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Miura Y, Ohgi K, Ashida R, Kato Y, Otsuka S, Dei H, Uesaka K, Sugiura T. Clinical significance of peritoneal lavage cytology in duodenal cancer. Surgery 2025; 181:109256. [PMID: 39987677 DOI: 10.1016/j.surg.2025.109256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 01/11/2025] [Accepted: 01/24/2025] [Indexed: 02/25/2025]
Abstract
BACKGROUND Although positive peritoneal lavage cytology has been established as an important prognostic factor in gastric and pancreatic cancers, its significance in duodenal cancer remains unclear. METHODS This study analyzed 74 consecutive patients with peritoneal lavage cytology who underwent surgical resection for duodenal cancer at our institution between 2002 and 2020. (pancreatoduodenectomy, n = 58; partial resection, n = 11; and pancreas-sparing total duodenectomy, n = 5). Clinicopathologic features and survival outcomes were analyzed, focusing on the peritoneal lavage cytology status. RESULTS Among the 8 peritoneal lavage cytology -positive patients, the primary tumor depth was classified as pT3 in 1 case and pT4 in 7 cases. The recurrence-free survival and overall survival rates were markedly worse in peritoneal lavage cytology-positive patients than in peritoneal lavage cytology-negative patients (5-year recurrence-free survival: 0.0% vs 78.0%, P < .001; 5-year overall survival: 12.5% vs 82.4%, P < .001). In a subgroup analysis of patients with T3 or T4 tumors (n = 38), the recurrence-free survival and overall survival were significantly poorer in patients with peritoneal lavage cytology-positive tumors than in those with peritoneal lavage cytology-negative tumors (5-year recurrence-free survival, 0.0% vs 51.8%, P = .001; 5-year overall survival, 12.5% vs 60.9%, P = .005). A multivariate analysis identified a peritoneal lavage cytology-positive status as an independent prognostic factor for the overall survival (hazard ratio, 3.38; P = .023). CONCLUSION Peritoneal lavage cytology positivity in patients with duodenal cancer was associated with advanced tumor progression and was a significant prognostic marker. This finding underscores the importance of peritoneal lavage cytology as a valuable tool for identifying patients who may require multidisciplinary treatment approaches.
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Affiliation(s)
- Yuya Miura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan. https://twitter.com/miu_y8
| | - Katsuhisa Ohgi
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yoshiyasu Kato
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Shimpei Otsuka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Hideyuki Dei
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
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Sasaki A, Chihara S, Okamoto R, Yoshino T, Nakamura Y. Exceptional response to brigatinib following alectinib failure in a patient with ALK fusion-positive duodenal carcinoma. Int Cancer Conf J 2025; 14:131-135. [PMID: 40160872 PMCID: PMC11950605 DOI: 10.1007/s13691-025-00745-2] [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: 11/03/2024] [Accepted: 01/06/2025] [Indexed: 04/02/2025] Open
Abstract
Patients with advanced duodenal carcinoma typically have a poor prognosis due to limited practical chemotherapy options. While studies on genotype-directed therapy in patients with duodenal carcinoma is progressing, clinical data assessing the efficacy of molecularly targeted therapy remains scarce. We report the case of a 65-year-old woman diagnosed with anaplastic lymphocyte kinase (ALK) fusion-positive advanced duodenal carcinoma. The patient had been treated with alectinib for approximately 2 years for ALK-positive duodenal carcinoma but developed progressive liver metastases, indicating alectinib failure. During the disease progression, circulating tumor DNA (ctDNA) sequencing revealed the emergence of ALK L1196M mutation, which demonstrated sensitivity to brigatinib. After switching to brigatinib, marked shrinkage of liver metastases was observed. The patient maintained brigatinib treatment for 7 months until tumor progression. This is the first report demonstrating the efficacy of brigatinib after alectinib failure in a patient with duodenal carcinoma harboring ALK fusion. Furthermore, this case suggests that ctDNA sequencing can detect specific acquired mutations and help expand optimal treatment options for patients.
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Affiliation(s)
- Akinori Sasaki
- Department of Gastroenterology, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, Chiba Japan
- Department of Oncology, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, Chiba Japan
| | - Sayaka Chihara
- Department of Gastroenterology, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, Chiba Japan
| | - Risa Okamoto
- Department of Gastroenterology, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, Chiba Japan
| | - Takayuki Yoshino
- Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Yoshiaki Nakamura
- Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
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Uijterwijk BA, Moekotte A, Boggi U, Mazzola M, Groot Koerkamp B, Dalle Valle R, Koek S, Bolm L, Mazzotta A, Luyer M, Goh BKP, Suarez Muñoz MA, Björnsson B, Kazemier G, Ielpo B, Pessaux P, Kleeff J, Ghorbani P, Mavroeidis VK, Fusai GK, Salvia R, Zerbi A, Roberts KJ, Alseidi A, Al-Sarireh B, Serradilla-Martín M, Vladimirov M, Korkolis D, Soonawalla Z, Gruppo M, Bouwense SAW, Vollmer CM, Behrman SW, Christein JD, Besselink MG, Abu Hilal M. Oncological resection and perioperative outcomes of robotic, laparoscopic and open pancreatoduodenectomy for ampullary adenocarcinoma: a propensity score matched international multicenter cohort study. HPB (Oxford) 2025; 27:318-329. [PMID: 39765373 DOI: 10.1016/j.hpb.2024.11.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 07/28/2024] [Accepted: 11/28/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND Ampullary adenocarcinoma (AAC) typically presents at an early stage due to biliary obstruction and therefore might be specifically suitable for minimally invasive pancreatoduodenectomy (MIPD). However, studies assessing MIPD specifically for AAC, including the robotic and laparoscopic approach, are limited. The aim of this study is to compare short- and long-term oncological resection and perioperative outcomes of robotic (RPD), laparoscopic (LPD) and open pancreatoduodenectomy (OPD) performed specifically for AAC. METHODS In this multicenter international cohort study, encompassing 35 centers from 11 countries, MIPD versus OPD and subgroup analyses of LPD versus RPD were undertaken. The primary outcomes regarded the oncological resection (R1 resection rate, lymph node yield) and 5-years overall survival. Secondary outcomes were perioperative outcomes (including intra-operative variables, surgical complications and hospital stay). RESULTS In total, patients with AAC who underwent OPD (1721) or MIPD (141) were included. After propensity-score matching, 134 patients per cohort were included. The MIPD group consisted of 53 RPDs and 71 LPDs (50 per group after PSM). There was no difference in overall survival between MIPD and OPD (61.6 % vs 56.2 %, P = 0.215). In the MIPD group, operative time was longer (439 vs 360 min, P < 0.001). Between RPD and LPD, overall survival was not significantly different (75.8 % vs 47.4 %, P = 0.098) and lymph node yield was higher in RPD (21 vs 18, P = 0.014). CONCLUSION In conclusion, patients with AAC seem to have comparable oncological resection and perioperative outcomes from MIPD compared to the traditional OPD. Both RPD as LPD appear to be safe alternatives for patients with AAC, which warrants confirmation by future randomized studies.
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Affiliation(s)
- Bas A Uijterwijk
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands.
| | - Alma Moekotte
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Ugo Boggi
- Department of Surgery, Pisa University Hospital, Pisa, Italy
| | - Michele Mazzola
- Division of Oncologic and Mini-invasive General Surgery, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | | | - Sharnice Koek
- Fiona Stanley Hospital, Department of Surgery, Perth, Australia
| | - Louisa Bolm
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany
| | - Alessandro Mazzotta
- Department of Digestive, Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Paris, France
| | - Misha Luyer
- Catharina Hospital Eindhoven, Department of Surgery, the Netherlands
| | - Brian K P Goh
- Singapore General Hospital, Department of Hepatopancreatobiliary and Transplant Surgery, Duke-National University of Singapore, Singapore
| | | | - Bergthor Björnsson
- Department of Surgery in Linköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Geert Kazemier
- Department of Surgery, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands
| | | | - Patrick Pessaux
- Hepatobiliary and Pancreatic Surgical Unit, Nouvel Hôpital Civil (NHC), Strasbourg, France
| | - Jorg Kleeff
- Department of Surgery, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany
| | - Poya Ghorbani
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - Vasileios K Mavroeidis
- Department of Academic Surgery, The Royal Marsden Hospital, London, UK; Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Giuseppe K Fusai
- Department of Surgery, Royal Free London NHS Foundation Trust, London, UK
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Pancreatic Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Keith J Roberts
- Faculty of Medicine, University of Birmingham, Birmingham, UK
| | | | | | - Mario Serradilla-Martín
- Instituto de Investigación Sanitaria Aragón, Department of Surgery, Miguel Servet University Hospital, Zaragoza, Spain
| | - Miljana Vladimirov
- Department of General Surgery, Paracelsus Medical University Nürnberg, 90419, Nürnberg, Germany; Department of Abdominal Surgery, University Hospital Lippe, University Bielefeld, Campus Detmold, Germany
| | - Dimitris Korkolis
- Department of Surgery, Hellenic Anticancer Hospital 'Saint Savvas', Athens, Greece
| | - Zahir Soonawalla
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Mario Gruppo
- Veneto Institute of Oncology IOV - IRCCS, Unit of Surgical Oncology of the Digestive Tract, Italy
| | - Stefan A W Bouwense
- Department of Surgery, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Charles M Vollmer
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA
| | - Stephen W Behrman
- Department of Surgery, University of Tennessee Health Science Center, Memphis, USA
| | - John D Christein
- Department of Surgery, University of Alabama School of Medicine, Birmingham, USA
| | - Marc G Besselink
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
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Fujii H, Shoji H, Hirano H, Hirose T, Okita N, Takashima A, Kato K. Exploring novel therapeutic targets in small bowel adenocarcinoma: insights from claudin 18.2, nectin-4, and HER3 expression analysis. ESMO Open 2025; 10:104098. [PMID: 39754977 PMCID: PMC11758419 DOI: 10.1016/j.esmoop.2024.104098] [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: 09/09/2024] [Revised: 11/23/2024] [Accepted: 11/29/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND Small bowel adenocarcinoma (SBA) is a rare malignancy with few established chemotherapy options and a dismal prognosis. We investigated the expression of claudin 18.2, nectin-4, human epidermal growth factor receptor 3 (HER3), and programmed death-ligand 1 (PD-L1) in SBA to identify potential antibody drug targets and analyzed associated clinicopathological features and prognosis. MATERIALS AND METHODS We retrospectively reviewed patients diagnosed with SBA who underwent adjuvant or palliative chemotherapy at our hospital between July 2010 and July 2023. Pathological samples were immunohistochemically stained for claudin 18.2, nectin-4, HER3, and PD-L1. Overall survival (OS) was assessed in patients receiving palliative chemotherapy to examine its association with the expression of each protein, excluding those with microsatellite instability-high who were treated with immunotherapy. RESULTS Pathological samples and clinical data were available for 51 patients. The primary lesion was in the duodenum in 49% of these patients and in the jejunum or ileum in 51%. Positive rates for claudin 18.2, nectin-4, and HER3 were 35%, 82%, and 88%, respectively. All cases expressed at least one of the proteins, and 25% expressed all three proteins. The PD-L1 combined positive score (CPS) was <1, 1-5, and ≥5 in 33%, 32%, and 35%, respectively; nectin-4-positive samples showed higher CPS. Neither claudin 18.2 nor HER3 positivity was associated with OS. However, nectin-4 positivity was associated with significantly shorter OS [12.6 versus 43.2 months, hazard ratio (HR) 5.12, P = 0.006]. Similarly, PD-L1 CPS ≥5 was associated with shorter OS relative to CPS <5 (9.7 versus 18.0 months, HR 2.60, P = 0.028). Multivariate analysis identified nectin-4 positivity (HR 4.55, P = 0.020) as an independent adverse prognostic factor for OS. CONCLUSIONS Claudin 18.2, nectin-4, and HER3 are potential therapeutic targets in SBA, and nectin-4 positivity is independently associated with an unfavorable prognosis. These proteins may represent new therapeutic targets for SBA.
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Affiliation(s)
- H Fujii
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - H Shoji
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan.
| | - H Hirano
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - T Hirose
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - N Okita
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - A Takashima
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - K Kato
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
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Uijterwijk BA, Lemmers DH, Ghidini M, Wilmink H, Zaniboni A, Salvia R, Kito Fusai G, Groot Koerkamp B, Koek S, Ghorbani P, Zerbi A, Nappo G, Luyer M, Goh BKP, Roberts KJ, Boggi U, Mavroeidis VK, White S, Kazemier G, Björnsson B, Serradilla-Martín M, House MG, Alseidi A, Ielpo B, Mazzola M, Jamieson N, Wellner U, Soonawalla Z, Cabús SS, Dalla Valle R, Pessaux P, Vladimirov M, Kent TS, Tang CN, Fisher WE, Kleeff J, Mazzotta A, Suarez Muñoz MA, Berger AC, Ball CG, Korkolis D, Bannone E, Ferarri C, Besselink MG, Abu Hilal M. The Five Periampullary Cancers, not Just Different Siblings but Different Families: An International Multicenter Cohort Study. Ann Surg Oncol 2024; 31:6157-6169. [PMID: 38888860 DOI: 10.1245/s10434-024-15555-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 05/21/2024] [Indexed: 06/20/2024]
Abstract
BACKGROUND Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. METHODS This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC. RESULTS Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size. CONCLUSIONS Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.
