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Xie QF, Long LS, Luo YY, Lu MT, Ming WK, Zhao LY, Liu H. Long-term survival outcomes of duodenal adenocarcinoma: A cohort study with 15-year single-center experience. World J Gastrointest Surg 2025; 17:101365. [DOI: 10.4240/wjgs.v17.i2.101365] [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: 09/12/2024] [Revised: 10/25/2024] [Accepted: 11/25/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Duodenal adenocarcinoma (DA), a rare gastrointestinal malignancy, lacks clear natural history and management strategies. This study aimed to investigate the long-term outcomes of patients with DA, focusing on long-term survival and the impact of tumor characteristics, surgery, and adjuvant therapy.
AIM To bridge this knowledge gap, we conducted a hospital-based cohort study in our 15-year experience with DA aimed at investigating the long-term outcomes of the patients with DA, along with analyzing the impact of the tumor characteristics, operations and adjuvant therapy on survival outcomes.
METHODS A retrospective analysis of 208 patients diagnosed with non-ampullary DA at a single institution between 2009 and 2023 was performed. This study used SPSS 26.0 software to make a comprehensive statistical analysis of demographic characteristics, clinical presentation, treatment modalities, and survival outcomes. The effectiveness of surgical resection and adjuvant therapy in 5-year oval survival (OS) and disease-free survival was evaluated using Kaplan-Meier survival curves, the Cox proportional hazards model, and statistical comparisons of survival distributions.
RESULTS The median OS time for the cohort was 39 months, with 3- and 5-year OS rates of 51.2% and 43.6%, respectively. Radical resection was performed in 82.6% of cases, and was significantly associated with an improved 5-year OS, with a rate of 57.8%. Adjuvant therapy showed a survival benefit in the specific patient subsets, particularly in tumor stage II or III tumors, with an improved OS. Adjuvant therapy (hazard ratio= 2.71, 95% confidence interval: 1.30-5.62, P = 0.008), pancreatic invasion and advanced tumor stage were identified as significant predictors of OS in multivariate analyses.
CONCLUSION Radical operation for DA is associated with a remarkable improvement in the 5-year OS. Importantly, postoperative adjuvant therapy can significantly prolong the OS time in patients with radical operation, especially in patients with stage III. It highlights the necessity for early diagnosis, tailored surgical approaches, and a nuanced understanding of the role of adjuvant therapy.
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Affiliation(s)
- Qing-Feng Xie
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Lian-Sheng Long
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
- Department of General Surgery, General Hospital of Southern Theater Command, Guangzhou 510515, Guangdong Province, China
| | - Yang-Yang Luo
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Meng-Ting Lu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Wai-Kit Ming
- Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong 999077, China
| | - Li-Ying Zhao
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Hao Liu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
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Finton S, Bolm L, Nebbia M, Petruch N, Férnandez-Del Castillo C, Qadan M, Lillemoe KD, Wellner UF, Distler M, Zimmermann C, Weitz J, Rückert F, Rahbari NN, Reissfelder C, Nappo G, Keck T, Zerbi A, Ferrone CR. The Role of Adjuvant Therapy in Duodenal Adenocarcinoma and Intestinal Subtype Ampullary Carcinoma After Curative Resection. Ann Surg 2024; 280:986-992. [PMID: 37830246 DOI: 10.1097/sla.0000000000006129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2023]
Abstract
OBJECTIVE To define the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC). BACKGROUND DAC and iAC share a similar histologic differentiation but the benefit of adjuvant therapy remains unclear. METHODS Patients undergoing curative intent surgical resection for DAC and iAC between 2010 and 2021 at 5 high-volume centers were included. Patient baseline, perioperative, and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM). RESULTS A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in patients with DAC was 101 months versus 155 months for patients with iAC ( P = 0.098). DAC had a higher rate of local (14.1% vs 1.2%, P < 0.001) and systemic recurrence (30.4% vs 3.5%, P < 0.001). Adjuvant therapy failed to improve OS in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors, had improved OS rates with adjuvant therapy (72 vs 44 m, P = 0.044). Patients with iAC with N+ (190 vs 57 m, P = 0.003), T3-T4 (177 vs 59 m, P = 0.050), and perineural invasion (150 vs 59 m, P = 0.019) had improved OS rates with adjuvant therapy. CONCLUSIONS While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved OS in patients with DAC with perineural invasion and in patients with iAC with T3-T4 tumors, positive lymph nodes, and perineural invasion.
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Affiliation(s)
- Sarah Finton
- Department of Gastrointestinal Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Louisa Bolm
- Department of Gastrointestinal Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany
| | - Martina Nebbia
- Department of Gastrointestinal Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
- Department of Surgery, Unit of Pancreatic Surgery, Humanitas Research Hospital, Milan, Italy
| | - Natalie Petruch
- Department of Gastrointestinal Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany
| | | | - Motaz Qadan
- Department of Gastrointestinal Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Keith D Lillemoe
- Department of Gastrointestinal Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Ulrich F Wellner
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany
| | - Marius Distler
- Department for Visceral, Thoracic and Vascular Surgery, University Hospital, Technical University Dresden, Dresden, Germany
| | - Carolin Zimmermann
- Department for Visceral, Thoracic and Vascular Surgery, University Hospital, Technical University Dresden, Dresden, Germany
| | - Jürgen Weitz
- Department for Visceral, Thoracic and Vascular Surgery, University Hospital, Technical University Dresden, Dresden, Germany
| | - Felix Rückert
- Department of Surgery, Diakonissen Hospital Speyer, Speyer, Germany
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Nuh N Rahbari
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Christoph Reissfelder
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Gennaro Nappo
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Tobias Keck
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Cristina R Ferrone
- Department of Gastrointestinal Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
- Department of Surgery, Cedars' Sinai Medical Center, Los Angeles, CA
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Zhu Z, Liu H, Zhong F. Clinicopathological Characteristics, Treatment and Prognosis in Duodenal Adenocarcinoma with Liver Metastasis: A SEER-Based Study. Clin Exp Gastroenterol 2024; 17:51-59. [PMID: 38434178 PMCID: PMC10906677 DOI: 10.2147/ceg.s439275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 02/12/2024] [Indexed: 03/05/2024] Open
Abstract
Background and Objectives Duodenal adenocarcinoma (DAC) is a rare tumor that is often accompanied by liver metastasis in advanced stages. The aim of this study was to evaluate the correlation between clinicopathological characteristics and survival in DAC patients with liver metastasis, and to explore appropriate treatment options. Methods 482 DAC patients with liver metastasis were retrospectively identified from the Surveillance, Epidemiology and End Results (SEER) database (2011-2020). Univariate and multivariate Cox regression analyses were performed to explore the clinicopathological factors related to survival. The Kaplan-Meier method was used to identify the independent risk factors associated with survival. Results The 1-year overall survival (OS) and cancer-specific survival (CSS) rates for the entire cohort were 25.4% and 28.3%, and the 5-year OS and CSS rates were 2.4% and 2.9% respectively. Univariable analysis and multivariate analysis identified chemotherapy and surgery as the independent risk factors for OS and CSS. Patients who underwent chemotherapy and surgery had better CSS and OS rates, whereas radiotherapy failed to improve outcomes. Conclusion We identified several prognostic factors of DAC with liver metastasis. Chemotherapy and surgery can prolong the survival of DAC patients with liver metastasis, which lays the foundation for identifying the optimal treatment strategy.
