|
1
|
Walter D, Schnitzbauer AA, Schulze F, Trojan J. The Diagnosis and Treatment of Ampullary Carcinoma. DEUTSCHES ARZTEBLATT INTERNATIONAL 2023; 120:729-735. [PMID: 37656482 DOI: 10.3238/arztebl.m2023.0195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 08/09/2023] [Accepted: 08/09/2023] [Indexed: 09/02/2023]
Abstract
BACKGROUND Ampullary or papillary carcinoma is a malignant tumor arising from the mucosa in the region of the major duodenal papilla, also known as the ampulla of Vater. Uniform treatment recommendations are lacking both for the adjuvant situation and for palliative care. METHODS A selective literature search was carried out in PubMed in order to identify the most informative publications concerning the epidemiology, clinico-pathological background, and surgical and medical treatment of this condition. RESULTS Ampullary carcinoma has an incidence of 0.5 to 0.9 per 100 000 persons and a poor prognosis, with a 5-year survival rate of 41% to 45% for locally confined and 4% to 7% for metastatic disease. Most such tumors are of an intestinal or a pan - creaticobiliary immunohistochemical subtype; the latter has a worse prognosis (median survival, 72-80 vs. 33-41 months). Targeted treatment is not yet available for either subtype, nor is there enough scientific evidence available for the formulation of specific therapeutic recommendations in either the adjuvant or the palliative situation. The treatment of choice for ampullary carcinoma is radical oncological resection of the head of the pancreas with systematic lymphadenectomy. Five-year overall survival is between 10% and 75% depending on the stage. No definitive recommendation for adjuvant therapy can be given. Palliative therapy can be oriented to the published treatment strategies for cancer of the colon, pancreas, and bile duct. CONCLUSION The current state of the evidence on the treatment of ampullary carcinoma is poor. Therapeutic decisions should be discussed in an interdisciplinary tumor board and should, in our opinion, take the histological subtype into account.
Collapse
Affiliation(s)
- Dirk Walter
- Department of Internal Medicine, J.W. Goethe University Hospital, Frankfurt/Main; Department of General, Visceral, Transplant- and Thoracic Surgery, J.W. Goethe University Hospital, Frankfurt/Main; Dr. Senckenberg Institute for Pathology, University Hospital Frankfurt, Goethe University Frankfurt am Main
| | | | | | | |
Collapse
|
|
2
|
Shin DW. [Treatment of Ampullary Adenocarcinoma]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 82:159-170. [PMID: 37876255 DOI: 10.4166/kjg.2023.110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 09/28/2023] [Accepted: 10/03/2023] [Indexed: 10/26/2023]
Abstract
The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary ampullary adenocarcinoma is a rare malignancy, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. Jaundice from a biliary obstruction is the most common symptom of ampullary adenocarcinoma. In the early stages, radical pancreatoduodenectomy is the standard surgical approach. On the other hand, no randomized controlled trial has provided evidence to guide physicians on the choice of adjuvant/palliative chemotherapy because of the rarity of the disease and the paucity of related research. This paper reports the biology, histology, current therapeutic strategies, and potential future therapies of ampullary adenocarcinoma.
Collapse
Affiliation(s)
- Dong Woo Shin
- Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
| |
Collapse
|
|
3
|
Teufel A, Meindl-Beinker NM, Hösel P, Gerken M, Roig A, Ebert MP, Herr W, Scheiter A, Pauer A, Schlitt HJ, Klinkhammer-Schalke M. Characteristics and outcome of patients with small bowel adenocarcinoma (SBA). J Cancer Res Clin Oncol 2023; 149:4579-4590. [PMID: 36163558 PMCID: PMC10349691 DOI: 10.1007/s00432-022-04344-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 08/31/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Small bowel adenocarcinoma (SBA) remains a rare malignancy accounting for less than 5% of all the gastrointestinal tract cancers. However, only limited data and expert guidelines are available for this entity. As a result, treatment concepts are predominantly derived from colorectal cancer. METHODS To substantiate data on the course of disease, diagnosis and treatment of SBA, we performed a population-based analysis from a Bavarian population of 2.2 million people. RESULTS We identified 223 patients with SBA. Mean age at diagnosis was 67.8 years and patients were diagnosed rather late (34.5% UICC stage IV). Largest proportion of these patients were diagnosed with adenocarcinoma of the duodenum (132 patients, 59.2%) and most patients were diagnosed with late stage cancer, stage IV (70 patients, 31.4%). With respect to treatment, most patients underwent primary surgery (187 patients, 84.6%). Systemic therapy seemed to have an impact in UICC stage IV patients but not in UICC stage IIB or III. The 5-year survival rate was 29.0%. This was significantly less compared to colon cancer in the same cohort, which was 50.0%. Furthermore, median survival of patients with small bowel cancer was only 2.0 years (95% CI 1.4-2.5) compared to 4.9 years (95% CI 4.8-5.1) of patients with colon cancer. CONCLUSION SBA showed a distinct epidemiology compared to colon cancer. Thus, data acquisition particularly on systemic treatment are paramount, with the objective to complement the available guidelines.
Collapse
Affiliation(s)
- Andreas Teufel
- Division of Hepatology, Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
- Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
| | - Nadja M Meindl-Beinker
- Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Pauline Hösel
- DKFZ-Hector Cancer Institute at the University Medical Center, Mannheim, Germany
| | - Michael Gerken
- Bavarian Cancer Registry, Regional Center Regensburg, Bavarian Health and Food Safety Authority, Regensburg, Germany
- Regensburg Tumor Center, Institute for Quality Assurance and Health Services Research at the University of Regensburg, Regensburg, Germany
| | - Ana Roig
- Division of Hepatology, Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Matthias P Ebert
- Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ-Hector Cancer Institute at the University Medical Center, Mannheim, Germany
- Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Wolfgang Herr
- Department of Internal Medicine III, University Medical Center Regensburg, Regensburg, Germany
| | | | - Armin Pauer
- Regensburg Tumor Center, Institute for Quality Assurance and Health Services Research at the University of Regensburg, Regensburg, Germany
| | - Hans J Schlitt
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany
| | - Monika Klinkhammer-Schalke
- Bavarian Cancer Registry, Regional Center Regensburg, Bavarian Health and Food Safety Authority, Regensburg, Germany
- Regensburg Tumor Center, Institute for Quality Assurance and Health Services Research at the University of Regensburg, Regensburg, Germany
| |
Collapse
|
|
4
|
Symons R, Daly D, Gandy R, Goldstein D, Aghmesheh M. Progress in the Treatment of Small Intestine Cancer. Curr Treat Options Oncol 2023; 24:241-261. [PMID: 36826686 DOI: 10.1007/s11864-023-01058-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2023] [Indexed: 02/25/2023]
Abstract
OPINION STATEMENT Small intestine cancer is rare, accounting for approximately 3% of all gastrointestinal malignancies. The most common histological subtypes include adenocarcinoma, neuroendocrine tumours (NETs) and gastrointestinal stromal tumours (GISTs). In localised disease, surgery remains the mainstay of treatment and the best approach to improve survival. Current treatment for small intestine adenocarcinoma (SIA) is extrapolated from small studies and data from colorectal cancer (CRC). There is limited evidence to guide therapy in the adjuvant setting. However, there are small phase II studies in the advanced setting providing evidence for the role of chemotherapy and immunotherapy. There is also limited evidence assessing the efficacy of targeted therapies. Small intestine NETs are rare, with evidence for somatostatin analogue therapy, particularly in the low to intermediate-grade well-differentiated tumours. Poorly differentiated NETs are generally managed with chemotherapy but have worse outcomes compared with well-differentiated NETs. The management of small intestine GISTs is largely targeting KIT mutations with imatinib. Recent trials have provided evidence for effective therapies in imatinib-resistant tumours and the potential role of immunotherapy. The aim of this article was to review the evidence for the current management and recent advances in the management of small intestine adenocarcinoma, NETs and GISTs.
Collapse
Affiliation(s)
- Rebecca Symons
- Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, High St, Randwick, Sydney, NSW, 2031, Australia
| | - Daniel Daly
- Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, High St, Randwick, Sydney, NSW, 2031, Australia.,University of New South Wales, Randwick, NSW, Australia
| | - Robert Gandy
- Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, High St, Randwick, Sydney, NSW, 2031, Australia.,University of New South Wales, Randwick, NSW, Australia
| | - David Goldstein
- Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, High St, Randwick, Sydney, NSW, 2031, Australia.,University of New South Wales, Randwick, NSW, Australia
| | - Morteza Aghmesheh
- Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, High St, Randwick, Sydney, NSW, 2031, Australia.
| |
Collapse
|
|
5
|
Chen X, Zhou R, Li Y, Qu X, Qu YC, Li WZ, Ye YS, Liu LR, Zhu YJ, Zhang HB. Case report: A case of duodenal adenocarcinoma achieving significantly long survival treating with immune checkpoint inhibitors and chemotherapy without positive biomarkers. Front Immunol 2022; 13:1046513. [PMID: 36531985 PMCID: PMC9755197 DOI: 10.3389/fimmu.2022.1046513] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 11/22/2022] [Indexed: 12/04/2022] Open
Abstract
Small bowel adenocarcinoma (SBA), particularly duodenal adenocarcinoma (DA), is a rare gastrointestinal cancer with a dismal prognosis. Data on SBA treatments are limited, and the therapeutic strategy remains uncertain. Currently, chemotherapy is the most used treatment; however, it has a poor median progression-free survival (mPFS) of no more than five months in the second-line setting. We report a case with DA that responded well to the immune checkpoint inhibitor (ICI) tislelizumab plus irinotecan in the second-line treatment. To our knowledge, this is the first report of administering ICIs plus chemotherapy to SBA. Despite the absence of microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB), the patient with TP53/KRAS mutation achieved a significantly long PFS of 17 months, and the benefit is still ongoing. The mechanism of this remarkable efficacy might be associated with an increase in tumor immunogenicity after chemotherapy. The current study presents a promising effect of ICIs plus chemotherapy on SBA, affirming the need to investigate the clinical value of this combination in SBA and the underlying mechanism behind it.
