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Liu FC, Wang CH, Chen PJ, Shih YL, Lin HH, Lin JC, Chang WK, Hsieh TY, Lin GM, Huang TY. Characteristics and prognosis of small bowel tumors: A retrospective study. World J Clin Cases 2024; 12:6696-6704. [PMID: 39650821 PMCID: PMC11514353 DOI: 10.12998/wjcc.v12.i34.6696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 09/02/2024] [Accepted: 09/25/2024] [Indexed: 10/12/2024] Open
Abstract
BACKGROUND Small bowel tumors (SBTs) are a heterogeneous group of difficult-to-diagnose tumors that account for 2%-5% of all gastrointestinal tumors. Single-balloon enteroscopy greatly enhances the diagnosis and treatment of SBTs. However, few epidemiological studies have been conducted in Taiwan to determine the clinical profile of SBTs. AIM To investigate the clinical characteristics, managements and prognosis of SBTs in a medical center in Taiwan. METHODS The study enrolled 51 patients aged 58.9 ± 8.8 years (range, 22-93) diagnosed with SBTs from November 2009 to July 2021. We retrospectively recorded clinical characteristics, indications, endoscopic findings, pathological results, management, and outcomes for further analysis. RESULTS A male preponderance was observed (56.8%). The most common indications were suspected small intestinal tumors (52.9%) and obscure gastrointestinal bleeding (39.2%). The most common tumor location was the ileum (41.2%). The performance of imaging studies (P = 0.004) and the types of findings (P = 0.005) differed significantly between malignant and benign SBTs. The most frequent imaging finding was a small intestinal mass (43.1%). The top three malignant tumor types were gastrointestinal stromal tumors (GISTs), adenocarcinomas, and lymphomas. Moreover, the proportions of benign and malignant tumors were 27.5% and 72.5%, respectively. The survival rates of patients with malignant tumors in the GIST and non-GIST groups differed significantly (P = 0.015). Kaplan-Meier survival analysis showed a significant difference in survival between patients in the malignant and benign groups (P = 0.04). All patients with lymphoma underwent chemotherapy (n = 7/8, 87.5%), whereas most patients with GISTs underwent surgery (n = 13/14, 92.8%). CONCLUSION Patients with GISTs have a significantly higher survival rate than those with other malignant SBTs. Therefore, a large-scale nationwide study is warranted to evaluate the population-based epidemiology of SBTs.
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Affiliation(s)
- Fang-Chen Liu
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Ching-Hsiang Wang
- Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan 325208, Taiwan
| | - Peng-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Yu-Lueng Shih
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Hsuan-Hwai Lin
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Jung-Chun Lin
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Wei-Kuo Chang
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
| | - Gen-Min Lin
- Department of Medicine, Tri-Service General Hospital and National Defense Medical Center, Taipei 114, Taiwan
- Department of Medicine, Hualien Armed Forces General Hospital, Hualien 970, Taiwan
| | - Tien-Yu Huang
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
- Taiwan Association for the Study of Small Intestinal Diseases, Taoyuan 33305, Taiwan
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Lu Y, Pan CC, Hu X, Sun J. Bibliometrics analysis on the research status and trends of small bowel adenocarcinoma: 1923-2023. Front Oncol 2024; 14:1407315. [PMID: 39234397 PMCID: PMC11371555 DOI: 10.3389/fonc.2024.1407315] [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: 03/28/2024] [Accepted: 08/05/2024] [Indexed: 09/06/2024] Open
Abstract
Objectives The aim of this research is to discuss the research status, hotspots, frontiers, and development trends in the field of small bowel adenocarcinoma based on bibliometrics and visual analysis by CiteSpace software. Methods The relevant research articles on SBA from 1923 to 2023 were retrieved from the Web of Science Core Collection database. CiteSpace software was used to form a visual knowledge map and conduct analysis for the countries/regions, journals, authors, keywords, clusters, research hotspots and frontiers of the included articles. Results There were 921 articles included, and the number of articles published during 1923-2023 is increasing. The country with the highest number of articles published was the United States (443, 38.76%), followed by Japan (84, 9.12%) and France (72, 7.82%). The author with the highest number of publications is Ansell, Overman MJ (33, 3.58%), and the author with the highest co-citation frequency is Overman MJ (218). Journal of Clinical Oncology is the journal with the highest publication frequency. The top five cluster groups were "chemotherapy", "inflammatory bowel disease", "celiac disease", "tumor" and "small intestine". The related disease, chemotherapy drugs, and treatment regimens of SBA form the main research fields, and prognosis and diagnosis are the research hotspots and trends. Conclusion The global research field in SBA has expanded in the past 100 years. The prognosis and new diagnosis of SBA are hotspots in this field and require further study in the future.
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Affiliation(s)
- Yao Lu
- Department of Community Nursing, School of Nursing, Peking University, Beijing, China
| | - Cheng C Pan
- Nanjing University of Finance and Economics, Nanjing, China
| | - Xin Hu
- Department of Community Nursing, School of Nursing, Peking University, Beijing, China
| | - Jing Sun
- Department of Community Nursing, School of Nursing, Peking University, Beijing, China
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An J, Fontenelle B, Chaudhari R, Mulloy R, El Djouzi S. An Unexpected Challenge: Marked Small Bowel Obstruction Arising From a Poorly Differentiated Metastatic Mucinous Adenocarcinoma of the Distal Ileum in a Risk-Free Healthy Patient. Cureus 2024; 16:e61528. [PMID: 38957234 PMCID: PMC11218847 DOI: 10.7759/cureus.61528] [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: 06/01/2024] [Indexed: 07/04/2024] Open
Abstract
Adenocarcinoma, while constituting the predominant variant among small bowel cancers, is a component of the broader category of primary small bowel malignancies, which are notably infrequent in occurrence. The diagnosis of such malignancies is often markedly delayed, a consequence of their insidious onset and the nonspecific nature of the abdominal symptoms presented. A 69-year-old Caucasian male presented to the emergency department manifesting acute, sharp, and colicky abdominal pain accompanied by a single episode of vomiting, all developing over one day. His medical history was notable for gastroesophageal reflux disease (GERD) and regionally confined prostate adenocarcinoma, which was under meticulous surveillance by the urological team. The patient's lifestyle was characterized by abstention from alcohol and tobacco, adherence to a nutritious diet, and a commitment to regular physical activity. Subsequent examination and surgical excision of an abnormal mass, as delineated on computed tomography (CT), culminated in the diagnosis of a stage IV, poorly differentiated adenocarcinoma. We have reported this case to spark research regarding early diagnostic techniques for small bowel adenocarcinoma (SBA). In this case, a healthy individual presented with vague abdominal pain and a single episode of vomiting. Diagnosis required the surgical resection of the tumor, where metastasis was also visualized. Due to the rare nature of SBA, we believe different diagnostic measures and adjuvant therapy should be researched for earlier diagnosis and subsequently better patient outcomes.
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Affiliation(s)
- Jennie An
- Medicine, St. James School of Medicine, Park Ridge, USA
| | | | | | - Rob Mulloy
- Medicine, St. James School of Medicine, Park Ridge, USA
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Li B, Chen Z, Wang G, Liu Y, Ning S. Synchronous Multiple Primary Malignant Adenocarcinoma of the Descending Colon and Fungating Bleeding Adenocarcinoma of the Terminal Ileum Presenting Massive Rectal Bleeding: A Trap for the Unwary. Onco Targets Ther 2024; 17:363-368. [PMID: 38711919 PMCID: PMC11073142 DOI: 10.2147/ott.s453682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 04/09/2024] [Indexed: 05/08/2024] Open
Abstract
Primary cancer of the ileum is rare, and when it occurs in conjunction with primary colon cancer, it becomes even more infrequent and challenging to diagnose prior to surgical intervention. Primary small bowel cancers can be overlooked and may be misidentified as small bowel mesenchymal tumours or advanced metastases from colon cancer. We present an exceedingly uncommon case of ruptured primary ileal cancer combined with primary descending colon cancer presenting with gastrointestinal bleeding. Based on our understanding, instances of dual tumours concurrently occurring are exceedingly infrequent. In this patient, there was a preoperative suspicion of bleeding from colon cancer in the descending region. However, intraoperative exploration revealed that the location of the bleeding was a terminal ileal mass. Following the surgical intervention, the patient recovered satisfactorily. Intraoperative exploration of the entire gastrointestinal tract is therefore necessary in patients with gastrointestinal haemorrhage, especially in those who require urgent surgery without adequate preoperative investigations. If a mass is detected at the end of the ileum, intraoperative pathology should be performed if feasible. Subsequently, if the diagnosis reveals an adenocarcinoma, terminal ileocolic resection and right hemicolectomy are necessary for appropriate resection.
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Affiliation(s)
- Baicheng Li
- Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning Province, 116023, People’s Republic of China
| | - Zhao Chen
- Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning Province, 116023, People’s Republic of China
| | - Guangzhi Wang
- Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning Province, 116023, People’s Republic of China
| | - Yaqing Liu
- Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning Province, 116023, People’s Republic of China
| | - Shili Ning
- Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning Province, 116023, People’s Republic of China
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de Bakker JK, Suurmeijer JA, Toennaer JGJ, Bonsing BA, Busch OR, van Eijck CH, de Hingh IH, de Meijer VE, Molenaar IQ, van Santvoort HC, Stommel MW, Festen S, van der Harst E, Patijn G, Lips DJ, Den Dulk M, Bosscha K, Besselink MG, Kazemier G. Surgical Outcome After Pancreatoduodenectomy for Duodenal Adenocarcinoma Compared with Other Periampullary Cancers: A Nationwide Audit Study. Ann Surg Oncol 2023; 30:2448-2455. [PMID: 36536196 PMCID: PMC10027630 DOI: 10.1245/s10434-022-12701-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 10/04/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Surgical outcome after pancreatoduodenectomy for duodenal adenocarcinoma could differ from pancreatoduodenectomy for other cancers, but large multicenter series are lacking. This study aimed to determine surgical outcome in patients after pancreatoduodenectomy for duodenal adenocarcinoma, compared with other periampullary cancers, in a nationwide multicenter cohort. METHODS After pancreatoduodenectomy for cancer between 2014 and 2019, consecutive patients were included from the nationwide, mandatory Dutch Pancreatic Cancer Audit. Patients were stratified by diagnosis. Baseline, treatment characteristics, and postoperative outcome were compared between groups. The association between diagnosis and major complications (Clavien-Dindo grade III or higher) was assessed via multivariable regression analysis. RESULTS Overall, 3113 patients, after pancreatoduodenectomy for cancer, were included in this study: 264 (8.5%) patients with duodenal adenocarcinomas and 2849 (91.5%) with other cancers. After pancreatoduodenectomy for duodenal adenocarcinoma, patients had higher rates of major complications (42.8% vs. 28.6%; p < 0.001), postoperative pancreatic fistula (International Study Group of Pancreatic Surgery [ISGPS] grade B/C; 23.1% vs. 13.4%; p < 0.001), complication-related intensive care admission (14.3% vs. 10.3%; p = 0.046), re-interventions (39.8% vs. 26.6%; p < 0.001), in-hospital mortality (5.7% vs. 3.1%; p = 0.025), and longer hospital stay (15 days vs. 11 days; p < 0.001) compared with pancreatoduodenectomy for other cancers. In multivariable analysis, duodenal adenocarcinoma was independently associated with major complications (odds ratio 1.14, 95% confidence interval 1.03-1.27; p = 0.011). CONCLUSION Pancreatoduodenectomy for duodenal adenocarcinoma is associated with higher rates of major complications, pancreatic fistula, re-interventions, and in-hospital mortality compared with patients undergoing pancreatoduodenectomy for other cancers. These findings should be considered in patient counseling and postoperative management.