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Affiliation(s)
- Zhengchun Zhu
- Department of Oncology, Fuyang Hospital of Anhui Medical University, Fuhe Modern Industrial Park, Fuyang, People’s Republic of China
| | - Hong Liu
- Department of Cardiovascular Medicine, Fuyang Hospital of Anhui Medical University, Fuhe Modern Industrial Park, Fuyang, People’s Republic of China
| | - Fei Zhong
- Department of Oncology, Fuyang Hospital of Anhui Medical University, Fuhe Modern Industrial Park, Fuyang, People’s Republic of China
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de Bakker JK, Meijer LL, Zonderhuis BM, van der Vliet HJ, Daams F, van Grieken NCT, Lissenberg-Witte BI, Kazemier G. Adjuvant chemotherapy for resected duodenal adenocarcinoma: a case-matched analysis in nation wide cohort. Acta Chir Belg 2023; 123:502-508. [PMID: 35727126 DOI: 10.1080/00015458.2022.2092961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 06/17/2022] [Indexed: 11/01/2022]
Abstract
BACKGROUND Duodenal adenocarcinoma (DA) is a rare tumor for which survival data on adjuvant chemotherapy in patients after surgical treatment are unclear. This case-matched study in a nationwide cohort aims to investigate the benefit of adjuvant chemotherapy for patients with resectable DA on overall survival. METHODS All patients diagnosed with DA and intestinal type periampullary adenocarcinoma (PVA) in the Netherlands between 2000 and 2015 were included (n = 1316). Patients with disease stages II and III who underwent resection and adjuvant chemotherapy were matched (1:2), based on identified covariates associated with OS, with patients who underwent surgery alone. Overall survival was compared using Kaplan-Meier estimates. RESULTS The median OS was 49.9 months in patients who underwent curative resection (n = 649). Univariate and multivariate analysis showed a significant influence of age, lymph node involvement, and T- stage on survival. The group of patients receiving adjuvant treatment consisted of 43 patients and the non-adjuvant group of 83 case-matched patients. The median OS of the complete matched cohort (n = 126) was 26.9 months. No statistically significant survival benefit was found for the adjuvant group as compared to the group treated with surgery alone (median OS = 34.4 months and 23.0 months, p = 0.20). CONCLUSION This population-based, case-matched analysis demonstrates no statistically significant survival benefit for adjuvant chemotherapy after curative resection in stages II and III patients. Future studies with specified treatment regimens as well as thorough stratification for prognostic factors will be required in order to more definitively determine the role of adjuvant therapy.
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Affiliation(s)
- J K de Bakker
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - L L Meijer
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - B M Zonderhuis
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - H J van der Vliet
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - F Daams
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - N C T van Grieken
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - B I Lissenberg-Witte
- Department of Epidemiology and Biostatistics, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - G Kazemier
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
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Altshuler E, Richhart R, King W, Aryan M, Mathavan A, Mathavan A, Hones K, Leech D, Pucci L, Riklan J, Haley P, Sahin I, Ramnaraign B, Rogers S, Nassour I, Hughes S, George TJ, Fabregas J. Importance of carbohydrate antigen (CA 19-9) and carcinoembrionic antigen (CEA) in the prognosis of patients with duodenal adenocarcinoma: a retrospective single-institution cohort study. Oncotarget 2023; 14:351-357. [PMID: 37068159 PMCID: PMC10109526 DOI: 10.18632/oncotarget.28406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/19/2023] Open
Abstract
BACKGROUND Duodenal adenocarcinoma (DA) is a rare malignancy without validated tumor markers. In practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) are often used in the management of DA, though their prognostic value is unknown. MATERIALS AND METHODS A single-institution retrospective review included patients diagnosed with biopsy-confirmed adenocarcinoma of the duodenum between 2006 and 2021. Peri-ampullary tumors were excluded. Levels of CA 19-9 and CEA were collected as continuous variables and were analyzed as binary variables: normal vs. high, using the maximum normal value as a cut-off (normal Ca 19-9 <35 U/ml; CEA <3 ng/ml). Survival analysis was conducted using Kaplan Meier curves, log-rank test and Cox proportional hazards model. RESULTS There were 68 patients included in the final analysis. Median age was 67 years old and median follow-up time was 22.2 months. CA 19-9 and CEA were elevated in 36.8% and 48.5% of patients, respectively. A concomitant elevation of both tumor markers was associated with worsened OS (HR 2.140, 95% CI: 1.114-4.112; p = 0.019). After controlling for age and sex on multivariate analysis, elevation in both CA 19-9 ≥35 and CEA ≥3.0 remained significantly associated with increased mortality (HR 2.278, 95% CI: 1.162-4.466; p = 0.016). CONCLUSIONS In summary, CA 19-9 and, to a lesser extent, CEA, show promise as prognostic markers in DA. Larger studies are needed to validate their use and to evaluate their performance as markers of recurrence.
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Affiliation(s)
- Ellery Altshuler
- Department of Internal Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Raymond Richhart
- Department of Internal Medicine, University of Florida, Gainesville, FL 32610, USA
| | - William King
- Department of Internal Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Mahmoud Aryan
- Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Akash Mathavan
- University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Akshay Mathavan
- University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Keegan Hones
- University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Daniel Leech
- University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Logan Pucci
- Department of Internal Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Joshua Riklan
- Department of Internal Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Pat Haley
- Department of Internal Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Ilyas Sahin
- Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
- University of Florida Health Cancer Center, Gainesville, FL 32610, USA
| | - Brian Ramnaraign
- Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
- University of Florida Health Cancer Center, Gainesville, FL 32610, USA
| | - Sherise Rogers
- Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
- University of Florida Health Cancer Center, Gainesville, FL 32610, USA
| | - Ibrahim Nassour
- Division of Surgical Oncology, Department of Surgery, University of Florida, Gainesville, FL 32610, USA
| | - Steven Hughes
- Division of Surgical Oncology, Department of Surgery, University of Florida, Gainesville, FL 32610, USA
| | - Thomas J George
- Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
- University of Florida Health Cancer Center, Gainesville, FL 32610, USA
| | - Jesus Fabregas
- Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
- University of Florida Health Cancer Center, Gainesville, FL 32610, USA
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Symons R, Daly D, Gandy R, Goldstein D, Aghmesheh M. Progress in the Treatment of Small Intestine Cancer. Curr Treat Options Oncol 2023; 24:241-261. [PMID: 36826686 DOI: 10.1007/s11864-023-01058-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2023] [Indexed: 02/25/2023]
Abstract
OPINION STATEMENT Small intestine cancer is rare, accounting for approximately 3% of all gastrointestinal malignancies. The most common histological subtypes include adenocarcinoma, neuroendocrine tumours (NETs) and gastrointestinal stromal tumours (GISTs). In localised disease, surgery remains the mainstay of treatment and the best approach to improve survival. Current treatment for small intestine adenocarcinoma (SIA) is extrapolated from small studies and data from colorectal cancer (CRC). There is limited evidence to guide therapy in the adjuvant setting. However, there are small phase II studies in the advanced setting providing evidence for the role of chemotherapy and immunotherapy. There is also limited evidence assessing the efficacy of targeted therapies. Small intestine NETs are rare, with evidence for somatostatin analogue therapy, particularly in the low to intermediate-grade well-differentiated tumours. Poorly differentiated NETs are generally managed with chemotherapy but have worse outcomes compared with well-differentiated NETs. The management of small intestine GISTs is largely targeting KIT mutations with imatinib. Recent trials have provided evidence for effective therapies in imatinib-resistant tumours and the potential role of immunotherapy. The aim of this article was to review the evidence for the current management and recent advances in the management of small intestine adenocarcinoma, NETs and GISTs.