Collapse
Affiliation(s)
- Xian Chen
- The Second Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China,Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Rui Zhou
- The Second Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yong Li
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Xin Qu
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Yan-chun Qu
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Wen-zhu Li
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Yong-song Ye
- Department of Image, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Li-rong Liu
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Yan-juan Zhu
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China,Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hai-bo Zhang
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China,Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,*Correspondence: Hai-bo Zhang,
| |
Collapse
|
|
6
|
Tesarikova J, Skalicky P, Kurfurstova D, Svebisova H, Urban O, Falt P, Zapletalova J, Klos D, Lovecek M. Surgical treatment of duodenal adenocarcinoma: ampullary vs. non-ampullary, short- and long-term outcomes. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2022; 166:290-296. [PMID: 34012147 DOI: 10.5507/bp.2021.028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 04/23/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND The aim of this study was to evaluate symptoms, diagnostic methods, short- and long-term outcomes of surgical treatment in patients with duodenal adenocarcinoma. PATIENTS AND METHODS A single center, retrospective, observational study of 52 consecutive patients with duodenal adenocarcinoma operated on with curative intent between 2006 - 2019. Duodenectomy as part of a hemipancreatoduodenectomy or total pancreatectomy procedure was performed for ADAC (ampullary duodenal/intestinal adenocarcinoma) or NADAC (non-ampullary duodenal adenocarcinoma). RESULTS Prevailing symptoms were obstructive jaundice in the ADAC group (P<0.0001) and bleeding in the NADAC group (P=0.005), with larger tumor size in patients with NADAC (P=0.001). Complication rate, morbidity and mortality were comparable. Primary total pancreatoduodenectomy predominated in the NADAC group, 16.6% vs. 2.9%, and salvage completion pancreatectomy in the ADAC group, 6% vs. 0%. Significant prognostic factors for OS were perineural invasion (P=0.006) and adjuvant chemotherapy (P=0.045) in the ADAC group, and for DFS the total number of resected lymph nodes (P=0.042) and lymph node ratio (P=0.031) in the NADAC group. Median OS is 21 months and 5-year survival 27.3% in the NADAC group and 41.5 months and 52% in the ADAC group. CONCLUSION Ampullary duodenal/intestinal adenocarcinomas are smaller than non-ampullary at diagnosis, with a higher rate of lymph node metastases, but with a better prognosis and long-term outcome in the presented cohort. Oral localisation of NADAC prevailed in the present cohort. Perineural invasion and postoperative oncological therapy are significant prognostic factors for OS in ADAC, but the total number of lymph nodes and lymph node ratio are significant prognostic factors for DFS in NADAC.
Collapse
Affiliation(s)
- Jana Tesarikova
- Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Pavel Skalicky
- Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Daniela Kurfurstova
- Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Hana Svebisova
- Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Ondrej Urban
- Department of Internal Medicine II - Gastroenterology and Geriatrics, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Premysl Falt
- Department of Internal Medicine II - Gastroenterology and Geriatrics, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Jana Zapletalova
- Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
| | - Dusan Klos
- Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - Martin Lovecek
- Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| |
Collapse
|
|
7
|
El Bakouri A, El Wassi A, Eddaoudi Y, Bouali M, ElHattabi K, Bensardi F, Fadil A. Early Discovery Of Small Bowel Adenocarcinoma In a Patient Admitted For 4 Acute Intestinal Intussusception case report. Ann Med Surg (Lond) 2022; 82:104776. [PMID: 36268363 PMCID: PMC9577972 DOI: 10.1016/j.amsu.2022.104776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 09/18/2022] [Accepted: 09/19/2022] [Indexed: 11/29/2022] Open
Abstract
Introduction Malignant tumours of the small bowel are uncommon in clinical practice. Adenocarcinoma is the most common of these tumours, accounting for approximately 35–45% of all tumours. It may occur sporadically, in association with familial adenomatous polyposis coli or Peutz-Jeghers syndrome or hereditary non-polyposis colorectal cancer, or in association with chronic inflammatory bowel changes (such as Crohn's disease or celiac disease). Materials and methods We report a case of Early Discovery Of Small Bowel Adenocarcinoma In A Patient Admitted For 4 Acute Intestinal Intussusception in the department of Emergency visceral surgery P35 of the ibn rochd hospital in casablanca. Results Our patient was admitted to the emergency room for sub-occlusive syndrome with generalized abdominal pain of chronic appearance dating back to one month before his admission With Abdominal and pelvic ultrasound showed: intestinal parietal thickening and minimal ascites (peritoneal and/or intestinal tuberculosis? Crohn's disease) The patient underwent an abdominal-pelvic CT scan which showed: Presence of diffuse small bowel thickening, involving several small intestines and the colonic angle with intestinal invaginations (at least 3) suspecting an inflammatory or tumoral origin? To be compared with histological data and infiltration of the mesenteric fat in the sub-umbilical region with a peritoneal effusion in the Douglas. the patient was operated on in the emergency room, approached by laparotomy and found on exploration: Presence of 3 invaginations in the small intestine located at 20cm and 90cm from the Duodenojejunal Angle (DIA) as well as at 25cm from the Last part of the small intestine (DAI), with Presence of a colonic invagination at the level of the left colonic angle. the patient underwent 3 small bowel resections and one segmental colonic resection including segmental small bowel resections: the 1st one of 30 cm taking away an invagination of the small intestine at 20cm from the ADJ, the 2nd one taking away 60cm of invaginated located at 90cm from the ADJ the 3rd one taking away 20cm of invaginated located at 25cm from the DAI and a 4th resection taking away an invagination of the left colonic angle with 3 Anastomosis of the T-T small intestine and a transverse Colostomy in Bouilley Volkman. On examination by the anapathomopathologist: consistent with a small bowel tumour: well-differentiated intestinal adenocarcinoma on degenerated adenomatous polyps measuring 2.5cm and 1.7cm with an estimated 10% mucinous component with no vascular emboli and no peri-nervous sheathing. TNM stage p: pT2 with healthy resection margins in the left colon: Presence of a tubular adenoma with low grade dysplasia. Conclusion The most common symptoms of adenocarcinoma of the small bowel are obstruction, overt or covert bleeding, weight loss and jaundice. Because the small bowel has long been relatively inaccessible to routine endoscopy, the diagnosis of small bowel adenocarcinoma was often delayed for several months after the onset of symptoms. Therefore, in case of suspicion of this type of cancer, a thorough evaluation should be undertaken. Nowadays, endoscopy of the small bowel is widely available, allowing an earlier non-invasive diagnosis.
Acute Intestinal Intussusception as a cause of intestinal obstruction is often a diagnostic challenge mimicking a wide spectrum of diseases. Malignant tumours of the small bowel are uncommon in clinical practice. Adenocarcinoma is the most common of these tumours. Its diagnosis is still very difficult. The treatment of Acute Intestinal Intussusception is in most cases surgical. The diagnosis of Acute Intestinal Intussusception is histological.
Collapse
|
|
8
|
Di Nardo P, Garattini SK, Torrisi E, Fanotto V, Miolo G, Buonadonna A, Puglisi F. Systemic Treatments for Advanced Small Bowel Adenocarcinoma: A Systematic Review. Cancers (Basel) 2022; 14:1502. [PMID: 35326652 PMCID: PMC8945891 DOI: 10.3390/cancers14061502] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/10/2022] [Accepted: 03/10/2022] [Indexed: 01/13/2023] Open
Abstract
Small bowel adenocarcinoma (SBA) is a rare disease for which scarce evidence is available. We summarized data available on systemic treatment of advanced SBA. METHODS Scientific literature was evaluated to find phase II or phase III clinical trials on systemic treatment for advanced SBA. MeSH terms were selected and combined for the initial search, then inclusion and exclusion criteria were set in a search protocol. Four medical oncologists looked for evidence on Medline, EMBASE and Cochrane databases. Moreover, abstracts from 2016 to June 2021 from the American Society for Clinical Oncology, European Society for Medical Oncology, Gastrointestinal Cancer Symposium and World Congress on Gastrointestinal Cancer were browsed. The selected studies, matching the inclusion and exclusion criteria, were finally tabulated and analyzed. RESULTS The trials finally selected were 18 phase II/III clinical trials. Four small phase II trials support the activity of oxaliplatin-based doublets in first-line treatment (CAPOX and mFOLFOX). CONCLUSION No good level evidence is available on the use of bevacizumab, anti-epidermal growth factor receptor, targeted agents or immunotherapy. First-line treatments are largely derived from colorectal cancer protocols, mainly oxaliplatin-based doublets.
Collapse
Affiliation(s)
- Paola Di Nardo
- Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (G.M.); (A.B.); (F.P.)
| | - Silvio Ken Garattini
- Department of Oncology, ASUFC University Hospital of Udine, 33100 Udine, Italy; (S.K.G.); (V.F.)
| | - Elena Torrisi
- Department of Medical Oncology, P.O. San Vincenzo, 98039 Taormina, Italy;
| | - Valentina Fanotto
- Department of Oncology, ASUFC University Hospital of Udine, 33100 Udine, Italy; (S.K.G.); (V.F.)
| | - Gianmaria Miolo
- Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (G.M.); (A.B.); (F.P.)
| | - Angela Buonadonna
- Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (G.M.); (A.B.); (F.P.)
| | - Fabio Puglisi
- Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (G.M.); (A.B.); (F.P.)