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Affiliation(s)
- Jacob K de Bakker
- Amsterdam UMC, Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - J Annelie Suurmeijer
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Amsterdam UMC, University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands
| | - Jurgen G J Toennaer
- Amsterdam UMC, Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Bert A Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Olivier R Busch
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Amsterdam UMC, University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands
| | - Casper H van Eijck
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Ignace H de Hingh
- Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands
| | - Vincent E de Meijer
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital and University Medical Center, Utrecht, The Netherlands
| | - Hjalmar C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital and University Medical Center, Utrecht, The Netherlands
| | - Martijn W Stommel
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | | | - Gijs Patijn
- Department of Surgery, Isala Clinics, Zwolle, The Netherlands
| | - Daan J Lips
- Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands
| | - Marcel Den Dulk
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Koop Bosscha
- Department of Surgery, Jeroen Bosch ziekenhuis, Den Bosch, The Netherlands
| | - Marc G Besselink
- Cancer Center Amsterdam, Amsterdam, The Netherlands.
- Amsterdam UMC, University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands.
| | - Geert Kazemier
- Amsterdam UMC, Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands.
- Cancer Center Amsterdam, Amsterdam, The Netherlands.
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Hosseini K, Beirami SM, Forouhandeh H, Vahed SZ, Eyvazi S, Ramazani F, Tarhriz V, Ardalan M. The role of circadian gene timeless in gastrointestinal cancers. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2022.101722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
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Fujimori S, Hamakubo R, Hoshimoto A, Nishimoto T, Omori J, Akimoto N, Tanaka S, Tatsuguchi A, Iwakiri K. Risk factors for small intestinal adenocarcinomas that are common in the proximal small intestine. World J Gastroenterol 2022; 28:5658-5665. [PMID: 36338888 PMCID: PMC9627424 DOI: 10.3748/wjg.v28.i39.5658] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/18/2022] [Accepted: 10/11/2022] [Indexed: 02/06/2023] Open
Abstract
The frequency of primary small intestinal adenocarcinoma is increasing but is still low. Its frequency is approximately 3% of that of colorectal adenocarcinoma. Considering that the small intestine occupies 90% of the surface area of the gastrointestinal tract, small intestinal adenocarcinoma is very rare. The main site of small intestinal adenocarcinoma is the proximal small intestine. Based on this characteristic, dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis. Since most nutrients are absorbed in the proximal small intestine, the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine. The proportion of aerobic bacteria is high in the proximal small intestine, but the absolute number of bacteria is low. In addition, the length and density of villi are greater in the proximal small intestine. However, the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas. On the other hand, the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there. Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma. In carcinogenesis experiments in which the positions of the small and large intestines were exchanged, tumors still occurred in the large intestinal mucosa more often. In other words, the influence of the intestinal contents is small, and there is a large difference in epithelial properties between the small intestine and the large intestine. In conclusion, small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium. It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.
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Affiliation(s)
- Shunji Fujimori
- Department of Gastroenterology, Chiba Hokusoh Hospital, Nippon Medical School, Chiba 270-1694, Japan
| | - Ryohei Hamakubo
- Department of Gastroenterology, Chiba Hokusoh Hospital, Nippon Medical School, Chiba 270-1694, Japan
| | - Aitoshi Hoshimoto
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
| | - Takayoshi Nishimoto
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
| | - Jun Omori
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
| | - Naohiko Akimoto
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
| | - Shu Tanaka
- Department of Gastroenterology, Tama-Nagayama Hospital, Nippon Medical School, Tokyo 206-0025, Japan
| | - Atsushi Tatsuguchi
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
| | - Katsuhiko Iwakiri
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
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Epidemiology, Risk Factors and Diagnosis of Small Bowel Adenocarcinoma. Cancers (Basel) 2022; 14:cancers14092268. [PMID: 35565398 PMCID: PMC9103761 DOI: 10.3390/cancers14092268] [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: 02/07/2022] [Revised: 04/10/2022] [Accepted: 04/22/2022] [Indexed: 12/17/2022] Open
Abstract
Simple Summary Small bowel adenocarcinoma is a rare tumor. Diagnosis is often obtained at an advanced stage and prognosis remains poor. The aim of this review is to report the recent epidemiological and risk factor data related to small bowel adenocarcinoma. New diagnostic tools are also described in this review. Abstract Adenocarcinomas of the small intestine are rare tumors but their incidence is increasing. There is a slight male predominance. The median age at diagnosis is the 6th decade. The most frequent primary location is the duodenum. There is no clearly identified environmental risk factor, but adenocarcinomas of the small intestine are associated in almost 20% of cases with predisposing diseases (Crohn’s disease, Lynch syndrome, familial adenomatous polyposis, Peutz–Jeghers syndrome and celiac disease).
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Liu Z, Liu K, Gao J, Jing C, Ma Y, Zheng S, Shan J. Prognostic Value of Lymph Node Evaluation in Stage II Small Bowel Adenocarcinoma: An Updated Analysis of Surveillance, Epidemiology, and End Results Database. Front Oncol 2022; 12:865745. [PMID: 35402228 PMCID: PMC8989959 DOI: 10.3389/fonc.2022.865745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Accepted: 03/03/2022] [Indexed: 11/25/2022] Open
Abstract
Background Due to the lack of large-scale clinical trials, the treatment strategies of small bowel adenocarcinoma (SBA) are controversial, especially for stage II patients. According to the National Comprehensive Cancer Network (NCCN) guideline, few lymph nodes (LNs) examined (<5 for duodenum or <8 for jejunal/ileal primary location) are one of the high-risk features for stage II patients, for whom adjuvant chemotherapy is recommended. This consensus is originally drawn from data in the Surveillance, Epidemiology, and End Results Database (SEER) between 1988 and 2010. However, the surgical modalities and chemotherapy strategies changed a lot after 2004 for SBA patients. The previous data may not represent a true picture of current therapeutics. Thus, we reanalyzed the SEER database and updated the cutoff point of LN numbers resected with respect to cancer-specific survival (CSS) using the latest SEER information. Methods Patients diagnosed with stage II SBA and who underwent curative surgery between 2004 and 2018 were extracted from the SEER database. CSS was calculated using the Kaplan–Meier method and compared by log-rank test. Maximum survival differences based on total LNs examined for duodenal and jejunoileal tumors were determined separately with the cut-point analysis and maximum log-rank χ2 statistic. A nomogram model was constructed based on the multivariate Cox analysis to predict 5‐ and 10‐year CSS and was then validated with an internal cohort. Results A total of 935 stage II SBA patients met the inclusion criteria. The greatest difference in survival was found in patients who had removal of at least 5 LNs for duodenal and 12 LNs for jejunoileal tumors. Multivariate Cox analysis showed that age, T stage, histology grade, primary site, and LN numbers were independent prognostic factors for survival. The C index of nomogram model was 0.701 (95% CI, 0.661–0.741, p < 0.001). Conclusions The number of LNs harvested is an important prognostic factor for survival in stage II SBA patients. LN number examined <5 remains a high-risk factor for duodenum, but the cutoff point for jejunal/ileal tumors should rise from 8 to 12. Appropriate radical lymphadenectomy should be performed in stage II SBA surgery.
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Affiliation(s)
- Zhen Liu
- Department of Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Cancer Institute (Key Laboratory for Cancer Intervention and Prevention, China National Ministry of Education, Zhejiang Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kun Liu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Clinical Center for Colorectal Cancer, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China.,National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jiale Gao
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Clinical Center for Colorectal Cancer, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China.,National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Chao Jing
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Clinical Center for Colorectal Cancer, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China.,National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Yanhong Ma
- Department of Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shu Zheng
- Cancer Institute (Key Laboratory for Cancer Intervention and Prevention, China National Ministry of Education, Zhejiang Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jianzhen Shan
- Department of Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Molecular Landscape of Small Bowel Adenocarcinoma. Cancers (Basel) 2022; 14:cancers14051287. [PMID: 35267592 PMCID: PMC8909755 DOI: 10.3390/cancers14051287] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 02/23/2022] [Accepted: 02/28/2022] [Indexed: 12/13/2022] Open
Abstract
Small bowel adenocarcinoma (SBA) is a rare malignancy, with lower incidence, later stage at diagnosis, and poor overall prognosis compared to other cancers of the gastrointestinal tract. Owing to the rarity of the disease along with the paucity of high-quality tissue samples and preclinical models, little is known about the molecular alterations characteristic of SBA. This is reflected by the fact that the clinical management of SBA is primarily extrapolated from colorectal cancer (CRC). Recent advances in genomic profiling have highlighted key differences between these tumors, establishing SBA as a molecularly unique intestinal cancer. Moreover, comprehensive molecular analysis has identified a relatively high incidence of potentially targetable genomic alterations in SBA, predictive of response to targeted and immunotherapies. Further advances in our knowledge of the mutational and transcriptomic landscape of SBA, guided by an increased understanding of the molecular drivers of SBA, will provide opportunities to develop novel diagnostic tools and personalized therapeutic strategies.
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11
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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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Huang TS, Lin HL, Chang WC, Chen YJ, Lin JC. Small bowel obstruction caused by metastasis of nasal cavity basal cell adenocarcinoma. JOURNAL OF CANCER RESEARCH AND PRACTICE 2022. [DOI: 10.4103/jcrp.jcrp_31_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Sekaran A, Dey D, Singh A, Das P. Pathology of Malignant Lesions of the Gastrointestinal Tract. SURGICAL PATHOLOGY OF THE GASTROINTESTINAL SYSTEM 2022:699-782. [DOI: 10.1007/978-981-16-6395-6_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Prognostic Value of LC3B and p62 Expression in Small Intestinal Adenocarcinoma. J Clin Med 2021; 10:jcm10225398. [PMID: 34830679 PMCID: PMC8624293 DOI: 10.3390/jcm10225398] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 11/12/2021] [Accepted: 11/16/2021] [Indexed: 12/14/2022] Open
Abstract
Autophagy, a mechanism that maintains cellular homeostasis, is involved in tumor cell growth and survival in cancer, and autophagy inhibitors have been tested clinical trials for anticancer therapy. To elucidate the clinical and prognostic implications of autophagy in small intestinal adenocarcinoma (SIAC), we assessed the expression of autophagy markers, LC3B and p62, in 171 surgically resected primary SIACs using automated quantitative analysis. Positive LC3B, p62 nuclear (p62Nu), and p62 cytoplasmic (p62Cy) expression was observed in 23 (13.5%), 52 (30.4%), and 43 (25.1%) carcinomas, respectively. LC3B+ expression was correlated with undifferentiated carcinoma (p < 0.001) and high histologic grade (p = 0.029). The combined expression of LC3B and p62Nu (LC3+/p62Nu+) was related to the older age of patients (p = 0.017), undifferentiated carcinoma (p < 0.001), and high grade (p = 0.031). LC3B+ (p = 0.006), p62Cy+ (p = 0.041), or p62Nu+ (p = 0.006) expression were associated with worse survival. In addition, SIAC patients with either LC3B+/p62Nu+ (p = 0.001) or LC3B+/p62Cy+ (p = 0.002) expression had shorter survival times. In multivariate analysis, LC3B expression remained an independent prognostic factor (p = 0.025) for overall survival. In conclusion, autophagy may play a role in the tumorigenesis of SIACs, and LC3B and p62 could be used as prognostic biomarkers and potential therapeutic targets for SIACs.