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Affiliation(s)
- Rebecca Symons
- Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, High St, Randwick, Sydney, NSW, 2031, Australia
| | - Daniel Daly
- Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, High St, Randwick, Sydney, NSW, 2031, Australia.,University of New South Wales, Randwick, NSW, Australia
| | - Robert Gandy
- Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, High St, Randwick, Sydney, NSW, 2031, Australia.,University of New South Wales, Randwick, NSW, Australia
| | - David Goldstein
- Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, High St, Randwick, Sydney, NSW, 2031, Australia.,University of New South Wales, Randwick, NSW, Australia
| | - Morteza Aghmesheh
- Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, High St, Randwick, Sydney, NSW, 2031, Australia.
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Turpin A, El Amrani M, Zaanan A. Localized Small Bowel Adenocarcinoma Management: Evidence Summary. Cancers (Basel) 2022; 14:2892. [PMID: 35740558 PMCID: PMC9220873 DOI: 10.3390/cancers14122892] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 06/06/2022] [Accepted: 06/09/2022] [Indexed: 12/04/2022] Open
Abstract
Small bowel cancers are rare diseases whose prognosis is poorer than that of colon cancers. Due to disease rarity, there is little data on small bowel adenocarcinoma (SBA) treatment, and most recommendations come from expert agreements or analogies to the management of colon cancer. Although relatively high rates of local recurrence are observed for duodenal malignancies, distant metastatic relapse remains common and requires adjuvant systemic therapy. Given the similarities between SBA and colorectal cancer, radiotherapy and chemotherapy strategies used for the latter disease are frequently pursued for the former disease, specifically for tumors located in the duodenum. However, no previous randomized study has evaluated the benefit of adjuvant chemotherapy on the overall survival of SBA patients. Most previous studies on treatment outcomes and prognostic factors in this context were based on large international databases, such as the Surveillance, Epidemiology, and End Results or the National Cancer Database. Studies are required to establish and validate prognostic and predictive markers relevant in this context to inform the use of (neo) adjuvant treatment. Among those, deficient mismatch repair tumors represent 20% of SBAs, but their impact on chemosensitivity remains unknown. Herein, we summarize the current evidence on the management of localized SBA, including future perspectives.
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Affiliation(s)
- Anthony Turpin
- UMR9020-UMR-S 1277 Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, 59000 Lille, France
- Medical Oncology Department, CHU Lille, University of Lille, 59000 Lille, France
| | - Mehdi El Amrani
- Department of Digestive Surgery and Transplantation, Lille University Hospital, 59000 Lille, France;
| | - Aziz Zaanan
- Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, AP-HP Centre, 75015 Paris, France;
- Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, MEPPOT, 75006 Paris, France
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Kaslow SR, Prendergast K, Vitiello GA, Hani L, Berman RS, Lee AY, Correa-Gallego C. Systemic therapy for duodenal adenocarcinoma: An analysis of the National Cancer Database (NCDB). Surgery 2022; 172:358-364. [DOI: 10.1016/j.surg.2022.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 02/21/2022] [Accepted: 03/03/2022] [Indexed: 10/18/2022]
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Gelsomino F, Balsano R, De Lorenzo S, Garajová I. Small Bowel Adenocarcinoma: From Molecular Insights to Clinical Management. Curr Oncol 2022; 29:1223-1236. [PMID: 35200603 PMCID: PMC8870676 DOI: 10.3390/curroncol29020104] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/10/2022] [Accepted: 02/14/2022] [Indexed: 12/03/2022] Open
Abstract
Small bowel adenocarcinoma (SBA) is a rare malignancy, with a rising incidence in recent decades, and accounts for roughly 40% of all cancers of the small bowel. The majority of SBAs arise in the duodenum and are associated with a dismal prognosis. Surgery remains the mainstay of treatment for localized disease, while systemic treatments parallel those used in colorectal cancer (CRC), both in the adjuvant and palliative setting. In fact, owing to the lack of prospective data supporting its optimal management, SBA has historically been treated in the same way as CRC. However, recent genetic and molecular data suggest a distinct profile from other gastrointestinal malignancies and support a more nuanced approach to its management. Herein, we briefly review the state-of-the-art in the clinical management of early-stage and advanced disease and recent discoveries of potentially actionable genetic alterations or pathways along with the most promising ongoing clinical trials, which will hopefully revolutionize the treatment landscape of this orphan disease in the foreseeable future.
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Affiliation(s)
- Fabio Gelsomino
- Department of Oncology and Hematology, Division of Oncology, University Hospital of Modena, 41124 Modena, Italy
| | - Rita Balsano
- Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy; (R.B.); (I.G.)
| | | | - Ingrid Garajová
- Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy; (R.B.); (I.G.)
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10
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Surgical results of non-ampullary duodenal cancer: a nationwide survey in Japan. J Gastroenterol 2022; 57:70-81. [PMID: 34988688 DOI: 10.1007/s00535-021-01841-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 11/26/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND As non-ampullary duodenal cancer is relatively rare, the optimal treatment strategy, including the appropriate surgical procedure and efficacy of adjuvant chemotherapy, remains unclear. This nationwide survey aimed to clarify the actual lymph node spread pattern and determine the optimal treatment strategy for this disease, using a large-scale database. METHODS We used a questionnaire and a retrospective registry of 1083 patients with non-ampullary duodenal cancer who had undergone surgery during 2008-2017 in 114 high-volume Japanese Society of Hepatobiliary and Pancreatic Surgery-certified training institutions. Propensity score-matched analyses were conducted to minimise background bias. Cox regression was performed to identify covariates associated with recurrence-free survival. There were distinct disparities in the nodal dissection rate according to the predominant tumor location and tumor invasion depth. Metastases were frequently observed in the peripancreatic nodes and those along the superior mesenteric artery, irrespective of tumor location. Their dissection seemed to be beneficial for improved survival. In the overall cohort, no survival benefit was observed in patients who received adjuvant chemotherapy when compared with that in patients who underwent surgery alone. Nevertheless, in the matched cohort, adjuvant chemotherapy for > 6 months was associated with a significant improvement in recurrence-free survival (median: 43.5 vs. 22.5 months, p = 0.016), particularly in patients with tumor invasion of the subserosa or deeper tumor invasion, lymph node metastasis, or elevated serum carbohydrate antigen 19-9 levels. CONCLUSION Pancreatoduodenectomy should be the standard procedure for advanced non-ampullary duodenal cancer. Adjuvant chemotherapy for > 6 months, especially for advanced tumors, significantly improves survival.
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11
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Zhu Z, Zhong F. Comparative Analysis of Outcomes and Clinicopathological Characteristics of Duodenal Adenocarcinoma: A SEER Analysis. Cancer Invest 2020; 38:543-548. [PMID: 33073637 DOI: 10.1080/07357907.2020.1824260] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Duodenal adenocarcinoma is an uncommon, malignant tumor usually accompanied by a poor prognosis. We identified 3150 duodenal adenocarcinoma cases from the SEER database (1988-2013) to analyze clinical characteristics and outcomes. The Kaplan-Meier method was used to evaluate cancer-specific survival (CSS). Cox regression analysis was used to explore the prognostic factors of CSS. Adverse prognostic factors include higher tumor grade, later stage, tumor size ≥ 2cm, positive regional lymph nodes, and not undergoing surgical resection. Our results suggest, surgery is the optimal treatment for duodenal cancer, and combined radiotherapy does not improve survival.