- Department of Medicine (DAME), University of Udine, 33100 Udine, Italy
| |
Collapse
|
|
9
|
Therapeutic Strategies for Patients with Advanced Small Bowel Adenocarcinoma: Current Knowledge and Perspectives. Cancers (Basel) 2022; 14:cancers14051137. [PMID: 35267446 PMCID: PMC8909230 DOI: 10.3390/cancers14051137] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/21/2022] [Accepted: 02/22/2022] [Indexed: 12/30/2022] Open
Abstract
Small bowel adenocarcinoma (SBA) is diagnosed at an advanced (unresectable or metastatic) tumor stage in approximately one-third of cases. This is partly due to the non-specific symptomatology and limitations in endoscopic and radiologic detection methods. In this context, the prognosis remains poor and systemic chemotherapy appears to benefit patients when compared to best supportive care alone, despite the absence of randomized controlled trials. The results of a recent large prospective cohort (ARCAD-NADEGE) reported that the absence of chemotherapy was a predictive factor for a lower overall survival (OS) even though poor differentiation and SBA associated with Crohn's disease correlate with poor prognosis. In retrospective series, the median OS ranges from approximately 9 to 18 months with current treatment approaches. A combination of a fluoropyrimidine and oxaliplatin (FOLFOX or CAPOX) appears to be the most utilized and effective first-line chemotherapy regimen. Other front-line alternatives are the combination of 5-FU and cisplatin or fluoropyrimidine and irinotecan (FOLFIRI). In second-line, FOLFIRI is an effective option after progression on platinum-based therapy. Taxane-based therapy appears to be an alternative option, but further evaluation in larger series is needed. To a limited extent, the role of surgical resection for metastatic disease appears to be a valid option, though this approach has not been evaluated in prospective clinical studies. Due to the rareness of the disease, inclusion in clinical trials should be prioritized, and there is hope that targeted therapies and immunotherapy may enter the therapeutic arsenal for these patients.
Collapse
|
|
10
|
Gelsomino F, Balsano R, De Lorenzo S, Garajová I. Small Bowel Adenocarcinoma: From Molecular Insights to Clinical Management. Curr Oncol 2022; 29:1223-1236. [PMID: 35200603 PMCID: PMC8870676 DOI: 10.3390/curroncol29020104] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/10/2022] [Accepted: 02/14/2022] [Indexed: 12/03/2022] Open
Abstract
Small bowel adenocarcinoma (SBA) is a rare malignancy, with a rising incidence in recent decades, and accounts for roughly 40% of all cancers of the small bowel. The majority of SBAs arise in the duodenum and are associated with a dismal prognosis. Surgery remains the mainstay of treatment for localized disease, while systemic treatments parallel those used in colorectal cancer (CRC), both in the adjuvant and palliative setting. In fact, owing to the lack of prospective data supporting its optimal management, SBA has historically been treated in the same way as CRC. However, recent genetic and molecular data suggest a distinct profile from other gastrointestinal malignancies and support a more nuanced approach to its management. Herein, we briefly review the state-of-the-art in the clinical management of early-stage and advanced disease and recent discoveries of potentially actionable genetic alterations or pathways along with the most promising ongoing clinical trials, which will hopefully revolutionize the treatment landscape of this orphan disease in the foreseeable future.
Collapse
Affiliation(s)
- Fabio Gelsomino
- Department of Oncology and Hematology, Division of Oncology, University Hospital of Modena, 41124 Modena, Italy
| | - Rita Balsano
- Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy; (R.B.); (I.G.)
| | | | - Ingrid Garajová
- Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy; (R.B.); (I.G.)
| |
Collapse
|
|
11
|
Pharmaceutical nanoformulation strategies to spatiotemporally manipulate oxidative stress for improving cancer therapies — exemplified by polyunsaturated fatty acids and other ROS-modulating agents. Drug Deliv Transl Res 2022; 12:2303-2334. [DOI: 10.1007/s13346-021-01104-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/30/2021] [Indexed: 12/18/2022]
|
|
12
|
Yu IS, Al-Hashami Z, Chapani P, Speers C, Davies JM, Lim HJ, Renouf DJ, Gill S, Stuart HC, Loree JM. Impact of Tumor Location on Patient Outcomes in Small Bowel Cancers. Clin Colorectal Cancer 2021; 21:107-113. [PMID: 34972663 DOI: 10.1016/j.clcc.2021.11.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 10/21/2021] [Accepted: 11/22/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Small bowel cancers are rare gastrointestinal malignancies and tumor location impact on outcomes is unclear. MATERIAL AND METHODS A retrospective review was performed on stage I to IV small bowel cancer cases from 2000 to 2017 in British Columbia, Canada. Baseline patient characteristics, disease-free survival (DFS) and overall survival (OS) were evaluated by tumor location and systemic therapy use patterns were summarized. RESULTS Of 340 patients included, primary tumor distribution was: duodenum (51.2%), ileum (19.1%), jejunum (18.5%), and unspecified (11.2%). Median DFS for stage I to III disease was 37.7, 49.1, and 26.7 months for duodenal, jejunal, and ileal tumors (P = .018). Median OS was 9.6, 35.2, and 20.1 months for duodenal, jejunal, and ileal tumors (P < .0001). Compared to duodenal primaries, both jejunal and ileal tumors were associated with significantly improved OS (HR 0.43, P < .001 for jejunal; HR 0.71, P = .035 for ileal). Adjuvant therapy was given to 21.6% of stage II and 50.6% of stage III cancers. Among patients with metastatic disease, median OS was 4.2, 11.4, and 6.9 months for duodenal, jejunal, and ileal tumors (P = .0019). Jejunal tumors had the best prognosis (HR 0.48, P = .001 vs. duodenum). CONCLUSION Survival differences exist when small bowel cancers were assessed by tumor location, and jejunal tumors portended better prognosis overall.
Collapse
Affiliation(s)
- Irene S Yu
- BC Cancer, Vancouver, British Columbia, Canada
| | | | - Parv Chapani
- University of British Columbia, Vancouver, British Columbia, Canada
| | - Caroline Speers
- Gastrointestinal Cancer Outcomes Unit, BC Cancer, Vancouver, British Columbia, Canada
| | - Janine M Davies
- BC Cancer, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada
| | - Howard J Lim
- BC Cancer, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada
| | - Daniel J Renouf
- BC Cancer, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada
| | - Sharlene Gill
- BC Cancer, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada
| | - Heather C Stuart
- BC Cancer, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada
| | - Jonathan M Loree
- BC Cancer, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada.
| |
Collapse
|
|
13
|
Liu T, Wu Y, Jiang T. Efficacy of surgery and chemotherapy for stage IV small bowel adenocarcinoma: A population-based analysis using Surveillance, Epidemiology, and End Result Program database. Cancer Med 2020; 9:6638-6645. [PMID: 32750232 PMCID: PMC7520278 DOI: 10.1002/cam4.3266] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Revised: 06/06/2020] [Accepted: 06/07/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The role of surgery and chemotherapy for stage IV small bowel adenocarcinoma (SBA) is still confused. The results from previous analyses have been limited by small sample sizes and different treatment regimens. METHODS Patients with stage IV SBA were identified in the Surveillance, Epidemiology, and End Result Program (SEER) database. Cause-specific survival (CSS) and overall survival (OS) were calculated with Kaplan-Meier methods and log-rank test. Multiple logistic and Cox regression identified covariates associated with treatment options and survival. RESULTS 1219 eligible patients were involved in this study. The median age was 67 (range, 20-95) with 655 (53.7%) males and 564 (46.3%) females. Age and primary tumor site were significantly associated with surgery performance, age was also significantly associated with chemotherapy (P < .01). To reduce bias, further six subgroups were divided by age (≤65 and >65) and primary tumor site (duodenum, jejunum and ileum). Chemotherapy and surgery conferred a benefit on survival of the whole cohort (the median CSS of different treatment groups were 17, 9, 4, and 1 month respectively, P < .001) and most subgroups (83.3%, 5/6). In multivariate analysis, surgery (P = .006), and chemotherapy (P = .038) are still independent factors of favorable CSS and OS. For patients with surgery (n = 362), radical surgery was not associated with better survival. CONCLUSION For stage IV SBA patients, the present study showed that age and primary tumor site were significantly associated with treatment preference. Surgery and chemotherapy were consistently correlated with favorable survival for the whole cohort or most specific subgroups. However, compared with palliative surgery, significant association was not found in patients with radical surgery with better outcome. More prospective well-defined cohorts would add knowledge for this rare disease.
Collapse
Affiliation(s)
- Tongtong Liu
- Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Yunlong Wu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tao Jiang
- Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
14
|
Nishikawa Y, Hoshino N, Horimatsu T, Funakoshi T, Hida K, Sakai Y, Muto M, Nakayama T. Chemotherapy for patients with unresectable or metastatic small bowel adenocarcinoma: a systematic review. Int J Clin Oncol 2020; 25:1441-1449. [PMID: 32448950 DOI: 10.1007/s10147-020-01703-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Accepted: 04/27/2020] [Indexed: 01/13/2023]
Abstract
BACKGROUND There is no standard chemotherapy available for unresectable or metastatic small bowel adenocarcinoma (SBA) because of its rarity. This systematic review aims to assess the efficacy and safety of chemotherapy for patients with unresectable or metastatic SBA. METHODS In accordance with the PRISMA statements, literature search was conducted using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. The included studies were prospective randomized, nonrandomized, or observational studies. Risk of bias was assessed the ROBINS-I tool. RESULTS Seven prospective single-arm Phase II studies were included in this review. Six of them were assessed as having a moderate risk of bias and one as having a serious risk of bias. A meta-analysis was not performed, because the studies were single-arm. Systemic chemotherapy based on fluoropyrimidine regimens achieved favorable outcomes with acceptable adverse effects as a first therapy; however, the regimens differed in each study. The object response rate was 18-50%, and the disease control rate was 29-87%. With 5-fluorouracil, adriamycin, and mitomycin-C regimen, one treatment-related death occurred. A second line of therapy including chemotherapy with nab-paclitaxel also showed favorable efficacy. The object response rate was 20%, and the disease control rate was 50%. CONCLUSIONS Systemic chemotherapy based on fluoropyrimidine regimens was mainly used for unresectable or metastatic SBA. While it may achieve favorable outcomes with acceptable adverse effects, further evidence is needed.