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Affiliation(s)
- Bas A Uijterwijk
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Daniël H Lemmers
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Michele Ghidini
- Department of Medical Oncology, Policlinico di Milano, Fondazione IRCCS Ca' Granda, Milano, Italy
| | - Hanneke Wilmink
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Alberto Zaniboni
- Department of Medical Oncology, Fondazione Poliambulanza, Brescia, Italy
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | | | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Sharnice Koek
- Department of Surgery, Fiona Stanley Hospital, Perth, Australia
| | - Poya Ghorbani
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Pancreatic Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Gennaro Nappo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Pancreatic Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Misha Luyer
- Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, The Netherlands
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Duke-National University of Singapore, Singapore, Singapore
| | - Keith J Roberts
- Faculty of Medicine, University of Birmingham, Birmingham, UK
| | - Ugo Boggi
- Department of Surgery, Pisa University Hospital, Pisa, Italy
| | - Vasileios K Mavroeidis
- Department of Academic Surgery, The Royal Marsden Hospital, London, UK
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Steven White
- Department of Surgery, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
| | - Geert Kazemier
- Department of Surgery, Amsterdam UMC, VUmc, Amsterdam, The Netherlands
| | | | | | - Michael G House
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Adnan Alseidi
- Department of Surgery, Virginia Mason, Seattle, WA, USA
| | | | - Michele Mazzola
- Division of Oncologic and Mini-invasive General Surgery, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Nigel Jamieson
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
| | - Ulrich Wellner
- Department of Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany
| | - Zahir Soonawalla
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | | | | | - Patrick Pessaux
- Hepatobiliary and Pancreatic Surgical Unit, Nouvel Hôpital Civil (NHC), Strasbourg, France
| | - Miljana Vladimirov
- Department of Surgery, Paracelsus Medical Private University (PMU, Nuremberg, Germany
| | - Tara S Kent
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Chung N Tang
- Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China
| | - William E Fisher
- Department of Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Jorg Kleeff
- Department of Surgery, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany
| | - Alessandro Mazzotta
- Department of Digestive, Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Paris, France
| | | | - Adam C Berger
- Department of Surgery, Jefferson Medical College, Philadelphia, PA, USA
| | - Chad G Ball
- Department of Surgery, University of Calgary, Calgary, Alberta, Canada
| | | | - Elisa Bannone
- Department of Hepato-Biliary and Pancreatic Surgery, Istituto Fondazione Poliambulanza, Brescia, Italy
| | - Clarissa Ferarri
- Department of Hepato-Biliary and Pancreatic Surgery, Istituto Fondazione Poliambulanza, Brescia, Italy
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Mohammed Abu Hilal
- Department of Hepato-Biliary and Pancreatic Surgery, Istituto Fondazione Poliambulanza, Brescia, Italy.
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Hautefeuille V, Williet N, Turpin A, Napoleon B, Dupré A, Huguet F, Bignon AL, Camus M, Chevaux JB, Coriat R, Cros J, Edeline J, Koch S, Neuzillet C, Perkins G, Regimbeau JM, Sefrioui D, Vitellius C, Vullierme MP, Bouché O, Gaujoux S. Ampullary tumors: French Intergroup Clinical Practice Guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, ACHBT, AFC, SFRO, RENAPE, SNFCP, AFEF, SFP, SFR). Dig Liver Dis 2024; 56:1452-1460. [PMID: 38845233 DOI: 10.1016/j.dld.2024.04.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 04/24/2024] [Accepted: 04/24/2024] [Indexed: 08/30/2024]
Abstract
BACKGROUND Management of ampullary tumors (AT) is challenging because of a low level of scientific evidence. This document is a summary of the French intergroup guidelines regarding the management of AT, either adenoma (AA) or carcinoma (AC), published in July 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS A collaborative work was conducted under the auspices of French medical, endoscopic, oncological and surgical societies involved in the management of AT. Recommendations are based on recent literature review and expert opinions and graded in three categories (A, B, C), according to quality of evidence. RESULTS Accurate diagnosis of AT requires at least duodenoscopy and EUS. All patients should be discussed in multidisciplinary tumor board before treatment. Surveillance may only be proposed for small AA in familial adenomatous polyposis. For AA, endoscopic papillectomy is the preferred option only if R0 resection can be achieved. When not possible, surgical papillectomy should be considered. For AC beyond pT1a N0, pancreaticoduodenectomy is the procedure of choice. Adjuvant monochemotherapy (gemcitabine, 5FU) may be proposed. For aggressive tumors (pT3/T4, pN+, R1, poorly differentiated AC, pancreatobiliary differentiation) with high risk of recurrence, 6 months polychemotherapy (CAPOX/FOLFOX for the intestinal subtype and mFOLFIRINOX for the pancreatobiliary or the mixed subtype) may be a valid alternative. Clinical and radiological follow up is recommended for 5 years. CONCLUSIONS These guidelines help to homogenize and highlight unmet needs in the management of AA and AC. Each individual case should be discussed by a multidisciplinary team.
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Affiliation(s)
- Vincent Hautefeuille
- Department of Gastroenterology and Digestive Oncology, Amiens University Hospital - Amiens, France.
| | - Nicolas Williet
- Department of Hepato-gastroenterology and Gastrointestinal Oncology, University Institute of Cancerology and Hematology of Saint-Etienne (ICHUSE)
| | - Anthony Turpin
- Department of Oncology, Lille University Hospital; CNRS UMR9020, INSERM UMR1277, University of Lille, Institut Pasteur, Lille, France
| | - Bertrand Napoleon
- Department of Digestive Endoscopy, Jean Mermoz Hospital, Ramsay Sante, Lyon, France
| | - Aurélien Dupré
- Department of Surgical Oncology, Centre Léon Bérard -Lyon, France
| | - Florence Huguet
- Department of Radiation Oncology, Tenon Hospital, AP-HP, Sorbonne University, Paris, France
| | - Anne Laure Bignon
- Department of Gastroenterology and Digestive Oncology, Caen University Hospital - Caen, France
| | - Marine Camus
- Sorbonne University CRSA & APHP Saint Antoine Hospital, Endoscopy Center, 184 rue du Faubourg St Antoine, 75012 Paris, France
| | | | - Romain Coriat
- Gastroenterology and digestive oncology Unit, Hôpital Cochin, GH APHP Centre, université Paris Cité, Paris, France
| | - Jérôme Cros
- Université Paris Cité, Department of Pathology, Beaujon/Bichat University Hospital (APHP), Clichy/Paris, France
| | - Julien Edeline
- INSERM, Univ Rennes, Department of Medical Oncology, CLCC Eugène Marquis, COSS (Chemistry Oncogenesis Stress Signaling) - UMR_S 1242, Rennes, France
| | - Stéphane Koch
- Endoscopy and Gastroenterology Unit, Besançon University Hospital, Besançon, France
| | - Cindy Neuzillet
- GI Oncology, Department of Medical Oncology, Institut Curie, Versailles Saint-Quentin University - Paris Saclay University, Saint Cloud, France
| | - Géraldine Perkins
- Department of Gastroenterology, Pontchaillou University Hospital, Rennes, France
| | - Jean Marc Regimbeau
- Department of Digestive Surgery, Amiens University Hospital - Amiens, France
| | - David Sefrioui
- Normandie University, UNIROUEN, Inserm U1245, IRON group, Department of Hepatogastroenterology, Rouen University Hospital, Rouen, France
| | - Carole Vitellius
- Department of Gastroenterology and Digestive Oncology, Angers University Hospital - Angers, France
| | - Marie-Pierre Vullierme
- Department of Medical Imaging, Université Paris-Cité, Annecy Genevois Hospital (CHANGE), Annecy, France
| | - Olivier Bouché
- Department of Gastroenterology and Digestive Oncology, CHU Reims, Reims, France
| | - Sébastien Gaujoux
- Department of HPB and Endocrine surgery; Pitié Salpétrière Hospital; Paris, France
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Kobayahshi K, Nojiri K, Suwa H, Yoshida K, Masui H. Radical Resection of Small Bowel Adenocarcinoma With Multiple Liver Metastases Following Neoadjuvant Chemotherapy: A Case Report. Cureus 2024; 16:e69776. [PMID: 39429309 PMCID: PMC11490939 DOI: 10.7759/cureus.69776] [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] [Accepted: 09/20/2024] [Indexed: 10/22/2024] Open
Abstract
Small bowel adenocarcinoma (SBA) is a relatively rare disease that is difficult to detect in the early stages; therefore, it often has a poor prognosis. We present a rare case of SBA and multiple liver metastases in a patient who underwent curative resection combined with neoadjuvant chemotherapy (NAC). A 70-year-old woman presented to the emergency department complaining of abdominal pain and bloating. She was diagnosed with bowel obstruction due to a primary jejunal tumor and was admitted to the hospital. After further imaging and histopathological examination, the patient was diagnosed with primary jejunal adenocarcinoma with multiple liver metastases, all of which were considered resectable. Since she had developed bowel obstruction due to the primary tumor, jejunal resection with draining lymph node removal was initially performed. The remaining multiple liver metastases were treated with four courses of capecitabine and oxaliplatin (CAPEOX) with bevacizumab as NAC, followed by hepatectomy. After NAC, the patient underwent radical liver resection. Based on a pathological examination, the five liver tumors were all diagnosed as liver metastases from jejunal adenocarcinoma. Six months after the liver resection, a single recurrence was observed in segment V of the liver. Therefore, four courses of CAPEOX with bevacizumab were administered again as NAC, and liver resection was performed again. At the time of writing this report, she has survived for more than four years after the first surgery, with no apparent recurrence. This is a rare case of a patient who underwent radical resection of SBA with multiple liver metastases following CAPEOX and bevacizumab as NAC.
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Affiliation(s)
- Kei Kobayahshi
- Department of Gastrointestinal Surgery, Yokosuka Kyosai Hospital, Yokosuka, JPN
| | - Kazunori Nojiri
- Department of Gastrointestinal Surgery, Yokosuka Kyosai Hospital, Yokosuka, JPN
| | - Hirokazu Suwa
- Department of Gastrointestinal Surgery, Yokosuka Kyosai Hospital, Yokosuka, JPN
| | - Kenichi Yoshida
- Department of Gastrointestinal Surgery, Yokosuka Kyosai Hospital, Yokosuka, JPN
| | - Hidenobu Masui
- Department of Gastrointestinal Surgery, Yokosuka Kyosai Hospital, Yokosuka, JPN
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Park SJ, Shin K, Hong TH, Lee SH, Kim IH, Kim Y, Lee M. Prognostic Significance of EGFR, HER2, and c-Met Overexpression in Surgically Treated Patients with Adenocarcinoma of the Ampulla of Vater. Cancers (Basel) 2024; 16:2756. [PMID: 39123483 PMCID: PMC11312068 DOI: 10.3390/cancers16152756] [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: 07/10/2024] [Revised: 07/28/2024] [Accepted: 08/02/2024] [Indexed: 08/12/2024] Open
Abstract
Adenocarcinoma of the ampulla of Vater (AAC) is a rare malignancy with heterogeneous tumors arising from various histologic subtypes, necessitating new therapeutic strategies. This study examines epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and c-Met expression in AAC, given their potential as druggable targets. Among 87 patients who underwent curative resection, EGFR overexpression was found in 87.4%, HER2 in 11.5%, and c-Met in 50%. EGFR overexpression was more common in the pancreatobiliary subtype (p = 0.018) and associated with a higher histologic grade (p = 0.008). HER2 did not correlate with clinicopathological features, while c-Met was more common in node-negative groups (p = 0.004) and often co-expressed with EGFR (p = 0.049). EGFR-positive patients had worse disease-free (HR = 2.89; 95% CI, 1.35-6.20; p = 0.061) and overall survival (HR = 6.89; 95% CI, 2.94-16.2; p = 0.026) than EGFR-negative patients. HER2-positive AAC showed a trend towards shorter survival, although not statistically significant, and c-Met had no impact on survival outcomes. In the context of systemic disease, survival outcomes did not vary according to EGFR, HER2, and c-Met expression, but the HER2-positive group showed a trend towards inferior progression-free survival (HR = 1.90; 95% CI, 0.56-6.41; p = 0.166). This study underscores the potential of EGFR, HER2, and c-Met as targets for personalized therapy in AAC, warranting further research to evaluate targeted treatments.
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Affiliation(s)
- Se Jun Park
- Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, Republic of Korea; (S.J.P.); (K.S.); (I.-H.K.)
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Kabsoo Shin
- Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, Republic of Korea; (S.J.P.); (K.S.); (I.-H.K.)
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Tae Ho Hong
- Department of General Surgery, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, Republic of Korea;
| | - Sung Hak Lee
- Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, Republic of Korea;
| | - In-Ho Kim
- Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, Republic of Korea; (S.J.P.); (K.S.); (I.-H.K.)
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Younghoon Kim
- Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, Republic of Korea;
| | - MyungAh Lee
- Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, Republic of Korea; (S.J.P.); (K.S.); (I.-H.K.)
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
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9
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Jang DK, Kim SJ, Chung HH, Lee JM, Yoon SB, Lee JC, Shin DW, Hwang JH, Jung MK, Lee YS, Lee HS, Park JK, Korean Society of Gastrointestinal Cancer. Outcomes of Palliative Chemotherapy for Ampulla of Vater Adenocarcinoma: A Multicenter Cohort Study. Gut Liver 2024; 18:729-736. [PMID: 38130162 PMCID: PMC11249934 DOI: 10.5009/gnl230164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 09/07/2023] [Accepted: 10/11/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND/AIMS : Palliative chemotherapy (PC) is not standardized for patients with advanced ampulla of Vater adenocarcinoma (AA). This multicenter, retrospective study evaluated first-line PC outcomes in patients with AA. METHODS : Patients diagnosed with AA between January 2010 and December 2020 who underwent PC were enrolled from 10 institutions. Overall survival (OS) and progression-free survival (PFS) according to the chemotherapy regimen were analyzed. RESULTS : Of 255 patients (mean age, 64.0±10.0 years; male, 57.6%), 14 (5.5%) had locally advanced AA and 241 (94.5%) had metastatic AA. Gemcitabine plus cisplatin (GP) was administered as first-line chemotherapy to 192 patients (75.3%), whereas capecitabine plus oxaliplatin (CAPOX) was administered to 39 patients (15.3%). The median OS of all patients was 19.8 months (95% confidence interval [CI], 17.3 to 22.3), and that of patients who received GP and CAPOX was 20.4 months (95% CI, 17.2 to 23.6) and 16.0 months (95% CI, 11.2 to 20.7), respectively. The median PFS of GP and CAPOX patients were 8.4 months (95% CI, 7.1 to 9.7) and 5.1 months (95% CI, 2.5 to 7.8), respectively. PC for AA demonstrated improved median outcomes in both OS and PFS compared to conventional bile duct cancers that included AA. CONCLUSIONS : While previous studies have shown mixed prognostic outcomes when AA was analyzed together with other biliary tract cancers, our study unveils a distinct clinical prognosis specific to AA on a large scale with systemic anticancer therapy. These findings suggest that AA is a distinct type of tumor, different from other biliary tract cancers, and AA itself could be expected to have a favorable response to PC.