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Affiliation(s)
- Zhengchun Zhu
- Department of Oncology, Fuyang Hospital of Anhui Medical University, Fuyang, China
| | - Fei Zhong
- Department of Oncology, Fuyang Hospital of Anhui Medical University, Fuyang, China
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12
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Li N, Shen W, Deng W, Yang H, Ma Y, Bie L, Wei C, Luo S. Clinical features and the efficacy of adjuvant chemotherapy in resectable small bowel adenocarcinoma: a single-center, long-term analysis. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:949. [PMID: 32953749 PMCID: PMC7475383 DOI: 10.21037/atm-20-1503] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background Small bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy. There is no standard regimen for adjuvant chemotherapy for treating SBA. This study aimed to assess the efficacy of adjuvant chemotherapy in patients with resectable SBA. Methods This retrospective study collected data from 148 eligible SBA patients who received radical resection at a single institution. The patients’ clinicopathological characteristics were reviewed and disease-free survival (DFS) time and overall survival time (OS) were estimated by the Kaplan-Meier method. Results The patients had a median age of 57 years at the time of diagnosis. In most cases, the primary tumor was located in the duodenum (75.68%). Of the 55 patients who received adjuvant chemotherapy, 43 received the combined regimen and 12 received single agent chemotherapy. During the follow-up period, 87 patients (58.87%) relapsed. The median DFS and the median OS were 19 and 32 months for all patients, respectively. Stage, N-stage, adjuvant chemotherapy, and having more than one symptom at the time of diagnosis were factors associated with DFS and OS. The 43 patients who received combined adjuvant chemotherapy generally exhibited better DFS and OS at 3 and 5 years (DFS: 75.7% and 57.3%, respectively; OS: 75.7% and 62.5%, respectively) than the patients who did not receive the same treatment. The survival time was significantly improved in patients with initial CA19-9 of less than 300 µ/mL or CEA of less than 10 ng/mL. Multivariate analysis revealed N stage and combined adjuvant chemotherapy were independent factors for DFS. However, only combined adjuvant chemotherapy could prolong OS for patients who underwent radical resection. Conclusions In our study, both N stage and combined adjuvant chemotherapy are found to influence postoperative recurrence of SBA. Moreover, combined adjuvant chemotherapy is an independent prognostic factor of DFS and OS.
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Affiliation(s)
- Ning Li
- Department of Oncology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Wei Shen
- Department of Oncology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Wenying Deng
- Department of Oncology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Han Yang
- Department of Oncology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Yijie Ma
- Department of Oncology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Liangyu Bie
- Department of Oncology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Chen Wei
- Department of Oncology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Suxia Luo
- Department of Oncology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
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Zhao J, Li X, Liu Q, Shi L, Zhang L, Yang H, Zhang Q. Clinical comparative analysis of various duodenal diseases in different age groups. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:489-496. [PMID: 32897221 DOI: 10.5152/tjg.2020.18712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND/AIMS This study aimed to investigate the differences and relevance of various common duodenal diseases in different parts in the aspects of age, gender, helicobacter pylori (H. pylori) infection, application of nonsteroidal anti-inflammatory drugs (NSAIDs), smoking, or alcohol consumption. MATERIALS AND METHODS The medical records of various duodenal diseases were collected and tested for difference using the χ2 test or the Fisher exact probability method. RESULTS 1) The proportions of duodenal ulcer (DU), inflammation, and duodenal bulb diseases in the adult group (A) (47.98%, 36.70%, and 66.63%) were higher than those in the elderly group (E) (41.38%, 29.83%, and 56.82%), but the proportions of duodenal diverticulum (DD) and tumor diseases in the descending and ascending segments (2.95%, 1.43%, 9.14%, and 0.14%) were lower than those in group E (13.73%, 3.69%, 19.41%, and 0.76%) (p<0.001). 2) The positive rate of H. pylori (63.64%) in the duodenal bulb diseases was higher than that in the bulb-descending segment (53.75%), but the application rate of NSAIDs (16.44%) in the duodenal bulb-descending diseases was lower than that in the descending segment (24.81%) (p<0.001). CONCLUSION 1) DU, inflammation, and duodenal bulb diseases are common in adults, but DD and tumor diseases in the descending and ascending segments are more common in the elderly. 2) Compared with the duodenal bulb-descending diseases, the application of NSAIDs has greater impact on the diseases in the descending segment, and the rate of H. pylori infection is higher in duodenal bulb diseases.
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Affiliation(s)
- Jin Zhao
- Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Xuelian Li
- Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Qi Liu
- Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Linyan Shi
- Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Ling Zhang
- Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Hong Yang
- Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Qianqian Zhang
- Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
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14
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Augustin T, Moslim MA, Cengiz TB, El-Hayek K, Simon R, Bhatt A, Tang A, Burke CA, Matthew Walsh R. Survival outcomes after surgical management of sporadic or familial adenomatous polyposis associated duodenal cancer. J Surg Oncol 2020; 122:1132-1144. [PMID: 33124067 DOI: 10.1002/jso.26131] [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: 12/01/2019] [Accepted: 06/08/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Duodenal cancer is the second most common cause of cancer death in familial adenomatous polyposis (FAP) patients. In this study, we compare oncologic outcomes between sporadic and FAP-associated duodenal cancer. METHODS In this retrospective study, all patients who underwent surgeries between 2000 and 2014 for either sporadic or FAP duodenal cancer were identified. The patients were grouped based on diagnoses and perioperative and survival outcomes were compared. RESULTS A total of 56 patients with duodenal cancer (43 sporadic, 13 FAP) who underwent surgery were identified. Pancreatoduodenectomy (PD) was the most common procedure performed. The overall median survival was 7.5 years (1 year: 92%; 5 years: 58.1%). FAP patients had earlier tumor, node, and metastasis stage, less margin involvement, less perineural, and angiolymphatic invasion but had a comparable survival to sporadic patients. The median survival for FAP duodenal cancer was 7.4 vs 9.6 years for sporadic (P = .97) with similar utilization of adjuvant chemotherapy. Although not statistically significant, PD had an improved median survival compared to segmental duodenal resection (SDR) (9.6 years for PD vs 3.6 years for SDR, P = .17). Non-periampullary location and presence of positive lymph nodes were significant predictors of mortality on multivariate analysis. CONCLUSIONS FAP duodenal cancer has no survival advantage compared to sporadic duodenal cancer despite an improved stage of resection with extraampullary lesions having a worse survival.
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Affiliation(s)
- Toms Augustin
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Maitham A Moslim
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Turgut Bora Cengiz
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Kevin El-Hayek
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Robert Simon
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Amit Bhatt
- Department of Gastroenterology and Hepatology, Digestive Disease, and Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Andrew Tang
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Carol A Burke
- Department of Gastroenterology and Hepatology, Digestive Disease, and Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio
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15
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Small Bowel Adenocarcinomas: Impact of Location on Survival. J Surg Res 2020; 252:116-124. [PMID: 32278965 DOI: 10.1016/j.jss.2020.03.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 02/26/2020] [Accepted: 03/13/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Proximal (duodenal) small bowel adenocarcinomas have a worse prognosis than distal (jejuno-ileal) tumors, but differences in patient, tumor, and treatment factors between locations remain unclear. METHODS Patients in the National Cancer Database with surgically resected pathologic stage I-IV small bowel adenocarcinomas between 2004 and 2015 were analyzed. Clinical stage IV patients were excluded. RESULTS Proximal tumors (n = 3767) were more likely to be higher grade (OR 1.52, CI 1.22-1.85 for moderately; OR 1.83, CI 1.49-2.33 for poorly differentiated, P < 0.01 for both) and have positive lymph nodes (OR 2.04, CI 1.30-3.23, P < 0.01), while distal tumors (n = 3252) were likely to be larger (OR 1.31, CI 1.07-1.60 for size > 5 cm, P < 0.01). Proximal tumors were associated with worse overall survival (OS) and stage-specific survival compared with distal tumors (all P < 0.01). Cox regression analysis of the entire cohort showed worse survival with community versus academic cancer programs, higher comorbidity scores, pathologic stage IV, poorly differentiated histology, positive nodal or margin status, and proximal location, while female gender, larger tumor size, and chemotherapy predicted better survival. On separate Cox regression analyses of each location, neoadjuvant chemotherapy was associated with better OS in the proximal cohort (HR 0.70, CI 0.55-0.88, P < 0.01), while adjuvant chemotherapy was associated with better OS for both proximal (HR 0.49, CI 0.42-0.57, P < 0.01) and distal tumors (HR 0.68, CI 0.57-0.81, P < 0.01). CONCLUSIONS Proximal small bowel adenocarcinomas are associated with worse overall and stage-specific survival. This may be due to tumor biologic differences as proximal tumors were more likely to have higher grade. Future studies should further investigate differences between proximal and distal tumors to guide targeted treatment algorithms.