Collapse
Affiliation(s)
- Yoshitaka Nishikawa
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
- Department of Health Informatics, Kyoto University School of Public Health, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
| | - Nobuaki Hoshino
- Department of Health Informatics, Kyoto University School of Public Health, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
- Department of Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Takahiro Horimatsu
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Taro Funakoshi
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Koya Hida
- Department of Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Yoshiharu Sakai
- Department of Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Manabu Muto
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Takeo Nakayama
- Department of Health Informatics, Kyoto University School of Public Health, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| |
Collapse
|
|
15
|
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.
Collapse
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
| |
Collapse
|
|
16
|
Regalla DKR, Jacob R, Manne A, Paluri RK. Therapeutic options for ampullary carcinomas. A review. Oncol Rev 2019; 13:440. [PMID: 31565197 PMCID: PMC6747019 DOI: 10.4081/oncol.2019.440] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 08/28/2019] [Indexed: 02/08/2023] Open
Abstract
Ampullary Carcinoma arises from a histologically heterogeneous region where three different epithelia converge. Even though Ampullary Carcinoma has a superior prognosis compared to pancreatic and biliary ductal neoplasms, at least half of the patients turn up at an advanced stage that limits the treatment prospects. In addition to surgery for early-stage disease, several studies have shown that chemoradiotherapy confers additional benefits in the management of Ampullary Carcinoma. Analogously, chemotherapy plays a crucial role in treating advanced Ampullary Carcinoma with distant metastasis/recurrences. Although, stage of the disease, lymph node status, and histo-morphology are three critical prognostic variables, recently much attention is being placed on the genetic landscape of Ampullary Carcinoma. In this review, we have discussed various studies describing the role of chemoradiation and chemotherapy in the treatment of early and advanced stage Ampullary Carcinoma. Also, we have summarized the molecular landscape of Ampullary Carcinoma and the novel therapeutic strategies which could possibly target the genetic alterations involving the tumor cells.
Collapse
Affiliation(s)
| | - Rojymon Jacob
- Radiation Oncology, University of Alabama at Birmingham Hospital, Birmingham, AL
| | - Ashish Manne
- Medical Oncology, University of South Alabama Hospital, Mobile, AL
| | - Ravi Kumar Paluri
- Hematology-Oncology, University of Alabama at Birmingham Hospital, Birmingham, AL, USA
| |
Collapse
|
|
17
|
Legué LM, Bernards N, Lemmens VE, de Hingh IH, Creemers GJ, van Erning FN. Palliative chemotherapy for patients with synchronous metastases of small-bowel adenocarcinoma: A reflection of daily practice. United European Gastroenterol J 2019; 7:1380-1388. [PMID: 31839964 DOI: 10.1177/2050640619858211] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 05/28/2019] [Indexed: 12/27/2022] Open
Abstract
Background As small-bowel adenocarcinoma (SBA) is scarce, no standard systemic regimen in metastatic disease has been defined. Objective To obtain insights into the use and effects of palliative chemotherapy in patients with metastatic SBA in a population-based setting. Methods Data from the Netherlands Cancer Registry of patients with metastatic SBA between 2007 and 2016 were used (n = 522). For patients treated with palliative chemotherapy, differences in treatment regimens and survival were evaluated. Results Palliative chemotherapy was received by 38% of patients (n = 199). First-line combination chemotherapy was administered to 80% of patients, mainly CAPOX/FOLFOX. Single-agent chemotherapy mostly consisted of capecitabine. Second-line treatment, mostly irinotecan-based (58%), was prescribed to 27% of patients. Age 70 years or older was an adverse predictive factor for receiving first-line combination chemotherapy (odds ratio (OR) 0.2, 95% confidence interval (CI) 0.08-0.62) and second-line therapy (OR 0.3, 95% CI 0.10-0.72). Median overall survival with palliative chemotherapy was 9.3 months, compared with 3.0 months without. In subanalyses, patients who received only first-line treatment had a median overall survival of 5.6 and 7.0 months after single-agent and combination chemotherapy, respectively. Conclusion A minority of patients were treated with palliative chemotherapy. First-line treatment consisted predominantly of oxaliplatin-based combination chemotherapy, whereas second-line treatment was mainly irinotecan-based. Population-based median overall survival for selected patients treated with chemotherapy amounted to nine months.
Collapse
Affiliation(s)
- Laura M Legué
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands.,Department of Research, Netherlands Comprehensive Cancer Organisation, Eindhoven, the Netherlands
| | - Nienke Bernards
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - Valery Epp Lemmens
- Department of Research, Netherlands Comprehensive Cancer Organisation, Eindhoven, the Netherlands.,Department of Public Health, Erasmus MC University Medical Centre, Rotterdam, the Netherlands
| | - Ignace Hjt de Hingh
- Department of Research, Netherlands Comprehensive Cancer Organisation, Eindhoven, the Netherlands.,Department of Surgical Oncology, Catharina Hospital, Eindhoven, the Netherlands.,GROW, School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands
| | - Geert-Jan Creemers
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - Felice N van Erning
- Department of Research, Netherlands Comprehensive Cancer Organisation, Eindhoven, the Netherlands
| |
Collapse
|
|
18
|
Mann K, Gilbert T, Cicconi S, Jackson R, Whelan P, Campbell F, Halloran C, Neoptolemos J, Ghaneh P. Tumour stage and resection margin status are independent survival factors following partial pancreatoduodenectomy for duodenal adenocarcinoma. Langenbecks Arch Surg 2019; 404:439-449. [PMID: 30972486 PMCID: PMC6614162 DOI: 10.1007/s00423-019-01779-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 03/20/2019] [Indexed: 01/14/2023]
Abstract
INTRODUCTION There is limited published evidence on duodenal carcinoma due to its rarity. This study aimed to evaluate gastric outlet obstruction and obstructive jaundice along with pathological variables as survival factors in patients with duodenal adenocarcinoma following resection. METHODS Survival factor analysis was undertaken in patients undergoing duodenal cancer surgery from 1997 to 2015 in a single centre. RESULTS There were 57 patients of whom 18 had gastric outlet obstruction and 14 had obstructive jaundice. Fifty-three had a partial pancreatoduodenectomy and four had palliative bypass. Perioperative mortality and morbidity were 4% (2/53) and 47% (25/53) respectively in resected patients. With a median (95% confidence interval, CI) follow-up of 72 (57-86) months, median overall and recurrence-free survival was 38 months (95% CI 28-113) and 27 months (95% CI 18-83) respectively. The 1 and 3-year overall survival rates were 84% (95% CI 74-95) and 52% (95% CI 39-69) respectively. Median overall survival was 19 months in patients with gastric outlet obstruction vs 53 months in those without (p = 0.026) and 28 months in patients with obstructive jaundice vs 38 months in those without (p = 0.611). Univariate analysis revealed that tumour stage, resection margin status, pre-operative albumin status, gastric outlet obstruction and age were associated with poorer overall and recurrence-free survival but multivariate analysis confirmed only tumour stage and resection margin status to be significant. CONCLUSION Whereas gastric outlet obstruction in duodenal cancer appeared to be an important survival factor following partial pancreatoduodenectomy, multivariate analysis showed that only tumour stage and resection margin status were the key independent survival factors. Further multicentre studies are required to elucidate further characteristics of duodenal carcinoma and develop neoadjuvant/adjuvant management strategies.
Collapse
Affiliation(s)
- Kulbir Mann
- Department of Molecular and Clinical Cancer Medicine, Institution of Translational Medicine, University of Liverpool, 2nd Floor Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK.
| | - T Gilbert
- Department of Molecular and Clinical Cancer Medicine, Institution of Translational Medicine, University of Liverpool, 2nd Floor Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK
| | - S Cicconi
- Statistics and Bioinformatics Unit, Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Block C, Waterhouse Building, 1-3 Brownlow Street, Liverpool, L69 3GL, UK
| | - R Jackson
- Statistics and Bioinformatics Unit, Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Block C, Waterhouse Building, 1-3 Brownlow Street, Liverpool, L69 3GL, UK
| | - P Whelan
- Department of Surgery, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK
| | - F Campbell
- Department of Pathology, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK
| | - C Halloran
- Department of Molecular and Clinical Cancer Medicine, Institution of Translational Medicine, University of Liverpool, 2nd Floor Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK
| | - J Neoptolemos
- Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - P Ghaneh
- Department of Molecular and Clinical Cancer Medicine, Institution of Translational Medicine, University of Liverpool, 2nd Floor Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK
| |
Collapse
|
|
19
|
Huffman BM, Jin Z, Yadav S, Patel S, Nagorney DM, Truty MJ, McWilliams RR, Halfdanarson TR, Mahipal A. Novel Prognostic Factors in Resected Small Bowel Adenocarcinoma. Clin Colorectal Cancer 2019; 18:218-225. [PMID: 31178274 DOI: 10.1016/j.clcc.2019.05.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 05/08/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Small bowel adenocarcinoma (SBA) is a rare malignancy affecting approximately 3000 patients per year in the United States, and there is limited evidence prognosticating patients with resected SBA. We aimed to evaluate prognostic factors and the role of adjuvant therapy in patients with resected SBA. PATIENTS AND METHODS Two hundred forty-one patients who had resected stage I-III SBA were retrospectively identified at a single tertiary referral institution. Overall survival (OS) analysis was performed by the Kaplan-Meier method, and Wilcoxon tests were used for statistical comparisons. Cox proportional hazards were performed to identify significant variables by univariate and multivariate analysis. RESULTS Median OS for the entire group was 54.5 months (95% confidence interval [CI], 37.2-81.2 months), with 5- and 10-year OS of 48% and 35%. Median follow-up was 113.7 months (95% CI, 97.9-126.6 months). For patients with stage III disease who received adjuvant therapy, the median OS was 33.8 months (95% CI, 27.8-78.8) compared to 24.7 months (95% CI, 11.5-37.8) for patients with no adjuvant therapy (P < .01). Male sex, advanced T stage, advanced N stage, increased positive lymph node ratio, lymphocyte-to-monocyte ratio < 1.56, presence of residual disease, and earlier date of diagnosis predicted worse survival on univariate analysis. Age > 60 years, lymphocyte-to-monocyte ratio < 1.56, and advanced T stage were identified as independent negative predictors of OS for all patients by multivariate analysis. CONCLUSION Advanced age, advanced T stage, and lymphocyte-to-monocyte ratio < 1.56 independently predicted survival in resected SBA. Adjuvant therapy is associated with improved survival in patients with resected stage III SBA.