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Amano T, Iijima H, Shinzaki S, Tashiro T, Iwatani S, Tani M, Otake Y, Yoshihara T, Sugimoto A, Egawa S, Yamaguchi S, Kinoshita K, Araki M, Hirao M, Sakakibara Y, Hiyama S, Ogawa H, Nagaike K, Murata J, Komori M, Okuda Y, Kizu T, Tsujii Y, Hayashi Y, Inoue T, Takahashi H, Mizushima T, Morii E, Takehara T. Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma. BMC Cancer 2021; 21:978. [PMID: 34465291 PMCID: PMC8406832 DOI: 10.1186/s12885-021-08724-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 08/22/2021] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. METHODS This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. RESULTS A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30-0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. CONCLUSION Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.
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Affiliation(s)
- Takahiro Amano
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hideki Iijima
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Shinichiro Shinzaki
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Taku Tashiro
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shuko Iwatani
- Department of Internal Medicine, Osaka Police Hospital, Osaka, Japan
| | - Mizuki Tani
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yuriko Otake
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Takeo Yoshihara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Aya Sugimoto
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan
| | - Satoshi Egawa
- Department of Internal Medicine, Osaka Police Hospital, Osaka, Japan
| | - Shinjiro Yamaguchi
- Department of Gastroenterology, Kansai Rosai Hospital, Amagasaki, Hyogo, Japan
| | - Kazuo Kinoshita
- Department of Gastroenterology, Otemae Hospital, Osaka, Japan
| | - Manabu Araki
- Department of Gastroenterology, National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Osaka, Japan
| | - Motohiro Hirao
- Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | - Yuko Sakakibara
- Department of Gastroenterology, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Satoshi Hiyama
- Department of Gastroenterology, Japan Community Healthcare Organization Osaka Hospital, Osaka, Japan
| | - Hiroyuki Ogawa
- Department of Gastroenterology, Nishinomiya Municipal Central Hospital, Nishinomiya, Hyogo, Japan
| | - Koji Nagaike
- Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Suita, Osaka, Japan
| | - Jun Murata
- Department of Gastroenterology, Higashiosaka City Medical Center, Higashiosaka, Osaka, Japan
| | - Masato Komori
- Department of Gastroenterology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
| | - Yorihide Okuda
- Department of Gastroenterology, Saiseikai Senri Hospital, Suita, Osaka, Japan
| | - Takashi Kizu
- Department of Gastroenterology, Yao Municipal Hospital, Yao, Osaka, Japan
| | - Yoshiki Tsujii
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshito Hayashi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Takahiro Inoue
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hidekazu Takahashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Tsunekazu Mizushima
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Eiichi Morii
- Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
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Adenocarcinoma of the Jejunum: A Case Report and Literature Review. SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2021. [DOI: 10.2478/sjecr-2019-0079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Abstract
Small intestine cancers account for 1-3% of all gastrointestinal tumors, with only 11-25% of these tumors located in the jejunum. We report the case of a woman who has been experiencing abdominal pain for the last six months, accompanied by nausea, vomiting and appearance of dark-colored stools, who has lost 20 kg in weight during the last few months. Laboratory findings indicated anemia and no significant changes were identified in the abdominal ultrasound. By endoscopic examination of the stomach and duodenum and by colonoscopy, no infiltrations were found. Serum markers were elevated and CT scan of the abdomen showed thickening of a part of the jejunum wall with swollen lymph nodes in the mesentery, along the inferior vena cava and abdominal aorta, in the retroperitoneal space. By opening the abdominal cavity, we observed an infiltration in the initial part of the jejunum with an infiltration of the entire wall. Resection of the jejunum with related mesenthery, vessels and lymph nodes therein was performed. Histopathology revealed an invasive adenocarcinoma of the small intestine, with an invasion of all layers of the wall and mesentery. Adjuvant FOLFOX chemotherapy was introduced, 6 cycles in total, and following each cycle, tumor markers have been constantly decreasing. No relapse has been identified after nine months. Due to often deep position in the small intestine, atypical symptomatology and lack of screening, an early diagnosis is difficult. Surgical resection of the affected small intestine followed by an additional chemotherapy is the optimal treatment strategy.
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Li T, Wang X, Chen C, Song X, Li J, Zhao Z, Zhang N, Li W, Zhang K, Liu T. Metachronous primary colon and periampullary duodenal cancer: A case report. Medicine (Baltimore) 2021; 100:e24378. [PMID: 33546078 PMCID: PMC7837966 DOI: 10.1097/md.0000000000024378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Accepted: 12/29/2020] [Indexed: 11/25/2022] Open
Abstract
RATIONALE Primary periampullary duodenal cancer accounts for 3% to 17% of periampullary cancers. There are no previous reports of metachronous primary colon and periampullary duodenal cancer. PATIENT CONCERNS We present a case of primary periampullary duodenal cancer that occurred metachronously after colon cancer. DIAGNOSES Imaging and endoscopic examinations, serum tumor marker levels, and pathology confirmed metachronous colon and periampullary duodenal cancer, with 14-month interval between the diagnoses of the 2 malignancies. INTERVENTION The patient received right hemicolectomy combined with mFOLFOX6 chemotherapy for colon cancer and pancreatoduodenectomy for periampullary duodenal cancer. OUTCOMES The patient has been followed up for 6 years since the pancreatoduodenectomy and shows no signs of recurrence or metastasis. LESSONS The risk of developing a second malignancy may be associated with the site of the first tumor. Patients with right colon cancer may have particularly high risk of developing small intestinal cancer, including duodenal cancer. Early detection and active surgical treatments can improve prognosis. Long-term regular follow-up is necessary to detect new malignancies occurring after the diagnosis colon cancer.
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Affiliation(s)
- Tao Li
- Department of Colorectal and Anal Surgery, the Second Hospital of Jilin University, Changchun
| | - Xinyu Wang
- Department of Colorectal and Anal Surgery, the Second Hospital of Jilin University, Changchun
| | - Chen Chen
- Department of Emergency Surgery, Jilin Province People's Hospital, Changchun
| | - Xiaobin Song
- Department of Emergency Surgery, Jilin Province People's Hospital, Changchun
| | - Jiannan Li
- Department of Colorectal and Anal Surgery, the Second Hospital of Jilin University, Changchun
| | - Zeyun Zhao
- Department of Colorectal and Anal Surgery, the Second Hospital of Jilin University, Changchun
| | - Nan Zhang
- Department of Colorectal and Anal Surgery, the Second Hospital of Jilin University, Changchun
- Department of Burn, the First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Wei Li
- Department of Colorectal and Anal Surgery, the Second Hospital of Jilin University, Changchun
| | - Kai Zhang
- Department of Colorectal and Anal Surgery, the Second Hospital of Jilin University, Changchun
| | - Tongjun Liu
- Department of Colorectal and Anal Surgery, the Second Hospital of Jilin University, Changchun
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Prognostic Value of Immune Environment Analysis in Small Bowel Adenocarcinomas with Verified Mutational Landscape and Predisposing Conditions. Cancers (Basel) 2020; 12:cancers12082018. [PMID: 32718028 PMCID: PMC7463640 DOI: 10.3390/cancers12082018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 07/20/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022] Open
Abstract
Background: Small bowel adenocarcinoma (SBA) is a rare yet insidious cancer with poor survival. The abundance of tumour-infiltrating lymphocytes is associated with improved survival, but the role of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway in tumour escape is controversial. We evaluated immune cell infiltration, PD1/PD-L1 expression and their prognostic value in a series of SBAs with previously verified predisposing conditions and exome-wide somatic mutation characterization. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 were analysed from 94 SBAs. An immune cell score (ICS) was formed from the amount of the CD3 and CD8 positive lymphocytes from the tumour centre and invasive margin. The PD-L1 and PD-1 positive immune cells (ICs) and ICS were combined into a variable called Immunoprofile. Results: High ICS, PD-L1IC and PD-1, individually and combined as Immunoprofile, were prognostic for better patient outcome. Sixty-five (69%) SBAs expressed ≥1% positive PD-L1IC. A high tumour mutation burden was common (19%) and associated with immune markers. Immunoprofile, adjusted for TNM stage, mismatch repair status, tumour location, sex and age were independent prognostic markers for disease-specific and overall survival. Conclusions: Analysing tumoral immune contexture provides prognostic information in SBA. Combining ICS, PD-1 and PD-L1IC as Immunoprofile enhanced the prognostic performance.
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Trends in incidence of small bowel cancer according to histology: a population-based study. J Gastroenterol 2020; 55:181-188. [PMID: 31630251 DOI: 10.1007/s00535-019-01636-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 10/05/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Small bowel cancer is not a single entity. Population-based studies taking into account histological diversity are scarce. The aim of this study was to report on their trends in incidence by histology in France over the past 20 years. METHODS All patients with a small bowel cancer diagnosed in 15 French administrative areas covered by a registry from the network of French cancer registries (FRANCIM) were included. Age-standardized incidence rates were estimated using the world standard population. Incidence rates were calculated by gender, age group, histology, and 5-year period. RESULTS The overall age-standardized incidence rates were 1.46/100,000 inhabitants in men and 0.9/100,000 inhabitants in women. Adenocarcinoma was the most common histological type (38%), followed by neuroendocrine tumors (35%), lymphoma (15%) and sarcoma (12%). Age at diagnosis and tumor location differed between adenocarcinoma and neuroendocrine tumors. The incidence of all four tumor types increased significantly over the 20-year period, with the exception of lymphoma in men. The annual percentage change for neuroendocrine tumors was 3.89% in men and 3.61% in women; for sarcoma, it was 3.38% and 4.08%, respectively. The incidence of adenocarcinoma and lymphoma also increased in women with an annual percentage change of 3.05% and 3.32%, respectively. CONCLUSION Small bowel cancer incidence has increased over time. This increase occurred with different amplitudes and patterns in the four major histological types. The improvement in imaging techniques could partly explain this increase. It is necessary to determine whether predisposing conditions may contribute to this change.
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Yasuda S, Harada S, Tsujimoto A, Aoki S, Takei T, Migita K, Ueno M, Tatsumi M, Watanabe A. A pathological complete response by chemotherapy with S-1 and oxaliplatin for a locally advanced duodenal adenocarcinoma in Lynch syndrome: a case report. Surg Case Rep 2019; 5:146. [PMID: 31637551 PMCID: PMC6803604 DOI: 10.1186/s40792-019-0712-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 09/27/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although primary duodenal adenocarcinoma (DA) is a rare malignancy representing ~ 0.5% of all gastrointestinal cancers, the incidence of DA is more frequent in Lynch syndrome. Because of its rarity, treatment strategies or optimal chemotherapeutic regimens have not been clearly defined for advanced DA. CASE PRESENTATION A 72-year-old woman with Lynch syndrome visited our hospital with a right upper abdominal pain. Computed tomography (CT) showed wall thickness with enhancement in the second portion of the duodenum and adjacent abdominal wall, which suggested direct tumor invasion to the abdominal wall. Upper gastrointestinal endoscopy (UGE) showed a large ulcerative tumor in the second portion of the duodenum, and histological analysis revealed a poorly differentiated adenocarcinoma. A cT4N0M0, cStage IIB (Union for International Control Cancer TNM staging) DA was diagnosed. After three courses of chemotherapy with S-1 and oxaliplatin (SOX), follow-up CT and UGE showed shrinkage of the duodenal tumor. Therefore, the patient underwent pancreaticoduodenectomy with lymph node dissection with curative intent. Histological examination showed a pathological complete response to SOX therapy. The postoperative course was uneventful, and the patient was discharged on postoperative day 29. The patient received no adjuvant chemotherapy, and there has been no evidence of recurrence 6 months after the operation. CONCLUSIONS SOX therapy provided a remarkable response and can be an optimal chemotherapeutic regimen for advanced DA in Lynch syndrome.