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16
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Zhang C, Wang GX, Zhu B. Application of antigen presenting cell-targeted nanovaccine delivery system in rhabdovirus disease prophylactics using fish as a model organism. J Nanobiotechnology 2020; 18:24. [PMID: 32000788 PMCID: PMC6993333 DOI: 10.1186/s12951-020-0584-x] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 01/22/2020] [Indexed: 12/15/2022] Open
Abstract
Background Targeted delivery of virus-associated antigens to professional antigen-presenting cells (APCs) is considered as an efficient strategy to enhance the pyrophytic effect of vaccines against rhabdovirus disease. Materials and methods In this study, we constructed a targeted carbon nanotubes-based vaccine deliver system (SWCNTs-MG) which can recognize the signature receptor (mannose) of APCs. An environmentally and economically important disease called spring viremia of carp (SVC) was studied as a model to evaluate the feasibility of single-walled carbon nanotubes (SWCNTs) conjugated with mannosylated antigen for rhabdovirus prevention. Results Results showed that SWCNTs-MG could cross into fish body and present to internal immune-related tissues through gill, muscle and intestine within 6 h immersed vaccination. With further modification of mannose moiety, the obtained nanovaccine showed enhanced uptake by carp macrophages and immune-related tissues, which would then trigger strong immune responses against spring viremia of carp virus (SVCV) infection. Moreover, the survival rate of fish vaccinated with SWCNTs-MG (30 mg/L) was 63.5% after SVCV infection, whereas it was 0% for the control group. Conclusion This study not only provide a theoretical basis and research template for the application of targeted nanovaccine system in aquatic animals, but also play an important role in supporting development of healthy aquaculture and ensuring the safety of aquatic products and ecology.![]()
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Affiliation(s)
- Chen Zhang
- College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China
| | - Gao-Xue Wang
- College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China
| | - Bin Zhu
- College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China. .,Northwest A&F University, Xinong Road 22nd, Yangling, Shaanxi, 712100, China.
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17
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Dave A, Wiseman JT, Cloyd JM. Duodenal adenocarcinoma: neoadjuvant and adjuvant therapy strategies. Expert Opin Orphan Drugs 2019. [DOI: 10.1080/21678707.2019.1684257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- Apeksha Dave
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jason T. Wiseman
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jordan M. Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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18
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Comparative Effectiveness of Inpatient Rehabilitation Interventions for Traumatic Brain Injury: Introduction. Arch Phys Med Rehabil 2019; 100:1986-1989. [PMID: 31561814 DOI: 10.1016/j.apmr.2019.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 04/14/2019] [Accepted: 04/16/2019] [Indexed: 11/22/2022]
Abstract
The Comparative Effectiveness of Inpatient Rehabilitation Interventions for Traumatic Brain Injury (TBI-CER) project used causal inference methods as an alternative to randomized controlled trials to evaluate rehabilitation practices. The TBI practice-based evidence dataset afforded the opportunity to compare the outcomes of different rehabilitation approaches while controlling for a large set of potential confounders using propensity score methods (PSMs). PSMs rely on 4 assumptions: positivity, exchangeability, consistency, and correct specification of the propensity score model. When these assumptions are met, PSMs provide a transparent means for evaluating potential causal relations between interventions and outcomes using observational data. In combination, the series of studies resulting from the TBI-CER project suggested that the content and approach used in treatment have a stronger effect on outcomes than the amount of time spent in treatment. Further, engagement of the patient and family in treatment is key to optimizing outcomes up to 9 months postdischarge from rehabilitation.
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19
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Mann K, Gilbert T, Cicconi S, Jackson R, Whelan P, Campbell F, Halloran C, Neoptolemos J, Ghaneh P. Tumour stage and resection margin status are independent survival factors following partial pancreatoduodenectomy for duodenal adenocarcinoma. Langenbecks Arch Surg 2019; 404:439-449. [PMID: 30972486 PMCID: PMC6614162 DOI: 10.1007/s00423-019-01779-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 03/20/2019] [Indexed: 01/14/2023]
Abstract
INTRODUCTION There is limited published evidence on duodenal carcinoma due to its rarity. This study aimed to evaluate gastric outlet obstruction and obstructive jaundice along with pathological variables as survival factors in patients with duodenal adenocarcinoma following resection. METHODS Survival factor analysis was undertaken in patients undergoing duodenal cancer surgery from 1997 to 2015 in a single centre. RESULTS There were 57 patients of whom 18 had gastric outlet obstruction and 14 had obstructive jaundice. Fifty-three had a partial pancreatoduodenectomy and four had palliative bypass. Perioperative mortality and morbidity were 4% (2/53) and 47% (25/53) respectively in resected patients. With a median (95% confidence interval, CI) follow-up of 72 (57-86) months, median overall and recurrence-free survival was 38 months (95% CI 28-113) and 27 months (95% CI 18-83) respectively. The 1 and 3-year overall survival rates were 84% (95% CI 74-95) and 52% (95% CI 39-69) respectively. Median overall survival was 19 months in patients with gastric outlet obstruction vs 53 months in those without (p = 0.026) and 28 months in patients with obstructive jaundice vs 38 months in those without (p = 0.611). Univariate analysis revealed that tumour stage, resection margin status, pre-operative albumin status, gastric outlet obstruction and age were associated with poorer overall and recurrence-free survival but multivariate analysis confirmed only tumour stage and resection margin status to be significant. CONCLUSION Whereas gastric outlet obstruction in duodenal cancer appeared to be an important survival factor following partial pancreatoduodenectomy, multivariate analysis showed that only tumour stage and resection margin status were the key independent survival factors. Further multicentre studies are required to elucidate further characteristics of duodenal carcinoma and develop neoadjuvant/adjuvant management strategies.