Collapse
Affiliation(s)
| | - Zhaohui Jin
- Division of Medical Oncology, Mayo Clinic, Rochester, MN
| | | | - Shruti Patel
- Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - David M Nagorney
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN
| | - Mark J Truty
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN
| | | | | | - Amit Mahipal
- Division of Medical Oncology, Mayo Clinic, Rochester, MN.
| |
Collapse
|
|
20
|
Tian J, Liu J, Guo C, Yang X, Yang Y, Gou H, Qiu M, Cao D. Prognostic factors and treatment outcomes in patients with non-ampullary small bowel adenocarcinoma: Long-term analysis. Medicine (Baltimore) 2019; 98:e15381. [PMID: 31027129 PMCID: PMC6831280 DOI: 10.1097/md.0000000000015381] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Small bowel adenocarcinoma (SBA) is a relatively rare malignancy in gastrointestinal tumors. In addition, the difficulty of early diagnosis, its poor prognosis compared to large bowel adenocarcinoma, and inadequate treatment experiences due to lack of prospective randomized trials make it necessary to explore the characteristics of the disease for early diagnosis and treatment.Patients diagnosed with primary malignant tumor of small intestine in West China Hospital of Sichuan University between January 2001 and 2013 were reviewed retrospectively. A total of 208 patients with SBA were selected and 160 patients with duodenal periampullary tumor were excluded. Forty-two cases of patients were finally enrolled for statistical analysis as 6 patients were lost of follow-up. The clinical characteristics, the response to treatment and their overall survival (OS) time were reviewed and analyzed.Of the 42 patients, 11 (26.2%) primary tumors were originated from duodenum, 29 (69.0%) from jejunum, and 2 (4.8%) from ileum. All patients (64.3% male; median age, 54.7 years) included in this study underwent primary resection of the tumor to confirm final diagnosis. Three-year survival rate is 21% and 5-year survival rate is 9%. Median OS were 24.2 months (95% CI: 4.0-72.0). The univariate predictors for prognosis of SBA were as follows: age (P = .021), severe intestinal symptoms at first diagnosis (P < .001), T4 of tumor stage (P = .011), tumor size (P = .004), relatively late clinical stage (P < .001), peritoneal metastasis (P < .001), and no chemotherapy (P = .011). The multivariate predictors for poor prognosis were age of more than 60 years old (P = .035), intestinal obstruction or perforation at first diagnosis (P = .026), relatively late clinical stage (P = .000), and no chemotherapy (P = .027).SBA was a relatively rare malignancy that was difficult for early diagnosis and treatment. Intestinal obstruction was the common clinical manifestation at first diagnosis, with a tendency of early peritoneal metastasis. Precaution of the disease in early phase, radical resection of the primary tumor while resectable, followed with in-time chemotherapy might improve prognosis and survival of patients with SBA.
Collapse
Affiliation(s)
| | - Jiewei Liu
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | | | - Xi Yang
- Department of Abdominal Oncology, Cancer Center
| | - Yu Yang
- Department of Abdominal Oncology, Cancer Center
| | | | - Meng Qiu
- Department of Abdominal Oncology, Cancer Center
| | - Dan Cao
- Department of Abdominal Oncology, Cancer Center
| |
Collapse
|
|
21
|
Abstract
OPINION STATEMENT Small bower cancer is a rare disease, despite its incidence is increasing in the last decade. Both benign and malignant tumors can arise from the small intestine. The main histological cancer types are adenocarcinomas, neuroendocrine tumors, sarcomas, gastrointestinal stromal tumors (GISTs), and lymphomas. Due to the rarity of these malignances, all the currently available data are based on small studies or retrospective series, although recent breakthroughs are redirecting our approach to these patients. Immunotherapy for small bowel adenocarcinomas, several multikinase inhibitors in resistant GIST patients, as well as everolimus and 177Lu-DOTATATE in neuroendocrine tumors are only few of the novel therapeutic options that have changed, or may change in the future, the therapeutic landscape of these rare cancers. Larger and more powerful studies on the molecular profile of these tumors may lead to a better design of clinical trials, which eventually would provide our patients with more efficacious treatments to improve both overall survival and quality of life.
Collapse
Affiliation(s)
- Alberto Puccini
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Suite 3456, Los Angeles, CA, 90033, USA.,Department of Medical Oncology, Ospedale Policlinico San Martino, Genoa, Italy
| | - Francesca Battaglin
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Suite 3456, Los Angeles, CA, 90033, USA.,Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV-IRCCS, 35128, Padua, Italy
| | - Heinz-Josef Lenz
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Suite 3456, Los Angeles, CA, 90033, USA.
| |
Collapse
|
|
22
|
Abstract
Small bowel adenocarcinoma is a clinically and anatomically distinct gastrointestinal cancer that lacks prospective data to support its optimal management. Patients with inflammatory bowel disease and inherited conditions that cause gastrointestinal polyps are at especially high risk. Due to a lack of effective surveillance programs resulting in missed or delayed diagnoses only when symptoms develop, this disease is generally discovered at an advanced stage. Surgical resection is the only treatment modality with a chance of cure. Currently accepted treatment considerations are often generalized from large bowel and pancreatic-biliary cancers, due to some anatomic and clinical parallels. Additional research, however, is desperately needed to characterize the unique molecular differences of this disease to better prognosticate patients and establish rational clinical trials that would improve their outcomes.
Collapse
Affiliation(s)
- Emerson Y Chen
- Division of Hematology and Medical Oncology, Department of Medicine, Knight Cancer Institute, Oregon Health & Sciences University, Portland, Oregon
| | - Gina M Vaccaro
- Division of Hematology and Medical Oncology, Department of Medicine, Knight Cancer Institute, Oregon Health & Sciences University, Portland, Oregon
| |
Collapse
|
|
23
|
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: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [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.
Collapse
Affiliation(s)
- Eelco de Bree
- Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
| | - Koen P. Rovers
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, The Netherlands
| | - Dimitris Stamatiou
- Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
| | - John Souglakos
- Department of Medical Oncology and Laboratory of Translational Oncology, Medical School of Crete University Hospital, Heraklion, Greece
| | - Dimosthenis Michelakis
- Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
| | - Ignace H. de Hingh
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, The Netherlands
| |
Collapse
|
|
24
|
Locher C, Batumona B, Afchain P, Carrère N, Samalin E, Cellier C, Aparicio T, Becouarn Y, Bedenne L, Michel P, Parc Y, Pocard M, Chibaudel B, Bouché O. Small bowel adenocarcinoma: French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO). Dig Liver Dis 2018; 50:15-19. [PMID: 29174568 DOI: 10.1016/j.dld.2017.09.123] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Revised: 09/11/2017] [Accepted: 09/12/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND This document is a summary of the French intergroup guidelines regarding the management of small bowel adenocarcinoma published in October 2016. METHOD This collaborative work, co-directed by most French Medical Societies, summarizes clinical practice recommendations (guidelines) on the management of small bowel adenocarcinoma. Given the lack of specific data in the literature, all references are given by analogy with colon cancer. The classification used is the AJCC (American Joint Committee on Cancer) pTNM classification (7th edition 2009). RESULTS Small bowel adenocarcinoma has a poor prognosis; less than 30% of patients survive for 5 years after the (first) diagnosis (5-year survival of less than 30%). Due to the rarity of the disease and the retrospective data, most recommendations are based on expert agreement. The initial evaluation is based on chest-abdomen-pelvis CT scan, CEA assay, GI endoscopy and colonoscopy in order detect lesions associated with a predisposing disease. Surgical treatment is currently the only curative option for stage I and II. Adjuvant chemotherapy can be discussed for Stage III and Stage II with T4 (expert agreement). With regard to metastatic tumors, treatment with fluoropyrimidine combined with platinum salts should be considered (expert agreement). CONCLUSION Few specific data exist in the literature on this type of tumor; most of the recommendations come from expert agreements or by analogy with colon cancer. Thus, each case must be discussed within a multidisciplinary team.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Yann Parc
- APHP Saint Antoine, Paris Cedex 12, France
| | | | - Benoit Chibaudel
- Institut Hospitalier Franco-Britannique, Levallois-Perret, France
| | | | | |
Collapse
|
|
25
|
Falcone R, Roberto M, Filetti M, Anselmi E, Marchetti P. Anti epidermal growth factor receptor therapy in small bowel adenocarcinoma: Case report and literature review. Medicine (Baltimore) 2018; 97:e9672. [PMID: 29505011 PMCID: PMC5779780 DOI: 10.1097/md.0000000000009672] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
RATIONALE Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal cancer, thus limited data about treatment for advanced disease are available. The lack of specific guidelines has justified the use of therapeutic protocols usually applied in advanced colorectal cancer. Few and preliminary data have suggested possible clinical benefit from the use of target therapy such as bevacizumab and cetuximab. PATIENT CONCERNS We present the case of a young woman who was admitted to the emergency department for acute abdominal pain, nausea, and vomiting related to a jejunal stenosis. DIAGNOSES An enteroscopy with jejunal biopsy showed poorly differentiated cancerous cells suggestive for primary intestinal cancer. There were no signs of metastatic disease at radiological evaluation. A jejunal resection was subsequently carried out and the diagnosis of mucinous adenocarcinoma of the jejunum was confirmed. INTERVENTIONS The computed tomography scan performed 1 month after surgery showed metastatic disease. Therefore, the patient received combined protocols of chemotherapy and either bevacizumab or the anti-epidermal growth factor receptor (EGFR) panitumumab. OUTCOMES A partial response (PR) was achieved with Folfox plus panitumumab and a maintenance therapy with panitumumab is being conducted with a mild toxicity and a progression free survival of 19 months since the beginning of panitumumab. LESSONS This is, to the best of our knowledge, the first report in the literature of a patient with SBA who has benefitted from panitumumab with an overall survival of 83 months.