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Affiliation(s)
- Dong Kee Jang
- Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - So Jeong Kim
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Hwe Hoon Chung
- Division of Gastroenterology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Min Lee
- Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
| | - Seung Bae Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jong-Chan Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Dong Woo Shin
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Min Kyu Jung
- Division of Gastroenterology, Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Yoon Suk Lee
- Division of Gastroenterology, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Hee Seung Lee
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Joo Kyung Park
- Division of Gastroenterology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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10
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Kim EJ. Challenges and Advancements in Palliative Chemotherapy for Ampullary Adenocarcinoma. Gut Liver 2024; 18:560-561. [PMID: 39005199 PMCID: PMC11249936 DOI: 10.5009/gnl240283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/16/2024] Open
Affiliation(s)
- Eui Joo Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
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11
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Ebrahimpour M, Hosseinzadeh H, Abedi F, Nodeh MM, Allahyari A, Sahebkar A, Arasteh O. Enhancing treatment strategies for small bowel cancer: a clinical review of targeted therapy and immunotherapy approaches. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:4601-4614. [PMID: 38329524 DOI: 10.1007/s00210-024-02992-1] [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: 10/31/2023] [Accepted: 01/30/2024] [Indexed: 02/09/2024]
Abstract
Small bowel cancer (SBC) is a rare and aggressive disease with a poor prognosis, necessitating the exploration of novel treatment approaches. This narrative review examines the current evidence on targeted therapy and immunotherapy for SBC, focusing on the two most common subtypes: adenocarcinoma and neuroendocrine tumor. A comprehensive search of PubMed, Scopus, and Google Scholar databases was conducted to identify relevant clinical trials and case reports published in English up to September 2023. The review includes 17 clinical trials and 10 case reports, indicating that targeted therapy and immunotherapy can have the potential to improve survival rates in patients with SBC. Notably, promising targeted medicines include bevacizumab, cetuximab, and trastuzumab, while pembrolizumab and nivolumab show potential as immunotherapies. However, it should be noted that the magnitude of the increase in survival rates with these interventions was small. Further research is needed to determine the optimal combination of targeted therapy and immunotherapy for individual patients with SBC.
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Affiliation(s)
| | | | - Farshad Abedi
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Moeini Nodeh
- Department of Hematology and Oncology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abolghasem Allahyari
- Department of Hematology and Oncology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Omid Arasteh
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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12
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Uijterwijk BA, Lemmers DH, Ghidini M, Wilmink JW, Zaniboni A, Fusai GK, Zerbi A, Koerkamp BG, Luyer M, Ghorbani P, Salvia R, White S, Ielpo B, Goh BKP, Boggi U, Kazemier G, House MG, Mavroeidis VK, Björnsson B, Mazzola M, Serradilla M, Korkolis D, Alseidi A, Roberts KJ, Soonawalla Z, Pessaux P, Fisher WE, Koek S, Kent TS, Vladimirov M, Bolm L, Jamieson N, Dalla Valle R, Kleeff J, Mazzotta A, Suarez Muñoz MA, Cabús SS, Ball CG, Berger AC, Ferarri C, Besselink MG, Hilal MA. The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study. Br J Cancer 2024; 131:117-125. [PMID: 38806725 PMCID: PMC11231293 DOI: 10.1038/s41416-024-02692-w] [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: 12/13/2023] [Revised: 03/25/2024] [Accepted: 04/10/2024] [Indexed: 05/30/2024] Open
Abstract
BACKGROUND Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. PATIENTS AND METHODS Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). RESULTS The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively). DISCUSSION Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.
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Affiliation(s)
- Bas A Uijterwijk
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy.
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands.
- Cancer Center Amsterdam, Amsterdam, the Netherlands.
| | - Daniël H Lemmers
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Michele Ghidini
- Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Johanna W Wilmink
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Alberto Zaniboni
- Department of Medical Oncology, Fondazione Poliambulanza, Brescia, Italy
| | | | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Department of Pancreatic Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Misha Luyer
- Catharina Hospital Eindhoven, Department of Surgery, Eindhoven, Netherlands
| | - Poya Ghorbani
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - Roberto Salvia
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - Steven White
- Department of Surgery, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
| | | | - Brian K P Goh
- Singapore General Hospital, Department of Hepatopancreatobiliary and Transplant Surgery, Duke-National University of Singapore, Singapore, Singapore
| | - Ugo Boggi
- Department of Surgery, Pisa University Hospital, Pisa, Italy
| | - Geert Kazemier
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Amsterdam UMC, location VUmc, Amsterdam, the Netherlands
| | - Michael G House
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Vasileios K Mavroeidis
- Department of Academic Surgery, The Royal Marsden Hospital, London, UK
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Bergthor Björnsson
- Department of Surgery in Linköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Michele Mazzola
- Division of Oncologic and Mini-invasive General Surgery, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Mario Serradilla
- Department of Surgery, Miguel Servet University Hospital, Zargosa, Spain
| | - Dimitris Korkolis
- Department of Surgery, Hellenic Anticancer Hospital 'Saint Savvas', Athens, Greece
| | - Adnan Alseidi
- Department of Surgery, Virginia Mason, Seattle, WA, USA
| | - Keith J Roberts
- Faculty of medicine, University of Birmingham, Birmingham, UK
| | - Zahir Soonawalla
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Patrick Pessaux
- Hepatobiliary and Pancreatic Surgical Unit, Nouvel Hôpital Civil (NHC), Strasbourg, France
| | | | - Sharnice Koek
- Fiona Stanley Hospital, Department of Surgery, Perth, WA, Australia
| | - Tara S Kent
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Miljana Vladimirov
- Department of General Surgery, Paracelsus Medical University Nürnberg, 90419, Nürnberg, Germany
| | - Louisa Bolm
- Department of Surgery, University Medical Center Schleswig-Holstein, campus Lübeck, Lübeck, Germany
| | - Nigel Jamieson
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
| | | | - Jorg Kleeff
- Department of Surgery, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany
| | - Alessandro Mazzotta
- Department of Digestive, Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Paris, France
| | | | | | - Chad G Ball
- Department of Surgery, University of Calgary, Calgary, AB, Canada
| | - Adam C Berger
- Department of Surgery, Jefferson Medical College, Philadelphia, USA
| | - Clarissa Ferarri
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
| | - Marc G Besselink
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Mohammed Abu Hilal
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy.
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13
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Lee S, Park SJ, Shin K, Hong TH, Kim IH, Lee MA. Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater. BMC Cancer 2024; 24:634. [PMID: 38783256 PMCID: PMC11119299 DOI: 10.1186/s12885-024-12398-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 05/17/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.
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Affiliation(s)
- Seunghwan Lee
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
| | - Se Jun Park
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kabsoo Shin
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Tae Ho Hong
- Department of General Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - In-Ho Kim
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Myung Ah Lee
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea.
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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14
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Miura Y, Ohgi K, Ashida R, Yamada M, Otsuka S, Sasaki K, Uesaka K, Sugiura T. Efficacy of lymph node dissection for duodenal cancer according to the lymph node station. Ann Gastroenterol Surg 2024; 8:51-59. [PMID: 38250683 PMCID: PMC10797846 DOI: 10.1002/ags3.12731] [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: 05/14/2023] [Revised: 07/23/2023] [Accepted: 08/03/2023] [Indexed: 01/23/2024] Open
Abstract
Background Lymph node metastasis (LNM) is associated with poor prognosis in patients with duodenal cancer (DC). However, the efficacy and optimal extent of lymph node (LN) dissection have not been thoroughly discussed. Methods A total of 98 consecutive patients with DC who underwent surgical resection (pancreatoduodenectomy, n = 55; partial resection, n = 32; pancreas-sparing total duodenectomy, n = 9) were retrospectively analyzed. The LN stations located upstream of the lymphatic flow were defined as Np stations according to tumor location, whereas the others were defined as Nd stations. The association between the dissection of each LN station and survival outcome was investigated using the efficacy index (EI; percentage of metastases to lymph nodes in each station multiplied by the 5-year survival rate of metastatic cases). Results The survival of patients with LNM at the Nd stations (n = 6) was significantly worse than that of patients with LNM only at the Np stations (n = 20) (relapse-free survival, median survival time [MST], 6.0 vs. 48.4 months, p < 0.001; overall survival, MST, 15.1 vs. 96.0 months, p < 0.001). Multivariate analysis identified LNM at Nd stations as an independent prognostic factor for overall survival (hazard ratio 9.92; p = 0.015). The Np stations had a high EI (range, 8.34-20.88), whereas the Nd stations had an EI of 0, regardless of the tumor location. Conclusions LN dissection of the Np stations contributed to acceptable survival, whereas LNM of the Nd stations led to poor survival, possibly reflecting advanced tumor progression to systemic disease in patients with DC.
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Affiliation(s)
- Yuya Miura
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Katsuhisa Ohgi
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Ryo Ashida
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Mihoko Yamada
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Shimpei Otsuka
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Keiko Sasaki
- Division of Diagnostic PathologyShizuoka Cancer CenterShizuokaJapan
| | - Katsuhiko Uesaka
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Teiichi Sugiura
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
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Mitome N, Machida N, Shichiri Y, Kuwashima H, Murai A, Maeda S. S-1 as an alternative treatment after 5-fluorouracil-induced coronary vasospasm in a patient with small bowel adenocarcinoma: a case report. Int Cancer Conf J 2024; 13:40-44. [PMID: 38187174 PMCID: PMC10764697 DOI: 10.1007/s13691-023-00633-7] [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: 05/30/2023] [Accepted: 08/25/2023] [Indexed: 01/09/2024] Open
Abstract
5-Fluorouracil (5-FU) is a chemotherapeutic agent used worldwide to treat various solid tumors. It may cause adverse cardiotoxic events, the most common of which is coronary vasospasm. Recently, the 2022 European Society for Medical Oncology guidelines for metastatic colorectal cancer recommended S-1 as an alternative therapy after 5-FU-induced cardiotoxicity; however, only limited data on Asian patients are available. Here, we report a case of safe administration of S-1 to a 72-year-old Japanese female patient with metastatic small bowel adenocarcinoma who developed 5-FU-induced coronary vasospasm. While receiving modified FOLFOX6 (5-FU plus leucovorin and oxaliplatin) as palliative chemotherapy, she experienced chest pain with electrocardiographic ST elevation. Chemotherapy was temporarily suspended, but treatment was resumed by switching from modified FOLFOX6 to SOX (S-1 plus oxaliplatin) as the tumor began to worsen. Owing to the adverse event of enteritis, the patient's treatment was switched to S-1 monotherapy after cycle 3, and S-1 monotherapy was continued without any cardiotoxicity. S-1 may be a promising alternative therapy after 5-FU-induced cardiotoxicity.
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Affiliation(s)
- Noriko Mitome
- Department of Internal Medicine, Yokohama Hodogaya Central Hospital, 43-1 Kamadai-cho, Hodogaya-ku, Yokohama, 240-8585 Japan
- Department of Gastroenterology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515 Japan
| | - Nozomu Machida
- Department of Gastroenterology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515 Japan
| | - Yoriko Shichiri
- Department of Internal Medicine, Yokohama Hodogaya Central Hospital, 43-1 Kamadai-cho, Hodogaya-ku, Yokohama, 240-8585 Japan
| | - Hirofumi Kuwashima
- Department of Internal Medicine, Yokohama Hodogaya Central Hospital, 43-1 Kamadai-cho, Hodogaya-ku, Yokohama, 240-8585 Japan
| | - Arisa Murai
- Department of Internal Medicine, Yokohama Hodogaya Central Hospital, 43-1 Kamadai-cho, Hodogaya-ku, Yokohama, 240-8585 Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University, 3-9, Fukuura, Kanazawa-ku, Yokohama, 236-0004 Japan
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16
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Huang CC, Ying LQ, Chen YP, Ji M, Zhang L, Liu L. Metachronous primary esophageal squamous cell carcinoma and duodenal adenocarcinoma: A case report and review of literature. World J Gastrointest Surg 2023; 15:2627-2638. [PMID: 38111767 PMCID: PMC10725532 DOI: 10.4240/wjgs.v15.i11.2627] [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: 07/10/2023] [Revised: 09/23/2023] [Accepted: 10/26/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND The prevalence of multiple primary malignant neoplasms (MPMNs) is increasing in parallel with the incidence of malignancies, the continual improvement of diagnostic models, and the extended life of patients with tumors, especially those of the digestive system. However, the co-existence of MPMNs and duodenal adenocarcinoma (DA) is rarely reported. In addition, there is a lack of comprehensive analysis of MPMNs regarding multi-omics and the tumor microenvironment (TME). CASE SUMMARY In this article, we report the case of a 56-year-old man who presented with a complaint of chest discomfort and abdominal distension. The patient was diagnosed with metachronous esophageal squamous cell carcinoma and DA in the Department of Oncology. He underwent radical resection and chemotherapy for the esophageal tumor, as well as chemotherapy combined with a programmed death-1 inhibitor for the duodenal tumor. The overall survival was 16.6 mo. Extensive evaluation of the multi-omics and microenvironment features of primary and metastatic tumors was conducted to: (1) Identify the reasons responsible for the poor prognosis and treatment resistance in this case; and (2) Offer novel diagnostic and therapeutic approaches for MPMNs. This case demonstrated that the development of a second malignancy may be independent of the location of the first tumor. Thus, tumor recurrence (including metastases) should be distinguished from the second primary for an accurate diagnosis of MPMNs. CONCLUSION Multi-omics characteristics and the TME may facilitate treatment selection, improve efficacy, and assist in the prediction of prognosis.