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Affiliation(s)
- Kulbir Mann
- Department of Molecular and Clinical Cancer Medicine, Institution of Translational Medicine, University of Liverpool, 2nd Floor Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK.
| | - T Gilbert
- Department of Molecular and Clinical Cancer Medicine, Institution of Translational Medicine, University of Liverpool, 2nd Floor Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK
| | - S Cicconi
- Statistics and Bioinformatics Unit, Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Block C, Waterhouse Building, 1-3 Brownlow Street, Liverpool, L69 3GL, UK
| | - R Jackson
- Statistics and Bioinformatics Unit, Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Block C, Waterhouse Building, 1-3 Brownlow Street, Liverpool, L69 3GL, UK
| | - P Whelan
- Department of Surgery, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK
| | - F Campbell
- Department of Pathology, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK
| | - C Halloran
- Department of Molecular and Clinical Cancer Medicine, Institution of Translational Medicine, University of Liverpool, 2nd Floor Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK
| | - J Neoptolemos
- Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - P Ghaneh
- Department of Molecular and Clinical Cancer Medicine, Institution of Translational Medicine, University of Liverpool, 2nd Floor Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK
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20
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Falcone R, Romiti A, Filetti M, Roberto M, Righini R, Botticelli A, Pilozzi E, Ghidini M, Pizzo C, Mazzuca F, Marchetti P. Impact of tumor site on the prognosis of small bowel adenocarcinoma. TUMORI JOURNAL 2019; 105:524-528. [DOI: 10.1177/0300891619839297] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Background: Because of a lack of large-scale prospective studies there is no clear indication about the management of patients with small bowel adenocarcinoma (SBA). This study evaluated clinical outcome of patients diagnosed with SBA at our institution. Methods: Clinicopathologic features, treatments, and clinical outcome of patients diagnosed with SBA between 2006 and 2017 were retrospectively analyzed. Median time of survival was calculated and compared using the log-rank test. Multivariate Cox regression was used to test independence of significant factors in univariate analysis. Results: Forty patients were included in the study; the majority (82.5%) had a tumor in the duodenum (including ampulla of Vater) and an early stage disease at the diagnosis. Median overall survival (OS) in the whole study population was 26.5 months. Patients with a tumor of the lower part of the small intestine (jejunum, ileum, and appendix) showed a better OS compared with that of patients with upper SBA (40 months vs 26 months, respectively; P=0.09). Primary tumor site and stage were independent predictors of OS. Conclusions: Our results suggest a prognostic role for the primary tumor site. This finding deserves to be further investigated to ensure better classification as well as more effective management strategies for SBA.
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Affiliation(s)
- Rosa Falcone
- Department of Molecular and Clinical Medicine, “Sapienza” University of Rome, Italy
| | - Adriana Romiti
- Department of Molecular and Clinical Medicine, “Sapienza” University of Rome, Italy
| | - Marco Filetti
- Department of Molecular and Clinical Medicine, “Sapienza” University of Rome, Italy
| | - Michela Roberto
- Department of Molecular and Clinical Medicine, “Sapienza” University of Rome, Italy
| | | | - Andrea Botticelli
- Department of Molecular and Clinical Medicine, “Sapienza” University of Rome, Italy
| | - Emanuela Pilozzi
- Department of Molecular and Clinical Medicine, “Sapienza” University of Rome, Italy
| | - Michele Ghidini
- Oncology Department, ASST Ospedale di Cremona, Cremona, Italy
| | - Claudio Pizzo
- Oncology Department, ASST Ospedale di Cremona, Cremona, Italy
| | - Federica Mazzuca
- Department of Molecular and Clinical Medicine, “Sapienza” University of Rome, Italy
| | - Paolo Marchetti
- Department of Molecular and Clinical Medicine, “Sapienza” University of Rome, Italy
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21
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Zhao P, Chen H, Wen D, Mou S, Zhang F, Zheng S. Personalized treatment based on mini patient-derived xenografts and WES/RNA sequencing in a patient with metastatic duodenal adenocarcinoma. Cancer Commun (Lond) 2018; 38:54. [PMID: 30139386 PMCID: PMC6108145 DOI: 10.1186/s40880-018-0323-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 08/14/2018] [Indexed: 01/07/2023] Open
Abstract
Background Treatment guidelines for a variety of cancers have been increasingly used in clinical practice, and have resulted in major improvement in patient outcomes. However, recommended regimens (even first-line treatments) are clearly not ideal for every patients. In the present study, we used mini patient-derived xenograft (mini-PDX) and next-generation sequencing to develop personalized treatment in a patient with metastatic duodenal adenocarcinoma. Methods Resected metachronous metastatic tumor tissues were implanted into SCID mice to determine the sensitivity to a variety of drug regimens. Mutation profiles were assessed using both DNA whole-exome sequencing (DNA–WES) and RNA sequencing. The results of the analyses were used to select optimal treatment for the patient with metastatic duodenal adenocarcinoma. Results Assessment with mini-PDX models took only 7 days. The results showed high sensitivity to S-1 plus cisplatin, gemcitabine plus cisplatin and everolimus alone. The patient received gemcitabine plus cisplatin initially, but the treatment was terminated due to toxicity. The patient was then switched to treatment with S-1 alone. The overall disease-free survival was 34 months. DNA–WES and RNA sequencing identified KRAS mutation (A146T), TP53 (C229Yfs*10) and RICTOR amplification in the metastatic duodenal adenocarcinoma. These findings provided further support to the results of the mini-PDX, and suggest mTOR inhibitors should be used if and when relapse eventually occurs in this patient. Conclusions Mini-PDX model combined with WES/RNA sequencing can rapidly assess drug sensitivity in cancer patients and reveal key genetic alterations. Further research on this technology for personalized therapy in patients with refractory malignant tumors is warranted. Electronic supplementary material The online version of this article (10.1186/s40880-018-0323-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Peng Zhao
- Cancer Biotherapy Center, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310003, P. R. China
| | - Hui Chen
- Department of General Surgery, Zhejiang Hospital, Hangzhou, 310013, P. R. China
| | - Danyi Wen
- LIDE Biotech Co., Ltd, Shanghai, P. R. China
| | - Shuo Mou
- OrigiMed Co., Ltd, Shanghai, P. R. China
| | | | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310003, P. R. China. .,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
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22
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Meta-analysis of postoperative adjuvant therapy for small bowel adenocarcinoma. PLoS One 2018; 13:e0200204. [PMID: 30096150 PMCID: PMC6086425 DOI: 10.1371/journal.pone.0200204] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Accepted: 06/21/2018] [Indexed: 12/31/2022] Open
Abstract
Objective The role of adjuvant therapy in small bowel adenocarcinoma (SBA), a rare malignancy with a poor prognosis, is controversial. The purpose of this article is to investigate the impact of adjuvant therapy on the survival of patients with SBA in a meta-analysis. Methods We performed a comprehensive search of PubMed, EMBASE and the Cochrane Library database between 2010 and 2017. Hazard ratios (HR) with 95% confidence intervals (95%CI) were used to assess the effect of adjuvant chemotherapy and/or radiation treatment after curative surgery in patients with SBA. Moreover, impact of age, sex, stage, differentiation, lymph node involvement, and margin status was also evaluated. Results We included 15 studies to evaluate the effect of adjuvant therapy on the survival of patients with SBA. The pooled HR of overall survival (OS) involving 5986 patients showed that adjuvant therapy did not have a statistically significant effect on the survival of patients with SBA (pooled HR = 0.89, 95% CI = 0.73–1.09, p = 0.25). Further, 607 patients with duodenal adenocarcinoma (DA) had similar results (pooled HR = 0.96, 95% CI = 0.75–1.23, p = 0.77). Similarly, adjuvant treatment vs. non-adjuvant treatment in terms of disease-free survival (DFS) or relapse-free survival (RFS) showed the same results (pooled HR = 0.89, 95% CI = 0.64–1.23, p = 0.48). However, we found that adjuvant therapy resulted in favorable postoperative survival in Europe according to the subgroup analysis (pooled HR = 0.63, 95% CI = 0.5–0.8, p = 0.0002). In addition, the pooled HR shows that stage, differentiation, lymph node involvement, and margin status were related to the OS of patients with SBA. Conclusion Patients with SBA who received adjuvant therapy after surgery did not receive a significant survival benefit. Adjuvant therapy may be more useful in advanced cancer or metastatic patients.