Collapse
|
|
26
|
Gulhati P, Raghav K, Shroff R, Varadhachary G, Javle M, Qiao W, Wang H, Morris J, Wolff R, Overman MJ. Phase II Study of Panitumumab in RAS Wild-Type Metastatic Adenocarcinoma of Small Bowel or Ampulla of Vater. Oncologist 2017; 23:277-e26. [PMID: 29259073 PMCID: PMC5905687 DOI: 10.1634/theoncologist.2017-0568] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Accepted: 10/13/2017] [Indexed: 12/27/2022] Open
Abstract
Lessons Learned.
Panitumumab has no clinical activity in metastatic RAS wild‐type small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC), possibly due to the foregut and midgut derivation of small bowel and ampulla. These results, along with findings from genomic characterization of SBA, suggest that SBA represents a unique intestinal malignancy and treatments should not be habitually extrapolated from colorectal cancer. Further studies evaluating the benefit of targeted therapies exclusively in SBA and AAC are warranted. Background. Given the benefit of epidermal growth factor receptor (EGFR) monoclonal antibodies in colorectal cancer (CRC), we sought to evaluate the efficacy of panitumumab in metastatic RAS wild‐type small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Methods. We conducted a single‐center, open‐label, single‐arm, Bayesian phase II trial. The primary objective was response rate (RR). Panitumumab was administered at a dose of 6 mg/kg intravenously (IV) every 14 days. Results. Nine patients (male/female 7:2, median age: 61 years [range: 40–74], Eastern Cooperative Oncology Group [ECOG] performance status 0/1: 2/7) were enrolled from September 2013 to October 2015. One patient had AAC (pancreaticobiliary subtype) and eight patients had SBA (three duodenal, five jejunal/ileal). Acneiform rash was the most common toxicity. The study was stopped early due to futility with no responses, stable disease (SD) in two patients, and progression of disease (PD) in seven patients. Median progression‐free survival (PFS) and overall survival (OS) were 2.4 and 5.7 months, respectively. No patients had extended RAS mutations (exons 2/3/4), but two patients had BRAF G469A and one patient had PIK3CA H1074R mutations. Conclusion. Panitumumab had no clinically meaningful activity in patients with metastatic RAS wild‐type SBA and AAC. Our findings may relate to the primarily midgut and foregut derivation of the small bowel and ampulla.
Collapse
Affiliation(s)
- Pat Gulhati
- Hematology/Oncology Fellowship Program, Division of Cancer Medicine, Houston, Texas, USA
| | - Kanwal Raghav
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, Houston, Texas, USA
| | - Rachna Shroff
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, Houston, Texas, USA
| | - Gauri Varadhachary
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, Houston, Texas, USA
| | - Milind Javle
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, Houston, Texas, USA
| | - Wei Qiao
- Department of Biostatistics and Applied Mathematics, Houston, Texas, USA
| | - Huamin Wang
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jeffrey Morris
- Department of Biostatistics and Applied Mathematics, Houston, Texas, USA
| | - Robert Wolff
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, Houston, Texas, USA
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, Houston, Texas, USA
| |
Collapse
|
|
27
|
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.
Collapse
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
| |
Collapse
|
|
28
|
Rovers KP, de Bree E, Yonemura Y, de Hingh IH. Treatment of peritoneal metastases from small bowel adenocarcinoma. Int J Hyperthermia 2017; 33:571-578. [DOI: 10.1080/02656736.2016.1266700] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Koen P. Rovers
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - Eelco de Bree
- Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
| | - Yutaka Yonemura
- Asian and Japanese School of Peritoneal Surface Oncology, Kyoto, Japan
| | - Ignace H. de Hingh
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| |
Collapse
|
|
29
|
Horimatsu T, Nakayama N, Moriwaki T, Hirashima Y, Fujita M, Asayama M, Moriyama I, Nakashima K, Baba E, Kitamura H, Tamura T, Hosokawa A, Yoshimura K, Muto M. A phase II study of 5-fluorouracil/L-leucovorin/oxaliplatin (mFOLFOX6) in Japanese patients with metastatic or unresectable small bowel adenocarcinoma. Int J Clin Oncol 2017; 22:905-912. [PMID: 28536826 PMCID: PMC5608770 DOI: 10.1007/s10147-017-1138-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Accepted: 05/08/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Several studies have suggested that chemotherapy prolonged survival in patients with metastatic or recurrent small bowel adenocarcinoma (SBA); however, there is still no standard chemotherapy regimen. Here, we evaluated the efficacy and safety of a 5-fluorouracil (5-FU)/L-leucovorin (l-LV)/oxaliplatin (mFOLFOX6) protocol as a first-line therapy for patients with SBA. PATIENTS AND METHODS This was a multicenter, single-arm, open-label phase II study. Eligibility criteria included histologically confirmed adenocarcinoma, age 20-80 years, and an Eastern Cooperative Oncology Group performance status (PS) of 0-2. The primary endpoint was 1-year progression-free survival (PFS). The secondary endpoints included overall response rate (ORR), overall survival (OS), overall PFS, and safety. RESULTS Between April 2010 and November 2012, 24 patients were enrolled from 12 institutions. The median age of the patients was 63 years (range 31-79) and there was a male/female ratio of 18/6. The number of PS 0/1 patients was 17/7 and locally advanced/metastatic disease was seen in 2/22 patients, respectively. The primary tumor site was the duodenum in 14 patients (58%) and jejunum in 10 patients (42%). The median follow-up time was 14.7 months (3.7-40.3). The 1-year PFS was 23.3%. The ORR was 9/20 (45%). The median PFS and OS times were 5.9 months (95% confidence interval [CI] 3.0-10.2) and 17.3 months (95% CI 11.7-19.0), respectively. Major grade 3/4 toxicities were neutropenia (38%), anemia/peripheral neuropathy (25%), and stenosis (17%). There were no treatment-related deaths. CONCLUSIONS Although the primary endpoint was not met, mFOLFOX6 showed effective and good tolerance as a first-line treatment for SBA.
Collapse
Affiliation(s)
- Takahiro Horimatsu
- Department of Therapeutic Oncology, Kyoto University Hospital, 54, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Norisuke Nakayama
- Department of Gastroenterology, Kanagawa Cancer Center, Kanazawa, Japan
| | | | - Yoshinori Hirashima
- Department of Medical Oncology and Hematology, Faculty of Medicine, Oita University, Oita, Japan
| | - Mikio Fujita
- Department of Gastroenterology and Hepetology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Masako Asayama
- Department of Gastroenterology, Saitama Cancer Center Hospital, Saitama, Japan
| | - Ichiro Moriyama
- Division of Clinical Study of Oncology, School of Medicine, Shimane University, Matsue, Japan
| | - Koji Nakashima
- First Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Eishi Baba
- Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hiroshi Kitamura
- Department of Internal Medicine, Medical Oncology, School of Medicine, Kyorin University, Tokyo, Japan
| | - Takao Tamura
- Department of Medical Oncology, Faculty of Medicine, Kinki University, Higashiosaka, Japan
| | - Ayumu Hosokawa
- Department of Gastroenterology and Hematology, Faculty of Medicine, University of Toyama, Toyama, Japan
| | - Kenichi Yoshimura
- Innovative Clinical Research Center (ICREK), Kanazawa University Hospital, Kanazawa, Japan
| | - Manabu Muto
- Department of Therapeutic Oncology, Kyoto University Hospital, 54, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| |
Collapse
|
|
30
|
McWilliams RR, Foster NR, Mahoney MR, Smyrk TC, Murray JA, Ames MM, Horvath LE, Schneider DJ, Hobday TJ, Jatoi A, Meyers JP, Goetz MP. North Central Cancer Treatment Group N0543 (Alliance): A phase 2 trial of pharmacogenetic-based dosing of irinotecan, oxaliplatin, and capecitabine as first-line therapy for patients with advanced small bowel adenocarcinoma. Cancer 2017; 123:3494-3501. [PMID: 28493308 DOI: 10.1002/cncr.30766] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 03/27/2017] [Accepted: 04/12/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Oxaliplatin in combination with either 5-fluorouracil or capecitabine is commonly used as first-line therapy for patients with small bowel adenocarcinoma. The addition of irinotecan improves survival in other gastrointestinal tumors but at the cost of hematologic toxicity. The authors performed a phase 2 cooperative group study (North Central Cancer Treatment Group N0543, Alliance) using genotype-dosed capecitabine, irinotecan, and oxaliplatin (gCAPIRINOX), with dosing assigned based on UDP glucuronosyltransferase family 1 member A1 (UGT1A1) genotype to test: 1) whether the addition of irinotecan would improve outcomes; and 2) whether UGT1A1 genotype-based dosing could optimize tolerability. METHODS Previously untreated patients with advanced small bowel adenocarcinoma received irinotecan (day 1), oxaliplatin (day 1), and capecitabine (days 2-15) in a 21-day cycle and were dosed with gCAPIRINOX according to UGT1A1*28 genotypes (6/6, 6/7, and 7/7). RESULTS A total of 33 patients (17 with the 6/6 genotype, 10 with the 6/7 genotype, and 6 with the 7/7 genotype) were enrolled from October 2007 to November 2013; 73% were male, with a mean age of 64 years (range, 41-77 years). Location of the primary tumor included the duodenum (58%), jejunum (30%), and ileum (9%). The regimen yielded a confirmed response rate of 37.5% (95% confidence interval, 21%-56%), with a median progression-free survival of 8.9 months and a median overall survival of 13.4 months. Neither hematologic toxicity (grade ≥3 in 52.9%, 30.0%, and 33.3%, respectively, of the 6/6, 6/7, and 7/7 genotype groups) nor tumor response rate (41.2%, 33%, and 33%, respectively) were found to differ significantly by UGT1A1 genotype. CONCLUSIONS UGT1A1 genotype-directed dosing (gCAPIRINOX) appears to be feasible with favorable rates of hematologic toxicity compared with prior 3-drug studies in unselected patients. Larger studies would be needed to determine the regimen's comparability to oxaliplatin and capecitabine (CapeOx) alone or if response/toxicity differs among patients with different UGT1A1 genotypes. Cancer 2017;123:3494-501. © 2017 American Cancer Society.