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Affiliation(s)
- Satoshi Yasuda
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan.
| | - Suzuka Harada
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Akinori Tsujimoto
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Satoko Aoki
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Takeshi Takei
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Kazuhiro Migita
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Masato Ueno
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Mitsutoshi Tatsumi
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Akihiko Watanabe
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
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Sato H, Shibasaki S, Okabe A, Tsukamoto T, Morise Z, Uyama I. Hematogenous intestinal metastases from sigmoid colon cancer presenting as iliopsoas abscess and bowel obstruction. Int Cancer Conf J 2019; 8:105-108. [PMID: 31218184 PMCID: PMC6545184 DOI: 10.1007/s13691-019-00364-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 02/11/2019] [Indexed: 10/27/2022] Open
Abstract
Intestinal metastases from colorectal cancer typically occur by intraperitoneal spread, whereas those occurring via hematogenous route are exceedingly rare. We report a case of intestinal metastases from sigmoid colon cancer that presented as iliopsoas abscess and ileus. A 78-year-old man who had undergone sigmoidectomy for sigmoid colon cancer 5 years ago was referred to our hospital with recurrent ileus and fever. Abdominal computed tomography showed a left iliopsoas abscess and a mass near the abscess that had ostensibly caused ileus. The patient underwent segmental resection of the jejunum including the mass. Histopathological examination of the resected specimen revealed moderately differentiated adenocarcinoma proliferating mainly in the submucosal and muscular layers, which was pathologically identical to the colon cancer resected 5 years ago. He died 18 months after the surgery because of liver metastases. This case report highlights the delayed occurrence of colorectal metastases at unusual sites, such as the small bowel, more than 5 years after the resection of the primary cancer. Intestinal metastases should be considered in patients with a history of colon cancer, particularly in those with recurrent ileus or abdominal abscess with no obvious cause.
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Affiliation(s)
- Harunobu Sato
- Department of Surgery, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan
| | - Susumu Shibasaki
- Department of Surgery, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan
| | - Asako Okabe
- Department of Pathology, School of Medicine, Fujita Health University, Toyoake, Japan
| | - Tetsuya Tsukamoto
- Department of Pathology, School of Medicine, Fujita Health University, Toyoake, Japan
| | - Zenichi Morise
- Department of Surgery, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan
| | - Ichiro Uyama
- Department of Surgery, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan
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Taghipour Zahir S, Heidarymeybodi Z, AleSaeidi S. Prognostic Factors and Survival Time in Patients with Small Bowel Tumors: A Retrospective Observational Study. Int J Surg Oncol 2019; 2019:2912361. [PMID: 31186956 PMCID: PMC6521306 DOI: 10.1155/2019/2912361] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Accepted: 03/31/2019] [Indexed: 12/20/2022] Open
Abstract
This study examines survival time in patients with small bowel tumors and determines its contributing factors. In this retrospective analytical study, the medical records of 106 patients with small bowel cancer (from 2006 to 2011) were investigated. The patients' data were extracted, including age, gender, clinical presentation, location of tumor, histological type, grade of tumor, site of metastasis, and type of treatment. The Kaplan-Meier test was used to estimate the overall survival time and the Log-rank test to compare the survival curves. The Cox regression was also used to evaluate the effect of the confounding variables on survival time. This study was conducted on 106 patients with a median age of 60 years (Min: 7, Max: 87). The tumor types included adenocarcinoma (n=78, 73.6%), MALToma (n=22, 20.8%), neuroendocrine tumors (n=4, 3.8%), and sarcoma (n=2. 1.8%). Grade 3 adenocarcinomas had a significantly lower survival time (HR: 1.48, 95% CI: 0.46-2.86; P=.001). Combined therapy (chemotherapy and surgery) vs. single-therapy (only surgery) had no significant effects on the survival of the patients with MALToma (5 vs. 3 months, 95% CI: 1.89-5.26; P=.06). There were no significant differences between the survival time in adenocarcinoma and MALToma (12 vs. 20 months, 95% CI: 6.24-24.76; P=.49). Tumor grade was the only independent prognostic factor that affected survival in adenocarcinoma. The patients diagnosed with MALToma in the study also had a poor prognosis, and the type of treatment had no significant effect on their survival.
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MESH Headings
- Adenocarcinoma/diagnosis
- Adenocarcinoma/mortality
- Adenocarcinoma/pathology
- Adenocarcinoma/therapy
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Child
- Female
- Follow-Up Studies
- Humans
- Intestinal Neoplasms/diagnosis
- Intestinal Neoplasms/mortality
- Intestinal Neoplasms/pathology
- Intestinal Neoplasms/therapy
- Intestine, Small
- Kaplan-Meier Estimate
- Lymphoma, B-Cell, Marginal Zone/diagnosis
- Lymphoma, B-Cell, Marginal Zone/mortality
- Lymphoma, B-Cell, Marginal Zone/pathology
- Lymphoma, B-Cell, Marginal Zone/therapy
- Male
- Middle Aged
- Neuroendocrine Tumors/diagnosis
- Neuroendocrine Tumors/mortality
- Neuroendocrine Tumors/pathology
- Neuroendocrine Tumors/therapy
- Prognosis
- Retrospective Studies
- Sarcoma/diagnosis
- Sarcoma/mortality
- Sarcoma/pathology
- Sarcoma/therapy
- Survival Analysis
- Young Adult
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Affiliation(s)
- Shokouh Taghipour Zahir
- Shahid Sadoughi General Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Zahra Heidarymeybodi
- Student Research Committee, Shahid Sadoughi General Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Sogol AleSaeidi
- Shahid Sadoughi General Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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23
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Broman KK, Bailey CE, Parikh AA. Sidedness of Colorectal Cancer Impacts Risk of Second Primary Gastrointestinal Malignancy. Ann Surg Oncol 2019; 26:2037-2043. [PMID: 30949861 DOI: 10.1245/s10434-019-07326-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Indexed: 01/09/2023]
Abstract
INTRODUCTION A history of colorectal cancer (CRC) increases the risk of subsequent gastrointestinal (GI) cancer. Cancers of the right colon, left colon, and rectum differ according to molecular profiles, responses to treatment, and outcomes. OBJECTIVE The purpose of this study was to determine if CRC location is associated with differential risk for secondary primary GI malignancy. METHODS A retrospective cohort of adults with CRC was compiled using the Surveillance, Epidemiology, and End Results database (1973-2015). Standardized incidence ratios (SIRs) for second primary GI malignancies were compared based on location of the index CRC (right colon, left colon, or rectum). RESULTS The cohort included 281,413 adults with CRC (30.3% right, 35.3% left, 34.3% rectum). With a median 4.9-year follow-up, 12,064 (4.3%) patients developed a second primary GI malignancy (64% CRC, 36% non-CRC). Those with CRC at any location had higher than expected incidences of small intestine, bile duct, and other CRCs, and lower incidences of liver and gallbladder cancer. The SIR for small intestinal cancer was higher after right colon cancer than after left colon or rectal cancer. The esophageal cancer SIR was higher after left colon cancer. Pancreas cancer was higher than expected for right colon cancer, but lower for left colon and rectal cancer. CONCLUSION The location of CRC leads to differences in the incidence and location of second primary GI malignancies and may be related to similarities in the associated carcinogenesis and molecular pathways or response to treatment. CRC location not only impacts treatment response and outcomes, but should also be considered during subsequent surveillance.
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Affiliation(s)
- Kristy K Broman
- Division of Surgical Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Christina E Bailey
- Division of Surgical Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Alexander A Parikh
- Division of Surgical Oncology, East Carolina University Brody School of Medicine, Greenville, NC, USA.
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Barsouk A, Rawla P, Barsouk A, Thandra KC. Epidemiology of Cancers of the Small Intestine: Trends, Risk Factors, and Prevention. Med Sci (Basel) 2019; 7:E46. [PMID: 30884915 PMCID: PMC6473503 DOI: 10.3390/medsci7030046] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 03/14/2019] [Accepted: 03/14/2019] [Indexed: 12/24/2022] Open
Abstract
The latest data from the United States and Europe reveal that rare small intestine cancer is on the rise, with the number of cases having more than doubled over the past 40 years in the developed world. Mortality has grown at a slower pace, thanks to improvements in early diagnosis and treatment, as well as a shift in the etiology of neoplasms affecting the small intestine. Nevertheless, 5-year survival for small intestine adenocarcinomas has lingered at only 35%. Lifestyle in developed nations, including the rise in obesity and physical inactivity, consumption of alcohol, tobacco, and red and processed meats, and occupational exposures may be to blame for the proliferation of this rare cancer. Identification of hereditary and predisposing conditions, likely to blame for some 20% of cases, may help prevent and treat cancers of the small intestine. Studies of the neoplasm have been limited by small sample sizes due to the rarity of the disease, leaving many questions about prevention and treatment yet to be answered.
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Affiliation(s)
- Adam Barsouk
- Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA.
| | - Prashanth Rawla
- Department of Medicine, Sovah Health, Martinsville, VA 24112, USA.
| | - Alexander Barsouk
- Hematologist-Oncologist, Allegheny Health Network, Pittsburgh, PA 15212, USA.
| | - Krishna Chaitanya Thandra
- Department of Pulmonary and Critical Care Medicine, Sentara Virginia Beach General Hospital, Virginia Beach, VA 23454, USA.
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25
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Maguire A, Sheahan K. Primary small bowel adenomas and adenocarcinomas-recent advances. Virchows Arch 2018; 473:265-273. [PMID: 29998424 DOI: 10.1007/s00428-018-2400-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 06/18/2018] [Accepted: 06/19/2018] [Indexed: 12/11/2022]
Abstract
The small intestine represents 75% of the length and 90% of the absorptive surface area of the gastrointestinal tract (GIT), yet only 2% of digestive system cancers occur at this site. Adenocarcinoma accounts for half of small bowel malignancies. There have been a number of important recent advances in our understanding, classification and treatment of small bowel tumours. Over recent years, ampullary tumours have become recognised as a form of small bowel carcinoma, distinct from head of pancreas and lower biliary tract tumours. This is reflected in separate TNM systems and increasing interest in separating intestinal from pancreatobiliary subtypes. The recognition of the importance of microsatellite (MSI) status and the advent of molecular pathology has also changed our approach to these neoplasms.
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Affiliation(s)
- Aoife Maguire
- Histopathology Department, St. James's Hospital, Dublin 2, Ireland
| | - Kieran Sheahan
- Pathology Department, & Centre for Colorectal Disease, UCD Medical School, St. Vincent's University Hospital, Dublin, Ireland.
