 (19.2%). No specimens showed grade 3 SOS. In a univariate analysis, the ECV fraction in grade 0 SOS was significantly lower than that in grade 1 + 2 SOS (26.3 ± 3.4% vs. 30.6 ± 7.0%; P = 0.025). The cutoff value and AUC value of the ECV fraction to distinguish between grades 0 and 1 + 2 were 27.5% and 0.771, respectively. Conclusions Measurement of the ECV fraction was found to be a potential noninvasive diagnostic method for determining early-stage histopathological sinusoidal injury induced by OX-based chemotherapy.
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14
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Kobayashi K, Inoue Y, Kitano Y, Sato S, Oba A, Ono Y, Sato T, Ito H, Mise Y, Saiura A, Takahashi Y. Optimizing the selection of technically unresectable colorectal liver metastases. Surgery 2023; 173:442-449. [PMID: 36384649 DOI: 10.1016/j.surg.2022.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 10/02/2022] [Accepted: 10/11/2022] [Indexed: 11/14/2022]
Abstract
BACKGROUND The prediction of conversion surgery in patients with technically unresectable colorectal liver metastases has not been generalized or well-established. We developed a predictive model for conversion surgery and assessed the long-term outcomes of patients with technically unresectable colorectal liver metastases. METHODS In this single-center, retrospective study, we analyzed the perioperative parameters and outcomes of 892 consecutive patients (2014-2021). Conversion surgery was indicated when the chemotherapy response allowed the complete resection of colorectal liver metastases with negative margins and adequate remnant liver volume. RESULTS Of the 892 patients, 122 had technically unresectable colorectal liver metastases; 61 underwent conversion surgery (conversion surgery group) and 61 did not (nonconversion surgery group). The median overall survival was significantly higher in the conversion surgery group than in the nonconversion surgery group (5.6 vs 1.8 years, P < .001). After univariate and multivariate analyses, the predictive model for conversion surgery was constructed using 4 predictive factors: Rat sarcoma viral oncogene homolog status (mutant, +2 points), tumor number (≥15, +1), hepatic vein contact (≥2 hepatic veins, +1), and the presence of preservable sections (absence of preservable sections, +2). The area under the curve for conversion surgery was 0.889. Patients were graded according to the scores (A [0-2], B [3-4], and C [5-6]), and the conversion rates were 91.5% (A), 32.6% (B), and 10.3% (C) (P < .001). Grade A patients (median survival time, 5.7 years) had significantly better overall survival than grade B and C patients (median survival time, 2.2 and 1.6 years, respectively; P < .001). CONCLUSION Patients who underwent conversion surgery for technically unresectable colorectal liver metastases had better prognoses, and our novel predictive model was useful in predicting conversion surgery and prognosis.
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Affiliation(s)
- Kosuke Kobayashi
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Inoue
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Yuki Kitano
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shoki Sato
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Atsushi Oba
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yoshihiro Ono
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takafumi Sato
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hiromichi Ito
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yoshihiro Mise
- Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Akio Saiura
- Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yu Takahashi
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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15
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Toda R, Seo S, Uemoto Y, Morino K, Nishino H, Nakamura N, Okuno M, Iguchi K, Sato M, Nakamura K, Taura K, Nakagawa S, Nakagawa T, Tsuruyama T, Manabe T, Kawaguchi H, Iwaisako K, Ikegawa M, Uemoto S, Hatano E. Clinically relevant model of oxaliplatin-induced sinusoidal obstruction syndrome. Hepatol Res 2023; 53:145-159. [PMID: 36149410 DOI: 10.1111/hepr.13842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 09/12/2022] [Accepted: 09/15/2022] [Indexed: 02/04/2023]
Abstract
AIM Sinusoidal obstruction syndrome (SOS) induced by oxaliplatin-including chemotherapies (OXCx) is associated with impaired hepatic reserve and higher morbidity after hepatic resection. However, in the absence of an appropriate animal experimental model, little is known about its pathophysiology. This study aimed to establish a clinically relevant reproducible model of FOLFOX-induced SOS and to compare the clinical/histopathological features between the clinical and animal SOS settings. METHODS We performed clinical/pathological analyses of colorectal liver metastasis (CRLM) patients who underwent hepatectomy with/without preoperative treatment of FOLFOX (n = 22/18). Male micro-minipigs were treated with 50% of the standard human dosage of the FOLFOX regimen. RESULTS In contrast to the monocrotaline-induced SOS model in rats, hepatomegaly, ascites, congestion, and coagulative necrosis of hepatocytes were absent in patients with CRLM with OXCx pretreatment and OXCx-treated micro-minipigs. In parallel to CRLM cases with OXCx pretreatment, OXCx-challenged micro-minipigs exhibited deteriorated indocyanine green clearance, morphological alteration of liver sinusoidal endothelial cells, and upregulated matrix metalloproteinase-9. Using our novel porcine SOS model, we identified the hepatoprotective influence of recombinant human soluble thrombomodulin in OXCx-SOS. CONCLUSIONS With distinct differences between monocrotaline-induced rat SOS and human/pig OXCx-SOS, our pig OXCx-SOS model serves as a preclinical platform for future investigations to dissect the pathophysiology of OXCx-SOS and seek preventive strategies.
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Affiliation(s)
- Rei Toda
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoru Seo
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yusuke Uemoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Koshiro Morino
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hiroto Nishino
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Naohiko Nakamura
- Department of Surgery, Kanazawa Medical University, Ishikawa, Japan
| | - Masayuki Okuno
- Department of Gastroenterological Surgery, Hyogo Medical University, Nishinomiya, Japan
| | - Kohta Iguchi
- Department of Gastrointestinal Medicine & Surgery, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan
| | - Motohiko Sato
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kojiro Nakamura
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.,Department of Surgery, Kobe City Nishi-Kobe Medical Center, Kobe, Japan
| | - Kojiro Taura
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shunsaku Nakagawa
- Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takayuki Nakagawa
- Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tatsuaki Tsuruyama
- Department of Drug Discovery Medicine, Division of Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.,Department of Diagnostic and Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshiaki Manabe
- Department of Diagnostic and Pathology, General Incorporated Association PaLaNA Initiative, Otsu, Japan
| | - Hiroaki Kawaguchi
- Laboratory of Veterinary Pathology, Kitasato University School of Veterinary Medicine, Aomori, Japan
| | - Keiko Iwaisako
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.,Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan
| | - Masaya Ikegawa
- Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan
| | - Shinji Uemoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.,Shiga University of Medical Science, Otsu, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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16
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Inhibition of Vascular Endothelial Growth Factor Protects against the Development of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome in Wild-Type but Not in CD39-Null Mice. Cancers (Basel) 2022; 14:cancers14235992. [PMID: 36497474 PMCID: PMC9739893 DOI: 10.3390/cancers14235992] [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: 09/18/2022] [Revised: 11/19/2022] [Accepted: 11/20/2022] [Indexed: 12/12/2022] Open
Abstract
(1) Background: Sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy is associated with unfavorable outcomes after partial hepatectomy for colorectal liver metastases (CLM). Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), may prevent SOS development. We investigated the impact of VEGF-inhibition on the development of SOS in a murine model. (2) Methods: Male wild-type and CD39-null mice received oxaliplatin, additional anti-VEGF (OxAV), or controls, and were sacrificed or subjected to major partial hepatectomy (MH). Specimen were used for histological analysis of SOS. Liver damage was assessed by plasma transaminases. The VEGF pathway was elucidated by quantitative PCR of liver tissue and protein analysis of plasma. (3) Results: Mice treated with oxaliplatin developed SOS. Concomitant anti-VEGF facilitated a reduced incidence of SOS, but not in CD39-null mice. SOS was associated with increased plasma VEGF-A and decreased hepatocyte growth factor (HGF). After OxAV treatment, VEGF-R2 was upregulated in wild-type but downregulated in CD39-null mice. Oxaliplatin alone was associated with higher liver damage after MH than in mice with concomitant VEGF-inhibition. (4) Conclusions: We established a murine model of oxaliplatin-induced SOS and provided novel evidence on the protective effect of VEGF-inhibition against the development of SOS that may be associated with changes in the pathway of VEGF and its receptor VEGF-R2.
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17
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Shimagaki T, Sugimachi K, Mano Y, Onishi E, Iguchi T, Uehara H, Sugiyama M, Yamamoto M, Morita M, Toh Y. Simple systemic index associated with oxaliplatin-induced liver damage can be a novel biomarker to predict prognosis after resection of colorectal liver metastasis. Ann Gastroenterol Surg 2022; 6:813-822. [PMID: 36338597 PMCID: PMC9628223 DOI: 10.1002/ags3.12580] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 05/02/2022] [Indexed: 12/01/2022] Open
Abstract
Aim Oxaliplatin, an anticancer drug for advanced colorectal cancer, causes liver sinusoidal damage, sometimes with portal hypertension. We conducted a retrospective comparative study of the relationship of liver sinusoidal disorders and liver function with the prognosis in patients who underwent hepatectomy for colorectal liver metastasis (CRLM). Methods In total, 158 patients who underwent hepatectomy for CRLM were included in the study, and the effect of chemotherapy-associated liver damage on the prognosis was examined. Results Preoperative oxaliplatin was used in 75 of 158 patients; of these 75 patients, 26 had intraoperative blue liver (BL). In a comparison of the BL group (n = 26) and non-BL group (n = 132), patients in the BL group had a significantly lower serum albumin concentration and a significantly higher indocyanine green test result, aspartate aminotransferase-to-platelet ratio index (APRI), and FIB-4 score. Operative morbidities were not significantly different between the two groups. The overall survival rate after hepatectomy was significantly worse in the BL group than in the non-BL group. In the univariate analysis, the serum albumin concentration, indocyanine green test, a high tumor burden score (TBS), and the APRI were statistically significant poor prognostic factors. In the multivariate analysis, the APRI and a high TBS were independent poor prognostic factors. Conclusion The APRI and TBS in patients with CRLM are prognostic predictors after hepatectomy for metastatic liver cancer. This study indicated that liver damage in patients treated with preoperative oxaliplatin has an effect on the prognosis.
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Affiliation(s)
- Tomonari Shimagaki
- Department of Hepatobiliary and Pancreatic SurgeryNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Keishi Sugimachi
- Department of Hepatobiliary and Pancreatic SurgeryNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Yohei Mano
- Department of Hepatobiliary and Pancreatic SurgeryNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Emi Onishi
- Department of Hepatobiliary and Pancreatic SurgeryNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Tomohiro Iguchi
- Department of Hepatobiliary and Pancreatic SurgeryNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Hideo Uehara
- Department of Gastroenterological SurgeryNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Masahiko Sugiyama
- Department of Gastroenterological SurgeryNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Manabu Yamamoto
- Department of Gastroenterological SurgeryNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Masaru Morita
- Department of Gastroenterological SurgeryNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Yasushi Toh
- Department of Gastroenterological SurgeryNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
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18
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Ashouri Y, Hsu CH, Riall TS, Konstantinidis IT, Maegawa FB. Aspartate Aminotransferase-to-Platelet Ratio Index Predicts Liver Failure After Resection of Colorectal Liver Metastases. Dig Dis Sci 2022; 67:4950-4958. [PMID: 34981310 DOI: 10.1007/s10620-021-07333-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 11/15/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Chemotherapy agents for metastatic colorectal cancer can cause liver injury, increasing the risk of post-hepatectomy liver failure after hepatectomy for metastases. The role of noninvasive fibrosis markers in this setting is not well established. AIMS To evaluate the aspartate aminotransferase-to-platelet ratio index (APRI) as a predictor of postoperative liver failure. METHODS The National Surgical Quality Improvement Program database was utilized to identify patients who received preoperative chemotherapy and underwent hepatectomy for colorectal metastases between 2015 and 2017. Concordance index analysis was conducted to determine APRI's contribution to the prediction of liver failure. The optimal cutoff value was defined and its ability to predict post-hepatectomy liver failure and perioperative bleeding were examined. RESULTS A total of 2374 patients were identified and included in the analysis. APRI demonstrated to be a better predictor of postoperative liver failure than MELD score, with a statistically significant larger area under the curve. The optimal APRI cutoff value to predict liver failure was 0.365. The multivariable logistic regression showed that APRI ≥ 0.365 was independently associated with PHLF, odds ratio (OR) 2.51, 95% confidence interval (CI) 1.67-3.77, P < .0001. Likewise, APRI ≥ 0.365 was independently associated with perioperative bleeding complications requiring transfusions, OR 1.41, 95% CI 1.13-1.77, P = 0.002. MELD score was not statistically associated with PHLF or bleeding complications. CONCLUSIONS APRI was independently associated with post-hepatectomy liver failure and perioperative bleeding requiring transfusions after resection of colorectal metastases in patients who received preoperative chemotherapy. Concordance index showed APRI to add significant contribution as a predictor of postoperative liver failure.