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23
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Meijer LL, Alberga AJ, de Bakker JK, van der Vliet HJ, Le Large TYS, van Grieken NCT, de Vries R, Daams F, Zonderhuis BM, Kazemier G. Outcomes and Treatment Options for Duodenal Adenocarcinoma: A Systematic Review and Meta-Analysis. Ann Surg Oncol 2018; 25:2681-2692. [PMID: 29946997 PMCID: PMC6097725 DOI: 10.1245/s10434-018-6567-6] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Indexed: 12/18/2022]
Abstract
Background Duodenal adenocarcinoma (DA) is a rare tumor for which survival data per treatment modality and disease stage are unclear. This systematic review and meta-analysis aims to summarize the current literature on patient outcome after surgical, (neo)adjuvant, and palliative treatment in patients with DA. Methods A systematic search was performed according to the preferred reporting items for systematic reviews and meta-analyses guidelines, to 25 April 2017. Primary outcome was overall survival (OS), specified for treatment strategy or disease stage. Random-effects models were used for the calculation of pooled odds ratios per treatment modality. Included papers were also screened for prognostic factors. Results A total of 26 observational studies, comprising 6438 patients with DA, were included. Of these, resection with curative intent was performed in 71% (range 53–100%) of patients, and 29% received palliative treatment (range 0–61%). The pooled 5-year OS rate was 46% after curative resection, compared with 1% in palliative-treated patients (OR 0.04, 95% confidence interval [CI] 0.02–0.09, p < 0.0001). Both segmental resection and pancreaticoduodenectomy allowed adequate assessment of lymph node involvement and resulted in similar OS. Lymph node involvement correlated with worse OS (pooled 5-year survival rate 21% for nodal metastases vs. 65% for node-negative disease; OR 0.17, 95% CI 0.11–0.27, p < 0.0001). In the current literature, no survival benefit for adjuvant therapy after curative resection was found. Conclusion Resection with curative intent, either pancreaticoduodenectomy or segmental resection, and lack of nodal metastases, favors survival for DA. Further studies exploring multimodality (neo)adjuvant therapy are warranted to investigate their benefit. Electronic supplementary material The online version of this article (10.1245/s10434-018-6567-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Laura L Meijer
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Anna J Alberga
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Jacob K de Bakker
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Hans J van der Vliet
- Department of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Tessa Y S Le Large
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.,Department of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.,Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Nicole C T van Grieken
- Department of Pathology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Ralph de Vries
- Medical Library, VU University Amsterdam, Amsterdam, The Netherlands
| | - Freek Daams
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Barbara M Zonderhuis
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Geert Kazemier
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
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24
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Role of Adjuvant Chemoradiotherapy for Duodenal Cancer: An Updated Analysis of Long-Term Follow-Up from Single Institution. World J Surg 2018; 42:3294-3301. [DOI: 10.1007/s00268-018-4692-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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25
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de Bree E, Rovers KP, Stamatiou D, Souglakos J, Michelakis D, de Hingh IH. The evolving management of small bowel adenocarcinoma. Acta Oncol 2018; 57:712-722. [PMID: 29381126 DOI: 10.1080/0284186x.2018.1433321] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 01/22/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Small bowel adenocarcinoma (SBA) is rare despite the fact that the small bowel represents the longest part and has the largest surface of all alimentary tract sections. Its incidence is 50-fold lower than that of colorectal carcinoma. It is often diagnosed at an advanced stage due to atypical and late symptoms, its low index of suspicion, difficult endoscopic access and poor detection by radiological imaging, resulting in impaired outcome. Due to its rarity and being molecularly a unique intestinal cancer, data regarding its optimal management are relatively sparse. MATERIAL AND METHODS A PubMed search was performed to identify relevant manuscripts that were recently published. Emerging data regarding the pathogenesis, the diagnosis and the treatment of SBA that resulted from recent research are discussed in this comprehensive review. RESULTS Genomic analysis has demonstrated that SBA is a molecularly unique intestinal cancer. Double balloon enteroscopy and capsule endoscopy are novel techniques which may result in earlier diagnosis and consequently in improvement of the generally poor prognosis. For clinically localized disease, the quality of surgery has recently been defined, with removal of at least 8-10 lymph nodes correlating with improved prognosis. Moreover, adjuvant chemotherapy seems to improve outcome of stage III disease. The combination of a fluoropyrimidine and oxaliplatin appears to be the most effective systemic chemotherapy for disseminated disease. Genomic profiling can identify potentially targetable genomic alterations in a significant proportion of SBA patients. The role of administration of targeted agents or immune checkpoint inhibitors is still unknown and subject of ongoing clinical trials. In the common case of peritoneal metastases, recent studies have shown that cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy may be an attractive treatment option in selected patients. CONCLUSIONS SBA is a rare and unique malignancy, whose diagnostic approach and treatment are evolving, resulting in improved outcome.
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Affiliation(s)
- Eelco de Bree
- a Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece
| | - Koen P Rovers
- b Department of Surgical Oncology , Catharina Hospital , Eindhoven , The Netherlands
| | - Dimitris Stamatiou
- a Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece
| | - John Souglakos
- c Department of Medical Oncology and Laboratory of Translational Oncology , Medical School of Crete University Hospital , Heraklion , Greece
| | - Dimosthenis Michelakis
- a Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece
| | - Ignace H de Hingh
- b Department of Surgical Oncology , Catharina Hospital , Eindhoven , The Netherlands
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26
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Li D, Si X, Wan T, Zhou Y. Outcomes of surgical resection for primary duodenal adenocarcinoma: A systematic review. Asian J Surg 2018; 42:46-52. [PMID: 29802028 DOI: 10.1016/j.asjsur.2018.04.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 02/03/2018] [Accepted: 04/16/2018] [Indexed: 01/01/2023] Open
Abstract
Primary duodenal adenocarcinoma (PDAC) is a rare malignancy. The aim of this study was to evaluate the published evidence for resection with curative intent in patients with PDAC. A literature search was conducted in PubMed and EMBASE databases for eligible studies that reported 5-year overall survival (OS) after surgical resection of PDAC from January 1990 to January 2018. Independent prognostic factors related to OS were evaluated using meta-analytical techniques. Odds ratio (OR) and hazard ratio (HR) with their 95% confidence interval (CI) were calculated as appropriate. Thirty-seven observational studies comprising a total of 1728 patients who underwent resection for PDAC were reviewed. The overall 30-day postoperative mortality was 3.2% (range, 0-16.0%) and the median 5-year OS was 46.4% (range, 16.6-71.1%). Surgical resection significantly improved the prognosis as compared with the palliative therapy (OR 15.76, P < 0.001). Lymph node metastasis (HR 2.58, P < 0.001), poor tumor differentiation (HR 1.43, P = 0.05), perineural invasion (HR 2.21, P = 0.002), and lymphovascular invasion (HR 2.18, 95% CI 1.18-4.03; P = 0.01) were found to be independently associated with decreased OS after surgical resection. The present study provides evidence that surgical resection can be performed safely for PDAC patients and offers a favorable long-term outcome. Tumor-specific factors have prognostic significance.
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Affiliation(s)
- Debang Li
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Xiaoying Si
- Department of Hepatobiliary & Pancreatovascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Tao Wan
- Department of Hepatobiliary & Pancreatovascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Yanming Zhou
- Department of Hepatobiliary & Pancreatovascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China.