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Affiliation(s)
- Chun-Chun Huang
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Le-Qian Ying
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Yan-Ping Chen
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Min Ji
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Lu Zhang
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Lin Liu
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province, 210009, China
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17
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Walter D, Schnitzbauer AA, Schulze F, Trojan J. The Diagnosis and Treatment of Ampullary Carcinoma. DEUTSCHES ARZTEBLATT INTERNATIONAL 2023; 120:729-735. [PMID: 37656482 DOI: 10.3238/arztebl.m2023.0195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 08/09/2023] [Accepted: 08/09/2023] [Indexed: 09/02/2023]
Abstract
BACKGROUND Ampullary or papillary carcinoma is a malignant tumor arising from the mucosa in the region of the major duodenal papilla, also known as the ampulla of Vater. Uniform treatment recommendations are lacking both for the adjuvant situation and for palliative care. METHODS A selective literature search was carried out in PubMed in order to identify the most informative publications concerning the epidemiology, clinico-pathological background, and surgical and medical treatment of this condition. RESULTS Ampullary carcinoma has an incidence of 0.5 to 0.9 per 100 000 persons and a poor prognosis, with a 5-year survival rate of 41% to 45% for locally confined and 4% to 7% for metastatic disease. Most such tumors are of an intestinal or a pan - creaticobiliary immunohistochemical subtype; the latter has a worse prognosis (median survival, 72-80 vs. 33-41 months). Targeted treatment is not yet available for either subtype, nor is there enough scientific evidence available for the formulation of specific therapeutic recommendations in either the adjuvant or the palliative situation. The treatment of choice for ampullary carcinoma is radical oncological resection of the head of the pancreas with systematic lymphadenectomy. Five-year overall survival is between 10% and 75% depending on the stage. No definitive recommendation for adjuvant therapy can be given. Palliative therapy can be oriented to the published treatment strategies for cancer of the colon, pancreas, and bile duct. CONCLUSION The current state of the evidence on the treatment of ampullary carcinoma is poor. Therapeutic decisions should be discussed in an interdisciplinary tumor board and should, in our opinion, take the histological subtype into account.
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Affiliation(s)
- Dirk Walter
- Department of Internal Medicine, J.W. Goethe University Hospital, Frankfurt/Main; Department of General, Visceral, Transplant- and Thoracic Surgery, J.W. Goethe University Hospital, Frankfurt/Main; Dr. Senckenberg Institute for Pathology, University Hospital Frankfurt, Goethe University Frankfurt am Main
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18
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Shin DW. [Treatment of Ampullary Adenocarcinoma]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 82:159-170. [PMID: 37876255 DOI: 10.4166/kjg.2023.110] [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: 09/13/2023] [Revised: 09/28/2023] [Accepted: 10/03/2023] [Indexed: 10/26/2023]
Abstract
The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary ampullary adenocarcinoma is a rare malignancy, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. Jaundice from a biliary obstruction is the most common symptom of ampullary adenocarcinoma. In the early stages, radical pancreatoduodenectomy is the standard surgical approach. On the other hand, no randomized controlled trial has provided evidence to guide physicians on the choice of adjuvant/palliative chemotherapy because of the rarity of the disease and the paucity of related research. This paper reports the biology, histology, current therapeutic strategies, and potential future therapies of ampullary adenocarcinoma.
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Affiliation(s)
- Dong Woo Shin
- Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
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19
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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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20
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Bellefkih FZ, Benchakroun N, Lalya I, Amaoui B, El Kacemi H, Acharki A, El Hfid M, El Mazghi A, Chekrine T, Bouchbika Z, Jouhadi H, Sahraoui S, Tawfiq N, Michalet M. Radiotherapy in the management of rare gastrointestinal cancers: A systematic review. Cancer Radiother 2023; 27:622-637. [PMID: 37500390 DOI: 10.1016/j.canrad.2023.06.010] [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: 06/06/2023] [Revised: 06/10/2023] [Accepted: 06/13/2023] [Indexed: 07/29/2023]
Abstract
The aim of this analysis is to assess radiotherapy's role and technical aspects in an array of rare gastrointestinal (GI) cancers for adult patients. Collection data pertaining to radiotherapy and digestive rare cancers were sourced from Medline, EMBASE, and Cochrane Library. Preoperative chemoradiotherapy improved outcomes for patients with esophageal undifferentiated carcinoma compared with esophageal salivary gland types of carcinomas. For rare gastric epithelial carcinoma, perioperative chemotherapy is the common treatment. Adjuvant chemoradiotherapy showed no benefice compared with adjuvant chemotherapy for duodenal adenocarcinoma. Small bowel sarcomas respond well to radiotherapy. By analogy to anal squamous cell carcinoma, exclusive chemoradiotherapy provided better outcomes for patients with rectal squamous cell carcinoma. For anal adenocarcinoma, neoadjuvant chemoradiotherapy, followed by radical surgery, was the most effective regimen. For pancreatic neuroendocrine tumors, chemoradiotherapy can be a suitable option as postoperative or exclusive for unresectable/borderline disease. The stereotactic body radiotherapy (SBRT) is a promising approach for hepatobiliary malignancy. Radiotherapy is a valuable option in gastrointestinal stromal tumors (GIST) for palliative intent, tyrosine kinase inhibitors (TKIs) resistant disease, and unresectable or residual disease. Involved field (IF) radiotherapy for digestive lymphoma provides good results, especially for gastric extranodal marginal zone lymphoma (MALT). In conclusion, radiotherapy is not an uncommon indication in this context. A multidisciplinary approach is needed for better management of digestive rare cancers.
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Affiliation(s)
- F Z Bellefkih
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco.
| | - N Benchakroun
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco; Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - I Lalya
- Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - B Amaoui
- Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - H El Kacemi
- Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - A Acharki
- Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - M El Hfid
- Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - A El Mazghi
- Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - T Chekrine
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco
| | - Z Bouchbika
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco
| | - H Jouhadi
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco
| | - S Sahraoui
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco; Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - N Tawfiq
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco
| | - M Michalet
- Service d'oncologie-radiothérapie, institut du cancer de Montpellier, Fédération d'oncologie-radiothérapie d'Occitanie Méditerranée (Forom), Montpellier, France
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21
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Linscott MP, Markus H, Sennett M, Abendroth C, Yee NS. Nab-Paclitaxel and Gemcitabine as First-Line Treatment of Metastatic Ampullary Adenocarcinoma with a Novel R-Spondin2 RNA Fusion and NTRK3 Mutation. Biomedicines 2023; 11:2326. [PMID: 37626821 PMCID: PMC10452745 DOI: 10.3390/biomedicines11082326] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 08/14/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
Ampullary adenocarcinoma is a rare malignancy that lacks standard systemic treatment. We describe a case of recurrent metastatic ampullary adenocarcinoma of the pancreaticobiliary subtype treated with nanoparticle albumin-bound (nab)-paclitaxel and gemcitabine as first-line treatment. This report also highlights the molecular profile of the ampullary adenocarcinoma and circulating tumor DNA (ctDNA). This is a case of pancreaticobiliary ampullary adenocarcinoma in a 67-year-old woman who initially presented with painless jaundice. Endoscopic and imaging evaluation revealed biliary ductal dilation secondary to an ampullary mass. Pathology confirmed the diagnosis of ampullary adenocarcinoma of the pancreaticobiliary subtype. She underwent surgical resection of the tumor, followed by adjuvant chemotherapy with gemcitabine and capecitabine. The tumor subsequently recurred in the liver. She received palliative chemotherapy with nab-paclitaxel and gemcitabine, resulting in an objective tumor response for 14 months. Molecular profiling of the tumor and ctDNA revealed a novel MATN2-RSPO RNA fusion and a novel NTRK3 mutation, respectively. Our report suggests that long-term durable response can be achieved in metastatic pancreaticobiliary ampullary adenocarcinoma using nab-paclitaxel and gemcitabine. Molecular profiling of the tumor identified a novel R-Spondin2 RNA fusion and NTRK3 mutation that can be potentially targeted for treatment.
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Affiliation(s)
- Maryknoll P. Linscott
- Medical Scientist Training Program, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (M.P.L.); (H.M.); (M.S.)
| | - Havell Markus
- Medical Scientist Training Program, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (M.P.L.); (H.M.); (M.S.)
| | - Mackenzie Sennett
- Medical Scientist Training Program, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (M.P.L.); (H.M.); (M.S.)
| | - Catherine Abendroth
- Department of Pathology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA 17033, USA;
| | - Nelson S. Yee
- Division of Hematology-Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
- Next-Generation Therapies Program, Penn State Cancer Institute, Penn State Health Milton S. Hershey Medical Center, Hershey, PA 17033, USA
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22
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Nappo G, Funel N, Laurenti V, Stenner E, Carrara S, Bozzarelli S, Spaggiari P, Zerbi A. Ampullary Cancer: Histological Subtypes, Markers, and Clinical Behaviour-State of the Art and Perspectives. Curr Oncol 2023; 30:6996-7006. [PMID: 37504367 PMCID: PMC10378042 DOI: 10.3390/curroncol30070507] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/15/2023] [Accepted: 07/20/2023] [Indexed: 07/29/2023] Open
Abstract
There are different cancers in the peri-ampullary region, including pancreatic ductal adenocarcinoma (PDAC), duodenum cancers (DCs), and ampullary adenocarcinoma (AAC). Here, significant morphological-molecular characterizations should be necessary for the distinction of primary tumours and classifications of their subtypes of cancers. The sub classification of AACs might include up to five different variants, according to different points of view, concerning the prevalence of the two more-cellular components found in the ampulla. In particular, regarding the AACs, the most important subtypes are represented by the intestinal (INT) and the pancreato-biliary (PB) ones. The subtyping of AACs is essential for diagnosis, and their identifications have been impacting clinical management responses to treatments and overall survival (os) after surgery. Pb is associated with a worse clinical outcome. Otherwise, the criteria, through which are possible to attribute its subtype classification, are not well established. A triage of immune markers represented by CK7, CK20, and CDX-2 seem to represent the best compromise in order to split the cohort of AAC patients in the INT and PB groups. The test of choice for the sub-classification of AACs is represented by the immuno-histochemical approach, in which its molecular classification acquires its diagnostic, predictive, and prognostic value for both the INT and PB patients.
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Affiliation(s)
- Gennaro Nappo
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy (A.Z.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy
| | - Niccola Funel
- USL Toscana Nordovest, Chemical-Clinical Analysis Laboratory, Department of Diagnostics, 56121 Pisa, Italy; (N.F.); (E.S.)
| | - Virginia Laurenti
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy (A.Z.)
| | - Elisabetta Stenner
- USL Toscana Nordovest, Chemical-Clinical Analysis Laboratory, Department of Diagnostics, 56121 Pisa, Italy; (N.F.); (E.S.)
| | - Silvia Carrara
- Endoscopic Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
| | - Silvia Bozzarelli
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
| | - Paola Spaggiari
- Pathology Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy;
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy (A.Z.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy
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23
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Teufel A, Meindl-Beinker NM, Hösel P, Gerken M, Roig A, Ebert MP, Herr W, Scheiter A, Pauer A, Schlitt HJ, Klinkhammer-Schalke M. Characteristics and outcome of patients with small bowel adenocarcinoma (SBA). J Cancer Res Clin Oncol 2023; 149:4579-4590. [PMID: 36163558 PMCID: PMC10349691 DOI: 10.1007/s00432-022-04344-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 08/31/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Small bowel adenocarcinoma (SBA) remains a rare malignancy accounting for less than 5% of all the gastrointestinal tract cancers. However, only limited data and expert guidelines are available for this entity. As a result, treatment concepts are predominantly derived from colorectal cancer. METHODS To substantiate data on the course of disease, diagnosis and treatment of SBA, we performed a population-based analysis from a Bavarian population of 2.2 million people. RESULTS We identified 223 patients with SBA. Mean age at diagnosis was 67.8 years and patients were diagnosed rather late (34.5% UICC stage IV). Largest proportion of these patients were diagnosed with adenocarcinoma of the duodenum (132 patients, 59.2%) and most patients were diagnosed with late stage cancer, stage IV (70 patients, 31.4%). With respect to treatment, most patients underwent primary surgery (187 patients, 84.6%). Systemic therapy seemed to have an impact in UICC stage IV patients but not in UICC stage IIB or III. The 5-year survival rate was 29.0%. This was significantly less compared to colon cancer in the same cohort, which was 50.0%. Furthermore, median survival of patients with small bowel cancer was only 2.0 years (95% CI 1.4-2.5) compared to 4.9 years (95% CI 4.8-5.1) of patients with colon cancer. CONCLUSION SBA showed a distinct epidemiology compared to colon cancer. Thus, data acquisition particularly on systemic treatment are paramount, with the objective to complement the available guidelines.