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Affiliation(s)
- Yazan Ashouri
- Department of Surgery, Southern Arizona VA Health Care System, University of Arizona, Tucson, AZ, USA
| | - Chiu-Hsieh Hsu
- Mel&Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA
| | - Taylor S Riall
- Department of Surgery, University of Arizona, Tucson, AZ, USA
| | | | - Felipe B Maegawa
- Division of General and GI Surgery, Department of Surgery, Emory University, 5673 Peachtree Dunwoody Road, Suite 680, Atlanta, GA, 30342, USA.
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Liu W, Chen FL, Wang K, Bao Q, Wang HW, Jin KM, Xing BC. Irinotecan- vs oxaliplatin-based regimens for neoadjuvant chemotherapy in colorectal liver metastasis patients: A retrospective study. World J Gastrointest Surg 2022; 14:904-917. [PMID: 36185567 PMCID: PMC9521480 DOI: 10.4240/wjgs.v14.i9.904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 04/28/2022] [Accepted: 08/26/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (NC) improves the survival outcomes of selected patients with colorectal liver metastasis (CRLM). The benefits of irinotecan-based regimens in these patients are still under debate.
AIM To compare the benefits of irinotecan- and oxaliplatin-based regimens in patients with resectable CRLM.
METHODS From September 2003 to August 2020, 554 patients received NC and underwent hepatectomy for CRLM. Based on a 1:1 propensity score matching (PSM) model, 175 patients who received irinotecan were matched to 175 patients who received oxaliplatin to obtain two balanced groups regarding demographic, therapeutic, and prognostic characteristics.
RESULTS Chemotherapy was based on oxaliplatin in 353 (63.7%) patients and irinotecan in 201 (36.3%). After PSM, the 5-year progression-free survival (PFS) and overall survival (OS) rates with irinotecan were 18.0% and 49.7%, respectively, while the 5-year PFS and OS rates with oxaliplatin were 26.0% and 46.8%, respectively. Intraoperative blood loss, operating time, and postoperative complications differed significantly between the two groups. In the multivariable analysis, carbohydrate antigen 19-9, RAS mutation, response to NC, tumor size > 5 cm, and tumor number > 1 were independently associated with PFS.
CONCLUSION In NC in patients with CRLM, irinotecan is similar to oxaliplatin in survival outcomes, but irinotecan is superior regarding operating time, intraoperative blood loss, and postoperative complications.
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Affiliation(s)
- Wei Liu
- Department of Hepatopancreatobiliary Surgery, Peking University School of Oncology, Beijing Cancer Hospital, Beijing 100142, China
| | - Feng-Lin Chen
- Department of Hepatopancreatobiliary Surgery, Peking University School of Oncology, Beijing Cancer Hospital, Beijing 100142, China
| | - Kun Wang
- Department of Hepatopancreatobiliary Surgery, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, China
| | - Quan Bao
- Department of Hepatopancreatobiliary Surgery, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, China
| | - Hong-Wei Wang
- Department of Hepatopancreatobiliary Surgery, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, China
| | - Ke-Min Jin
- Department of Hepatopancreatobiliary Surgery, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, China
| | - Bao-Cai Xing
- Department of Hepatopancreatobiliary Surgery, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, China
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20
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Wang J, Zheng Z, Wu T, Li W, Wang J, Pan Y, Peng W, Hu D, Hou J, Xu L, Zhang Y, Chen M, Zhang R, Zhou Z. Hepatic Arterial Infusion Chemotherapy as a Timing Strategy for Conversion Surgery to Treat Hepatocellular Carcinoma: A Single-Center Real-World Study. J Hepatocell Carcinoma 2022; 9:999-1010. [PMID: 36132426 PMCID: PMC9483136 DOI: 10.2147/jhc.s379326] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 09/09/2022] [Indexed: 01/27/2023] Open
Abstract
Objective To evaluate whether surgery-related complications are increased after hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin plus fluorouracil/leucovorin for conversion compared with primary hepatocellular carcinoma (HCC) resection and the optimal timing of conversion surgery (CS). Background HAIC has been widely used for advanced HCC, especially initially unresectable HCC, to facilitate conversion to curative-intent resection in approximately 23.8% of cases. However, the optimal timing of surgery to reduce surgical complications must be clarified. Methods Data from 320 HCC patients, including 107 initially unresectable patients in the HAIC-Surgery group and 213 patients in the Surgery group, were retrospectively collected and analyzed. Survival outcomes and the incidence of surgery-related complications were compared. Results There was no significant difference in recurrence-free survival (RFS) between the HAIC-Surgery group and the Surgery group (HR: 1.140, 95% CI: 0.8027-1.618, p=0.444). The HAIC-Surgery group had a higher incidence of surgery-related complications than the Surgery group [biliary leakage (10.3% vs 4.2%, p=0.035), abdominal bleeding (10.3% vs 3.8%, p=0.020), pleural effusion (56.1% vs 23.0%, p<0.0001) and ascites effusion (17.8% vs 5.2%, p<0.0001)]. In the HAIC-Surgery group, postoperative liver function decreased and abdominal bleeding increased with more preoperative HAIC cycles (Spearman=0.229, p=0.042, Spearman=0.198, p=0.041, respectively). The pathological complete remission (pCR) rate after 3-5 HAIC cycles was significantly higher than that after 1-2 cycles (29.4% vs 13.2%, p=0.043). Conclusion The prognosis of advanced HCC after conversion surgery is comparable to that after direct surgery. Rather than increasing pCR, more HAIC cycles can exacerbate liver dysfunction and surgery-related complications.
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Affiliation(s)
- Jiongliang Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Zhikai Zheng
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Tianqing Wu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Wenxuan Li
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Juncheng Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Yangxun Pan
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Wei Peng
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Dandan Hu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Jiajie Hou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Li Xu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Yaojun Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Rongxin Zhang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
| | - Zhongguo Zhou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
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21
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Saito R, Kawamoto Y, Nishida M, Iwai T, Kikuchi Y, Yokota I, Takagi R, Yamamura T, Ito K, Harada K, Yuki S, Komatsu Y, Sakamoto N. Usefulness of ultrasonography and elastography in diagnosing oxaliplatin-induced sinusoidal obstruction syndrome. Int J Clin Oncol 2022; 27:1780-1790. [PMID: 36042137 PMCID: PMC9606101 DOI: 10.1007/s10147-022-02235-4] [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] [Received: 11/06/2021] [Accepted: 08/08/2022] [Indexed: 11/15/2022]
Abstract
Background Sinusoidal obstruction syndrome (SOS) refers to liver injury caused by hematopoietic stem cell transplantation (HSCT) and anticancer drugs including oxaliplatin. Increased splenic volume (SV) on computed tomography (CT) indicates oxaliplatin-induced SOS. Similarly, ultrasonography and liver stiffness measurement (LSM) by shear-wave elastography (SWE) can help diagnose SOS after HSCT; however, their usefulness for diagnosing oxaliplatin-induced SOS remains unclear. We investigated the usefulness of the Hokkaido ultrasonography-based scoring system with 10 ultrasonographic parameters (HokUS-10) and SWE in diagnosing oxaliplatin-induced SOS early. Methods In this prospective observational study, ultrasonography and SWE were performed before and at 2, 4, and 6 months after oxaliplatin-based chemotherapy. HokUS-10 was used for assessment. CT volumetry of the SV was performed in clinical practice, and an SV increase ≥ 30% was considered the diagnostic indicator of oxaliplatin-induced SOS. We assessed whether HokUS-10 and SWE can lead to an early detection of oxaliplatin-induced SOS before an increased SV on CT. Results Of the 30 enrolled patients with gastrointestinal cancers, 12 (40.0%) with an SV increase ≥ 30% on CT were diagnosed with SOS. The HokUS-10 score was not correlated with an SV increase ≥ 30% (r = 0.18). The change in rate of three HokUS-10 parameters were correlated with an SV increase ≥ 30% (r = 0.32–0.41). The change in rate of LSM by SWE was correlated with an SV increase ≥ 30% (r = 0.40). Conclusions The usefulness of HokUS-10 score was not demonstrated; however, some HokUS-10 parameters and SWE could be useful for the early diagnosis of oxaliplatin-induced SOS. Supplementary Information The online version contains supplementary material available at 10.1007/s10147-022-02235-4.
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Affiliation(s)
- Rika Saito
- Division of Cancer Center, Hokkaido University Hospital, Kita-15, Nishi-7, Kita-ku, Sapporo, Japan
| | - Yasuyuki Kawamoto
- Division of Cancer Center, Hokkaido University Hospital, Kita-15, Nishi-7, Kita-ku, Sapporo, Japan
| | - Mutsumi Nishida
- Diagnostic Center for Sonography, Hokkaido University Hospital, Sapporo, Japan
| | - Takahito Iwai
- Diagnostic Center for Sonography, Hokkaido University Hospital, Sapporo, Japan
| | - Yasuka Kikuchi
- Department of Diagnostic Imaging, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Isao Yokota
- Department of Biostatistics, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Ryo Takagi
- Department of Biostatistics, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Takahiro Yamamura
- Division of Cancer Center, Hokkaido University Hospital, Kita-15, Nishi-7, Kita-ku, Sapporo, Japan
| | - Ken Ito
- Division of Cancer Center, Hokkaido University Hospital, Kita-15, Nishi-7, Kita-ku, Sapporo, Japan
| | - Kazuaki Harada
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
| | - Satoshi Yuki
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
| | - Yoshito Komatsu
- Division of Cancer Center, Hokkaido University Hospital, Kita-15, Nishi-7, Kita-ku, Sapporo, Japan.
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
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22
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Ahmed S, Bosma N, Moser M, Ahmed S, Brunet B, Davies J, Doll C, Dueck DA, Kim CA, Ji S, Le D, Lee-Ying R, Lim H, McGhie JP, Mulder K, Park J, Ravi D, Renouf DJ, Schellenberg D, Wong RPW, Zaidi A. Systemic Therapy and Its Surgical Implications in Patients with Resectable Liver Colorectal Cancer Metastases. A Report from the Western Canadian Gastrointestinal Cancer Consensus Conference. Curr Oncol 2022; 29:1796-1807. [PMID: 35323347 PMCID: PMC8947455 DOI: 10.3390/curroncol29030147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/20/2022] [Accepted: 03/04/2022] [Indexed: 11/24/2022] Open
Abstract
The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) convened virtually on 4 November 2021. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals, including surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals from across four Western Canadian provinces, British Columbia, Alberta, Saskatchewan, and Manitoba, who are involved in the care of patients with gastrointestinal cancer. They participated in presentation and discussion sessions for the purpose of developing recommendations on the role of systemic therapy and its optimal sequence in patients with resectable metastatic colorectal cancer.