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26
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de Bree E, Rovers KP, Stamatiou D, Souglakos J, Michelakis D, de Hingh IH. The evolving management of small bowel adenocarcinoma. Acta Oncol 2018; 57:712-722. [PMID: 29381126 DOI: 10.1080/0284186x.2018.1433321] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 01/22/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Small bowel adenocarcinoma (SBA) is rare despite the fact that the small bowel represents the longest part and has the largest surface of all alimentary tract sections. Its incidence is 50-fold lower than that of colorectal carcinoma. It is often diagnosed at an advanced stage due to atypical and late symptoms, its low index of suspicion, difficult endoscopic access and poor detection by radiological imaging, resulting in impaired outcome. Due to its rarity and being molecularly a unique intestinal cancer, data regarding its optimal management are relatively sparse. MATERIAL AND METHODS A PubMed search was performed to identify relevant manuscripts that were recently published. Emerging data regarding the pathogenesis, the diagnosis and the treatment of SBA that resulted from recent research are discussed in this comprehensive review. RESULTS Genomic analysis has demonstrated that SBA is a molecularly unique intestinal cancer. Double balloon enteroscopy and capsule endoscopy are novel techniques which may result in earlier diagnosis and consequently in improvement of the generally poor prognosis. For clinically localized disease, the quality of surgery has recently been defined, with removal of at least 8-10 lymph nodes correlating with improved prognosis. Moreover, adjuvant chemotherapy seems to improve outcome of stage III disease. The combination of a fluoropyrimidine and oxaliplatin appears to be the most effective systemic chemotherapy for disseminated disease. Genomic profiling can identify potentially targetable genomic alterations in a significant proportion of SBA patients. The role of administration of targeted agents or immune checkpoint inhibitors is still unknown and subject of ongoing clinical trials. In the common case of peritoneal metastases, recent studies have shown that cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy may be an attractive treatment option in selected patients. CONCLUSIONS SBA is a rare and unique malignancy, whose diagnostic approach and treatment are evolving, resulting in improved outcome.
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Affiliation(s)
- Eelco de Bree
- a Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece
| | - Koen P Rovers
- b Department of Surgical Oncology , Catharina Hospital , Eindhoven , The Netherlands
| | - Dimitris Stamatiou
- a Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece
| | - John Souglakos
- c Department of Medical Oncology and Laboratory of Translational Oncology , Medical School of Crete University Hospital , Heraklion , Greece
| | - Dimosthenis Michelakis
- a Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece
| | - Ignace H de Hingh
- b Department of Surgical Oncology , Catharina Hospital , Eindhoven , The Netherlands
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27
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Lech G, Korcz W, Kowalczyk E, Słotwiński R, Słodkowski M. Primary small bowel adenocarcinoma: current view on clinical features, risk and prognostic factors, treatment and outcome. Scand J Gastroenterol 2017; 52:1194-1202. [PMID: 28737049 DOI: 10.1080/00365521.2017.1356932] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Small bowel adenocarcinoma (SBA) is a rare but increasing cause of gastrointestinal malignancy, being both a diagnostic and therapeutic challenge. The goal of treatment is margin negative resection of a lesion and local lymphadenectomy, followed by modern adjuvant chemotherapy combinations in selected cases. Improved outcomes in patients with SBA are encouraging, but elucidation of mechanisms of carcinogenesis and risk factors as well as improved treatment for this malignancy is very needed.
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Affiliation(s)
- Gustaw Lech
- a Department of General, Gastroenterological and Oncological Surgery , Medical University of Warsaw , Warsaw , Poland
| | - Wojciech Korcz
- a Department of General, Gastroenterological and Oncological Surgery , Medical University of Warsaw , Warsaw , Poland
| | - Emilia Kowalczyk
- a Department of General, Gastroenterological and Oncological Surgery , Medical University of Warsaw , Warsaw , Poland
| | - Robert Słotwiński
- b Department of Surgical Research and Transplantology , Polish Academy of Sciences, Mossakowski Medical Research Centre , Warsaw , Poland.,c Department of Immunology, Biochemistry and Nutrition , Medical University of Warsaw , Warsaw , Poland
| | - Maciej Słodkowski
- a Department of General, Gastroenterological and Oncological Surgery , Medical University of Warsaw , Warsaw , Poland
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28
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Duerr D, Ellard S, Zhai Y, Taylor M, Rao S. A Retrospective Review of Chemotherapy for Patients with Small Bowel Adenocarcinoma in British Columbia. J Cancer 2016; 7:2290-2295. [PMID: 27994666 PMCID: PMC5166539 DOI: 10.7150/jca.16606] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Accepted: 09/18/2016] [Indexed: 12/18/2022] Open
Abstract
Background: Small bowel adenocarcinoma (SBA) is associated with a poor prognosis. It is an uncommon malignancy and therefore difficult to study. Randomized phase III trials are not available to guide best approaches. The Provincial Cancer Registry of the British Columbia Cancer Agency contains long-term data on patients with SBA. The authors analyzed characteristics and treatment outcomes for SBA patients diagnosed between 1990 and 2008. Material and methods: Charts of 150 patients with a histological diagnosis of SBA were retrospectively analyzed. Epidemiological and treatment data were collected. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: Baseline characteristics, such as median age at diagnosis (64.5 years), tumor stage (I-II 33%, III-IV 58%, unknown 9%), and location (duodenum 48%, jejunum 31%, ileum 21%) were consistent with published data. 55% of patients had a positive family history of cancer. DFS and OS of 29 patients treated with adjuvant chemotherapy were not significantly different to that of 47 patients without (p = 1 and p = 0.211, respectively). In the palliative setting patients treated with polychemotherapy (21 patients) had statistically better OS than patients treated with monochemotherapy (12 patients) (p = 0.0228). Conclusions: Our study suggests a survival benefit for advanced-stage SBA patients treated with poly- versus monochemotherapy. This, however, was a retrospective analysis with several potential confounders. Nevertheless, our study adds to the evidence suggesting that chemotherapy may be beneficial for patients with SBA, at least in the palliative setting.
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Affiliation(s)
- Donat Duerr
- Department of Medical Oncology / Hematology, City Hospital Triemli, Zurich, Switzerland
| | - Susan Ellard
- BC Cancer Agency - Centre for the Southern Interior, Kelowna, Canada
| | | | - Marianne Taylor
- BC Cancer Agency - Centre for the Southern Interior, Kelowna, Canada
| | - Sanjay Rao
- BC Cancer Agency - Centre for the Southern Interior, Kelowna, Canada
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29
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RETRACTED ARTICLE: Mouse models of intestinal inflammation and cancer. Arch Toxicol 2016; 90:2109-2130. [DOI: 10.1007/s00204-016-1747-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 06/01/2016] [Indexed: 12/19/2022]
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30
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Barral M, Dohan A, Allez M, Boudiaf M, Camus M, Laurent V, Hoeffel C, Soyer P. Gastrointestinal cancers in inflammatory bowel disease: An update with emphasis on imaging findings. Crit Rev Oncol Hematol 2016; 97:30-46. [DOI: 10.1016/j.critrevonc.2015.08.005] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2014] [Revised: 06/15/2015] [Accepted: 08/04/2015] [Indexed: 12/20/2022] Open
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31
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Bennett CM, Coleman HG, Veal PG, Cantwell MM, Lau CCL, Murray LJ. Lifestyle factors and small intestine adenocarcinoma risk: A systematic review and meta-analysis. Cancer Epidemiol 2015; 39:265-273. [PMID: 25736860 DOI: 10.1016/j.canep.2015.02.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Revised: 01/15/2015] [Accepted: 02/08/2015] [Indexed: 01/10/2023]
Abstract
BACKGROUND Although the incidence of small intestinal adenocarcinoma (SIA) is low, rates are increasing and little information regarding modifiable lifestyle risk factors is available. AIM To provide a systematic review of lifestyle factors and SIA risk. METHODS Ovid MEDLINE, EMBASE and Web of science were searched from inception to week 1 October 2013. Nine publications that reported on SIA risk in relation to alcohol intake (n=6), tobacco smoking (n=6), diet (n=5), body mass (n=3), physical activity (n=1), hormone use (n=1) and/or socio-economic status (n=3) were retrieved. Results for alcohol, smoking and SIA risk were pooled using random-effects meta-analyses to produce relative risks (RR) and 95% confidence intervals (CI). RESULTS The summary RR for individuals consuming the highest versus lowest category of alcohol intake was 1.51 (95% CI 0.83-2.75; n=5 studies) with significant increased risks emerging in sensitivity analysis with reduced heterogeneity (RR: 1.82, 95% CI: 1.05-3.15; n=4 studies). The pooled SIA RR for individuals in the highest versus lowest category of smoking was 1.24 (95% CI 0.71-2.17; n=5 studies). In relation to dietary factors, high fibre intakes and normal body weight may be protective, while high intakes of red/processed meat and sugary drinks may increase SIA risk. Evidence on socio-economic status and SIA risk was equivocal. Data on other factors were too sparse to draw any conclusions. CONCLUSIONS Alcohol may be associated with an increased risk of SIA. Further investigation of lifestyle factors, particularly alcohol, smoking and diet, in the aetiology of this cancer is warranted in large consortial studies.
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Affiliation(s)
- Caoimhe M Bennett
- Cancer Epidemiology & Health Services Research Group, Centre for Public Health, Queens University Belfast, United Kingdom
| | - Helen G Coleman
- Cancer Epidemiology & Health Services Research Group, Centre for Public Health, Queens University Belfast, United Kingdom.
| | - Philip G Veal
- Cancer Epidemiology & Health Services Research Group, Centre for Public Health, Queens University Belfast, United Kingdom; Public Health Agency, United Kingdom
| | - Marie M Cantwell
- Cancer Epidemiology & Health Services Research Group, Centre for Public Health, Queens University Belfast, United Kingdom
| | - Charlotte C L Lau
- Cancer Epidemiology & Health Services Research Group, Centre for Public Health, Queens University Belfast, United Kingdom
| | - Liam J Murray
- Cancer Epidemiology & Health Services Research Group, Centre for Public Health, Queens University Belfast, United Kingdom
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Kumagai R, Kohashi K, Takahashi S, Yamamoto H, Hirahashi M, Taguchi K, Nishiyama K, Oda Y. Mucinous phenotype and CD10 expression of primary adenocarcinoma of the small intestine. World J Gastroenterol 2015; 21:2700-2710. [PMID: 25759539 PMCID: PMC4351221 DOI: 10.3748/wjg.v21.i9.2700] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2014] [Revised: 11/13/2014] [Accepted: 12/22/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To clarify the correlation with phenotypic expression, clinicopathological features, genetic alteration and microsatellite-instability status in small intestinal adenocarcinoma (SIA).
METHODS: The cases of 47 patients diagnosed with primary SIAs that were surgically resected at our institution in 1975-2005 were studied. We reviewed clinicopathological findings (age, gender, tumor size, gross appearance, histological morphologic type, invasion depth, lymphatic permeation, venous invasion, and lymph node metastasis), and the immunohistochemical expression of MUC5AC, MUC6, MUC2, CD10, and mismatch-repair (MMR) proteins (MLH1 and MSH2). We analyzed KRAS and BRAF gene mutations, and the microsatellite instability (MSI) status. The immunohistochemical staining of CD10, MUC2, MUC5AC and MUC6 was considered positive when distinct staining in > 5% of the adenocarcinoma cells was recorded. To evaluate of MMR protein expression, we used adjacent normal tissue including lymphoid follicles, inflammatory cells, and stromal cells as an internal positive control. Sections without nuclear staining in the tumor cells were considered to have lost the expression of the respective MMR protein.