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Affiliation(s)
- Andreas Teufel
- Division of Hepatology, Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
- Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
| | - Nadja M Meindl-Beinker
- Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Pauline Hösel
- DKFZ-Hector Cancer Institute at the University Medical Center, Mannheim, Germany
| | - Michael Gerken
- Bavarian Cancer Registry, Regional Center Regensburg, Bavarian Health and Food Safety Authority, Regensburg, Germany
- Regensburg Tumor Center, Institute for Quality Assurance and Health Services Research at the University of Regensburg, Regensburg, Germany
| | - Ana Roig
- Division of Hepatology, Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Matthias P Ebert
- Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ-Hector Cancer Institute at the University Medical Center, Mannheim, Germany
- Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Wolfgang Herr
- Department of Internal Medicine III, University Medical Center Regensburg, Regensburg, Germany
| | | | - Armin Pauer
- Regensburg Tumor Center, Institute for Quality Assurance and Health Services Research at the University of Regensburg, Regensburg, Germany
| | - Hans J Schlitt
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany
| | - Monika Klinkhammer-Schalke
- Bavarian Cancer Registry, Regional Center Regensburg, Bavarian Health and Food Safety Authority, Regensburg, Germany
- Regensburg Tumor Center, Institute for Quality Assurance and Health Services Research at the University of Regensburg, Regensburg, Germany
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24
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Park SJ, Shin K, Kim IH, Hong TH, Kim Y, Lee MA. Role of adjuvant chemotherapy on recurrence and survival in patients with resected ampulla of Vater carcinoma. World J Gastrointest Oncol 2023; 15:677-688. [PMID: 37123060 PMCID: PMC10134206 DOI: 10.4251/wjgo.v15.i4.677] [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: 12/24/2022] [Revised: 02/20/2023] [Accepted: 03/22/2023] [Indexed: 04/12/2023] Open
Abstract
BACKGROUND Owing to rarity of disease and lack of prospective studies, data supporting the role of adjuvant chemotherapy in ampulla of Vater (AoV) carcinoma is limited. AIM To evaluate whether adjuvant chemotherapy cases for AoV carcinoma had better disease-free survival (DFS) rates than cases of observation following curative surgery. METHODS We retrospectively analyzed the association between adjuvant chemotherapy and DFS and overall survival (OS) in patients with stage IB-III AoV carcinoma who underwent curative surgical resection. Fluorouracil-based adjuvant chemotherapy was administered after surgery at the discretion of the physician. Adjusted multivariate regression models were used to evaluate the association between adjuvant chemotherapy and survival outcomes. RESULTS Of the total 104 patients who underwent curative surgery, 52 received adjuvant chemotherapy. Multivariate analysis revealed that higher histologic grade [hazard ratio (HR) = 2.24, P = 0.046], advanced tumor stage (HR = 1.85, P = 0.030), and vascular invasion (HR = 2.14, P = 0.010) were associated with shorter DFS. Adjuvant chemotherapy improved DFS compared to the observation group (HR = 0.50, P = 0.015) and tended to be associated with a longer OS, although the difference was not statistically significant (HR = 0.58, P = 0.098). CONCLUSION Among patients with resected AoV carcinoma, the adjuvant chemotherapy group was not associated with a significant survival benefit compared to the observation group. However, on multivariate analysis adjusting for prognostic factors, adjuvant chemotherapy following surgery was an independent prognostic factor for DFS in patients with resected AoV carcinoma. Further studies are needed to investigate the effectiveness of adjuvant chemotherapy according to histologic phenotype.
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Affiliation(s)
- Se Jun Park
- Division of Medical Oncology, Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, South Korea
| | - Kabsoo Shin
- Division of Medical Oncology, Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, South Korea
| | - In-Ho Kim
- Division of Medical Oncology, Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, South Korea
| | - Tae Ho Hong
- Department of General Surgery, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, South Korea
| | - Younghoon Kim
- Department of Pathology, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, South Korea
| | - Myung-ah Lee
- Division of Medical Oncology, Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul 06591, South Korea
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25
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Mauri G, Gori V, Patelli G, Roazzi L, Rizzetto F, De Carlis L, Mariani A, Cavallari U, Prada E, Cipani T, Aquilano MC, Bonoldi E, Vanzulli A, Siena S, Sartore-Bianchi A. Multimodal treatment with curative intent in a germline BRCA2 mutant metastatic ampullary adenocarcinoma: a case report. World J Surg Oncol 2023; 21:118. [PMID: 36998040 PMCID: PMC10064505 DOI: 10.1186/s12957-023-02976-0] [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: 11/25/2022] [Accepted: 02/27/2023] [Indexed: 04/01/2023] Open
Abstract
BACKGROUND Cancers of the Vater ampulla (ampullary cancers, ACs) account for less than 1% of all gastrointestinal tumors. ACs are usually diagnosed at advanced stage, with poor prognosis and limited therapeutic options. BRCA2 mutations are identified in up to 14% of ACs and, differently from other tumor types, therapeutic implications remain to be defined. Here, we report a clinical case of a metastatic AC patient in which the identification of a BRCA2 germline mutation drove a personalized multimodal approach with curative-intent. CASE PRESENTATION A 42-year-old woman diagnosed with stage IV BRCA2 germline mutant AC underwent platinum-based first line treatment achieving major tumor response but also life-threatening toxicity. Based on this, as well as on molecular findings and expected low impact of available systemic treatment options, the patient underwent radical complete surgical resection of both primary tumor and metastatic lesions. Following an isolated retroperitoneal nodal recurrence, given the expected enhanced sensitivity to radiotherapy in BRCA2 mutant cancers, the patient underwent imaging-guided radiotherapy leading to long-lasting complete tumor remission. After more than 2 years, the disease remains radiologically and biochemically undetectable. The patient accessed a dedicated screening program for BRCA2 germline mutation carriers and underwent prophylactic bilateral oophorectomy. CONCLUSIONS Even considering the intrinsic limitations of a single clinical report, we suggest that the finding of BRCA germline mutations in ACs should be taken into consideration, together with other clinical variables, given their potential association with remarkable response to cytotoxic chemotherapy that might be burdened with enhanced toxicity. Accordingly, BRCA1/2 mutations might offer the opportunity of personalizing treatment beyond PARP inhibitors up to the choice of a multimodal approach with curative-intent.
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Affiliation(s)
- Gianluca Mauri
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Viviana Gori
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Giorgio Patelli
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Laura Roazzi
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Francesco Rizzetto
- Department of Services, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Luciano De Carlis
- Department of Surgery and Transplantation, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Università degli Studi di Milano-Bicocca, Milan, Italy
| | - Anna Mariani
- Department of Surgery and Transplantation, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Ugo Cavallari
- Department of Laboratory Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Elisabetta Prada
- Department of Laboratory Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Tiziana Cipani
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Maria Costanza Aquilano
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Emanuela Bonoldi
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Angelo Vanzulli
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy
- Department of Services, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Salvatore Siena
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Andrea Sartore-Bianchi
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy.
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
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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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27
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de Back T, Nijskens I, Schafrat P, Chalabi M, Kazemier G, Vermeulen L, Sommeijer D. Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas: A Systematic Review and Meta-analysis. JAMA Netw Open 2023; 6:e230631. [PMID: 36826817 PMCID: PMC9958532 DOI: 10.1001/jamanetworkopen.2023.0631] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 01/09/2023] [Indexed: 02/25/2023] Open
Abstract
Importance Although small intestinal adenocarcinomas (SIAs) are rare, they have a poor prognosis, and the optimal treatment strategies are largely unknown. Because of the lack of high-quality evidence, guidelines for colorectal cancer are often followed in the treatment of SIAs. Objective To review the current evidence regarding survival benefit of systemic therapies, including chemotherapy, targeted agents, and immunotherapy, for patients with SIAs. Data Sources Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses, MEDLINE and Embase were searched for articles published from January 1, 2005, until June 1, 2022. Study Selection Retrospective cohort studies and prospective phase 2 or 3 trials describing survival after systemic therapies for patients with SIAs were eligible for inclusion. Assessment of study eligibility was blinded and performed by 3 reviewers. Data Extraction and Synthesis The reviewers independently extracted data. Random effects, inverse variance, pairwise meta-analyses were performed. Main Outcomes and Measures Primary outcomes were overall survival (OS) and progression-free survival (PFS) of patients with SIAs after systemic therapies. Measures of interest included hazard ratios for survival and median survival times. Results Overall, 57 retrospective cohort and phase 2 studies of 35 176 patients were included. Adjuvant chemotherapy, generally fluoropyrimidine-based, was associated with increased OS in stage I to III SIAs (hazard ratio [HR], 0.60; 95% CI, 0.53-0.68), especially in stage III tumors (HR, 0.55; 95% CI, 0.48-0.64), irrespective of tumor localization. Palliative chemotherapy was also associated with an OS benefit (HR, 0.48; 95% CI, 0.40-0.58). Fluoropyrimidine-oxaliplatin combinations were superior to other regimens (OS: HR, 0.54; 95% CI, 0.30-0.99; PFS: HR, 0.46; 95% CI, 0.30-0.71). Furthermore, bevacizumab added to chemotherapy compared with chemotherapy alone was associated with significantly prolonged PFS (HR, 0.62; 95% CI, 0.43-0.89). Immunotherapy showed a 50% overall response rate in previously treated defective mismatch repair tumors. Conclusions and Relevance In this systematic review and meta-analysis, adjuvant and palliative chemotherapy were both associated with improved survival of patients with SIAs, especially fluoropyrimidine-based regimens and fluoropyrimidine-oxaliplatin combinations. Adding bevacizumab to chemotherapy appears to prolong PFS and deserves further investigation. Immunotherapy seems beneficial and should be considered for patients with defective mismatch repair tumors. International collaborations should be undertaken to confirm and improve efficacy of systemic therapies for patients with SIAs.
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Affiliation(s)
- Tim de Back
- Center for Experimental and Molecular Medicine, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, the Netherlands
- Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Isabelle Nijskens
- Department of Internal Medicine, Flevohospital, Almere, the Netherlands
| | - Pascale Schafrat
- Center for Experimental and Molecular Medicine, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, the Netherlands
- Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Myriam Chalabi
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Geert Kazemier
- Department of Pathology, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
- Department of Surgery, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
- Imaging and Biomarkers, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Louis Vermeulen
- Center for Experimental and Molecular Medicine, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, the Netherlands
- Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
| | - Dirkje Sommeijer
- Center for Experimental and Molecular Medicine, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Internal Medicine, Flevohospital, Almere, the Netherlands
- Department of Medical Oncology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
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28
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Chen X, Zhou R, Li Y, Qu X, Qu YC, Li WZ, Ye YS, Liu LR, Zhu YJ, Zhang HB. Case report: A case of duodenal adenocarcinoma achieving significantly long survival treating with immune checkpoint inhibitors and chemotherapy without positive biomarkers. Front Immunol 2022; 13:1046513. [PMID: 36531985 PMCID: PMC9755197 DOI: 10.3389/fimmu.2022.1046513] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 11/22/2022] [Indexed: 12/04/2022] Open
Abstract
Small bowel adenocarcinoma (SBA), particularly duodenal adenocarcinoma (DA), is a rare gastrointestinal cancer with a dismal prognosis. Data on SBA treatments are limited, and the therapeutic strategy remains uncertain. Currently, chemotherapy is the most used treatment; however, it has a poor median progression-free survival (mPFS) of no more than five months in the second-line setting. We report a case with DA that responded well to the immune checkpoint inhibitor (ICI) tislelizumab plus irinotecan in the second-line treatment. To our knowledge, this is the first report of administering ICIs plus chemotherapy to SBA. Despite the absence of microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB), the patient with TP53/KRAS mutation achieved a significantly long PFS of 17 months, and the benefit is still ongoing. The mechanism of this remarkable efficacy might be associated with an increase in tumor immunogenicity after chemotherapy. The current study presents a promising effect of ICIs plus chemotherapy on SBA, affirming the need to investigate the clinical value of this combination in SBA and the underlying mechanism behind it.
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Affiliation(s)
- Xian Chen
- The Second Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China,Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Rui Zhou
- The Second Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yong Li
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Xin Qu
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Yan-chun Qu
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Wen-zhu Li
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Yong-song Ye
- Department of Image, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Li-rong Liu
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Yan-juan Zhu
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China,Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hai-bo Zhang
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China,Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,*Correspondence: Hai-bo Zhang,
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29
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Zhang Z, Lei Y, Wang D, Yang L, Lou C. Case Report: A case of advanced duodenal adenocarcinoma in complete remission after chemotherapy combined with targeted therapy and radiotherapy. Front Oncol 2022; 12:968110. [PMID: 36353566 PMCID: PMC9638098 DOI: 10.3389/fonc.2022.968110] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 09/12/2022] [Indexed: 12/02/2022] Open
Abstract
Duodenal adenocarcinoma (DA) is an extremely rare and highly aggressive malignant tumor of the digestive system. Due to the lack of specific clinical characteristics, it is easy to misdiagnosis and miss diagnosis, and the lack of specific consensus and recommendation for treatment, so it often refers to stomach cancer and colorectal cancer. Now, we report a case of a patient with advanced DA who achieved complete remission (CR) after undergoing chemoradiotherapy combined with targeted therapy. The patient was pathologically diagnosed with DA after radical surgery in October 2020, and he failed to undergo adjuvant chemotherapy on time due to the COVID-19 outbreak. The patient found multiple lymph node liver and abdominal metastases 6 months after the operation. Considering the progression of the disease, XELOX regimen (oxaliplatin + capecitabine) chemotherapy was given for 1 cycle. After 1 cycle of treatment, the tumor markers remained elevated; the carcinoembryonic antigen (CEA) was 5.03 ng/ml (0–5 ng/ml), and the carbohydrate antigen 19-9 (CA19-9) was 747.30 U/ml (0–37 U/ml). The patient also developed intolerable capecitabine-related treatment-related adverse events (TRAEs), namely, hand–foot syndrome. For the above reasons, capecitabine was replaced as S-1 at cycle 2, and the chemotherapy regimen became SOX (oxaliplatin + S-1); bevacizumab injection was also added to the SOX regimen, and it was further treated regularly for 7 cycles with the regimen of SOX plus bevacizumab. Liver metastases showed a continuous narrowing trend throughout the treatment period; tumor markers also showed a downward trend. Finally, the patient achieved complete remission (CR) at cycle 7. After completion of chemotherapy, radiotherapy was administered to the resistant metastatic lymph nodes present in the patient’s abdominal cavity for a total of 10 times. However, the patient developed severe bone marrow suppression and obstructive jaundice during the course of radiotherapy and finally failed to complete the radiotherapy plan. Currently, the patient continued maintenance therapy with bevacizumab and S-1 and showed no recurrence or metastasis after review. In this case of advanced DA, we referred to both CRC and gastric cancer in the treatment regimen of the patient. At the same time, targeted drugs and radiotherapy were also added to the basis of chemotherapy, which has no clear consensus recommendation or case for reference in the treatment of advanced DA. Thankfully, the patient’s disease was controlled and remained stable after treatment with this regimen. Therefore, for patients with advanced DA who lack standardized treatment regimens and guidelines, the combination of chemotherapy with targeted therapy and radiotherapy may be one of the effective treatment modalities.