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Affiliation(s)
- Shahid Ahmed
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, 20 Campus Drive, University of Saskatchewan, Saskatoon, SK S7N 4H4, Canada; (B.B.); (D.-A.D.); (D.L.)
| | - Nicholas Bosma
- British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (N.B.); (J.D.); (H.L.); (D.J.R.)
| | - Michael Moser
- Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada;
| | - Shahida Ahmed
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (S.A.); (C.A.K.); (R.P.W.W.)
| | - Bryan Brunet
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, 20 Campus Drive, University of Saskatchewan, Saskatoon, SK S7N 4H4, Canada; (B.B.); (D.-A.D.); (D.L.)
- Department of Radiation Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
| | - Janine Davies
- British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (N.B.); (J.D.); (H.L.); (D.J.R.)
| | - Corinne Doll
- Arnie Charbonneau Cancer Institute, Alberta Health Service, Calgary, AB T2N 4Z6, Canada; (C.D.); (R.L.-Y.)
| | - Dorie-Anna Dueck
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, 20 Campus Drive, University of Saskatchewan, Saskatoon, SK S7N 4H4, Canada; (B.B.); (D.-A.D.); (D.L.)
- Department of Medical Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
| | - Christina A. Kim
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (S.A.); (C.A.K.); (R.P.W.W.)
| | - Shuying Ji
- Shared Health, Winnipeg, MB R3B 2K6, Canada;
| | - Duc Le
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, 20 Campus Drive, University of Saskatchewan, Saskatoon, SK S7N 4H4, Canada; (B.B.); (D.-A.D.); (D.L.)
- Department of Radiation Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
| | - Richard Lee-Ying
- Arnie Charbonneau Cancer Institute, Alberta Health Service, Calgary, AB T2N 4Z6, Canada; (C.D.); (R.L.-Y.)
| | - Howard Lim
- British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (N.B.); (J.D.); (H.L.); (D.J.R.)
| | | | - Karen Mulder
- Cross Cancer Institute, Alberta Health Services, Edmonton, AB T6G 1Z2, Canada;
| | - Jason Park
- Department of Surgery, University of Manitoba, Winnipeg, MB R3T 2N2, Canada;
| | - Deepti Ravi
- Saskatchewan Health Authority, Saskatoon, SK S7K 0M7, Canada;
| | - Daniel J. Renouf
- British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (N.B.); (J.D.); (H.L.); (D.J.R.)
| | | | - Ralph P. W. Wong
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (S.A.); (C.A.K.); (R.P.W.W.)
| | - Adnan Zaidi
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, 20 Campus Drive, University of Saskatchewan, Saskatoon, SK S7N 4H4, Canada; (B.B.); (D.-A.D.); (D.L.)
- Department of Medical Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
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23
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Miyamoto T, Domoto R, Sekiguchi F, Kamaguchi R, Nishimura R, Matsuno M, Tsubota M, Fujitani M, Hatanaka S, Koizumi Y, Wang D, Nishibori M, Kawabata A. Development of hepatic impairment aggravates chemotherapy-induced peripheral neuropathy following oxaliplatin treatment: Evidence from clinical and preclinical studies. J Pharmacol Sci 2022; 148:315-325. [PMID: 35177211 DOI: 10.1016/j.jphs.2022.01.006] [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: 11/02/2021] [Revised: 12/08/2021] [Accepted: 01/11/2022] [Indexed: 10/19/2022] Open
Abstract
Oxaliplatin often induces peripheral neuropathy, a dose-limiting adverse reaction, and in rare cases leads to sinusoidal obstruction syndrome. We thus conducted a retrospective cohort study to examine the relationship between oxaliplatin-induced peripheral neuropathy (OIPN) and hepatic impairment, and then perform a fundamental study to analyze the underlying mechanisms. Analysis of medical records in cancer patients treated with oxaliplatin indicated that laboratory test parameters of hepatic impairment including AST, ALT and APRI (AST to platelet ratio index) moderately increased during oxaliplatin treatment, which was positively correlated with the severity of OIPN (grades 1-4), and associated with later incidence of survivors with OIPN grades ≥2. In mice, hepatic injury induced by CCl4 or ethanol accelerated OIPN in mice, an effect prevented by inactivation of high mobility group box 1 (HMGB1), known to participate in OIPN, by the neutralizing antibody or thrombomodulin alfa capable of promoting its thrombin-dependent degradation. Oxaliplatin also aggravated the hepatic injury in mice. CCl4 released HMGB1 from cultured hepatic parenchymal cells, and oxaliplatin at clinically achievable concentrations released HMGB1 from hepatic parenchymal and non-parenchymal cells. Our clinical and preclinical data suggest that the development of mild hepatic impairment during oxaliplatin treatment is associated with later aggravation of OIPN.
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Affiliation(s)
- Tomoyoshi Miyamoto
- Laboratory of Pharmacology & Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan; Department of Pharmacy, Seichokai Fuchu Hospital, Izumi, Japan
| | - Risa Domoto
- Laboratory of Pharmacology & Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan
| | - Fumiko Sekiguchi
- Laboratory of Pharmacology & Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan
| | - Riki Kamaguchi
- Laboratory of Pharmacology & Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan
| | - Rika Nishimura
- Laboratory of Pharmacology & Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan
| | - Misato Matsuno
- Laboratory of Pharmacology & Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan
| | - Maho Tsubota
- Laboratory of Pharmacology & Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan
| | | | | | - Yuichi Koizumi
- Department of Pharmacy, Seichokai Fuchu Hospital, Izumi, Japan
| | - Dengli Wang
- Department of Pharmacology, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Masahiro Nishibori
- Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Atsufumi Kawabata
- Laboratory of Pharmacology & Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan.
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Björnsson ES, Andrade RJ. Long-term sequelae of drug-induced liver injury. J Hepatol 2022; 76:435-445. [PMID: 34688732 DOI: 10.1016/j.jhep.2021.10.011] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 09/29/2021] [Accepted: 10/14/2021] [Indexed: 02/06/2023]
Abstract
Drug-induced liver injury (DILI) has a very variable clinical and biochemical phenotype and differs widely in severity, from mild injury to life-threatening liver failure. Chronic injury has also been reported to occur at a variable frequency, ranging from 3.4% to 39%, 6-12 months after discontinuing the implicated agent. This wide range is probably related to various definitions of chronic liver injury and variable selection of patients. The long-term sequalae of this chronic injury in terms of morbidity and mortality are unclear, although rare vanishing bile duct syndrome is associated with an unfavourable prognosis, with increased risk of chronic liver failure and need for liver transplantation. Other forms of long-term sequalae associated with DILI are progressive fibrosis, autoimmune-like hepatitis, secondary sclerosing cholangitis, sinusoidal obstruction syndrome and, as a common final stage, the development of cirrhosis, portal hypertension and its complications. Immune checkpoint inhibitors, which can cause an autoimmune-like phenotype have also recently been shown to cause sclerosing cholangitis with cytotoxic T CD8+ cell infiltration in biliary tracts. DILI has been shown to have a significant impact on health-related quality of life but very little is known about its psychological consequences in the long-term. Further investigations with structured long-term follow-up and periodic quality of life surveys are needed to assess the impact of DILI on psychological outcomes, particularly in those with chronic sequelae.
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Affiliation(s)
- Einar S Björnsson
- Faculty of Medicine, University of Iceland, Iceland; Department of Gastroenterology, Landspitali University Hospital Reykjavik, Iceland.
| | - Raul J Andrade
- Unidad de Gestión Clínica de Enfermedades Digestivas, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Malaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
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Staal FCR, Beets-Tan RGH, Heeres BC, Houwers J, de Boer M, van Dorth D, Lambregts DMJ, Maas M. Magnetic resonance assessment of sinusoidal obstruction syndrome after neoadjuvant chemotherapy for colorectal liver metastases is not reproducible. Acta Radiol 2021; 62:1133-1141. [PMID: 32972213 DOI: 10.1177/0284185120957988] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Sinusoidal obstruction syndrome (SOS) due to chemotherapy can cause severe hepatotoxicity, leading to impaired outcome in patients with colorectal cancer. A previous study introduced gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) to diagnose SOS. PURPOSE To assess the reproducibility of Gd-EOB-MRI-based SOS diagnosis and its relationship with response to chemotherapy and long-term outcome. MATERIAL AND METHODS Twenty-six Gd-EOB-MRI scans of patients undergoing chemotherapy for colorectal liver metastases (CRLM) were retrospectively analyzed. Three radiologists, blinded to clinical data, independently scored presence and severity of SOS on a 5-point scale (0, definitely not present to 4, definitely present). Patients with a score ≥3 were considered SOS+. Inter-observer agreement between readers was assessed with kappa statistics. Response (RECIST 1.1.), occurrence of new CRLM during follow-up (hepatic progression) and overall survival (OS) were compared between patients with and without SOS. RESULTS The inter-observer agreement of SOS scores was poor, with quadratic kappas of 0.17-0.40. For the binary outcome of SOS+ (confidence level [CL] 3-4) vs. SOS- (CL 0-2) agreement was poor, with kappas of 0.03-0.37. Median follow-up was 24 months (range 4-44 months). Response and OS between patients with and without SOS did not differ significantly for any of the readers. CONCLUSION Inter-observer agreement for the diagnosis of SOS on Gd-EOB-MRI is poor. No significant correlation with relevant outcomes was found for any of the readers. Therefore, MRI for SOS diagnosis might be less useful than previously reported. Other techniques should be explored to accurately diagnose SOS in absence of histological confirmation.
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Affiliation(s)
- Femke CR Staal
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Regina GH Beets-Tan
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
- Department of Radiology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Birthe C Heeres
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Janneke Houwers
- Institute of Regional Health Research, University of Southern Denmark, Denmark
| | - Myrte de Boer
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Danielle van Dorth
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Doenja MJ Lambregts
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Monique Maas
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
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Bolhuis K, Grosheide L, Wesdorp NJ, Komurcu A, Chapelle T, Dejong CHC, Gerhards MF, Grünhagen DJ, van Gulik TM, Huiskens J, De Jong KP, Kazemier G, Klaase JM, Liem MSL, Molenaar IQ, Patijn GA, Rijken AM, Ruers TM, Verhoef C, de Wilt JHW, Punt CJA, Swijnenburg RJ. Short-Term Outcomes of Secondary Liver Surgery for Initially Unresectable Colorectal Liver Metastases Following Modern Induction Systemic Therapy in the Dutch CAIRO5 Trial. ANNALS OF SURGERY OPEN 2021; 2:e081. [PMID: 37635815 PMCID: PMC10455233 DOI: 10.1097/as9.0000000000000081] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 06/14/2021] [Indexed: 12/15/2022] Open
Abstract
Objective To present short-term outcomes of liver surgery in patients with initially unresectable colorectal liver metastases (CRLM) downsized by chemotherapy plus targeted agents. Background The increase of complex hepatic resections of CRLM, technical innovations pushing boundaries of respectability, and use of intensified induction systemic regimens warrant for safety data in a homogeneous multicenter prospective cohort. Methods Patients with initially unresectable CRLM, who underwent complete resection after induction systemic regimens with doublet or triplet chemotherapy, both plus targeted therapy, were selected from the ongoing phase III CAIRO5 study (NCT02162563). Short-term outcomes and risk factors for severe postoperative morbidity (Clavien Dindo grade ≥ 3) were analyzed using logistic regression analysis. Results A total of 173 patients underwent resection of CRLM after induction systemic therapy. The median number of metastases was 9 and 161 (93%) patients had bilobar disease. Thirty-six (20.8%) 2-stage resections and 88 (51%) major resections (>3 liver segments) were performed. Severe postoperative morbidity and 90-day mortality was 15.6% and 2.9%, respectively. After multivariable analysis, blood transfusion (odds ratio [OR] 2.9 [95% confidence interval (CI) 1.1-6.4], P = 0.03), major resection (OR 2.9 [95% CI 1.1-7.5], P = 0.03), and triplet chemotherapy (OR 2.6 [95% CI 1.1-7.5], P = 0.03) were independently correlated with severe postoperative complications. No association was found between number of cycles of systemic therapy and severe complications (r = -0.038, P = 0.31). Conclusion In patients with initially unresectable CRLM undergoing modern induction systemic therapy and extensive liver surgery, severe postoperative morbidity and 90-day mortality were 15.6% and 2.7%, respectively. Triplet chemotherapy, blood transfusion, and major resections were associated with severe postoperative morbidity.