RESULTS: There were 29 males and 18 females patients (mean age 59.9 years, range: 23-87 years). Tumors were located in the duodenum in 14 cases (30%), the jejunum in 21 cases (45%), and the ileum in 12 cases (25%). A phenotypic expression analysis revealed 20 MUC2-positive tumors (42.6%), 11 MUC5AC-positive (23.4%), 4 MUC6-positive (8.5%), and 7 CD10-positive (14.9%). The tumor sizes of the MUC2(+) tumors were significantly larger than those of the MUC2(-) tumors (mean, 5.7 ± 1.4 cm vs 4.7 ± 2.1 cm, P < 0.05). All three tumors with adenomatous component were positive for MUC2 (P < 0.05). Polypoid appearance was seen significantly more frequently in the CD10(+) group than in the CD10(-) group (P < 0.05). The tumor size was significantly larger in the CD10 (+) group than in the CD10(-) group (mean, 5.9 ± 1.4 cm vs 5.0 ± 2.1 cm, P < 0.05). Of 34 SIAs with successfully obtained MSI data, 4 were MSI-high. Of the 4 SIAs positive for both MUC5AC and MUC2, 3 showed MSI-H (75%) and 3 were mucinous adenocarcinoma (75%). KRAS mutations were detected in 4 SIAs. SIAs had KRAS mutation expressed only MUC2, but were negative for MUC5AC, MUC6 and CD10.
CONCLUSION: These findings suggest that the phenotypic expression of SIAs is correlated with their biological behavior, genetic alteration, and MSI status.
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MESH Headings
- Adenocarcinoma, Mucinous/genetics
- Adenocarcinoma, Mucinous/immunology
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Mucinous/surgery
- Adult
- Aged
- Aged, 80 and over
- Biomarkers, Tumor/analysis
- Biomarkers, Tumor/genetics
- Biopsy
- DNA Mutational Analysis
- Female
- Humans
- Immunohistochemistry
- Intestinal Neoplasms/genetics
- Intestinal Neoplasms/immunology
- Intestinal Neoplasms/pathology
- Intestinal Neoplasms/surgery
- Intestine, Small/immunology
- Intestine, Small/pathology
- Intestine, Small/surgery
- Male
- Microsatellite Instability
- Middle Aged
- Mucin 5AC/analysis
- Mucin-2/analysis
- Mucin-6/analysis
- Mucins/analysis
- Mutation
- Neprilysin/analysis
- Phenotype
- Prognosis
- Proto-Oncogene Proteins/genetics
- Proto-Oncogene Proteins B-raf/genetics
- Proto-Oncogene Proteins p21(ras)
- Retrospective Studies
- Young Adult
- ras Proteins/genetics
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33
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Suzuki H, Hirata Y, Suzuki N, Ihara S, Sakitani K, Kobayashi Y, Kinoshita H, Hayakawa Y, Yamada A, Watabe H, Tateishi K, Ikenoue T, Yamaji Y, Koike K. Characterization of a new small bowel adenocarcinoma cell line and screening of anti-cancer drug against small bowel adenocarcinoma. THE AMERICAN JOURNAL OF PATHOLOGY 2014; 185:550-62. [PMID: 25478808 DOI: 10.1016/j.ajpath.2014.10.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Revised: 09/29/2014] [Accepted: 10/02/2014] [Indexed: 12/22/2022]
Abstract
Small bowel adenocarcinoma (SBA) is a rare, aggressive malignancy with a poor prognosis, and the mechanisms of carcinogenesis in SBA remain unclear. Our aims were to investigate the molecular mechanisms underlying SBA and to identify treatments by establishing and characterizing an SBA cell line and performing anti-cancer drug screening. SIAC1 cells, established from jejunal SBA, showed epithelial characteristics and formed organoids in 3D culture. SIAC1 cells had a heterozygous β-catenin deletion mutation, resulting in a stable β-catenin protein with enhanced Wnt/β-catenin activity. SIAC1 cells lacked MLH1 and MSH6 expression, and target genes such as TGFBR2 and ACVR2 showed frameshift mutations. Among 10 clinical SBA samples, 2 (20%) had interstitial deletions in β-catenin, expression of mismatch repair protein was aberrant in 4 (40%), and heterozygous frameshift mutations of three target genes were found in all 10 samples. On screening assay using 140 compounds, eribulin significantly inhibited SIAC1 cell growth both in vitro and in vivo by inhibition of the Wnt/β-catenin pathway via enhanced degradation of β-catenin. In conclusion, we established an SBA cell line with molecular characteristics similar to those of clinical SBA samples, including β-catenin deletion and mismatch repair protein deficiency, that will be useful for SBA research. Eribulin might be a candidate for SBA treatment due to its inhibitory effect on Wnt/β-catenin signaling.
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Affiliation(s)
- Hirobumi Suzuki
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
| | - Yoshihiro Hirata
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
| | - Nobumi Suzuki
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Sozaburo Ihara
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Kosuke Sakitani
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yuka Kobayashi
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Hiroto Kinoshita
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yoku Hayakawa
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Atsuo Yamada
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Hirotsugu Watabe
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Keisuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Tsuneo Ikenoue
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yutaka Yamaji
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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Guo X, Mao Z, Su D, Jiang Z, Bai L. The clinical pathological features, diagnosis, treatment and prognosis of small intestine primary malignant tumors. Med Oncol 2014; 31:913. [PMID: 24639284 DOI: 10.1007/s12032-014-0913-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2014] [Accepted: 03/06/2014] [Indexed: 02/06/2023]
Abstract
The aim of the study was to describe and analyze the clinicopathological features and diagnosis of Chinese patients with small intestine primary malignant tumors and to explore the best therapy to small bowel adenocarcinoma (SBA). More than 26,000 patients with digestive tract malignant tumors received treatment in PLA hospital from 2000 to 2011, and among them, there were 887 patients who had small intestine primary malignant tumors, and 666 of 887 patients had the completed basic clinical documents. We retrospectively analyzed the correlation between clinical and pathological features of the 666 patients and analyzed the survival and prognosis of 173 SBA patients with follow-up data. Both the number of patients with primary malignant tumors of the small intestine and the number of patients who received chemotherapy showed an increasing trend. The ratio of male to female was 1.58:1. The male patients significantly exceed the female patients with tumors of non-ampullary duodenum, jejunum and duodenal ampulla; and most of the patients are over 60 years of age. For patients burdened with either of the pathological types of tumors, the males exceeded the females, but there was no significant difference. Abdominal pain was the main clinical manifestation for patients with tumors of non-ampullary duodenum, jejunum and ileum, and the most common clinical manifestations were jaundice and abdominal pain for patients with ampullary duodenal tumors, adenocarcinoma, neuroendocrine tumors and sarcoma. In addition, patients with stromal tumors were prone to gastrointestinal bleeding. Gastrointestinal endoscopy was the most common examinational procedure. Patients under 60 years of age were prone to surgery and chemotherapy after surgery, and patients over 60 years of age were prone to supportive treatment and chemotherapy without surgery. The medium overall survival of patients who received surgery without chemotherapy, chemotherapy after surgery, chemotherapy without surgery and supportive treatment were 40.0, 35.0, 9.0 and 7.5 months, respectively. For the 173 SBA patients with follow-up data, treatment, age and distant metastasis were important prognostic factors; 149 of 173 SBA patients received only surgery, and the depth of tumor invasion, lymph node metastasis and surgical approach were important prognostic factors. Adjuvant chemotherapy had not provided significant benefit to prolong OS in patients with adenocarcinoma. The incidence of small intestine primary malignant tumors is very low, and it is difficult to diagnose. The patients should be aggressively treated and regularly followed up with related clinical and pathological features. Currently, surgery is the most effective treatment, and the role of chemotherapy needs further large-scale clinical studies.
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Affiliation(s)
- Xiaochuan Guo
- Department of Oncology, PLA General Hospital, Beijing, 100853, People's Republic of China
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35
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Aparicio T, Zaanan A, Svrcek M, Laurent-Puig P, Carrere N, Manfredi S, Locher C, Afchain P. Small bowel adenocarcinoma: epidemiology, risk factors, diagnosis and treatment. Dig Liver Dis 2014; 46:97-104. [PMID: 23796552 DOI: 10.1016/j.dld.2013.04.013] [Citation(s) in RCA: 199] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Accepted: 04/29/2013] [Indexed: 12/11/2022]
Abstract
Small bowel adenocarcinomas are rare tumours, but their incidence is increasing. Their most common primary location is the duodenum. The few studies that have collected data regarding small bowel adenocarcinoma are not homogeneous and are widely spread over time. Even though these tumours are most often sporadic, some predisposing diseases have been identified, among which Crohn's disease and genetic syndromes. Early diagnosis of small bowel adenocarcinoma remains difficult despite significant radiological and endoscopic progress. After surgical resection the main prognostic factor is node invasion; in this case, adjuvant chemotherapy can be expected to be beneficial, although this has not been established by randomised trials. For metastatic disease, platinum-based chemotherapy seems to be the most effective treatment. Targeted therapies have not yet been evaluated in this type of cancer.
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Affiliation(s)
- Thomas Aparicio
- Gastroenterology and Digestive Oncology Unit, Avicenne Hospital, HUPSSD, APHP, Université Paris 13, Sorbonne Paris Cité, Bobigny, France.
| | - Aziz Zaanan
- Gastroenterology and Digestive Oncology Unit, Georges Pompidou Hospital, APHP, Paris, France; UMR-S775, INSERM, Paris, France
| | - Magali Svrcek
- Anatomopathology Unit, Saint Antoine Hospital, APHP, Paris France
| | | | | | - Sylvain Manfredi
- Hepato-Gastroenterology Unit, Pontchaillou Hospital, Rennes, France
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36
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Egan L, D'Inca R, Jess T, Pellino G, Carbonnel F, Bokemeyer B, Harbord M, Nunes P, Van der Woude J, Selvaggi F, Triantafillidis J. Non-colorectal intestinal tract carcinomas in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (II). J Crohns Colitis 2014; 8:19-30. [PMID: 23664498 DOI: 10.1016/j.crohns.2013.04.009] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Accepted: 04/05/2013] [Indexed: 02/08/2023]
Abstract
Patients with inflammatory bowel diseases (IBD) have an excess risk of certain gastrointestinal cancers. Much work has focused on colon cancer in IBD patients, but comparatively less is known about other more rare cancers. The European Crohn's and Colitis Organization established a pathogenesis workshop to review what is known about these cancers and formulate proposals for future studies to address the most important knowledge gaps. This article reviews the current state of knowledge about small bowel adenocarcinoma, ileo-anal pouch and rectal cuff cancer, and anal/perianal fistula cancers in IBD patients.