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Alfagih A, Alrehaili M, Asmis T. Small Bowel Adenocarcinoma: 10-Year Experience in a Cancer Center-The Ottawa Hospital (TOH). Curr Oncol 2022; 29:7439-7449. [PMID: 36290862 PMCID: PMC9600419 DOI: 10.3390/curroncol29100585] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 09/27/2022] [Accepted: 10/04/2022] [Indexed: 11/05/2022] Open
Abstract
(1) Background: Small bowel adenocarcinoma (SBA) is one of the predominant primary small bowel cancers that has a dismal outcome. We aim to report 10 years of experience in SBA management at a regional cancer centre in Canada.; (2) Methods: We retrospectively analysed clinical and pathological data of patients diagnosed with an SBA between 2011 and 2021 at the Ottawa Hospital (TOH), Ottawa, Canada. We describe the clinicopathological features and outcomes, including survival. Potential prognostic factors were analysed using the Cox proportional hazard model for multivariate analysis.; (3) Results: We identified 115 patients with SBA. The duodenum was the most common SBA location representing 61% (70) of the total patients, followed by the jejunum (17%) and ileum (10%). Around 24% (27) of cases presented with bowel obstructions. The majority of patients (56%, 64) had stage IV disease on presentation. Seven patients had MSI-high tumours, while 24% (27) were MS-stable. In terms of management, 48 patients underwent curative surgical resection, 17 of whom received adjuvant chemotherapy. On the other hand, 57 patients (49.5%) with the advanced disease received palliative systemic therapy, and 18 patients (16%) had supportive care only. Over a median follow-up of 21.5 months (range 0-122), the median overall survival was 94, 61, and 34 months for stages II, III, and IV, respectively (p < 0.05). The median recurrence-free survival was 93 and 23 months for stages II and III, respectively. However, there was no statistically significant difference between TNM stages in RFS, p = 0.069. Multivariate Cox regression analysis showed only poor performance status at diagnosis as a predictor for shorter overall survival (p < 0.05). The univariate analysis didn't show any significant correlation between RFS and covariants.; (4) Conclusions: SBA remains one of the most aggressive tumours with a dismal prognosis even after surgical resection. The optimal chemotherapy regimen has not been established. Further studies are needed to explore the role of adjuvant chemotherapy for stages I-III SBA.
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Affiliation(s)
- Abdulhameed Alfagih
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, Ottawa, ON K1H 8L6, Canada
- Medical Oncology Department, Comprehensive Cancer Center, King Fahad Medical City, Riyadh 11525, Saudi Arabia
| | - Mohammad Alrehaili
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, Ottawa, ON K1H 8L6, Canada
| | - Timothy Asmis
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, Ottawa, ON K1H 8L6, Canada
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31
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Tesarikova J, Skalicky P, Kurfurstova D, Svebisova H, Urban O, Falt P, Zapletalova J, Klos D, Lovecek M. Surgical treatment of duodenal adenocarcinoma: ampullary vs. non-ampullary, short- and long-term outcomes. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2022; 166:290-296. [PMID: 34012147 DOI: 10.5507/bp.2021.028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 04/23/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND The aim of this study was to evaluate symptoms, diagnostic methods, short- and long-term outcomes of surgical treatment in patients with duodenal adenocarcinoma. PATIENTS AND METHODS A single center, retrospective, observational study of 52 consecutive patients with duodenal adenocarcinoma operated on with curative intent between 2006 - 2019. Duodenectomy as part of a hemipancreatoduodenectomy or total pancreatectomy procedure was performed for ADAC (ampullary duodenal/intestinal adenocarcinoma) or NADAC (non-ampullary duodenal adenocarcinoma). RESULTS Prevailing symptoms were obstructive jaundice in the ADAC group (P<0.0001) and bleeding in the NADAC group (P=0.005), with larger tumor size in patients with NADAC (P=0.001). Complication rate, morbidity and mortality were comparable. Primary total pancreatoduodenectomy predominated in the NADAC group, 16.6% vs. 2.9%, and salvage completion pancreatectomy in the ADAC group, 6% vs. 0%. Significant prognostic factors for OS were perineural invasion (P=0.006) and adjuvant chemotherapy (P=0.045) in the ADAC group, and for DFS the total number of resected lymph nodes (P=0.042) and lymph node ratio (P=0.031) in the NADAC group. Median OS is 21 months and 5-year survival 27.3% in the NADAC group and 41.5 months and 52% in the ADAC group. CONCLUSION Ampullary duodenal/intestinal adenocarcinomas are smaller than non-ampullary at diagnosis, with a higher rate of lymph node metastases, but with a better prognosis and long-term outcome in the presented cohort. Oral localisation of NADAC prevailed in the present cohort. Perineural invasion and postoperative oncological therapy are significant prognostic factors for OS in ADAC, but the total number of lymph nodes and lymph node ratio are significant prognostic factors for DFS in NADAC.
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Affiliation(s)
- Jana Tesarikova
- Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Pavel Skalicky
- Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Daniela Kurfurstova
- Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Hana Svebisova
- Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Ondrej Urban
- Department of Internal Medicine II - Gastroenterology and Geriatrics, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Premysl Falt
- Department of Internal Medicine II - Gastroenterology and Geriatrics, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Jana Zapletalova
- Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
| | - Dusan Klos
- Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Martin Lovecek
- Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
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El Bakouri A, El Wassi A, Eddaoudi Y, Bouali M, ElHattabi K, Bensardi F, Fadil A. Early Discovery Of Small Bowel Adenocarcinoma In a Patient Admitted For 4 Acute Intestinal Intussusception case report. Ann Med Surg (Lond) 2022; 82:104776. [PMID: 36268363 PMCID: PMC9577972 DOI: 10.1016/j.amsu.2022.104776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 09/18/2022] [Accepted: 09/19/2022] [Indexed: 11/29/2022] Open
Abstract
Introduction Malignant tumours of the small bowel are uncommon in clinical practice. Adenocarcinoma is the most common of these tumours, accounting for approximately 35–45% of all tumours. It may occur sporadically, in association with familial adenomatous polyposis coli or Peutz-Jeghers syndrome or hereditary non-polyposis colorectal cancer, or in association with chronic inflammatory bowel changes (such as Crohn's disease or celiac disease). Materials and methods We report a case of Early Discovery Of Small Bowel Adenocarcinoma In A Patient Admitted For 4 Acute Intestinal Intussusception in the department of Emergency visceral surgery P35 of the ibn rochd hospital in casablanca. Results Our patient was admitted to the emergency room for sub-occlusive syndrome with generalized abdominal pain of chronic appearance dating back to one month before his admission With Abdominal and pelvic ultrasound showed: intestinal parietal thickening and minimal ascites (peritoneal and/or intestinal tuberculosis? Crohn's disease) The patient underwent an abdominal-pelvic CT scan which showed: Presence of diffuse small bowel thickening, involving several small intestines and the colonic angle with intestinal invaginations (at least 3) suspecting an inflammatory or tumoral origin? To be compared with histological data and infiltration of the mesenteric fat in the sub-umbilical region with a peritoneal effusion in the Douglas. the patient was operated on in the emergency room, approached by laparotomy and found on exploration: Presence of 3 invaginations in the small intestine located at 20cm and 90cm from the Duodenojejunal Angle (DIA) as well as at 25cm from the Last part of the small intestine (DAI), with Presence of a colonic invagination at the level of the left colonic angle. the patient underwent 3 small bowel resections and one segmental colonic resection including segmental small bowel resections: the 1st one of 30 cm taking away an invagination of the small intestine at 20cm from the ADJ, the 2nd one taking away 60cm of invaginated located at 90cm from the ADJ the 3rd one taking away 20cm of invaginated located at 25cm from the DAI and a 4th resection taking away an invagination of the left colonic angle with 3 Anastomosis of the T-T small intestine and a transverse Colostomy in Bouilley Volkman. On examination by the anapathomopathologist: consistent with a small bowel tumour: well-differentiated intestinal adenocarcinoma on degenerated adenomatous polyps measuring 2.5cm and 1.7cm with an estimated 10% mucinous component with no vascular emboli and no peri-nervous sheathing. TNM stage p: pT2 with healthy resection margins in the left colon: Presence of a tubular adenoma with low grade dysplasia. Conclusion The most common symptoms of adenocarcinoma of the small bowel are obstruction, overt or covert bleeding, weight loss and jaundice. Because the small bowel has long been relatively inaccessible to routine endoscopy, the diagnosis of small bowel adenocarcinoma was often delayed for several months after the onset of symptoms. Therefore, in case of suspicion of this type of cancer, a thorough evaluation should be undertaken. Nowadays, endoscopy of the small bowel is widely available, allowing an earlier non-invasive diagnosis.
Acute Intestinal Intussusception as a cause of intestinal obstruction is often a diagnostic challenge mimicking a wide spectrum of diseases. Malignant tumours of the small bowel are uncommon in clinical practice. Adenocarcinoma is the most common of these tumours. Its diagnosis is still very difficult. The treatment of Acute Intestinal Intussusception is in most cases surgical. The diagnosis of Acute Intestinal Intussusception is histological.
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Hu W, Duan Z, Zhang Y, Liu J, Bao J, Gao R, Tang Y, Liu T, Xiong H, Li W, Fu X, Liao S, Fang L, Liang B. Remission from the 5-Fu-Based Chemotherapy to Gemcitabine-Based Chemotherapy-Based on the Pathological Classification of Periampullary Carcinoma: A Case Report and Literature Review. Onco Targets Ther 2022; 15:891-896. [PMID: 36046466 PMCID: PMC9423042 DOI: 10.2147/ott.s372053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 08/03/2022] [Indexed: 11/23/2022] Open
Abstract
Background Periampullary carcinoma, which includes ampullary carcinoma, pancreatic head cancer, distal common bile duct cancer, and duodenal papillary cancer, is a relatively rare malignancy with uncertain therapeutic options. Although several studies have investigated the efficacy of multiple adjuvant chemotherapy regimens for periampullary carcinoma treatment, the optimal regimen remains to be determined. The inherent heterogeneity of the mucosal origin divides periampullary carcinoma into intestinal and pancreaticobiliary types. Therefore, the selection of chemotherapy regimens based on pathological type may have potential therapeutic significance. Case Presentation A 72-year-old woman with moderately differentiated periampullary adenocarcinoma experienced disease progression after receiving FOLFOX regimen. Subsequently, the sample was subtyped first by H&E evaluation and then by the evaluation of an IHC panel composed of CK20, CDX2, MUC1, MUC2, and MUC5AC. The pathologists concluded that the patient’s sample was of the pancreaticobiliary (PB) subtype. The subsequent change to gemcitabine plus S-1 adjuvant therapy achieved remission of liver metastases based on the pathological classification of the cancer. Conclusion Based on the pathological classification, adjuvant chemotherapy with gemcitabine may be beneficial for patients with PB subtype periampullary carcinoma. 5-Fu-based adjuvant chemotherapy may be beneficial for patients with intestinal subtype periampullary carcinoma.
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Affiliation(s)
- Wei Hu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Zhiqing Duan
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Yinuo Zhang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Jing Liu
- Department of Pathology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Jing Bao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Ruqing Gao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Yajie Tang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Tiande Liu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Hu Xiong
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Wen Li
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Xiaowei Fu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Shousheng Liao
- Department of Pathology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Lu Fang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
| | - Bo Liang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
- Correspondence: Bo Liang; Lu Fang, Email ;
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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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Duan Z, Zhang Y, Tang Y, Gao R, Bao J, Liang B. Adjuvant therapy for periampullary carcinoma and the significance of histopathological typing: A systematic review. Transl Oncol 2022; 20:101414. [PMID: 35397420 PMCID: PMC9006738 DOI: 10.1016/j.tranon.2022.101414] [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] [Received: 03/09/2022] [Revised: 03/24/2022] [Accepted: 03/30/2022] [Indexed: 12/19/2022] Open
Abstract
The efficacy of adjuvant therapy for periampullary carcinoma is controversial. There is a trend of classification periampullary carcinoma into PB-type and IN-type, and the prognosis of different subtypes may be significantly different. The PB-type patients who accepted gemcitabine based chemotherapy and IN-type patients who accepted 5-FU based chemotherapy, maybe improved the prognosis. Chemoradiotherapy appears to be more effective in patients with advanced stages. There are few related studies on targeted therapy and immunotherapy, and further research is needed. Objective This review investigates the role of adjuvant therapy (AT) and the importance of histopathological typing in periampullary carcinoma (PAC) treatment. Background PAC is a relatively rare gastrointestinal malignancy. The regimen and effect of AT in PAC are still controversial. However, there is a treatment based on histopathological types (pancreaticobiliary-type, PB-type or intestinal-type, IN-type), but there are no clear guidelines indicating that typing can be used to guide the selection of AT drugs. Methods A literature search of PubMed and Web of Science databases was conducted for studies published from January 2001 to August 2021 on the use of AT in PAC. Results A total of 75 studies were included in this review. According to existing studies, AT for PAC is mostly based on 5-FU or gemcitabine, but the effect is unknown. However, when PAC is classified into different histopathological types, AT with gemcitabine is beneficial for patients with the PB-type of PAC, while 5-FU-based AT is beneficial for patients with the IN-type of PAC. In addition, the benefits of AT are more pronounced in patients with a high-risk disease, such as patients with stage II/III, T3/T4 tumors, or positive lymph node involvement. There are few studies on targeted therapy and immunotherapy for PAC. Conclusions This review suggests that AT has potential survival benefits, especially when based on the histopathologic type that helps the choice of drugs during AT in PAC patients.