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Affiliation(s)
- Karen Bolhuis
- From the Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Lodi Grosheide
- From the Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Nina J. Wesdorp
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, The Netherlands
| | - Aysun Komurcu
- The Netherlands Netherlands Comprehensive Cancer Center, Utrecht, The Netherlands
| | - Thiery Chapelle
- Department of Hepatobiliary, Transplantation, and Endocrine Surgery, University of Antwerp, Belgium
| | - Cornelis H. C. Dejong
- Maastricht University Medical Center, Department of Surgery, Maastricht, The Netherlands and Universitätsklinikum Aachen, Aachen, Germany
| | | | - Dirk J. Grünhagen
- Erasmus MC Cancer Institute, Department of Surgery, Rotterdam, The Netherlands
| | - Thomas M. van Gulik
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
| | | | - Koert P. De Jong
- Department of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, Groningen
| | - Geert Kazemier
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, The Netherlands
| | - Joost M. Klaase
- Department of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, Groningen
| | - Mike S. L. Liem
- Department of Surgery, Medical Spectrum Twente, Enschede, the Netherlands
| | - I. Quintus Molenaar
- Regional Academic Cancer Center Utrecht, Department of Surgery, University Medical Center Utrecht and St Antonius Hospital Nieuwegein, The Netherlands
| | | | - Arjen M. Rijken
- Amphia hospital, Department of Surgery, Breda, The Netherlands
| | - Theo M. Ruers
- Amphia hospital, Department of Surgery, Breda, The Netherlands
| | - Cornelis Verhoef
- Erasmus MC Cancer Institute, Department of Surgery, Rotterdam, The Netherlands
| | | | - Cornelis J. A. Punt
- From the Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
- Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht University, Department of Epidemiology, Utrecht, The Netherlands
| | - Rutger-Jan Swijnenburg
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
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Kohnken R, Falahatpisheh H, Janardhan KS, Guffroy M. Anatomic and Clinical Pathology Characterization of Drug-Induced Sinusoidal Obstruction Syndrome (Veno-Occlusive Disease) in Cynomolgus Macaques. Toxicol Pathol 2021; 50:13-22. [PMID: 34414838 DOI: 10.1177/01926233211037932] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Sinusoidal obstruction syndrome (SOS) is a unique form of liver injury that occurs after exposure to chemotherapeutic drugs and toxins. The diagnosis of SOS in humans remains a challenge as the clinical criteria have low specificity and there are no reliable noninvasive biomarkers. The mechanism of injury is believed to be damage to liver endothelial cells, primarily sinusoidal endothelial cells (SECs), which leads to sinusoidal dilation, central venous fibrosis, and/or nodular regeneration. Nonclinical data suggest that this uncommon liver toxicity can be recapitulated in cynomolgus monkeys, and it is critical that pathologists are familiar with its characteristic clinicopathologic features. Elevations in liver enzymes, in particular aspartate aminotransferase, associated with isolated thrombocytopenia, should raise the suspicion of SEC injury for specific drug classes. Characterization of liver microscopic findings in monkeys benefits from the use of appropriate stains, such as reticulin stain, and VEGFR2 and CD34 immunohistochemical (IHC) stains. CD41 IHC demonstrates platelet accumulation in injured sinusoids, the likely cause of thrombocytopenia commonly reported in SOS. In conclusion, this report provides a comprehensive characterization of the pathology findings of drug-induced SOS in monkeys with the objectives of ensuring appropriate nonclinical recognition of the liability and informing clinical development strategy and monitoring.
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Affiliation(s)
| | - Hadi Falahatpisheh
- Oncology Discovery, AbbVie Inc., South San Francisco, CA, USA. Falahatpisheh is now with Translational Sciences, Samumed LLC, San Diego, CA, USA
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Cha DI, Song KD, Ha SY, Hong JY, Hwang JA, Ko SE. Long-term follow-up of oxaliplatin-induced liver damage in patients with colorectal cancer. Br J Radiol 2021; 94:20210352. [PMID: 34133224 PMCID: PMC8248204 DOI: 10.1259/bjr.20210352] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/27/2021] [Accepted: 06/02/2021] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVES To report the long-term follow-up data including computed tomography (CT) findings of oxaliplatin-induced liver damage in patients with colorectal cancer. METHODS Three hundred and fifty-six patients who underwent surgery followed by oxaliplatin-based chemotherapy (OBC) for colorectal cancer between January 2013 and December 2014 were included. Abdominal CT images and laboratory results (serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total bilirubin, and platelet counts) were reviewed immediately before (as baseline), during, and after adjuvant OBC. Abdominal CT images were reviewed to assess the heterogeneous liver parenchyma, increase in size of the spleen, development of acute portosystemic shunts during OBC, and imaging findings of chronic portal hypertension. RESULTS During OBC, 90.2% (321/356) of the patients developed parenchymal heterogeneity. Increase in the spleen size during the OBC period was seen in 62.4% (225/356) of patients. The overall rate of development of acute portosystemic shunts during OBC was 23.9% (85/356). These findings were resolved after cessation of OBC except in 1.4% (5/356) of the patients in whom chronic portal hypertension persisted even after completion of OBC. Serum AST, ALT, and total bilirubin levels increased and platelet counts decreased during OBC and returned to normal after completion of OBC; however, they did not reach the pre-OBC levels. CONCLUSION Although most changes associated with liver damage reversed to normal range after completion of OBC, some parameters did not reverse to the pretreatment level, and chronic portal hypertension developed in a small number of patients. ADVANCES IN KNOWLEDGE Chronic, persistent oxaliplatin-induced liver damage was not an infrequent complication after oxaliplatin-based chemotherapy for patients with colorectal cancer. It may cause non-cirrhotic portal hypertension and associated complications such as variceal bleeding.
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Affiliation(s)
- Dong Ik Cha
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyoung Doo Song
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sang Yun Ha
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jung Yong Hong
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jeong Ah Hwang
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Seong Eun Ko
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Hobeika C, Tribillon E, Marchese U, Faermark N, Ghedira A, Bonnet S, Nassar A, Gayet B, Fuks D. Validation of the IMM classification in laparoscopic repeat liver resections for colorectal liver metastases. Surgery 2021; 170:1448-1456. [PMID: 34176600 DOI: 10.1016/j.surg.2021.05.034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 05/05/2021] [Accepted: 05/17/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND To validate the Institut Mutualiste Montsouris classification as a difficulty scoring system applicable to laparoscopic repeat liver resections and identify risk-factors of unexpected difficulty. METHODS From a prospectively collected database between 2000 and 2019, patients undergoing laparoscopic repeat liver resections were classified according to the Institut Mutualiste Montsouris classification. Doubly robust estimators (weighted regressions) were used to assess the effect of factors on intra- and postoperative outcomes and allowed for strong adjustment on age, body mass index, American Society of Anesthesiologists, carcinoembryonic antigen, number, and size of lesions. Unexpected difficulty was defined as a composite indicator which included substantial blood loss and/or substantial operative time and/or conversion. RESULTS Of 205 laparoscopic repeat liver resections patients, 87, 25, and 93 procedures were classified as grade 1, 2, and 3 laparoscopic repeat liver resections, respectively. After doubly robust adjustment, the IMM classification was associated with blood loss (Cohen f2 0.12; P = 0.001), operative time (Cohen f2 0.07; P = .001), and length of stay (Cohen f2 0.13; P = .001), as well as with the risk of both minor and severe complications (odd ratio = 2.94; 95% confidence interval: 2.06-4.20) and the chances of achieving textbook outcome (relative risk = 0.57; 95% confidence interval: 0.41-0.81). Independently from the Institut Mutualiste Montsouris classification, a first major hepatectomy (relative risk = 1.15, 95% confidence interval: 1.03-1.29) as well as sinusoidal obstruction syndrome (relative risk = 1.24, 95% confidence interval: 1.09-1.41) were independent risk factors of unexpected difficulty. A first major resection was associated with decreased chances of textbook outcome (relative risk = 0.53; 95% confidence interval: 0.33-0.85). CONCLUSION The Institut Mutualiste Montsouris classification is a valuable difficulty scoring system for laparoscopic repeat liver resections procedures, while previous major resection and presence of sinusoidal obstruction syndrome are likely to jeopardize the outcomes.
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Affiliation(s)
- Christian Hobeika
- Department of Digestive, Oncologic, and Metabolic Surgery, Institut Mutualiste Montsouris, Université de Paris, Paris, France.
| | - Ecoline Tribillon
- Department of Digestive, Oncologic, and Metabolic Surgery, Institut Mutualiste Montsouris, Université de Paris, Paris, France
| | - Ugo Marchese
- Department of Digestive, Oncologic, and Metabolic Surgery, Institut Mutualiste Montsouris, Université de Paris, Paris, France
| | - Nicole Faermark
- Department of Digestive, Oncologic, and Metabolic Surgery, Institut Mutualiste Montsouris, Université de Paris, Paris, France
| | - Abdessalem Ghedira
- Department of Digestive, Oncologic, and Metabolic Surgery, Institut Mutualiste Montsouris, Université de Paris, Paris, France
| | - Stéphane Bonnet
- Department of Digestive, Oncologic, and Metabolic Surgery, Institut Mutualiste Montsouris, Université de Paris, Paris, France
| | - Alexandra Nassar
- Department of Digestive, Oncologic, and Metabolic Surgery, Institut Mutualiste Montsouris, Université de Paris, Paris, France
| | - Brice Gayet
- Department of Digestive, Oncologic, and Metabolic Surgery, Institut Mutualiste Montsouris, Université de Paris, Paris, France
| | - David Fuks
- Department of Digestive, Oncologic, and Metabolic Surgery, Institut Mutualiste Montsouris, Université de Paris, Paris, France
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Costa G, Cavinato L, Masci C, Fiz F, Sollini M, Politi LS, Chiti A, Balzarini L, Aghemo A, di Tommaso L, Ieva F, Torzilli G, Viganò L. Virtual Biopsy for Diagnosis of Chemotherapy-Associated Liver Injuries and Steatohepatitis: A Combined Radiomic and Clinical Model in Patients with Colorectal Liver Metastases. Cancers (Basel) 2021; 13:3077. [PMID: 34203103 PMCID: PMC8234168 DOI: 10.3390/cancers13123077] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 05/16/2021] [Accepted: 06/16/2021] [Indexed: 12/12/2022] Open
Abstract
Non-invasive diagnosis of chemotherapy-associated liver injuries (CALI) is still an unmet need. The present study aims to elucidate the contribution of radiomics to the diagnosis of sinusoidal dilatation (SinDil), nodular regenerative hyperplasia (NRH), and non-alcoholic steatohepatitis (NASH). Patients undergoing hepatectomy for colorectal metastases after chemotherapy (January 2018-February 2020) were retrospectively analyzed. Radiomic features were extracted from a standardized volume of non-tumoral liver parenchyma outlined in the portal phase of preoperative post-chemotherapy computed tomography. Seventy-eight patients were analyzed: 25 had grade 2-3 SinDil, 27 NRH, and 14 NASH. Three radiomic fingerprints independently predicted SinDil: GLRLM_f3 (OR = 12.25), NGLDM_f1 (OR = 7.77), and GLZLM_f2 (OR = 0.53). Combining clinical, laboratory, and radiomic data, the predictive model had accuracy = 82%, sensitivity = 64%, and specificity = 91% (AUC = 0.87 vs. AUC = 0.77 of the model without radiomics). Three radiomic parameters predicted NRH: conventional_HUQ2 (OR = 0.76), GLZLM_f2 (OR = 0.05), and GLZLM_f3 (OR = 7.97). The combined clinical/laboratory/radiomic model had accuracy = 85%, sensitivity = 81%, and specificity = 86% (AUC = 0.91 vs. AUC = 0.85 without radiomics). NASH was predicted by conventional_HUQ2 (OR = 0.79) with accuracy = 91%, sensitivity = 86%, and specificity = 92% (AUC = 0.93 vs. AUC = 0.83 without radiomics). In the validation set, accuracy was 72%, 71%, and 91% for SinDil, NRH, and NASH. Radiomic analysis of liver parenchyma may provide a signature that, in combination with clinical and laboratory data, improves the diagnosis of CALI.