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27
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He C, Mao Y, Wang J, Duan F, Lin X, Li S. Nomograms predict long-term survival for patients with periampullary adenocarcinoma after pancreatoduodenectomy. BMC Cancer 2018; 18:327. [PMID: 29580215 PMCID: PMC5870913 DOI: 10.1186/s12885-018-4240-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Accepted: 03/16/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The prognosis of patients with periampullary adenocarcinoma after pancreatoduodenectomy is diverse and not yet clearly illustrated. The aim of this study was to develop a nomogram to predict individual risk of overall survival (OS) and progression-free survival (PFS) in patients with periampullary adenocarcinoma after pancreatoduodenectomy. METHODS A total of 205 patients with periampullary adenocarcinoma after pancreatoduodenectomy were retrospectively included. OS and PFS were evaluated by the Kaplan-Meier method. Two nomograms for predicting OS and PFS were established, and the predictive accuracy was measured by the concordance index (Cindex) and calibration plots. RESULTS Lymph node ratio (LNR), carbohydrate antigen 19-9 (CA19-9) and anatomical location were incorporated into the nomogram for OS prediction and LNR, CA19-9; anatomical location and tumor differentiation were incorporated into the nomogram for PFS prediction. All calibration plots for the probability of OS and PFS fit well. The Cindexes of the nomograms for OS and PFS prediction were 0.678 and 0.68, respectively. The OS and PFS survival times were stratified significantly using the nomogram-predicted survival probabilities. CONCLUSIONS The present nomograms for OS and PFS prediction can provide valuable information for tailored decision-making for patients with periampullary adenocarcinoma after pancreatoduodenectomy.
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Affiliation(s)
- Chaobin He
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Yize Mao
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Jun Wang
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Fangting Duan
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Xiaojun Lin
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Shengping Li
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
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28
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Effect of postoperative radiotherapy on survival in duodenal adenocarcinoma: a propensity score-adjusted analysis of Surveillance, Epidemiology, and End Results database. Int J Clin Oncol 2017; 23:473-481. [DOI: 10.1007/s10147-017-1226-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Accepted: 12/12/2017] [Indexed: 12/18/2022]
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29
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Chandrasegaram MD, Gill AJ, Samra J, Price T, Chen J, Fawcett J, Merrett ND. Ampullary cancer of intestinal origin and duodenal cancer - A logical clinical and therapeutic subgroup in periampullary cancer. World J Gastrointest Oncol 2017; 9:407-415. [PMID: 29085567 PMCID: PMC5648984 DOI: 10.4251/wjgo.v9.i10.407] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 06/26/2017] [Accepted: 08/16/2017] [Indexed: 02/05/2023] Open
Abstract
Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can result in difficulty in defining the primary site of origin in all but the smallest tumors due to anatomical proximity and architectural distortion. This has led to variation in the reported proportions of resected periampullary cancers. Pancreatic cancer is the most common cancer resected with a pancreaticoduodenectomy followed by ampullary (16%-50%), bile duct (5%-39%), and duodenal cancer (3%-17%). Patients with resected duodenal and ampullary cancers have a better reported median survival (29-47 mo and 22-54 mo) compared to pancreatic cancer (13-19 mo). The poorer survival with pancreatic cancer relates to differences in tumour characteristics such as a higher incidence of nodal, neural and vascular invasion. While small ampullary cancers can present early with biliary obstruction, pancreatic cancers need to reach a certain size before biliary obstruction ensues. This larger size at presentation contributes to a higher incidence of resection margin involvement in pancreatic cancer. Ampullary cancers can be subdivided into intestinal or pancreatobiliary subtype cancers with histomolecular staining. This avoids relying on histomorphology alone, as even some poorly differentiated cancers preserve the histomolecular profile of their mucosa of origin. Histomolecular profiling is superior to anatomic location in prognosticating survival. Ampullary cancers of intestinal subtype and duodenal cancers are similar in their intestinal origin and form a logical clinical and therapeutic subgroup of periampullary cancers. They respond to 5-FU based chemotherapeutic regimens such as capecitabine-oxaliplatin. Unlike pancreatic cancers, KRAS mutation occurs in only approximately a third of ampullary and duodenal cancers. Future clinical trials should group ampullary cancers of intestinal origin and duodenal cancers together given their similarities and their response to fluoropyrimidine therapy in combination with oxaliplatin. The addition of anti-epidermal growth factor receptor therapy in this group warrants study.
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Affiliation(s)
- Manju D Chandrasegaram
- the Prince Charles Hospital, Brisbane, Queensland 4032, Australia
- School of Medicine, University of Queensland, Queensland 4006, Australia
| | - Anthony J Gill
- Sydney Medical School, University of Sydney, New South Wales 2006, Australia
- Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia
| | - Jas Samra
- Sydney Medical School, University of Sydney, New South Wales 2006, Australia
- Department of Surgery, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia
| | - Tim Price
- Queen Elizabeth Hospital, Adelaide, South Australia 5011, Australia
- University of Adelaide, South Australia 5005, Australia
| | - John Chen
- Flinders Medical Centre, Adelaide, South Australia 5042, Australia
- Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia
| | - Jonathan Fawcett
- School of Medicine, University of Queensland, Queensland 4006, Australia
- Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia
| | - Neil D Merrett
- Department of Upper GI Surgery, Bankstown Hospital, Sydney, New South Wales 2200, Australia
- Discipline of Surgery, Western Sydney University, Sydney, New South Wales 2560, Australia
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30
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Ecker BL, Vining CC, Roses RE, Maggino L, Lee MK, Drebin JA, Fraker DL, Vollmer CM, Datta J. Identification of Patients for Adjuvant Therapy After Resection of Carcinoma of the Extrahepatic Bile Ducts: A Propensity Score-Matched Analysis. Ann Surg Oncol 2017; 24:3926-3933. [PMID: 28952140 DOI: 10.1245/s10434-017-6095-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Resectability rates for extrahepatic cholangiocarcinoma have increased over time, but long-term survival after resection alone with curative intent remains poor. Recent series suggest improved survival with adjuvant therapy. Patient subsets benefiting most from adjuvant therapy have not been clearly defined. METHODS Patients with extrahepatic cholangiocarcinoma who underwent resection with curative intent and received adjuvant therapy (chemotherapy ± radiotherapy) or surgery alone (SA) were identified in the U.S. National Cancer Data Base (2004-2014). Cox regression identified covariates associated with overall survival (OS). Adjuvant therapy and SA cohorts were matched (1:1) by propensity scores based on the survival hazard in Cox modeling. Overall survival was compared by Kaplan-Meier estimates. RESULTS Of 4872 patients, adjuvant chemotherapy was used frequently for 2416 (49.6%), often in conjunction with radiotherapy (RT) (n = 1555, 64.4%). Adjuvant chemotherapy with or without RT was used increasingly for cases with higher T classification [reference: T1-2; T3: 1.36; 95% confidence interval (CI), 1.19-1.55; T4: 1.77; 95% CI 1.38-2.26], nodal positivity [odds ratio (OR), 1.26; 95% CI 1.01-1.56], lymphovascular invasion (OR 1.21; 95% CI 1.01-1.46), or margin-positive resection (OR 1.85; 95% CI 1.61-2.12), and was associated with significant improvements in OS for each high-risk subset in the propensity score-matched cohort. Adjuvant therapy was associated with improved median OS for hilar tumors (40.0 vs 30.6 months; p = 0.025) but not distal tumors (33.0 vs 30.3 months; p = 0.123). Chemoradiotherapy was associated with superior outcomes compared with chemotherapy alone in the subset of margin-positive resection [hazard ratio (HR), 0.63; 95% CI 0.42-0.94]. CONCLUSIONS Adjuvant multimodality therapy is associated with improved survival for patients with resected extrahepatic cholangiocarcinoma and high-risk features.
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Affiliation(s)
- Brett L Ecker
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Charles C Vining
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Robert E Roses
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Laura Maggino
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.,Department of Surgery, Pancreas Institute, University of Verona, Verona, Italy
| | - Major K Lee
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Jeffrey A Drebin
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
| | - Douglas L Fraker
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Charles M Vollmer
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Jashodeep Datta
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. .,Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
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