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Affiliation(s)
- Zhiqing Duan
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yinuo Zhang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yajie Tang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Ruqing Gao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jing Bao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Bo Liang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
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Di Nardo P, Garattini SK, Torrisi E, Fanotto V, Miolo G, Buonadonna A, Puglisi F. Systemic Treatments for Advanced Small Bowel Adenocarcinoma: A Systematic Review. Cancers (Basel) 2022; 14:1502. [PMID: 35326652 PMCID: PMC8945891 DOI: 10.3390/cancers14061502] [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] [Received: 02/14/2022] [Revised: 03/10/2022] [Accepted: 03/10/2022] [Indexed: 01/13/2023] Open
Abstract
Small bowel adenocarcinoma (SBA) is a rare disease for which scarce evidence is available. We summarized data available on systemic treatment of advanced SBA. METHODS Scientific literature was evaluated to find phase II or phase III clinical trials on systemic treatment for advanced SBA. MeSH terms were selected and combined for the initial search, then inclusion and exclusion criteria were set in a search protocol. Four medical oncologists looked for evidence on Medline, EMBASE and Cochrane databases. Moreover, abstracts from 2016 to June 2021 from the American Society for Clinical Oncology, European Society for Medical Oncology, Gastrointestinal Cancer Symposium and World Congress on Gastrointestinal Cancer were browsed. The selected studies, matching the inclusion and exclusion criteria, were finally tabulated and analyzed. RESULTS The trials finally selected were 18 phase II/III clinical trials. Four small phase II trials support the activity of oxaliplatin-based doublets in first-line treatment (CAPOX and mFOLFOX). CONCLUSION No good level evidence is available on the use of bevacizumab, anti-epidermal growth factor receptor, targeted agents or immunotherapy. First-line treatments are largely derived from colorectal cancer protocols, mainly oxaliplatin-based doublets.
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Affiliation(s)
- Paola Di Nardo
- Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (G.M.); (A.B.); (F.P.)
| | - Silvio Ken Garattini
- Department of Oncology, ASUFC University Hospital of Udine, 33100 Udine, Italy; (S.K.G.); (V.F.)
| | - Elena Torrisi
- Department of Medical Oncology, P.O. San Vincenzo, 98039 Taormina, Italy;
| | - Valentina Fanotto
- Department of Oncology, ASUFC University Hospital of Udine, 33100 Udine, Italy; (S.K.G.); (V.F.)
| | - Gianmaria Miolo
- Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (G.M.); (A.B.); (F.P.)
| | - Angela Buonadonna
- Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (G.M.); (A.B.); (F.P.)
| | - Fabio Puglisi
- Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (G.M.); (A.B.); (F.P.)
- Department of Medicine (DAME), University of Udine, 33100 Udine, Italy
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Jensen KK, Storkholm JH, Chen I, Burgdorf SK, Hansen CP. Long-term results after resection of primary duodenal adenocarcinoma: A retrospective cohort study. Int J Surg 2022; 100:106599. [DOI: 10.1016/j.ijsu.2022.106599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 02/16/2022] [Accepted: 03/02/2022] [Indexed: 10/18/2022]
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Therapeutic Strategies for Patients with Advanced Small Bowel Adenocarcinoma: Current Knowledge and Perspectives. Cancers (Basel) 2022; 14:cancers14051137. [PMID: 35267446 PMCID: PMC8909230 DOI: 10.3390/cancers14051137] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/21/2022] [Accepted: 02/22/2022] [Indexed: 12/30/2022] Open
Abstract
Small bowel adenocarcinoma (SBA) is diagnosed at an advanced (unresectable or metastatic) tumor stage in approximately one-third of cases. This is partly due to the non-specific symptomatology and limitations in endoscopic and radiologic detection methods. In this context, the prognosis remains poor and systemic chemotherapy appears to benefit patients when compared to best supportive care alone, despite the absence of randomized controlled trials. The results of a recent large prospective cohort (ARCAD-NADEGE) reported that the absence of chemotherapy was a predictive factor for a lower overall survival (OS) even though poor differentiation and SBA associated with Crohn's disease correlate with poor prognosis. In retrospective series, the median OS ranges from approximately 9 to 18 months with current treatment approaches. A combination of a fluoropyrimidine and oxaliplatin (FOLFOX or CAPOX) appears to be the most utilized and effective first-line chemotherapy regimen. Other front-line alternatives are the combination of 5-FU and cisplatin or fluoropyrimidine and irinotecan (FOLFIRI). In second-line, FOLFIRI is an effective option after progression on platinum-based therapy. Taxane-based therapy appears to be an alternative option, but further evaluation in larger series is needed. To a limited extent, the role of surgical resection for metastatic disease appears to be a valid option, though this approach has not been evaluated in prospective clinical studies. Due to the rareness of the disease, inclusion in clinical trials should be prioritized, and there is hope that targeted therapies and immunotherapy may enter the therapeutic arsenal for these patients.
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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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Khosla D, Dey T, Madan R, Gupta R, Goyal S, Kumar N, Kapoor R. Small bowel adenocarcinoma: An overview. World J Gastrointest Oncol 2022; 14:413-422. [PMID: 35317322 PMCID: PMC8918997 DOI: 10.4251/wjgo.v14.i2.413] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 08/09/2021] [Accepted: 01/22/2022] [Indexed: 02/06/2023] Open
Abstract
Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract. However, these tumors are among those with worst prognosis. Vague clinical signs and symptoms and radiological diagnostic challenges often delay treatment, which negatively impacts the prognosis of the patients. However, recent advances in imaging technology, like multidetector computed tomography, magnetic resonance imaging, and capsule endoscopy, have made earlier and accurate diagnosis possible. Surgery is the treatment of choice followed by adjuvant therapy. However, there are no strict treatment guidelines available for the management of SBA. Most of the available evidence from colorectal and gastric carcinoma has been extrapolated to adequately manage SBA. Prognosis for SBA is better than gastric carcinoma but worse than colorectal carcinoma. Currently, there is not enough information on the molecular characteristics and tumor pathogenesis. Because the incidence of SBA is very low, there is a need for further studies to evaluate the possible application of newer investigative agents and strategies to obtain a better outcome within the framework of international collaborations.
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Affiliation(s)
- Divya Khosla
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Treshita Dey
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Renu Madan
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rahul Gupta
- Department of Gastroenterology, Shalby Multispeciality Hospital, Mohali 160062, Punjab, India
| | - Shikha Goyal
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Narendra Kumar
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rakesh Kapoor
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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Sun H, Liu Y, Lv L, Li J, Liao X, Gong W. Prognostic Factors and Clinical Characteristics of Duodenal Adenocarcinoma With Survival: A Retrospective Study. Front Oncol 2022; 11:795891. [PMID: 34976838 PMCID: PMC8715708 DOI: 10.3389/fonc.2021.795891] [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: 10/15/2021] [Accepted: 11/16/2021] [Indexed: 12/03/2022] Open
Abstract
Background To evaluate the clinical risk factors that influence the overall survival in patients with duodenal adenocarcinoma (DA) after tumor resection. Methods This study retrospectively analyzed 188 patients who underwent tumor resection for DA between January 2005 and June 2020 at Xiangyang Central Hospital. Results The median survival of the patients who underwent resectional operation was 54 months, longer than of those who underwent palliative surgery (20.8 months) (2,916.17; 95% CI, 916.3−9,280.5; p < 0.001). Survival of non-ampullary duodenal carcinoma patients (50.3 months; 95% CI, 39.7−61.8) was similar to that of ampullary duodenal carcinoma patients (59.3 months; 95% CI, 38.6−66.7) but was significantly better than that of papillary adenocarcinoma patients (38.9 months; 95% CI, 29.8−54.8; p = 0.386). Those with intestinal-type ductal adenocarcinomas had a longer median overall survival than those with the gastric type (61.8 vs. 46.7 months; p < 0.01) or pancreatic type (32.2 months; p < 0.001). Clinical DA samples had significantly diverse expressions of ATG12, IRS2, and IGF2. Higher expressions of the ATG12 and IRS2 proteins were significantly correlated with worse survival. Multivariate Cox regression analysis revealed that lymph node metastasis (hazard ratio (HR), 6.44; 95% CI, 3.68−11.27; p < 0.0001), margin status (HR, 4.94; 95% CI, 2.85−8.54; p < 0.0001), and high expression of ATG12 (HR, 1.89; 95% CI, 1.17−3.06; p = 0.0099) were independent prognostic factors negatively associated with survival in patients undergoing curative resection. There was no survival difference between the groups with ampullary, non-ampullary, and papillary adenocarcinomas treated with adjuvant chemotherapy (p = 0.973). Conclusion Gastric/pancreatic type, high expression of ATG12, lymph node metastases, and margin status were negative prognosticators of survival in patients with DAs than in those with tumor anatomical location. Curative resection is the best treatment option for appropriate patients.
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Affiliation(s)
- Huapeng Sun
- Department of General Surgery, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
| | - Yi Liu
- Department of Medicinal Chemistry, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Long Lv
- Department of General Surgery, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
| | - Jingwen Li
- Department of Oncology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
| | - Xiaofeng Liao
- Department of General Surgery, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
| | - Wei Gong
- Department of Oncology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
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Yu IS, Al-Hashami Z, Chapani P, Speers C, Davies JM, Lim HJ, Renouf DJ, Gill S, Stuart HC, Loree JM. Impact of Tumor Location on Patient Outcomes in Small Bowel Cancers. Clin Colorectal Cancer 2021; 21:107-113. [PMID: 34972663 DOI: 10.1016/j.clcc.2021.11.006] [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: 08/26/2021] [Revised: 10/21/2021] [Accepted: 11/22/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Small bowel cancers are rare gastrointestinal malignancies and tumor location impact on outcomes is unclear. MATERIAL AND METHODS A retrospective review was performed on stage I to IV small bowel cancer cases from 2000 to 2017 in British Columbia, Canada. Baseline patient characteristics, disease-free survival (DFS) and overall survival (OS) were evaluated by tumor location and systemic therapy use patterns were summarized. RESULTS Of 340 patients included, primary tumor distribution was: duodenum (51.2%), ileum (19.1%), jejunum (18.5%), and unspecified (11.2%). Median DFS for stage I to III disease was 37.7, 49.1, and 26.7 months for duodenal, jejunal, and ileal tumors (P = .018). Median OS was 9.6, 35.2, and 20.1 months for duodenal, jejunal, and ileal tumors (P < .0001). Compared to duodenal primaries, both jejunal and ileal tumors were associated with significantly improved OS (HR 0.43, P < .001 for jejunal; HR 0.71, P = .035 for ileal). Adjuvant therapy was given to 21.6% of stage II and 50.6% of stage III cancers. Among patients with metastatic disease, median OS was 4.2, 11.4, and 6.9 months for duodenal, jejunal, and ileal tumors (P = .0019). Jejunal tumors had the best prognosis (HR 0.48, P = .001 vs. duodenum). CONCLUSION Survival differences exist when small bowel cancers were assessed by tumor location, and jejunal tumors portended better prognosis overall.
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Affiliation(s)
- Irene S Yu
- BC Cancer, Vancouver, British Columbia, Canada
| | | | - Parv Chapani
- University of British Columbia, Vancouver, British Columbia, Canada
| | - Caroline Speers
- Gastrointestinal Cancer Outcomes Unit, BC Cancer, Vancouver, British Columbia, Canada
| | - Janine M Davies
- BC Cancer, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada
| | - Howard J Lim
- BC Cancer, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada
| | - Daniel J Renouf
- BC Cancer, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada
| | - Sharlene Gill
- BC Cancer, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada
| | - Heather C Stuart
- BC Cancer, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada
| | - Jonathan M Loree
- BC Cancer, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada.
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Abstract
OPINION STATEMENT ACs are rare tumors, and thus, there is a lack of prospective trials supporting treatment decisions. Moreover, although anatomically uniform, ACs comprise of biologically distinct entities, depending on what cell type they arise from. This makes the interpretation of limited data even more challenging. Overall, the clinical outcomes of patients with AC are better than those with pancreatic cancer. However, recurrence rates remain high after curative resection. Despite the absence of definitive evidence, we believe that these high recurrence rates are a rational justification for consideration of adjuvant therapy in resected disease, and therapy selection should take tumor biology, stage, resection margins, as well as patient comorbidities and performance status into account. Largely extrapolating from pancreas cancer, we recommend consideration of adjuvant chemotherapy with 6 months of dose-modified FOLFIRINOX in fit patients with pancreatobiliary subtype tumors. Alternative regimens include gemcitabine in combination with capecitabine. If chemoradiotherapy is being added, 6 weeks of radiotherapy in conjunction with 5-FU or capecitabine can be considered. For intestinal subtypes, we recommend 3-6 months of adjuvant FOLFOX. Future studies are needed to evaluate the role of contemporary, multi-agent chemotherapy and chemoradiotherapy in patients with resected and advanced ampullary adenocarcinoma. However, the logistics of performing large randomized trials in patients with a rare cancer is challenging, and the data collection, even in a carefully designed study, would likely take many years. As such, relying on data from basket trials and retrospective analysis will likely serve as guidance for treatment decisions in the near future. Treatment of metastatic disease should employ regimens that are typically used to treat pancreas cancer for tumors of pancreatobiliary subtype and 5-FU-based regimens for intestinal subtypes. Studies specific for patients with advanced AC are much needed. Molecular testing using next-generation sequencing and testing for microsatellite instability (MSI) should be performed on all tumors. We now have disease agnostic options based on these results. Pembrolizumab is approved for MSI-H tumors and tumors with high tumor mutational burden regardless of the primary site. Larotrectinib is approved for tumors with NTRK fusions. At a time when numerous therapeutic agents are in development, for example, those targeting specific K-RAS alterations or NRG fusions, identifying molecular aberrations can significantly impact patient outcomes as well as provide further insights into the biology of disease. In addition, based on recent data suggesting a significant prevalence of germline alterations in patients with ampullary tumors, referral to genetics counselors and germline testing is warranted in a significant proportion of patients with AC.
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Small bowel adenocarcinoma: Case reports and review of the literature. Arab J Gastroenterol 2021; 22:240-245. [PMID: 34531134 DOI: 10.1016/j.ajg.2021.07.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 04/24/2021] [Accepted: 07/27/2021] [Indexed: 11/20/2022]
Abstract
Small bowel adenocarcinomas (SBAs) are rare tumors of the gastrointestinal tract. Patients often present with advanced disease due to nonspecific symptoms and delayed diagnoses. In combination with non-uniform treatment paradigms, patients who present with SBA often have poor prognoses. In this case series, we present four cases of SBA and review the most recent literature with regard to diagnosis and management. One patient presented with iron-deficient anemia (IDA), and three patients presented with clinical obstruction. The patient with IDA was subjected to protracted investigations, whereas the three patients with obstruction were diagnosed quickly after presentation. All four patients underwent surgical resection, and one patient was eligible for post-operative adjuvant chemotherapy. SBA should be highly suspected in patients who present with occult gastrointestinal bleeds, and appropriate investigations must be initiated. Following diagnosis, surgical resection is the mainstay of treatment for this disease. Our review supports the use of both neoadjuvant and adjuvant chemotherapy in localized disease.