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Affiliation(s)
- Guido Costa
- Division of Hepatobiliary and General Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, Rozzano, 20189 Milan, Italy; (G.C.); (G.T.)
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (M.S.); (L.S.P.); (A.C.); (A.A.); (L.d.T.)
| | - Lara Cavinato
- MOX Laboratory, Department of Mathematics, Politecnico di Milano, 20133 Milan, Italy; (L.C.); (C.M.)
| | - Chiara Masci
- MOX Laboratory, Department of Mathematics, Politecnico di Milano, 20133 Milan, Italy; (L.C.); (C.M.)
| | - Francesco Fiz
- Department of Nuclear Medicine, IRCCS Humanitas Research Hospital, 20189 Milan, Italy;
| | - Martina Sollini
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (M.S.); (L.S.P.); (A.C.); (A.A.); (L.d.T.)
- Department of Nuclear Medicine, IRCCS Humanitas Research Hospital, 20189 Milan, Italy;
| | - Letterio Salvatore Politi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (M.S.); (L.S.P.); (A.C.); (A.A.); (L.d.T.)
- Department of Radiology, IRCCS Humanitas Research Hospital, Rozzano, 20189 Milan, Italy;
| | - Arturo Chiti
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (M.S.); (L.S.P.); (A.C.); (A.A.); (L.d.T.)
- Department of Nuclear Medicine, IRCCS Humanitas Research Hospital, 20189 Milan, Italy;
| | - Luca Balzarini
- Department of Radiology, IRCCS Humanitas Research Hospital, Rozzano, 20189 Milan, Italy;
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (M.S.); (L.S.P.); (A.C.); (A.A.); (L.d.T.)
- Division of Internal Medicine and Hepatology, Department of Internal Medicine, IRCCS Humanitas Research Hospital, Rozzano, 20189 Milan, Italy
| | - Luca di Tommaso
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (M.S.); (L.S.P.); (A.C.); (A.A.); (L.d.T.)
- Pathology Unit, IRCCS Humanitas Research Hospital, 20189 Milan, Italy
| | - Francesca Ieva
- MOX Laboratory, Department of Mathematics, Politecnico di Milano, 20133 Milan, Italy; (L.C.); (C.M.)
- CADS—Center for Analysis, Decisions and Society, Human Technopole, 20157 Milan, Italy
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, Rozzano, 20189 Milan, Italy; (G.C.); (G.T.)
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (M.S.); (L.S.P.); (A.C.); (A.A.); (L.d.T.)
| | - Luca Viganò
- Division of Hepatobiliary and General Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, Rozzano, 20189 Milan, Italy; (G.C.); (G.T.)
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (M.S.); (L.S.P.); (A.C.); (A.A.); (L.d.T.)
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Starlinger P, Pereyra D, Hackl H, Ortmayr G, Braunwarth E, Santol J, Najarnia S, Driedger MR, Gregory L, Alva‐Ruiz R, Glasgow A, Assinger A, Nagorney DM, Habermann EB, Staetttner S, Cleary SP, Smoot RL, Gruenberger T. Consequences of Perioperative Serotonin Reuptake Inhibitor Treatment During Hepatic Surgery. Hepatology 2021; 73:1956-1966. [PMID: 33078426 PMCID: PMC8251772 DOI: 10.1002/hep.31601] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/14/2020] [Accepted: 10/01/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Platelet-stored serotonin critically affects liver regeneration in mice and humans. Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenalin reuptake inhibitors (SNRIs) reduce intraplatelet serotonin. As SSRIs/SNRIs are now one of the most commonly prescribed drugs in the United States and Europe and given serotonin's impact on liver regeneration, we evaluated whether perioperative use of SSRIs/SNRIs affects outcome after hepatic resection. APPROACH AND RESULTS Consecutive patients undergoing hepatic resection (n = 754) were retrospectively included from prospectively maintained databases from two European institutions. Further, an independent cohort of 495 patients from the United States was assessed to validate our exploratory findings. Perioperative intake of SSRIs/SNRIs was recorded, and patients were followed up for postoperative liver dysfunction (LD), morbidity, and mortality. Perioperative intraplatelet serotonin levels were significantly decreased in patients receiving SSRI/SNRI treatment. Patients treated with SSRIs/SNRIs showed a higher incidence of morbidity, severe morbidity, LD, and LD requiring intervention. Associations were confirmed in the independent validation cohort. Combined cohorts documented a significant increase in deleterious postoperative outcome (morbidity odds ratio [OR], 1.56; 95% confidence interval [CI], 1.07-2.31; severe morbidity OR, 1.86; 95% CI, 1.22-2.79; LD OR, 1.96; 95% CI, 1.23-3.06; LD requiring intervention OR, 2.22; 95% CI, 1.03-4.36). Further, multivariable analysis confirmed the independent association of SSRIs/SNRIs with postoperative LD, which was closely associated with postoperative 90-day mortality and 1-year overall survival. CONCLUSIONS We observed a significant association of perioperative SSRI/SNRI intake with adverse postoperative outcome after hepatic resection. This indicates that SSRIs/SNRIs should be avoided perioperatively in patients undergoing hepatic resections.
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Affiliation(s)
- Patrick Starlinger
- Department of SurgeryMedical University of ViennaGeneral HospitalViennaAustria
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - David Pereyra
- Department of SurgeryMedical University of ViennaGeneral HospitalViennaAustria
| | - Hubert Hackl
- Institute of BioinformaticsBiocenterMedical University of InnsbruckInnsbruckAustria
| | - Gregor Ortmayr
- Department of SurgeryMedical University of ViennaGeneral HospitalViennaAustria
| | - Eva Braunwarth
- Department of Visceral, Transplantation and Thoracic SurgeryMedical University InnsbruckInnsbruckAustria
| | - Jonas Santol
- Department of SurgeryMedical University of ViennaGeneral HospitalViennaAustria
| | - Sina Najarnia
- Department of SurgeryMedical University of ViennaGeneral HospitalViennaAustria
| | - Michael R. Driedger
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Lindsey Gregory
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Roberto Alva‐Ruiz
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Amy Glasgow
- Robert D. and Patricia E. Kern Center for the Science of Health Care DeliverMayo ClinicRochesterMN
| | - Alice Assinger
- Center of Physiology and PharmacologyMedical University of ViennaViennaAustria
| | - David M. Nagorney
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Elizabeth B. Habermann
- Robert D. and Patricia E. Kern Center for the Science of Health Care DeliverMayo ClinicRochesterMN
| | - Stefan Staetttner
- Department of Visceral, Transplantation and Thoracic SurgeryMedical University InnsbruckInnsbruckAustria
- Department of General, Visceral and Vascular SurgerySKG KlinikumVöcklabruckAustria
| | - Sean P. Cleary
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Rory L. Smoot
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Thomas Gruenberger
- Department of SurgeryHPB CenterViennese Health NetworkClinic Favoriten and Sigmund Freud Private UniversityViennaAustria
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Vigano L, Sollini M, Ieva F, Fiz F, Torzilli G. Chemotherapy-Associated Liver Injuries: Unmet Needs and New Insights for Surgical Oncologists. Ann Surg Oncol 2021; 28:4074-4079. [PMID: 33929618 DOI: 10.1245/s10434-021-10069-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 04/14/2021] [Indexed: 12/15/2022]
Affiliation(s)
- Luca Vigano
- Division of Hepatobiliary and General Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. .,Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
| | - Martina Sollini
- Department of Nuclear Medicine, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Francesca Ieva
- MOX laboratory, Department of Mathematics, Politecnico di Milano, Milan, Italy.,CADS - Center for Analysis, Decisions and Society, Human Technopole, Milan, Italy
| | - Francesco Fiz
- Department of Nuclear Medicine, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
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Ding Y, Rao SX, Wang WT, Chen CZ, Li RC, Zeng M. Gd-EOB-DTPA-enhanced MR findings in chemotherapy-induced sinusoidal obstruction syndrome in colorectal liver metastases. J Int Med Res 2021; 48:300060520926031. [PMID: 32500783 PMCID: PMC7278311 DOI: 10.1177/0300060520926031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Background We assessed the clinical presentations, biomarkers, and Gd-EOB-DTPA-enhanced MRI features that were associated with oxaliplatin-induced sinusoidal obstruction syndrome (SOS) to detect chemotherapy-associated SOS in a timely manner. Methods Fifty-seven patients who underwent oxaliplatin-based chemotherapy and Gd-EOB-DTPA-enhanced MRI were included. Post-oxaliplatin heterogeneity in liver parenchyma was scored on a grading scale of 0 to 3. Abnormal clinical findings, including splenomegaly, hepatomegaly, gall bladder wall thickening, and hepatic vein narrowing, were also assessed. Additionally, alanine transaminase (ALT) levels, aspartate aminotransferase (AST) levels, and platelet counts were measured. Results For SOS, 21 patients were scored grade 0, 24 were grade 1, seven were grade 2, and five were grade 3. Hepatomegaly, splenomegaly, gall bladder wall thickening, and hepatic vein narrowing were significantly correlated with the grade for non-tumorous hepatic parenchymal heterogeneity. For laboratory findings, ALT and AST levels, the AST-to-platelet ratio index score, and platelet counts were significantly associated with a high grade (≥2) of non-tumorous hepatic parenchymal heterogeneity. Conclusions We assessed the clinical presentations, biomarkers, and Gd-EOB-DTPA-enhanced MRI features that were associated with oxaliplatin-induced sinusoidal obstruction syndrome (SOS) to detect chemotherapy-associated SOS in a timely manner. Additionally, specific laboratory findings were significantly associated with a high grade (≥2).