Collapse
Affiliation(s)
| | - Nathan R Foster
- Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota
| | | | - Thomas C Smyrk
- Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota
| | - Joseph A Murray
- Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota
| | - Matthew M Ames
- Division of Pharmacology, Mayo Clinic, Rochester, Minnesota
| | | | - Daniel J Schneider
- Metro-Minnesota Community Oncology Research Consortium, Saint Paul, Minnesota
| | | | - Aminah Jatoi
- Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota
| | - Jeffrey P Meyers
- Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota
| | - Matthew P Goetz
- Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota
| |
Collapse
|
|
31
|
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.
Collapse
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
| |
Collapse
|
|
32
|
Gulhati P, Raghav K, Shroff RT, Varadhachary GR, Kopetz S, Javle M, Qiao W, Wang H, Morris J, Wolff RA, Overman MJ. Bevacizumab combined with capecitabine and oxaliplatin in patients with advanced adenocarcinoma of the small bowel or ampulla of vater: A single-center, open-label, phase 2 study. Cancer 2016; 123:1011-1017. [PMID: 27859010 DOI: 10.1002/cncr.30445] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Revised: 09/22/2016] [Accepted: 10/19/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Capecitabine with oxaliplatin (CAPOX) has previously demonstrated clinical activity in patients with small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Herein, the authors conducted a phase 2 trial to evaluate the benefit of adding bevacizumab to CAPOX. METHODS In this phase 2, single-arm, single-center, open-label study, patients aged ≥18 years with untreated, advanced SBA or AAC were recruited. Patients received capecitabine at a dose of 750 mg/m2 orally twice daily on days 1 to 14, oxaliplatin at a dose of 130 mg/m2 intravenously on day 1, and bevacizumab at a dose of 7.5 mg/kg intravenously on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary objectives included response rate, overall PFS, overall survival, and toxicity. RESULTS Between August 2011 and November 2014, a total of 30 patients were enrolled into the study (male/female ratio of 13/17; median age of 63 years [range, 33-78 years]; and 7 patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 0, 20 patients with an ECOG PS of 1, and 3 patients with an ECOG PS of 2). Of the 30 patients, 23 (77%) had SBA (18 of duodenal origin and 5 of jejunal/ileal origin) and 7 patients (23%) had AAC (5 of pancreaticobiliary subtype, 1 of mixed subtype, and 1 of intestinal subtype). The most common grade 3 toxicities observed were fatigue and hypertension (7 patients each [23%]), neutropenia (6 patients [20%]), and diarrhea (3 patients [10%]) (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). The probability of PFS at 6 months was 68% (95% confidence interval [95% CI], 52% to 88%). The response rate was 48.3%, with 1 complete response and 13 partial responses; 10 patients achieved stable disease. At a median follow-up of 25.9 months, the median PFS was 8.7 months (95% CI, 4.9-10.5 months) and the median overall survival was 12.9 months (95% CI, 9.2-19.7 months). CONCLUSIONS The results of the current study indicate that CAPOX with bevacizumab is an active and well-tolerated regimen for patients with SBA and AAC. These findings support the need for further investigation into the clinical benefit of targeting angiogenesis in patients with SBA and AAC. Cancer 2017;123:1011-17. © 2016 American Cancer Society.
Collapse
Affiliation(s)
- Pat Gulhati
- Hematology/Oncology Fellowship Program, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Kanwal Raghav
- Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Rachna T Shroff
- Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Gauri R Varadhachary
- Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Scott Kopetz
- Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Milind Javle
- Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Wei Qiao
- Department of Biostatistics and Applied Mathematics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Huamin Wang
- Department of Biostatistics and Applied Mathematics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jeffrey Morris
- Department of Biostatistics and Applied Mathematics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Robert A Wolff
- Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Michael J Overman
- Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| |
Collapse
|
|
33
|
Abstract
Small bowel adenocarcinomas (SBAs) are rare tumors, but their incidence is increasing. The most common primary location is the duodenum. Even though SBAs are more often sporadic, some diseases are risk factors. Early diagnosis of small bowel adenocarcinoma remains difficult, despite significant radiologic and endoscopic progress. After R0 surgical resection, the main prognostic factor is lymph node invasion. An international randomized trial (BALLAD [Benefit of Adjuvant Chemotherapy For Small Bowel Adenocarcinoma] study) will evaluate the benefit of adjuvant chemotherapy. For metastatic disease, retrospectives studies suggest that platinum-based chemotherapy is the most effective treatment. Phase II studies are ongoing to evaluate targeted therapy in metastatic SBA.
Collapse
Affiliation(s)
- Thomas Aparicio
- Gastroenterology and Digestive Oncology Unit, Avicenne Hospital, HUPSSD, APHP, Université Paris 13, Sorbonne Paris Cité, 125 rue de Stalingrad, Bobigny 93000, France.
| | - Aziz Zaanan
- Gastroenterology and Digestive Oncology Unit, Georges Pompidou Hospital, APHP, Paris Descartes University, 20 Rue Leblanc, Paris 75015, France
| | - Florence Mary
- Gastroenterology and Digestive Oncology Unit, Avicenne Hospital, HUPSSD, APHP, Université Paris 13, Sorbonne Paris Cité, 125 rue de Stalingrad, Bobigny 93000, France
| | - Pauline Afchain
- Oncology Unit, Saint Antoine Hospital, APHP, 184 Rue du Faubourg Saint-Antoine, Paris 75012, France
| | - Sylvain Manfredi
- Hepato-Gastroenterology Unit, Dijon Hospital, 14 rue Paul Gaffarel, Dijon 21079, France
| | - Thomas Ronald Jeffry Evans
- Translational Cancer Therapeutics department, The Beatson West of Scotland Cancer Centre, University of Glasgow, 1053 Great Western Road, Glasgow G12 0YN, UK
| |
Collapse
|
|
34
|
Abstract
Despite representing the longest segment of the alimentary tract, small bowel adenocarcinomas are rare. The diagnosis of small bowel adenocarcinoma is frequently delayed because of the nonspecific clinical symptoms and the limitations of small bowel imaging. The majority of patients will present with either lymph node or distant metastatic disease. Though the role of adjuvant therapy for resected small bowel adenocarcinoma is unclear, recent research efforts have led to an improvement in our management of advanced disease. Prospective phase II studies have successfully enrolled patients with this rare tumor type and have established the combination of a fluoropyrimidine and oxaliplatin as the most appropriate front-line chemotherapy for patients with advanced disease. Currently, five prospective clinical trials have been designed for patients with small bowel adenocarcinoma and enrollment to these clinical trials should be encouraged.
Collapse
Affiliation(s)
- Michael J Overman
- From the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| |
Collapse
|
|
35
|
Advanced small bowel adenocarcinoma: Molecular characteristics and therapeutic perspectives. Clin Res Hepatol Gastroenterol 2016; 40:154-60. [PMID: 26547136 DOI: 10.1016/j.clinre.2015.09.008] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Revised: 08/29/2015] [Accepted: 09/23/2015] [Indexed: 02/04/2023]
Abstract
Small bowel cancer represents less than 5% of all gastrointestinal cancers, while small bowel adenocarcinoma (SBA) accounts for about one third of all cancers of the small bowel. Although SBA frequently appears sporadically, some diseases are risk factors, such as Crohn's disease and some genetic predispositions to cancer. Progress in the identification of molecular alterations suggests some similarities in carcinogenesis between SBA and colorectal cancer. Evidence levels for the treatment and prognosis of these tumors are insufficient because of the scarcity of this disease and the absence of randomized trials. Chemotherapy based on fluoropyrimidine plus a platinum salt appears to be the most effective treatment regimen in non-randomized prospective trials for advanced SBA. Targeted therapy, against the angiogenic pathway or the epidermal growth factor receptor (EGFR) pathway, for example, is not yet established, but seems promising given the over-expression of vascular epithelial growth factor (VEGF)-A or EGFR observed in SBA. Phase I and II studies are currently evaluating the safety and efficacy of these targeted therapies in SBA treatment. The low incidence of SBA should promote the development of international collaborations to improve our knowledge of the biological mechanisms underlying these tumors and to set up therapeutic trials.
Collapse
|
|
36
|
Cloyd JM, George E, Visser BC. Duodenal adenocarcinoma: Advances in diagnosis and surgical management. World J Gastrointest Surg 2016; 8:212-221. [PMID: 27022448 PMCID: PMC4807322 DOI: 10.4240/wjgs.v8.i3.212] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 11/02/2015] [Accepted: 12/14/2015] [Indexed: 02/06/2023] Open
Abstract
Duodenal adenocarcinoma is a rare but aggressive malignancy. Given its rarity, previous studies have traditionally combined duodenal adenocarcinoma (DA) with either other periampullary cancers or small bowel adenocarcinomas, limiting the available data to guide treatment decisions. Nevertheless, management primarily involves complete surgical resection when technically feasible. Surgery may require pancreaticoduodenectomy or segmental duodenal resection; either are acceptable options as long as negative margins are achievable and an adequate lymphadenectomy can be performed. Adjuvant chemotherapy and radiation are important components of multi-modality treatment for patients at high risk of recurrence. Further research would benefit from multi-institutional trials that do not combine DA with other periampullary or small bowel malignancies. The purpose of this article is to perform a comprehensive review of DA with special focus on the surgical management and principles.