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Affiliation(s)
- Laurence Egan
- Discipline of Pharmacology & Therapeutics, NUI, Galway, Ireland.
| | - Renata D'Inca
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Italy
| | - Tine Jess
- Department of Epidemiology Research, Statens Serum Institut, National Health Surveillance & Research, Denmark
| | | | - Franck Carbonnel
- Service de Gastroentérologie, CHU de Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris Sud, France
| | - Bernd Bokemeyer
- Department of General Internal Medicine I, Christian-Albrechts-University, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Marcus Harbord
- Chelsea & Westminster Hospital, 369 Fulham Road, London, UK
| | - Paula Nunes
- Lisbon University & Higher School of Health Technology of Lisbon, Lisbon, Portugal; Hospital Cuf Descobertas, Lisbon, Portugal
| | | | | | - John Triantafillidis
- Department of Gastroenterology and Center for IBD "Saint Panteleimon" Hospital, Nicea, Greece
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Whitcomb E, Liu X, Xiao SY. Crohn enteritis-associated small bowel adenocarcinomas exhibit gastric differentiation. Hum Pathol 2013; 45:359-67. [PMID: 24331840 DOI: 10.1016/j.humpath.2013.09.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 09/18/2013] [Indexed: 01/13/2023]
Abstract
Primary small bowel adenocarcinoma is rare. Although generally similar to colonic adenocarcinoma, some small bowel adenocarcinomas exhibit unique morphologic features, particularly those arising in association with Crohn disease. In this study, 15 sporadic small bowel adenocarcinomas and 11 Crohn enteritis-associated small bowel adenocarcinomas were examined for histology and immunohistochemical profile including cytokeratins (CK) 7 and 20, intestinal markers CDX2 and MUC2, and gastric epithelial markers MUC5AC and MUC6. We found that Crohn enteritis-associated small bowel adenocarcinomas frequently resemble gastric tubular adenocarcinoma histologically. In addition, when compared to sporadic small bowel adenocarcinoma, the former expressed MUC5AC and MUC6 with much higher frequency (82% vs. 7% and 73% vs. 0%, respectively). Ten of 11 Crohn enteritis-associated small bowel adenocarcinomas (91%) were positive for at least one gastric-type marker (MUC5AC or MUC6). Expression of CK7 was also more frequent in Crohn enteritis-associated small bowel adenocarcinoma (73% versus 27%) while expression of CK20 was less frequent (64% vs. 100%). There was no difference between sporadic and Crohn enteritis-associated small bowel adenocarcinoma in expression of CDX2 (100% vs. 91%) and MUC2 (93% vs. 73%). These observations suggest that there is a difference in the morphologic and immunohistochemical characteristics of sporadic versus Crohn enteritis-associated small bowel adenocarcinoma, particularly in their expression of gastric-type mucin. The findings also suggest that gastric differentiation in Crohn enteritis-associated small bowel adenocarcinoma is related to gastric metaplasia, a common phenomenon in Crohn disease.
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Affiliation(s)
- Emma Whitcomb
- Department of Pathology, University of Chicago Hospitals, Chicago, IL 60637
| | - Xiuli Liu
- Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH 44195
| | - Shu-Yuan Xiao
- Department of Pathology, University of Chicago Hospitals, Chicago, IL 60637.
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Wang Y, Jiang CQ, Guan J, Yang GF, Yue JQ, Chen HL, Xue JL, Xu ZG, Qian Q, Fan LF. Molecular alterations of EGFR in small intestinal adenocarcinoma. Int J Colorectal Dis 2013; 28:1329-35. [PMID: 23644682 DOI: 10.1007/s00384-013-1689-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/18/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Molecular testing for epidermal growth factor receptor (EGFR) mutations has recently become a standard practice for the management of patients with non-squamous none small cell lung cancer. Primary small intestine adenocarcinoma (SIA) is an uncommon malignancy, and EGFR mutation in the cancer has not been well characterized due to its rarity. METHODS A micro-tissue array with 53 SIAs and 24 surgically resected primary non-ampullary SIAs were studied. EGFR mutations were analyzed by DNA sequencing in 24 cases with formalin-fixed paraffin-embedded blocks. All 77 cases were examined by immunohistochemistry (IHC) using antibodies specific for the EGFR E746-A750 deletion in exon 19 (DEL), L858R point mutation in exon 21 (L858R), and total EGFR. EGFR amplifications were detected by fluorescence in situ hybridization. RESULTS A positive reaction of DEL-specific, L858R-specific, and total EGFR antibodies was detected in seven (9.1%), 5 (6.5%) and 35 (45.5%) of 77 SIAs by IHC, respectively. Positive reaction of the three antibodies was not significantly correlated with patient's age, gender, differentiation, and stage. EGFR gene amplification was assayed in 77 SIAs in micro-tissue array. Of 24 SIA samples that had DNA sequencing, two (8.3%) harbored exon 19 deletion and one (4.2%) harbored L858R point mutation. Only one case with EGFR amplification and two cases with polysomy were shown. CONCLUSIONS Our findings suggested that mutations and amplification in EGFR genes are minor events, and most of SIAs may be unsuitable to EGFR-TKIs treatment.
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Affiliation(s)
- Yan Wang
- Department of Pathology, School of Basic Medical Science, Wuhan University, 185 Donghu Road, Wuchang District, 430071, Wuhan, China
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Roh J, Knight S, Chung JY, Eo SH, Goggins M, Kim J, Cho H, Yu E, Hong SM. S100A4 expression is a prognostic indicator in small intestine adenocarcinoma. J Clin Pathol 2013; 67:216-21. [PMID: 24062356 DOI: 10.1136/jclinpath-2013-201883] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
AIMS Due to the rarity of small intestine adenocarcinoma (SIAC), estimating the prognosis for patients with surgically resected SIAC is difficult. Overexpression of S100A4 has been linked to worse patient survival in several malignant neoplasms, but its significance in SIAC has not been determined. METHODS S100A4 protein expression was assessed in 197 surgically resected SIAC cases and compared with clinicopathological factors, including patient survival. RESULTS A progressive increase in S100A4 labelling was observed in normal intestinal epithelium, adenoma and adenocarcinoma (p<0.001), and 50 SIAC cases (26.2%) showed strong S100A4 expression. Patients with SIAC with strong S100A4 expression had a higher pT classification (p=0.05), as well as increased lymph node metastasis (p=0.009) and perineural invasion (p=0.002). Patients with SIAC with strong S100A4 expression had significantly worse survival (median survival, 21 months) than those with weak/no S100A4 expression (42.5 months) by univariable (p=0.04) and multivariable (p=0.01) analyses. CONCLUSIONS S100A4 overexpression is observed in a subset of SIACs, is associated with advanced disease and can be used as a prognostic indicator of poor prognosis in patients with SIAC.
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Affiliation(s)
- Jin Roh
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, , Seoul, Republic of Korea
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Small bowel adenocarcinoma in Crohn disease: CT-enterography features with pathological correlation. ACTA ACUST UNITED AC 2012; 37:338-49. [PMID: 21671043 DOI: 10.1007/s00261-011-9772-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE The aim of this study was to analyze the clinical, pathological, and CT-enterography findings of small bowel adenocarcinomas in Crohn disease patients. MATERIALS AND METHODS Clinical, histopathological, and imaging findings were retrospectively evaluated in seven Crohn disease patients with small bowel adenocarcinoma. CT-enterography examinations were reviewed for morphologic features and location of tumor, presence of stratification, luminal stenosis, proximal dilatation, adjacent lymph nodes, and correlated with findings at histological examination. RESULTS The tumor was located in the terminal (n = 6) or distal (n = 1) ileum. On CT-enterography, the tumor was visible in five patients, whereas two patients had no visible tumor. Four different patterns were individualized including small bowel mass (n = 2), long stenosis with heterogeneous submucosal layer (n = 2), short and severe stenosis with proximal small bowel dilatation (n = 2), and sacculated small bowel loop with irregular and asymmetric circumferential thickening (n = 1). Stratification, fat stranding, and comb sign were present in two, two, and one patients, respectively. CONCLUSION Identification of a mass being clearly visible suggests strongly the presence of small bowel adenocarcinoma in Crohn disease patients but adenocarcinoma may be completely indistinguishable from benign fibrotic or acute inflammatory stricture. Knowledge of these findings is critical to help suggest the diagnosis of this rare but severe complication of Crohn disease.
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Kim G, Chung JY, Jun SY, Eom DW, Bae YK, Jang KT, Kim J, Yu E, Hong SM. Loss of S100A14 expression is associated with the progression of adenocarcinomas of the small intestine. Pathobiology 2012; 80:95-101. [PMID: 23038644 DOI: 10.1159/000342394] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2012] [Accepted: 08/07/2012] [Indexed: 01/13/2023] Open
Abstract
OBJECTIVES Small intestinal adenocarcinoma (SIAC) is an exceedingly rare human malignant tumor, and its association with the S100A14 gene is not known yet. We aimed to investigate the clinicopathological correlations between S100A14 expression and SIAC. METHODS Immunohistochemical analyses of S100A14, p21 and p53 were performed using tissue microarray analysis of 175 surgically resected SIACs. RESULTS Of 175 SIACs, loss of S100A14 expression was observed in 128 cases (73.1%). Loss of S100A14 expression was associated with lymph node metastasis (p = 0.009) and advanced disease stage (p = 0.013), and was more frequently observed in distal than duodenal tumors (p = 0.043). The majority of SIACs lost p21 expression (93.7%), and significant loss of p21 expression was observed in cancers with high pT stages (pT(3) and pT(4); p = 0.011), lymph node metastasis (p = 0.029) and advanced cancer stage defined by the American Joint Committee on Cancer (p = 0.005). Overexpression of p53 was found in 23.4% of cases. Positive expression of p53 was associated with distally located SIACs (jejunum or ileum; p = 0.006). There was no association between the expression of S100A14 and p21 or p53. CONCLUSION Loss of S100A14 in SIAC is common and is associated with higher metastatic potential and advanced clinical stage.
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Affiliation(s)
- Gwangil Kim
- Department of Pathology, Bundang CHA Medical Center, CHA University, Seongnam, Korea
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Halfdanarson TR, Grothey A. Establishing a standard of care for small bowel adenocarcinomas: challenges and lessons learned. Oncologist 2012; 17:1133-4. [PMID: 22923454 DOI: 10.1634/theoncologist.2012-0323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Pan SY, Morrison H. Epidemiology of cancer of the small intestine. World J Gastrointest Oncol 2011; 3:33-42. [PMID: 21461167 PMCID: PMC3069308 DOI: 10.4251/wjgo.v3.i3.33] [Citation(s) in RCA: 143] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2010] [Revised: 02/08/2011] [Accepted: 02/15/2011] [Indexed: 02/05/2023] Open
Abstract
Cancer of the small intestine is very uncommon. There are 4 main histological subtypes: adenocarcinomas, carcinoid tumors, lymphoma and sarcoma. The incidence of small intestine cancer has increased over the past several decades with a four-fold increase for carcinoid tumors, less dramatic rises for adenocarcinoma and lymphoma and stable sarcoma rates. Very little is known about its etiology. An increased risk has been noted for individuals with Crohn’s disease, celiac disease, adenoma, familial adenomatous polyposis and Peutz-Jeghers syndrome. Several behavioral risk factors including consumption of red or smoked meat, saturated fat, obesity and smoking have been suggested. The prognosis for carcinomas of the small intestine cancer is poor (5 years relative survival < 30%), better for lymphomas and sarcomas, and best for carcinoid tumors. There has been no significant change in long-term survival rates for any of the 4 histological subtypes. Currently, with the possible exceptions of obesity and cigarette smoking, there are no established modifiable risk factors which might provide the foundation for a prevention program aimed at reducing the incidence and mortality of cancers of the small intestine. More research with better quality and sufficient statistical power is needed to get better understanding of the etiology and biology of this cancer. In addition, more studies should be done to assess not only exposures of interest, but also host susceptibility.