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Affiliation(s)
- Ying Ding
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Sheng-Xiang Rao
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Wen-Tao Wang
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Cai-Zhong Chen
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Ren-Chen Li
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai, China
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Liver surface nodularity: a novel predictor of post-hepatectomy liver failure in patients with colorectal liver metastases following chemotherapy. Eur Radiol 2021; 31:5830-5839. [PMID: 33666699 DOI: 10.1007/s00330-020-07683-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 12/16/2020] [Accepted: 12/29/2020] [Indexed: 12/16/2022]
Abstract
OBJECTIVES The goal of this study was to assess the relationship between liver surface nodularity (LSN), chemotherapy-associated liver injury (CALI), and clinically relevant post-hepatectomy liver failure (CR-PHLF) (i.e., ≥ grade B) in patients undergoing hepatectomy for colorectal liver metastases (CLM). METHODS Preoperative CT scans of patients who underwent chemotherapy followed by hepatectomy for CLM between 2010 and 2017 were retrospectively analyzed. LSN was measured using semi-automated CT software CT images in patients who had available preoperative CT scans within 6 weeks before hepatectomy, and was computed based on the means of one to 10 measurements by two abdominal radiologists consensually. The association of LSN, CALI, and CR-PHLF was analyzed. RESULTS Two hundred fifty-six patients were analyzed (149 men and 107 women; overall median age, 61 [range, 29-88 years]). A total of 26 patients (10.2%) developed CR-PHLF. The optimal LSN cut-off value for detecting CR-PHLF was 2.5, as determined by receiver operative characteristic analysis (p < 0.001). LSN ≥ 2.5 was associated with prolonged chemotherapy (> 6 cycles, p = 0.018), but not with CALIs. After propensity score matching, LSN remained significantly associated with CR-PHLF (p = 0.031). Furthermore, multivariate analysis identified LSN ≥ 2.50 and future liver remnant (FLR) < 30% as significant preoperative predictors of CR-PHLF in 102 patients undergoing major hepatectomy. LSN ≥ 2.50 was more frequent in patients undergoing major hepatectomy despite FLR ≥ 30% (p = 0.008). CONCLUSION LSN quantified on CT is an independent surrogate of CR-PHLF in patients who undergo chemotherapy followed by hepatectomy for CLM and may provide a valuable additional tool in the preoperative assessment of these patients. KEY POINTS • LSN was not associated with chemotherapy- associated liver injury but high LSN (defined ≥ 2.5) was associated with prolonged chemotherapy (> 6 cycles). • High LSN was an independent predictor of clinically relevant postoperative liver failure in patients undergoing hepatectomy for CRLM. • LSN ≥ 2.50 was more frequent in patients with PHLF after major hepatectomy despite a future liver remnant ≥ 30%.
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Qin S, Cui R, Wang Y, Chen Y, Huang Y, Liu GJ. Contrast-Enhanced Ultrasound Imaging Features of Focal Chemotherapy-Induced Sinusoidal Injury in Patients With Colorectal Cancer: Initial Experience. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2021; 40:141-149. [PMID: 32697388 DOI: 10.1002/jum.15384] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 04/02/2020] [Accepted: 06/12/2020] [Indexed: 06/11/2023]
Abstract
OBJECTIVES Increasing studies have reported focal chemotherapy-induced sinusoidal injury (CSI) mimicking colorectal liver metastasis (CRLM) on imaging studies, resulting in unnecessary lobectomy. This study aimed to investigate the contrast-enhanced ultrasound (CEUS) imaging features of focal CSI. METHODS We retrospectively evaluated 16 patients who had a pathologic diagnosis of focal CSI and underwent CEUS between January 2013 and January 2019. The images were compared with those obtained from 27 patients with CRLM. RESULTS On CEUS, 14 (87.5%) focal CSIs showed heterogeneous isoenhancement, 1 (6.3%) peripheral hyperenhancement, and 1 (6.3%) homogeneous hyperenhancement during the arterial phase. Compared with the adjacent liver parenchyma, the initial enhancement time of focal CSI was earlier in 2 (12.5%), simultaneous in 9 (56.3%), and later in 5 (31.3%) patients. In the portal and late phases, all of the focal CSI cases showed hypoenhancement compared with the adjacent liver parenchyma. Focal CSI had the following CEUS findings, which were different from those of CRLM: (1) heterogeneous isoenhancement in the arterial phase (87.5% versus 0%; P < .001); (2) an initial enhancement time later than that of the liver parenchyma (mean ± SD, 0.5 ± 1.5 versus -1.5 ± 1.9; P < .001); (3) a longer time to peak (30.5 ± 5.6 versus 22.5 ± 4.4 seconds; P < .001); and (4) a later time to wash-out (51.0 ± 12.5 versus 35.0 ± 6.2 seconds; P = .002). CONCLUSIONS Focal CSI usually shows heterogeneous isoenhancement in arterial phase and hypoenhancement in portal and late phases on CEUS, with slow contrast wash-in and wash-out, which can be helpful in the differential diagnosis with CRLM.
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Affiliation(s)
- Si Qin
- Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Rui Cui
- Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yimin Wang
- Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yao Chen
- Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yan Huang
- Department of Pathology, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Guang Jian Liu
- Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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Yang L, Ding Y, Rao S, Chen C, Zeng M. T 1 Mapping on Gd-EOB-DTPA-Enhanced MRI for the Prediction of Oxaliplatin-Induced Liver Injury in a Mouse Model. J Magn Reson Imaging 2020; 53:896-902. [PMID: 32979019 DOI: 10.1002/jmri.27377] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 09/06/2020] [Accepted: 09/08/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Oxaliplatin-induced liver injury (OILI) not only impairs hepatic regeneration but also increases postoperative morbidity and mortality. Therefore, noninvasive, accurate, and early diagnosis of OILI is mandatory. PURPOSE To evaluate the potential of T1 mapping on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI for assessing OILI in a mouse model. STUDY TYPE Case control, animal model. ANIMAL MODEL Thirty oxaliplatin-treated mice and 10 control mice were included. FIELD STRENGTH Volumetric interpolated breath-hold examination sequence: 3T scanner with a phased-array animal 8-channel coil. T1 mapping before and at hepatobiliary phase (HBP) after injection of Gd-EOB-DTPA were undertaken. ASSESSMENT T1 relaxation times of the liver parenchyma were measured and the reduction rate (ΔT1 %) was calculated. Histological findings were used as a standard reference. STATISTICAL TESTS The Kruskal-Wallis test with pairwise comparisons using the Mann-Whitney U-test were applied to compare the parameters across groups. Spearman's rank correlation test and receiver operating characteristics (ROC) analyses were performed. Areas under the curves (AUCs) were compared using the DeLong method. RESULTS Histologically, mice were classified as normal (n = 10), hepatocellular degeneration without fibrosis (n = 16), and hepatocellular degeneration with fibrosis (n = 14). HBP T1 relaxation time increased with the severity of OILI (rho = 0.60, P < 0.05), and ΔT1 % decreased with the severity of OILI (rho = -0.78, P < 0.05). AUC was 0.92 for ΔT1 % in differentiating hepatocellular degeneration without fibrosis from normal liver, but HBP T1 relaxation time could not distinguish them (P = 0.09). AUCs were 0.96 and 0.95 for HBP T1 relaxation time, and 0.90 and 0.84 for ΔT1 % in discriminating OILI with fibrosis from normal liver and OILI without fibrosis. DATA CONCLUSION HBP T1 relaxation time and ΔT1 % of Gd-EOB-DTPA enhanced MRI was useful for assessing OILI. ΔT1 % may be more sensitive than HBP T1 relaxation time in detecting early stage of liver injury. LEVEL OF EVIDENCE 2. TECHNICAL EFFICACY STAGE 5.
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Affiliation(s)
- Li Yang
- Department of Radiology, Zhongshan, Hospital of Fudan University, Shanghai, China
| | - Ying Ding
- Department of Radiology, Zhongshan, Hospital of Fudan University, Shanghai, China
| | - Shengxiang Rao
- Department of Radiology, Zhongshan, Hospital of Fudan University, Shanghai, China
| | - Caizhong Chen
- Department of Radiology, Zhongshan, Hospital of Fudan University, Shanghai, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan, Hospital of Fudan University, Shanghai, China
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Parmar KL, O'Reilly D, Valle JW, Braun M, Naish JH, Williams SR, Lloyd WK, Malcomson L, Cresswell K, Bamford C, Renehan AG. Prospective study of change in liver function and fat in patients with colorectal liver metastases undergoing preoperative chemotherapy: protocol for the CLiFF Study. BMJ Open 2020; 10:e027630. [PMID: 32967864 PMCID: PMC7513559 DOI: 10.1136/bmjopen-2018-027630] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Preoperative chemotherapy in patients undergoing resection for colorectal liver metastases (CLM) improves oncological outcomes. However, chemotherapy-associated liver injury (occurring in two patterns: vascular and fat deposition) is a real clinical concern prior to hepatic resection. After major liver resection, regeneration of the residual liver is a prerequisite for recovery and avoidance of liver failure, but this regenerative capacity may be hindered by chemotherapy. Thus, there is a need to predict for this serious complication. Over the past two decades, several tests and derived indices have been developed, which have failed to achieve clinical utility, mainly as they were indirect measurements of liver function. Here, we will use a novel test of liver function (the liver maximum capacity (LiMAx) test), and measure liver fat using MRI. METHODS AND ANALYSIS This prospective study will assess changes in liver function longitudinally, measured by the LiMAx test, and liver fat, measured by advanced MRI using both MR spectroscopy and the modified Dixon method, in up to 35 patients undergoing preoperative chemotherapy for CLM. The primary outcomes will be the changes in liver function and fat compared with baseline prechemotherapy measurements. Secondary outcome measures include: routinely measured liver function blood tests, anthropometric measurements, postoperative histology and digital quantification of fat, postoperative complications and mortality and quality of life. ETHICS AND DISSEMINATION The study was approved by a National Health Service Research Ethics Committee and registered with the Health Research Authority. Dissemination will be via international and national conferences and the National Institute for Health Research network. Manuscripts will be published. TRIAL REGISTRATION NUMBER This study is registered online at www.clinicaltrials.gov (registration number NCT03562234).
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Affiliation(s)
- Kat L Parmar
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
- Manchester Cancer Research Centre, Manchester, UK
| | - Derek O'Reilly
- Hepatobiliary Surgery, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Juan W Valle
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
- Oncology, Christie NHS Foundation Trust, Manchester, UK
| | - Michael Braun
- Oncology, Christie NHS Foundation Trust, Manchester, UK
| | - Jo H Naish
- Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK
| | - Steve R Williams
- Centre for Imaging Sciences, University of Manchester, Manchester, UK
| | - William K Lloyd
- Centre for Imaging Sciences, University of Manchester, Manchester, UK
| | - Lee Malcomson
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
- Surgery, Christie NHS Foundation Trust, Manchester, UK
| | - Katharine Cresswell
- Public Programmes Team, Research and Innovation Division, Manchester University NHS Foundation Trust, Manchester, UK
| | - Colin Bamford
- Cancer Patient and Public Advisory Group, NIHR Manchester Biomedical Research Centre, Manchester, UK
| | - Andrew G Renehan
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
- Surgery, Christie NHS Foundation Trust, Manchester, UK
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Issues to be considered to address the future liver remnant prior to major hepatectomy. Surg Today 2020; 51:472-484. [PMID: 32894345 DOI: 10.1007/s00595-020-02088-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 07/08/2020] [Indexed: 02/08/2023]
Abstract
An accurate preoperative evaluation of the hepatic function and application of portal vein embolization in selected patients have helped improve the safety of major hepatectomy. In planning major hepatectomy, however, several issues remain to be addressed. The first is which cut-off values for serum total bilirubin level and prothrombin time should be used to define post-hepatectomy liver failure. Other issues include what minimum future liver remnant (FLR) volume is required; whether the total liver volume measured using computed tomography or the standard liver volume calculated based on the body surface area should be used to assess the adequacy of the FLR volume; whether there is a discrepancy between the FLR volume and function during the recovery period after portal vein embolization or hepatectomy; and how best the function of a specific FLR can be assessed. Various studies concerning these issues have been reported with controversial results. We should also be aware that different strategies and management are required for different types of liver damage, such as cirrhosis in hepatocellular carcinoma, cholangitis in biliary tract cancer, and chemotherapy-induced hepatic injury.