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Reißig TM, Siveke JT. [Multimodal treatment of periampullary carcinoma]. Chirurg 2021; 92:803-808. [PMID: 34228145 DOI: 10.1007/s00104-021-01454-1] [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: 06/01/2021] [Indexed: 10/20/2022]
Abstract
Ampullary carcinoma is a rare malignant neoplasm and arises in the region of Vater's ampulla. The differentiation from pancreatic and distal cholangiocarcinoma can be difficult. The prognosis is more favorable than for pancreatic ductal adenocarcinoma but recurrences are frequent. An exact diagnostic clarification and differentiation from pancreatic carcinoma is therefore essential. Although the resection of periampullary carcinoma is established, prospectively controlled studies on the role of multimodal treatment are rare. Adjuvant chemotherapy is oriented to the protocols for pancreatic carcinoma and could be of benefit in lymph node metastases, advanced T stage and low differentiation of tumors. Intestinal and pancreatobiliary subtypes can be differentiated histologically, which is relevant for systemic treatment strategies. Patients with pancreatobiliary differentiated tumors in particular could benefit from gemcitabine-based treatment but insufficient evidence exists for chemoradiotherapy. The role of neoadjuvant and perioperative treatment strategies is currently unclear. Molecular characterization can help to identify familial risk constellations and targeted treatment strategies for this rare tumor entity.
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Affiliation(s)
- Timm M Reißig
- Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum, Universitätsklinikum Essen, Essen, Deutschland
- Brückeninstitut für Experimentelle Tumortherapie (BIT), Westdeutsches Tumorzentrum, Universitätsklinikum Essen, Essen, Deutschland
- Abteilung für Translationale Onkologie Solider Tumore, Deutsches Konsortium für Translationale Krebsforschung (DKTK) und Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland
| | - Jens T Siveke
- Brückeninstitut für Experimentelle Tumortherapie (BIT), Westdeutsches Tumorzentrum, Universitätsklinikum Essen, Essen, Deutschland.
- Abteilung für Translationale Onkologie Solider Tumore, Deutsches Konsortium für Translationale Krebsforschung (DKTK) und Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland.
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Mazlom H, Teuwen LA, Peeters M. Management of small bowel adenocarcinoma: making the most of the available evidence to inform routine practice. Curr Opin Oncol 2021; 33:368-371. [PMID: 33882527 DOI: 10.1097/cco.0000000000000747] [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: 11/26/2022]
Abstract
PURPOSE OF REVIEW Small bowel adenocarcinoma (SBA) is a rare disease, for which few studies have been conducted so far. Therefore, most treatment recommendations have been extrapolated from trials in colorectal cancer. In this review, we revise available data that could improve the management of SBA, with a particular focus on systemic therapy. RECENT FINDINGS For advanced/irresectable disease, first-line doublet chemotherapy remains standard of care. It is uncertain whether extending treatment to triplet chemotherapy brings added benefit. Pembrolizumab is an accepted treatment modality for mismatch repair-deficient tumors, yet might also be active in microsatellite stable tumors. More trials with immunotherapy are underway. Although there is no place for anti-EGFR monotherapy, the addition of cetuximab to chemotherapy should be investigated further. Two trials suggest an added value of bevacizumab to chemotherapy, yet larger trials are needed to confirm these data. For localized disease, the role of (neo)adjuvant chemotherapy is under investigation. SUMMARY For decades, patients with SBA have probably been treated suboptimal by basing treatment recommendations on data from colorectal cancer. An effort for SBA-specific trials and/or inclusion of SBA patients in basket trials is of utmost importance in order to improve outcome for these patients.
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Affiliation(s)
| | | | - Marc Peeters
- University Hospital Antwerp, Edegem
- Antwerp University, Antwerp, Belgium
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Bhamidipati D, Colina A, Hwang H, Wang H, Katz M, Fournier K, Serpas V, Thomas J, Sun R, Wolff RA, Raghav K, Overman MJ. Metastatic small bowel adenocarcinoma: role of metastasectomy and systemic chemotherapy. ESMO Open 2021; 6:100132. [PMID: 33940348 PMCID: PMC8111574 DOI: 10.1016/j.esmoop.2021.100132] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/03/2021] [Accepted: 04/08/2021] [Indexed: 12/04/2022] Open
Abstract
Background Metastatic small bowel adenocarcinoma (SBA) has a poor prognosis. Due to its rarity, high-quality data are lacking to guide treatment. This retrospective analysis was conducted to help characterize the treatment options for patients with metastatic SBA while providing clinically meaningful prognostic information. Patients and methods In total, 437 patients who initially presented with or developed metastatic SBA between September 1977 and September 2019 were identified from the MD Anderson Tumor Registry. Clinical data were collected from review of the medical record. Overall response rates (ORR), time to progression (TTP), and overall survival (OS) were assessed across various treatments and treatment lines. Results The median OS from diagnosis of metastatic disease was 15.9 months [95% confidence interval (CI): 14.3-17.9]. Seventy-five patients (17.1%) underwent metastasectomy, which was associated with a median OS of 34.5 versus 17.1 months among patients who received chemotherapy alone (P < 0.001). Fluoropyrimidine plus platinum (n = 164) was the most common first-line chemotherapy, associated with an ORR of 59% and TTP of 8.1 months. Irinotecan with 5-FU (n = 101) was the most common second-line therapy associated with an ORR of 31% and TTP of 4.0 months. Twenty-two patients received immunotherapy; 5 of 6 patients with deficient mismatch repair (dMMR) responded, while 0 of 16 with proficient mismatch repair (pMMR) responded. Taxane-based chemotherapy was given to 34 patients with an ORR of 21% and a median TTP of 2.4 months. Among 11 patients who received anti-epidermal-growth-factor-receptor (EGFR) monotherapy, the best response was stable disease (SD) in 1 patient. Conclusions In well-selected patients with SBA, metastasectomy appears to be associated with improved OS. This improvement was seen across metastasectomy sites, including liver, lung and peritoneal. Anti-programmed cell death protein 1 (PD-1) based immunotherapy was active for dMMR SBA but not pMMR SBA. While taxane-based chemotherapy demonstrates therapeutic activity, the activity of anti-EGFR therapy was limited.
Metastasectomy for well-selected metastatic SBA patients was associated with improved OS. Anti-PD1-based immunotherapy was active for dMMR SBA but not pMMR SBA. Taxane-based chemotherapy demonstrated clinical activity in refractory SBA. Anti-EGFR therapy demonstrated minimal activity in SBA.
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Affiliation(s)
- D Bhamidipati
- Department of Internal Medicine, Baylor College of Medicine, Houston, USA
| | - A Colina
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - H Hwang
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - H Wang
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - M Katz
- Department of Surgery, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - K Fournier
- Department of Surgery, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - V Serpas
- MD Anderson Oncology Fellowship, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - J Thomas
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - R Sun
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - R A Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - K Raghav
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - M J Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
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Vacchelli E, Galluzzi L, Fridman WH, Galon J, Sautès-Fridman C, Tartour E, Kroemer G. Trial watch: Chemotherapy with immunogenic cell death inducers. Oncoimmunology 2021; 1:179-188. [PMID: 22720239 PMCID: PMC3376992 DOI: 10.4161/onci.1.2.19026] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The long-established notion that apoptosis would be immunologically silent, and hence it would go unnoticed by the immune system, if not tolerogenic, and hence it would actively suppress immune responses, has recently been revisited. In some instances, indeed, cancer cells undergo apoptosis while emitting a spatiotemporally-defined combination of signals that renders them capable of eliciting a long-term protective antitumor immune response. Importantly, only a few anticancer agents can stimulate such an immunogenic cell death. These include cyclophosphamide, doxorubicin and oxaliplatin, which are currently approved by FDA for the treatment of multiple hematologic and solid malignancies, as well as mitoxantrone, which is being used in cancer therapy and against multiple sclerosis. In this Trial Watch, we will review and discuss the progress of recent (initiated after January 2008) clinical trials evaluating the off-label use of cyclophosphamide, doxorubicin, oxaliplatin and mitoxantrone.
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Affiliation(s)
- Erika Vacchelli
- U848; Villejuif, France; INSERM; Université Paris-Sud/Paris XI; Paris, France
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Zhang G, Lin L, Dong D, Qiu H, Liu T, Lian L, Shen G. Nivolumab plus regorafenib in patients with small bowel adenocarcinoma: A case report. Medicine (Baltimore) 2021; 100:e24295. [PMID: 33530218 PMCID: PMC7850762 DOI: 10.1097/md.0000000000024295] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 12/23/2020] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Small bowel adenocarcinomas (SBAs) are rare cancers that have a distinct clinical characteristic and genetic profile. The only potentially curative treatment for localized SBAs is surgery, and treatment options are limited for patients in the advanced stage of disease. PATIENT CONCERNS A 39-year-old woman presented in October 2015 with a complaint of persistent vomiting for 8 months. DIAGNOSIS The patient had obstruction caused by a 3 × 2 cm mass at the ascending part of the duodenum and suspected metastasis in the right adnexal region. Postoperative pathology showed a moderately differentiated adenocarcinoma with serosal invasion. The diagnosis was stage IV duodenum adenocarcinoma with right adnexal metastasis. INTERVENTIONS After the failure of multi-line treatment with chemotherapy and targeted therapy, she was treated with the immune checkpoint inhibitor nivolumab plus regorafenib. OUTCOMES Disease control lasted for 15 months with markedly improved symptoms. CONCLUSION To the best of our knowledge, this is the first case of small bowel adenocarcinoma that has been treated with nivolumab combined with regorafenib. This case highlights the potential efficacy of combining nivolumab and regorafenib in the treatment of SBAs.
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Affiliation(s)
- Gairong Zhang
- Department of Oncology, Beijing Huian Hospital of Integrated TCM and Western Medicine
| | - Li Lin
- Department of Oncology, Peking University International Hospital, the 8th Clinical Medical College
| | - Dapeng Dong
- Department of Oncology, Beijing Huian Hospital of Integrated TCM and Western Medicine
| | - Hui Qiu
- Department of Oncology, Beijing Huian Hospital of Integrated TCM and Western Medicine
| | - Tao Liu
- Department of Oncology, Beijing Huian Hospital of Integrated TCM and Western Medicine
| | - Li Lian
- Department of Oncology, Beijing Huian Hospital of Integrated TCM and Western Medicine
| | - Ge Shen
- Department of Oncology, Beijing Huian Hospital of Integrated TCM and Western Medicine
- Department of Oncology, Beijing Fengtai You’anmen Hospital, Beijing, China
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Dai ZH, Wang QW, Zhang QW, Yan XL, Aparicio T, Zhou YY, Wang H, Zhang CH, Zaanan A, Afchain P, Zhang Y, Chen HM, Gao YJ, Ge ZZ. Personalized four-category staging for predicting prognosis in patients with small bowel Adenocarcinoma: an international development and validation study. EBioMedicine 2020; 60:102979. [PMID: 32980692 PMCID: PMC7519244 DOI: 10.1016/j.ebiom.2020.102979] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 08/13/2020] [Accepted: 08/13/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Log odds of positive lymph nodes (LODDS) classification showed superiority over 8th edition N staging in predicting survival of small bowel adenocarcinoma (SBA) patients. The aim of this study was to develop and validate the Tumor, LODDS, and Metastasis (TLM) staging of SBA. METHODS Totally 1789 SBA patients from the Surveillance, Epidemiology, and End Results (SEER) database between 1988-2010, 437 patients from SEER database between 2011-2013 and 166 patients from multicenters were categorized into development, validation and test cohort, respectively. The TLM staging was developed in the development cohort using Ensemble Algorithm for Clustering Cancer Data (EACCD) method. C-index was used to assess the performance of the TLM staging in predicting cancer-specific survival (CSS) and was compared with the traditional 8th edition TNM staging. FINDINGS Four-category TLM staging designed for the development cohort showed higher discriminatory power than TNM staging in predicting CSS in the development cohort (0.682 vs. 0.650, P < 0.001), validation cohort (0.682 vs. 0.654, P = 0.022), and test cohort (0.659 vs. 0.611, P = 0.023), respectively. TLM staging continued to show its higher predictive efficacy than the 8th TNM in TNM stage II/III patients or in patients with lymph node yield less than 8. INTERPRETATION TLM staging showed a better prognostic performance than the 8th TNM staging especially TNM stage II/III or patients with lymph node yield less than 8 and therefore, could serve to complement the TNM staging in patients with SBA. FUNDING A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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Affiliation(s)
- Zi-Hao Dai
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease;145 Middle Shandong Road, Shanghai 200001, China
| | - Qi-Wen Wang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease;145 Middle Shandong Road, Shanghai 200001, China
| | - Qing-Wei Zhang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease;145 Middle Shandong Road, Shanghai 200001, China
| | - Xia-Lin Yan
- Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Thomas Aparicio
- Gastroenterology department, Saint Louis Hospital, APHP, University Paris Diderot, Paris, France
| | - Yang-Yang Zhou
- Department of Rheumatology and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Huan Wang
- Department of Biostatistics, The George Washington University, Washington, DC, United States
| | - Chi-Hao Zhang
- Department of General Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Baoshan, 201999, Shanghai, China
| | - Aziz Zaanan
- Gastroenterology and Digestive Oncology department, Georges Pompidou Hospital, APHP, Paris, France
| | - Pauline Afchain
- Oncology department, Saint Antoine Hospital, APHP, Paris, France
| | - Yan Zhang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease;145 Middle Shandong Road, Shanghai 200001, China
| | - Hui-Min Chen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease;145 Middle Shandong Road, Shanghai 200001, China
| | - Yun-Jie Gao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease;145 Middle Shandong Road, Shanghai 200001, China.
| | - Zhi-Zheng Ge
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease;145 Middle Shandong Road, Shanghai 200001, China.
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