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Affiliation(s)
- Sai Yi Pan
- Sai Yi Pan, Howard Morrison, Science Integration Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, Ottawa, Ontario, K1A 0K9, Canada
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Chan OT, Chen ZME, Chung F, Kawachi K, Phan DC, Himmelfarb E, Lin F, Perry A, Wang HL. Lack of HER2 overexpression and amplification in small intestinal adenocarcinoma. Am J Clin Pathol 2010; 134:880-5. [PMID: 21088150 DOI: 10.1309/ajcpk6qhnnoemjim] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
HER2 overexpression and amplification have been studied as a therapeutic and prognostic target in a number of human cancers, including esophageal, gastric, and colorectal adenocarcinomas. However, HER2 status has not been well investigated in primary small intestinal adenocarcinoma, probably because of its rarity. In this study, we conducted immunohistochemical analysis and fluorescence in situ hybridization (FISH) for HER2 on 49 primary nonampullar small intestinal adenocarcinomas. The results showed a complete lack of HER2 protein expression in 47 cases (96%) by immunohistochemical analysis. Only 2 cases (4%) showed a 1+ staining pattern. No tumors exhibited 2+ or 3+ HER2 immunoreactivity. By FISH, none of the tumors, including those with 1+ HER2 immunoreactivity, exhibited HER2 gene amplification. These observations demonstrate that HER2 protein overexpression and gene amplification are infrequent events, if they occur at all, in small intestinal adenocarcinoma. Thus, routine immunohistochemical and/or FISH testing for HER2 for potential targeted anti-HER2 therapy may not be beneficial for patients with primary small intestinal adenocarcinoma.
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Westbrook AM, Szakmary A, Schiestl RH. Mechanisms of intestinal inflammation and development of associated cancers: lessons learned from mouse models. Mutat Res 2010; 705:40-59. [PMID: 20298806 PMCID: PMC2878867 DOI: 10.1016/j.mrrev.2010.03.001] [Citation(s) in RCA: 86] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2009] [Revised: 02/21/2010] [Accepted: 03/08/2010] [Indexed: 12/15/2022]
Abstract
Chronic inflammation is strongly associated with approximately 1/5th of all human cancers. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli; however, over time, this results in continuous tissue destruction and promotion and maintenance of carcinogenesis. Here we focus on intestinal inflammation and its associated cancers, a group of diseases on the rise and affecting millions of people worldwide. Intestinal inflammation can be widely grouped into inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and celiac disease. Long-standing intestinal inflammation is associated with colorectal cancer and small-bowel adenocarcinoma, as well as extraintestinal manifestations, including lymphomas and autoimmune diseases. This article highlights potential mechanisms of pathogenesis in inflammatory bowel diseases and celiac disease, as well as those involved in the progression to associated cancers, most of which have been identified from studies utilizing mouse models of intestinal inflammation. Mouse models of intestinal inflammation can be widely grouped into chemically induced models; genetic models, which make up the bulk of the studied models; adoptive transfer models; and spontaneous models. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen, in combination with loss of epithelial barrier function, and dysfunction and dysregulation of the innate and adaptive immune responses lead to chronic intestinal inflammation. Transcriptional changes in this environment leading to cell survival, hyperplasia, promotion of angiogenesis, persistent DNA damage, or insufficient repair of DNA damage due to an excess of proinflammatory mediators are then thought to lead to sustained malignant transformation. With regards to extraintestinal manifestations such as lymphoma, however, more suitable models are required to further investigate the complex and heterogeneous mechanisms that may be at play.
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Affiliation(s)
- Aya M. Westbrook
- Molecular Toxicology Interdepartmental Program, UCLA School of Medicine and School of Public Health, University of California at Los Angeles, Los Angeles, CA 90095
- Department of Pathology and Lab Medicine, UCLA School of Medicine and School of Public Health, University of California at Los Angeles, Los Angeles, CA 90095
| | - Akos Szakmary
- Institute for Cancer Research, Medical University of Vienna, Austria
| | - Robert H. Schiestl
- Molecular Toxicology Interdepartmental Program, UCLA School of Medicine and School of Public Health, University of California at Los Angeles, Los Angeles, CA 90095
- Department of Pathology and Lab Medicine, UCLA School of Medicine and School of Public Health, University of California at Los Angeles, Los Angeles, CA 90095
- Institute for Cancer Research, Medical University of Vienna, Austria
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Trikudanathan G, Dasanu CA. Evolving pharmacotherapeutic strategies for small bowel adenocarcinoma. Expert Opin Pharmacother 2010; 11:1695-704. [DOI: 10.1517/14656566.2010.484421] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Chang HK, Yu E, Kim J, Bae YK, Jang KT, Jung ES, Yoon GS, Kim JM, Oh YH, Bae HI, Kim GI, Jung SJ, Gu MJ, Kim JY, Jang KY, Jun SY, Eom DW, Kwon KW, Kang GH, Park JB, Hong S, Lee JS, Park JY, Hong SM. Adenocarcinoma of the small intestine: a multi-institutional study of 197 surgically resected cases. Hum Pathol 2010; 41:1087-96. [PMID: 20334897 DOI: 10.1016/j.humpath.2010.01.006] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2009] [Revised: 01/12/2010] [Accepted: 01/13/2010] [Indexed: 12/27/2022]
Abstract
Small intestinal adenocarcinoma is a rare malignant neoplasm, and its clinicopathologic characteristics have not been well elucidated. A total of 197 small intestinal adenocarcinoma cases were collected from 22 institutions in South Korea and were evaluated for clinicopathologic factors that affect the prognosis of small intestinal adenocarcinoma patients using univariate and multivariate analyses. The mean patient age was 59 years, and the male-to-female ratio was 1.7:1. Tumors were located in the duodenum of 108 cases (55%), the jejunum in 59 (30%), and the ileum in 30 (15%). Predisposing conditions were observed in 23 cases (12%), including 17 cases with sporadic adenomas, 3 with Peutz-Jeghers syndrome, 2 with Meckel diverticulum, and 1 with Crohn disease. Synchronous or metachronous malignant tumors were identified in 31 cases (16%), including 13 colorectal and 10 stomach cancers. About 90% of tumors were classified as either pT3 (63 cases) or pT4 (112 cases). The median survival time for all small intestinal adenocarcinoma patients was 39.7 months. Compared with small intestinal adenocarcinomas without accompanying sporadic adenomas, small intestinal adenocarcinomas with accompanying adenomas were more well differentiated (P < .0001), with a more polypoid growth pattern (P < .0001), a lower pT classification (P < .0001), less perineural invasion (P = .01), and less lymphatic invasion (P = .03). Small intestinal adenocarcinoma patients with associated sporadic adenomas (77%) had a significantly better 5-year survival rate than those without sporadic adenomas (38%, P = .02). By univariate analysis, small intestinal adenocarcinoma patients had significantly different survival based on pT classification (P = .003), lymph node metastasis (P < .0001), distal location (jejunal and ileal carcinomas) (P = .003), retroperitoneal tumor seeding (P < .0001), vascular invasion (P = .007), lymphatic invasion (P = .001), peritumoral dysplasia (P = .004), and radiation therapy (P = .006). By multivariate analysis, lymph node metastasis (P = .01) and distal location (P = .003) were independent predictors of a worse prognosis. In conclusion, (1) small intestinal adenocarcinomas are diagnosed at an advanced disease stage; therefore, the development of strategies for detection at an earlier stage is needed. (2) Small intestinal adenocarcinoma patients with an adenomatous component had a better survival than those without an adenomatous component. (3) Lymph node metastasis and distal location (jejunum and ileum) of tumor are the most important independent prognostic factors.
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Affiliation(s)
- Hee-Kyung Chang
- Department of Pathology, Kosin University College of Medicine, Pusan, 602-702 South Korea
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Mitsui K, Tanaka S, Yamamoto H, Kobayashi T, Ehara A, Yano T, Goto H, Nakase H, Tanaka S, Matsui T, Iida M, Sugano K, Sakamoto C. Role of double-balloon endoscopy in the diagnosis of small-bowel tumors: the first Japanese multicenter study. Gastrointest Endosc 2009; 70:498-504. [PMID: 19555947 DOI: 10.1016/j.gie.2008.12.242] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2008] [Accepted: 12/23/2008] [Indexed: 02/08/2023]
Abstract
BACKGROUND The early diagnosis of small-bowel tumors (SBT) was a difficult task until the advent of capsule endoscopy (CE) and double-balloon endoscopy (DBE) allowed access to the disease site. However, although CE and DBE have greatly simplified the task, DBE studies have yet to provide sufficient data on the diagnosis and outcome of patients with SBTs. OBJECTIVE To determine the efficacy of DBE examination in the detection and diagnosis of SBT. DESIGN A retrospective analysis of cross-sectional case series. SETTING Seven major medical centers in Japan. PATIENTS The first 1035 consecutive DBE cases at these major Japanese centers since the introduction of DBE. MAIN OUTCOME MEASUREMENTS The percentage of subjects with SBT and a diagnosis of SBT, their indications for DBE, and diagnostic and therapeutic DBE procedures carried out for SBT. RESULTS SBTs were identified in 144 of 1035 subjects (13.9%) who underwent DBE between September 2000 and December 2005. For subjects with SBT, the most common indication for DBE was the suspected presence of a SBT (61/144 [42.4%]). For subjects without SBT, the most common indication was obscure GI bleeding (OGIB) (419/891 [47.0%]). Malignant lymphoma and GI stromal tumor (GIST) were the most frequent (31/144 [21.5%]) and the second-most frequent SBTs (27/144 [18.8%]), respectively, in this database. We also performed 85 biopsies and 45 therapeutic procedures for the evaluation and treatment of SBTs in 144 patients. Although complications were encountered in 5.3% of cases (14/266 sessions), none of these were life threatening in the present study. CONCLUSION DBE proved a valuable tool for the detection and diagnosis of SBTs, especially when tumors were suspected. Biopsies and therapeutic procedures were also possible in most of these patients, which directed our management of the disease.
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Affiliation(s)
- Keigo Mitsui
- Division of Gastroenterology, Department of Medicine, Nippon Medical School, Tokyo, Japan
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Zouhairi ME, Venner A, Charabaty A, Pishvaian MJ. Small bowel adenocarcinoma. Curr Treat Options Oncol 2009; 9:388-99. [PMID: 19365735 DOI: 10.1007/s11864-009-0098-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2008] [Accepted: 03/23/2009] [Indexed: 12/31/2022]
Abstract
Small bowel cancers are rare, accounting for only about 6000 cases/year in the United States, approximately 25% of which are small bowel adenocarcinomas. Small bowel adenocarcinomas have traditionally been considered to be highly fatal due to their nonspecific presentation at the time of diagnosis, and to the lack of responsiveness to older chemotherapy regimens. However, that paradigm may be changing. Newer diagnostic techniques such as video capsule and double balloon enteroscopy may facilitate earlier diagnosis. In addition, modern chemotherapy regimens have produced improved response rates and survival rates, when compared to historical controls. Still, there remains great need for multi-institutional, cooperative group studies to define the optimal treatment of small bowel adenocarcinoma, both in the adjuvant and advanced/metastatic setting.
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Affiliation(s)
- Majed El Zouhairi
- Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road, NW, Washington, DC 20007, USA
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