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de Lédinghen V, Villate A, Robin M, Decraecker M, Valla D, Hillaire S, Hernandez-Gea V, Dutheil D, Bureau C, Plessier A. Sinusoidal obstruction syndrome. Clin Res Hepatol Gastroenterol 2020; 44:480-485. [PMID: 32253162 DOI: 10.1016/j.clinre.2020.03.019] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 03/03/2020] [Indexed: 02/04/2023]
Abstract
Sinusoidal obstruction syndrome (SOS), previously known as veno-occlusive disease, is characterized by concentric and non-thrombotic obstruction of the sinusoid and central vein lumen with no identified primitive or thrombotic hepatic vein lesions. The initial lesion is a result of endothelial denudation, corresponding to the migration of damaged sinusoidal cells to the central veins of the hepatic lobules, leading to sinusoidal and veno-occlusive congestive obstruction. SOS may be associated with other lesions such as centrilobular perisinusoidal fibrosis, peliosis, or nodular regenerative hyperplasia. The first cases of SOS were documented in 1920 in South Africa, after ingestion of food sources contaminated by pyrrolizidine alkaloids. SOS is a well-known complication of hematopoietic stem cell transplantation (HSCT). Numerous toxins and drugs have been associated with SOS, mainly chemotherapies and immunosuppressive therapies, as well as total body or liver irradiation and ABO mismatch platelet transfusion. The pathogenesis of this entity remains unknown.
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Affiliation(s)
- Victor de Lédinghen
- Department of Hepatology and INSERM U1053, Haut-Lévêque Hospital, University Hospital of Bordeaux, avenue Magellan, 33600 Pessac, France.
| | - Alban Villate
- Department of Hematology, Bretonneau Hospital, University hospital of Tours, 2, boulevard Tonnellé, 37000 Tours, France
| | - Marie Robin
- Department of Hematology, Saint-Louis Hospital, AP-HP, 1, avenue Claude-Vellefaux, 75475 Paris cedex 10, France
| | - Marie Decraecker
- Department of Hepatology and INSERM U1053, Haut-Lévêque Hospital, University Hospital of Bordeaux, avenue Magellan, 33600 Pessac, France
| | - Dominique Valla
- Department of Hepatology, DHU Unity, Beaujon Hospital, AP-HP, 100, boulevard du Général-Leclerc, 92118 Clichy, France; French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital, AP-HP, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France
| | - Sophie Hillaire
- Department of Internal Medicine, Foch Hospital, 40, rue Worth, 92150 Suresnes, France
| | - Virginia Hernandez-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd). Health Care Provider of the European Reference Network onRare Liver Disorders (ERN-Liver), Spain
| | - Danielle Dutheil
- Liver Vascular Disease Patient Organisation (AMVF), Beaujon Hospital, Department of Hepatology, 100, boulevard du Général-Leclerc, 92118 Clichy, France
| | - Christophe Bureau
- Department of Gastroenterology and Hepatology, Rangueil Hospital, University Hospital of Toulouse, 1, avenue du Professeur-Jean-Poulhès, 31400 Toulouse, France
| | - Aurélie Plessier
- Department of Hepatology, DHU Unity, Beaujon Hospital, AP-HP, 100, boulevard du Général-Leclerc, 92118 Clichy, France; French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital, AP-HP, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; Reference center of vascular liver diseases, European Reference Network (ERN) 'Rare-Liver', France
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40
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Truant S, Baillet C, Gnemmi V, Fulbert M, Turpin A, Dardenne S, Leteurtre E, El Amrani M, Dharancy S, Dubuquoy L, Huglo D, Chesné C, Pruvot FR. The Impact of Modern Chemotherapy and Chemotherapy-Associated Liver Injuries (CALI) on Liver Function: Value of 99mTc-Labelled-Mebrofenin SPECT-Hepatobiliary Scintigraphy. Ann Surg Oncol 2020; 28:1959-1969. [PMID: 32833150 DOI: 10.1245/s10434-020-08988-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 04/16/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Chemotherapy is increasingly used before hepatic resection, with controversial impact regarding liver function. This study aimed to assess the capacity of 99mTc-labelled-mebrofenin SPECT-hepatobiliary scintigraphy (HBS) to predict liver dysfunction due to chemotherapy and/or chemotherapeutic-associated liver injuries (CALI), such as sinusoidal obstruction syndrome (SOS) and nonalcoholic steatohepatitis (NASH) activity score (NAS). METHODS From 2011 to 2015, all consecutive noncirrhotic patients scheduled for a major hepatectomy (≥ 3 segments) gave informed consent for preoperative SPECT-HBS allowing measurements of segmental liver function. As primary endpoint, HBS results were compared between patients with versus without (1) preoperative chemotherapy (≤ 3 months); and (2) CALI, mainly steatosis, NAS (Kleiner), or SOS (Rubbia-Brandt). Secondary endpoints were (1) other factors impairing function; and (2) impact of chemotherapy, and/or CALI on hepatocyte isolation outcome via liver tissues. RESULTS Among 115 patients, 55 (47.8%) received chemotherapy. Sixteen developed SOS and 35 NAS, with worse postoperative outcome. Overall, chemotherapy had no impact on liver function, except above 12 cycles. In patients with CALI, a steatosis ≥ 30% significantly compromised function, as well as NAS, especially grades 2-5. Conversely, SOS had no impact, although subjected to very low patients number with severe SOS. Other factors impairing function were diabetes, overweight/obesity, or fibrosis. Similarly, chemotherapy in 73 of 164 patients had no effect on hepatocytes isolation outcome; regarding CALI, steatosis ≥ 30% and NAS impaired the yield and/or viability of hepatocytes, but not SOS. CONCLUSIONS In this first large, prospective study, HBS appeared to be a valuable tool to select heavily treated patients at risk of liver dysfunction through steatosis or NAS.
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Affiliation(s)
- Stéphanie Truant
- Department of Digestive Surgery and Transplantation, Univ. Lille, CHRU Lille, Lille, France. .,CANTHER laboratory Cancer Heterogeneity, Plasticity and Resistance to Therapies UMR-S1277 INSERM, Team Mucins, Cancer and Drug Resistance, 59000, Lille, France.
| | - Clio Baillet
- Department of Nuclear Medicine, Univ. Lille, Lille, France
| | | | - Maxence Fulbert
- Department of Digestive Surgery and Transplantation, Univ. Lille, CHRU Lille, Lille, France
| | - Anthony Turpin
- Department of Medical Oncology, Univ. Lille, Lille, France
| | - Sabrina Dardenne
- Department of Digestive Surgery and Transplantation, Univ. Lille, CHRU Lille, Lille, France
| | | | - Mehdi El Amrani
- Department of Digestive Surgery and Transplantation, Univ. Lille, CHRU Lille, Lille, France.,CANTHER laboratory Cancer Heterogeneity, Plasticity and Resistance to Therapies UMR-S1277 INSERM, Team Mucins, Cancer and Drug Resistance, 59000, Lille, France
| | - Sébastien Dharancy
- Hepatology Unit, Univ. Lille, Lille, France.,LIRIC-Lille Inflammation Research International Center-U995, Univ. Lille, Inserm, CHU Lille, Lille, France
| | - Laurent Dubuquoy
- Hepatology Unit, Univ. Lille, Lille, France.,LIRIC-Lille Inflammation Research International Center-U995, Univ. Lille, Inserm, CHU Lille, Lille, France
| | - Damien Huglo
- Department of Nuclear Medicine, Univ. Lille, Lille, France
| | | | - François-René Pruvot
- Department of Digestive Surgery and Transplantation, Univ. Lille, CHRU Lille, Lille, France
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Truant S, Pruvot FR. ASO Author Reflections: Usage of Single Photon Emission CT (SPECT) Hepatobiliary Scintigraphy to Detect the Impact of Chemotherapy-Associated Liver Injuries (CALI) on Liver Function Before a Major Hepatectomy. Ann Surg Oncol 2020; 27:882-883. [PMID: 32813204 DOI: 10.1245/s10434-020-08996-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 06/08/2020] [Indexed: 11/18/2022]
Affiliation(s)
- Stéphanie Truant
- Department of Digestive Surgery and Transplantation, University of Lille, Lille, France. .,CANTHER Laboratory "Cancer Heterogeneity, Plasticity and Resistance to Therapies", UMR-S1277 INSERM, 59000, Lille, France.
| | - François-René Pruvot
- Department of Digestive Surgery and Transplantation, University of Lille, Lille, France
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The protective effect of sildenafil on liver sinusoidal obstructive syndrome after oxaliplatin-based chemotherapy: An experimental animal study. JOURNAL OF SURGERY AND MEDICINE 2020. [DOI: 10.28982/josam.679489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Lyu J, Yang G, Mei Y, Guo L, Guo Y, Zhang X, Xu Y, Feng Y. Non-Gaussian Diffusion Models and T 1 rho Quantification in the Assessment of Hepatic Sinusoidal Obstruction Syndrome in Rats. J Magn Reson Imaging 2020; 52:1110-1121. [PMID: 32246796 DOI: 10.1002/jmri.27156] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 03/18/2020] [Accepted: 03/18/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Non-Gaussian diffusion models and T1 rho quantification may reflect the changes in tissue heterogeneity in hepatic sinusoidal obstruction syndrome (SOS). PURPOSE To investigate the feasibility of diffusion kurtosis imaging (DKI), stretched exponential model (SEM), and T1 rho quantification in detecting and staging SOS in a monocrotaline (MCT)-induced rat model. STUDY TYPE Animal study. POPULATION Thirty male Sprague-Dawley rats gavaged with MCT to induce hepatic SOS and six male rats without any intervention. FIELD STRENGTH/SEQUENCE 3.0T, DWI with five b-values (0-2000 s/mm2 ) and T1 rho with five spin lock times (1-60 msec). ASSESSMENT MRI was performed 1 day before and 1, 3, 5, 7, and 10 days after MCT administration. The corrected apparent diffusion coefficient (Dapp ), kurtosis coefficient (Kapp ), distributed diffusion coefficient (DDC), and intravoxel water molecular diffusion heterogeneity (α) were calculated from the corresponding non-Gaussian diffusion model. The T1 rho value was calculated using a monoexponential model. Specimens obtained from the six timepoints were categorized into normal liver (n = 6), early-stage (n = 16), and late-stage (n = 14) SOS in accordance with the pathological score. STATISTICAL TESTS Parametric statistical methods and receiver operating characteristic (ROC) curves were employed to determine diagnostic accuracy. RESULTS The Dapp , Kapp , DDC, α, and T1 rho values were correlated with pathological score with r values of -0.821, 0.726, -0.828, -0.739, and 0.714 (all P < 0.001), respectively. DKI (combined Dapp and Kapp ) and SEM (combined DDC and α) were better than T1 rho for staging SOS. The areas under the ROC curve of DKI, SEM, and T1 rho for differentiating normal liver and early-stage SOS were 0.97, 1.00, and 0.79, whereas those of DKI, SEM, and T1 rho for differentiating early-stage and late-stage SOS were 1.00, 0.97, and 0.92, respectively. DATA CONCLUSION DKI, SEM, and T1 rho may be helpful in staging SOS. LEVEL OF EVIDENCE 2 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:1110-1121.
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Affiliation(s)
- Jian Lyu
- School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Medical Image Processing, Southern Medical University, Guangzhou, Guangdong, China
| | - Guixiang Yang
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.,Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, Guangdong, China
| | - Yingjie Mei
- Philips Healthcare, Guangzhou, Guangdong, China
| | - Li Guo
- School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Medical Image Processing, Southern Medical University, Guangzhou, Guangdong, China.,Department of MRI, The First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-sen University), Foshan, Guangdong, China
| | - Yihao Guo
- School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Medical Image Processing, Southern Medical University, Guangzhou, Guangdong, China
| | - Xinyuan Zhang
- School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Medical Image Processing, Southern Medical University, Guangzhou, Guangdong, China
| | - Yikai Xu
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.,Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, Guangdong, China
| | - Yanqiu Feng
- School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Medical Image Processing, Southern Medical University, Guangzhou, Guangdong, China
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Abstract
Chemotherapy-induced hepatopathy includes a wide variety of parenchymal and vascular hepatic changes on imaging, including diffuse or focal hepatopathies (i.e. hepatitis, steatosis, fibrosis, pseudocirrhosis, or sinusoidal obstruction). These changes can profoundly alter the hepatic parenchyma on imaging and result in both false negative and false-positive diagnoses of hepatic metastases and lead to errors in patient management strategies. It is therefore important for radiologists to have a comprehensive knowledge of the imaging patterns that may develop following chemotherapy. The purpose of this review is to explore the broad spectrum of hepatic parenchymal and vascular chemotherapy-induced changes on CT and MR imaging.
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Phelip JM, Tougeron D, Léonard D, Benhaim L, Desolneux G, Dupré A, Michel P, Penna C, Tournigand C, Louvet C, Christou N, Chevallier P, Dohan A, Rousseaux B, Bouché O. Metastatic colorectal cancer (mCRC): French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR). Dig Liver Dis 2019; 51:1357-1363. [PMID: 31320305 DOI: 10.1016/j.dld.2019.05.035] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 05/28/2019] [Accepted: 05/30/2019] [Indexed: 12/11/2022]
Abstract
INTRODUCTION This document is a summary of the French intergroup guidelines regarding the management of metastatic colorectal cancer (mCRC) published in January 2019, and available on the French Society of Gastroenterology website (SNFGE) (www.tncd.org). METHODS This collaborative work was realized by all French medical and surgical societies involved in the management of mCRC. Recommendations are graded in three categories (A, B and C), according to the level of evidence found in the literature, up until December 2018. RESULTS The management of metastatic colorectal cancer has become complex because of increasing available medical, radiological and surgical treatments alone or in combination. The therapeutic strategy should be defined before the first-line treatment, mostly depending on the presentation of the disease (resectability of the metastases, symptomatic and/or threatening disease), of the patient's condition (ECOG PS, comorbidities), and tumor biology (RAS, BRAF, MSI). The sequence of targeted therapies also seems to have an impact on the outcome (angiogenesis inhibition beyond progression). Surgical resection of metastases was the only curative intent treatment to date, joined recently by percutaneous tumor ablation tools (radiofrequency, microwave). Localized therapies such as hepatic intra-arterial infusion, radioembolization and hyperthermic intraperitoneal chemotherapy, also have seen their indications specified (liver-dominant disease and resectable peritoneal carcinomatosis). New treatments have been developed in heavily pretreated patients, increasing overall survival and preserving quality of life (regorafenib and trifluridine/tipiracil). Finally, immune checkpoint inhibitors have demonstrated high efficacy in MSI mCRC. CONCLUSION French guidelines for mCRC management are put together to help offer the best personalized therapeutic strategy in daily clinical practice, as the mCRC therapeutic landscape is complexifying. These recommendations are permanently being reviewed and updated. Each individual case must be discussed within a multidisciplinary team (MDT).
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Affiliation(s)
- Jean Marc Phelip
- Department of Gastroenterology and Digestive Oncology, University Hospital of Saint Etienne, Saint Etienne, France.
| | - David Tougeron
- Department of Gastroenterology, University Hospital of Poitiers, Poitiers, France
| | - David Léonard
- Department of Surgical Oncology, Clinique de la Loire, Saumur, France
| | - Leonor Benhaim
- Department of Surgical Oncology, GustaveRoussy Cancer Center, UNICANCER, Villejuif, France
| | - Grégoire Desolneux
- Department of Surgical Oncology, Bergonie Institute, UNICANCER, Bordeaux, France
| | - Aurélien Dupré
- Department of Surgical Oncology, Leon Berard Cancer Center, UNICANCER, Lyon, France
| | - Pierre Michel
- Department of Gastroenterology and Digestive Oncology, University Hospital of Rouen, Rouen, France
| | - Christophe Penna
- Department of Surgical Oncology, Bicêtres Hospital, APHP, Paris, France
| | - Christophe Tournigand
- Department of Gastroenterology and Digestive Oncology, Henri-Mondor University Hospital, APHP, Creteil, France
| | - Christophe Louvet
- Department of Medical Oncology, Institut Mutualiste Montsouris (IMM), Paris, France
| | - Nikki Christou
- Department of Digestive, Endocrine and General Surgery, University Hospital of Limoges, France
| | | | - Anthony Dohan
- Department of Abdominal and Interventional Radiology, Cochin Unversity Hospital, APHP, Paris, France
| | - Benoist Rousseaux
- Department of Medical Oncology, Henri Mondor Hospital, APHP, Creteil, France; Memorial Sloan Kettering Cancer Center, Solid Tumor Department, New York, USA
| | - Olivier Bouché
- Department of Digestive Oncology, University Hospital of Reims, Reims, France
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Han H, Yang J, Li X, Zhuge YZ, Zhu CK, Chen J, Fu Y, Wu M. Role of Virtual Touch Tissue Imaging Quantification in the Assessment of Hepatic Sinusoidal Obstruction Syndrome in a Rat Model. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2019; 38:2039-2046. [PMID: 30561767 DOI: 10.1002/jum.14893] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 11/07/2018] [Accepted: 11/09/2018] [Indexed: 06/09/2023]
Abstract
OBJECTIVES To investigate the value of liver stiffness in rats with various degrees of hepatic sinusoidal obstruction syndrome (HSOS) induced by monocrotaline by comparing liver histopathologic findings. METHODS Seventy rats were randomly divided into a control group (n = 10), a low-dose monocrotaline group (n = 30), and a high-dose monocrotaline group (n = 30). After successful modeling, the liver shear wave velocity (SWV) by Virtual Touch tissue imaging quantification (Siemens Medical Solutions, Mountain View, CA) and the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels of the groups were obtained on days 3 and 5, and the intergroup differences were compared. Liver histopathologic characteristics were analyzed to evaluate the degrees of HSOS, and the scores were recorded. RESULTS On days 3 and 5, the total bilirubin, AST, and ALT, levels and liver SWV in the low- and high-dose groups were elevated; the portal vein velocity (PVV) of these groups was decreased compared with the control group; and the high-dose rats showed higher serum AST and ALT levels than the low-dose rats. The high-dose rats had a lower PVV than the low-dose rats at day 3. The liver SWV values had significant correlations with the histologic score and PVV. In a multivariate analysis, the liver SWV (β = 0.813; P < .001) was independently associated with the histopathologic score. CONCLUSIONS Liver stiffness as measured by Virtual Touch tissue imaging quantification increases with the severity of HSOS and can be recommended as a marker for diagnosis and assessment of HSOS.
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Affiliation(s)
- Hao Han
- Departments of Ultrasound, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jian Yang
- Departments of Ultrasound, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xia Li
- Departments of Ultrasound, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yu-Zheng Zhuge
- Departments of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Cheng-Kai Zhu
- Departments of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jun Chen
- Departments of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yao Fu
- Departments of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Min Wu
- Departments of Ultrasound, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
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Corbacioglu S, Jabbour EJ, Mohty M. Risk Factors for Development of and Progression of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome. Biol Blood Marrow Transplant 2019; 25:1271-1280. [DOI: 10.1016/j.bbmt.2019.02.018] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 02/18/2019] [Indexed: 12/17/2022]
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Hong EK, Joo I, Park J, Lee K. Assessment of hepatic sinusoidal obstruction syndrome with intravoxel incoherent motion diffusion-weighted imaging: An experimental study in a rat model. J Magn Reson Imaging 2019; 51:81-89. [PMID: 31094055 DOI: 10.1002/jmri.26790] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 04/29/2019] [Accepted: 04/29/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters may reflect perfusion and diffusion changes in hepatic sinusoidal obstruction syndrome (SOS). PURPOSE To investigate the feasibility of IVIM-DWI in the noninvasive assessment of hepatic SOS in an experimental rat model. STUDY TYPE Animal study. POPULATION/SUBJECTS Forty-four rats were administered different doses (90 or 160 mg/kg) of monocrotaline by gavage either 48 or 72 hours before MRI to induce different degrees of hepatic SOS, and another 10 rats served as controls. FIELD STRENGTH/SEQUENCE 3T scanner, IVIM-DWI using nine b values (0-800 sec/mm2 ). ASSESSMENT Histologically, rats were classified as having none (n = 10), mild (n = 8), moderate (n = 19), or severe SOS (n = 17). The apparent diffusion coefficient (ADC) and IVIM-derived parameters (D: true diffusion coefficient, D*: pseudo-diffusion coefficient, and f: perfusion fraction) of the liver parenchyma were measured. STATISTICAL TESTS IVIM-DWI parameters were compared according to histologic grades of SOS (none, mild, moderate, and severe), and receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy. RESULTS ADC, D, and f of the liver parenchyma were significantly different according to SOS severity groups (Ps < 0.01) and significantly decreased as SOS severity increased (rho = -0.323, -0.313, and -0.700; P = 0.017, 0.021, and <0.001, respectively). Means of f in none, mild, moderate, and severe SOS were 17.2%, 13.3%, 12.3%, and 11.1%, respectively. Among ADC and IVIM-derived parameters, f provided the highest area under the ROC curves for detecting ≥mild, ≥moderate, and severe SOS (0.991, 0.890, and 0.803, respectively). DATA CONCLUSION IVIM-DWI may be useful in the diagnosis and severity assessment of hepatic SOS. LEVEL OF EVIDENCE 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:81-89.
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Affiliation(s)
- Eun Kyoung Hong
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Juil Park
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Kyoungbun Lee
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
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Yamazaki S, Takayama T. Current topics in liver surgery. Ann Gastroenterol Surg 2019; 3:146-159. [PMID: 30923784 PMCID: PMC6422805 DOI: 10.1002/ags3.12233] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 11/02/2018] [Accepted: 12/04/2018] [Indexed: 01/01/2023] Open
Abstract
Liver resection is one of the main treatment strategies for liver malignancies. Mortality and morbidity of liver surgery has improved significantly with progress in selection criteria, development of operative procedures and improvements in perioperative management. Safe liver resection has thus become more available worldwide. We have identified four current topics related to liver resection (anatomical liver resection, laparoscopic liver resection, staged liver resection and chemotherapy-induced liver injury). The balance between treatment effect and patient safety needs to be considered when planning liver resection. Progress in this area has been rapid thanks to the efforts of many surgeons, and outcomes have improved significantly as a result. These topics remain to be solved and more robust evidence is needed. Precise selection of the optimal procedure and risk evaluation should be standardized with further development of each topic. The present article reviews these four current topics with a focus on safety and efficacy in recent series.
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Affiliation(s)
- Shintaro Yamazaki
- Department of Digestive SurgeryNihon University School of MedicineTokyoJapan
| | - Tadatoshi Takayama
- Department of Digestive SurgeryNihon University School of MedicineTokyoJapan
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