Collapse
|
|
37
|
Ecker BL, McMillan MT, Datta J, Mamtani R, Giantonio BJ, Dempsey DT, Fraker DL, Drebin JA, Karakousis GC, Roses RE. Efficacy of adjuvant chemotherapy for small bowel adenocarcinoma: A propensity score-matched analysis. Cancer 2015; 122:693-701. [PMID: 26717303 DOI: 10.1002/cncr.29840] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Revised: 11/08/2015] [Accepted: 11/16/2015] [Indexed: 01/13/2023]
Abstract
BACKGROUND The role of adjuvant chemotherapy (AC) in the treatment of small bowel adenocarcinoma is poorly defined. Previous analyses have been limited by small sample sizes and have failed to demonstrate a survival advantage. METHODS Patients with resected small bowel adenocarcinoma (American Joint Committee on Cancer [AJCC] pathologic stage I-III) who were receiving AC (n = 1674) or surgery alone (SA; n = 3072) were identified in the NCDB (1998-2011). Cox regression identified covariates associated with overall survival (OS). AC and SA cohorts were matched (1:1) by propensity scores based on the likelihood of receiving AC or the survival hazard from Cox modeling. OS was compared with Kaplan-Meier estimates. RESULTS The omission of AC conferred an increased risk of death (hazard ratio, 1.36; 95% confidence interval, 1.24-1.50; P < .001). After propensity score matching, there was a nonsignificant trend toward improved OS with AC in AJCC stage I patients (158.8 vs 110.7 months; P = .226) and AJCC stage II patients (104.0 vs 79.6 months; P = .185), including the subset with a T4 tumor classification (64.0 vs 47.4 months; P = .130) or a positive resection margin (44.4 vs 31.0 months; P = .333). Median OS was superior for patients with AJCC stage III disease who were receiving AC versus SA (42.4 vs 26.1 months; P < .001). CONCLUSIONS These data support the use of AC for resected stage III small bowel adenocarcinoma. The trend toward improved OS for patients without nodal metastasis, including those who have T4 tumors or have undergone positive-margin resection, may justify the use of AC in select patients with earlier stage disease. Cancer 2016;122:693-701. © 2015 American Cancer Society.
Collapse
Affiliation(s)
- Brett L Ecker
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Matthew T McMillan
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jashodeep Datta
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Ronac Mamtani
- Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Bruce J Giantonio
- Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Daniel T Dempsey
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Douglas L Fraker
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jeffrey A Drebin
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Robert E Roses
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| |
Collapse
|
|
38
|
Negoi I, Paun S, Hostiuc S, Stoica B, Tanase I, Negoi RI, Beuran M. Most small bowel cancers are revealed by a complication. ACTA ACUST UNITED AC 2015; 13:500-5. [PMID: 26676271 PMCID: PMC4878621 DOI: 10.1590/s1679-45082015ao3380] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Accepted: 08/19/2015] [Indexed: 12/25/2022]
Abstract
Objective To characterize the pattern of primary small bowel cancers in a tertiary East-European hospital. Methods A retrospective study of patients with small bowel cancers admitted to a tertiary emergency center, over the past 15 years. Results There were 57 patients with small bowel cancer, representing 0.039% of admissions and 0.059% of laparotomies. There were 37 (64.9%) men, mean age of 58 years; and 72 years for females. Out of 57 patients, 48 (84.2%) were admitted due to an emergency situation: obstruction in 21 (38.9%), perforation in 17 (31.5%), upper gastrointestinal bleeding in 8 (14.8%), and lower gastrointestinal bleeding in 2 (3.7%). There were 10 (17.5%) duodenal tumors, 21 (36.8%) jejunal tumors and 26 (45.6%) ileal tumors. The most frequent neoplasms were gastrointestinal stromal tumor in 24 patients (42.1%), adenocarcinoma in 19 (33.3%), lymphoma in 8 (14%), and carcinoids in 2 (3.5%). The prevalence of duodenal adenocarcinoma was 14.55 times greater than that of the small bowel, and the prevalence of duodenal stromal tumors was 1.818 time greater than that of the small bowel. Obstruction was the complication in adenocarcinoma in 57.9% of cases, and perforation was the major local complication (47.8%) in stromal tumors. Conclusion Primary small bowel cancers are usually diagnosed at advanced stages, and revealed by a local complication of the tumor. Their surgical management in emergency setting is associated to significant morbidity and mortality rates.
Collapse
Affiliation(s)
- Ionut Negoi
- Carol Davila University of Medicine and Pharmacy Bucharest, Bucharest, Romania
| | - Sorin Paun
- Carol Davila University of Medicine and Pharmacy Bucharest, Bucharest, Romania
| | - Sorin Hostiuc
- Carol Davila University of Medicine and Pharmacy Bucharest, Bucharest, Romania
| | | | - Ioan Tanase
- Emergency Hospital of Bucharest, Bucharest, Romania
| | | | - Mircea Beuran
- Carol Davila University of Medicine and Pharmacy Bucharest, Bucharest, Romania
| |
Collapse
|
|
39
|
Abstract
Ampullary cancers are rare, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. They arise from the ampullary complex, distal to the confluence of the common bile and pancreatic duct (Fig. 1). In contrast to other periampullary malignancies, true ampullary cancers present earlier in their disease course with symptoms that result from biliary obstruction. It is often difficult to distinguish primary ampullary cancers from other periampullary cancers preoperatively. In early stages, ampullary cancers are surgically treated, similar to pancreatic cancers, and typically with a pancreatico-duodenoectomy (or Whipple procedure). Because of their earlier presentation, resection rates for all patients are much higher than other periampullary carcinomas. Moreover, their prognosis tends to be better than those with other periampullary- and pancreatic-originating cancers. In patients with true ampullary cancer, there is very limited data to guide physicians on the choice of therapy, largely because of the rarity of the disease and the paucity of related research. Herein, we provide an overview of the biology, histology, current therapeutic strategies, and potential future therapies for carcinomas arising from the ampulla of Vater.
Collapse
Affiliation(s)
- Daniel H Ahn
- From the Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus OH
| | - Tanios Bekaii-Saab
- From the Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus OH
| |
Collapse
|
|
40
|
Oyasiji T, Alosi J, Tan W, Wilfong C, Wilkinson N. Duodenal Adenocarcinoma: Profile and Predictors of Survival Outcomes. Am Surg 2015. [DOI: 10.1177/000313481508101124] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Duodenal adenocarcinoma is rare. We aimed to evaluate survival outcome and prognostic factors for survival in patients with duodenal adenocarcinoma in recent years, marked by advancement in chemotherapy for gastrointestinal cancers. All patients treated for duodenal adenocarcinoma at our institution between January 2000 and July 2013 were reviewed. Thirty-nine patients were identified: 27 operative patients [21(53.8%) curative and 6 (15.4%) palliative operations] and 12 nonoperative patients [primary systemic chemotherapy, 4 (10.3%), palliative radiotherapy, 1 (2.6%), and no treatment, 7 (17.9%)]. Curative resections included 13 pancreaticoduodenectomies and eight segmental resections. Median overall survival (OS) for entire cohort was 14.4 months. Median OS and one-, three-, and five-year OS were operative group (41.4 months; 79.1%, 50.6%, and 10.6%, respectively); nonoperative group (7.4 months; 25.0%, 8.3%, and 0%, respectively); curative surgery (45.4 months; 92.9%, 62.5%, and 16.7%, respectively) and palliative surgery (5.4 months; 33.3%, 16.7%, and 0%, respectively). Female gender ( P = 0.04), curative resection ( P = 0.03), nodal metastasis ( P = 0.047) and advanced T stage ( P = 0.047) were predictive of OS. Two factors were independently predictive of OS—female gender and curative resection. Overall survival still hinges on curative resection. This favors early detection. Adjuvant treatment modalities such as chemotherapy and radiation require further investigation.
Collapse
Affiliation(s)
- Tolutope Oyasiji
- Departments of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York
| | - Julie Alosi
- Departments of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York
| | - Wei Tan
- Departments of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York
| | - Chandler Wilfong
- Departments of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York
| | - Neal Wilkinson
- Departments of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York
| |
Collapse
|
|
41
|
Wang L, Song Q, Li J, Chen X. S-1 treatment leading to complete remission of advanced duodenal adenocarcinoma: A case report. Mol Clin Oncol 2015; 3:1184-1186. [PMID: 26623074 DOI: 10.3892/mco.2015.607] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Accepted: 07/09/2015] [Indexed: 12/29/2022] Open
Abstract
Primary duodenal adenocarcinoma (DA) is a rare malignant neoplasm, accounting for 1% of all gastrointestinal tract carcinomas. This is the case report of a 40-year-old male patient with a duodenal lesion detected on abdominal magnetic resonance imaging and diagnosed by endoscopy and biopsy as DA. Following surgical resection and histopathological examination, the tumor was confirmed as differentiated duodenal neuroendocrine carcinoma with liver metastasis (TxNxM1). The patient received 8 cycles of palliative chemotherapy with oxaliplatin and S-1 and achieved a clinically complete response, with a treatment-related toxicity profile that was considered as tolerable. Therefore, this regimen exhibited favorable efficacy and a tolerable toxicity profile for the treatment of DA in this case.
Collapse
Affiliation(s)
- Lijun Wang
- Department of Computerized Tomography, Shandong Medical Sciences, Jinan, Shandong 250000, P.R. China
| | - Quanmao Song
- Oncology Department, PKU Care Luzhong Hospital, Zibo, Shandong 255000, P.R. China
| | - Jinpeng Li
- Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
| | - Xiaohua Chen
- Oncology Department, PKU Care Luzhong Hospital, Zibo, Shandong 255000, P.R. China
| |
Collapse
|
|
42
|
Fadavi P, Zare M. Adenocarcinoma of Small Bowel. Rare Tumors 2015; 7:5517. [PMID: 26266005 PMCID: PMC4508636 DOI: 10.4081/rt.2015.5517] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Revised: 11/07/2014] [Accepted: 11/11/2014] [Indexed: 01/13/2023] Open
Abstract
Small bowel cancer is one of the rarest cancers in the gastrointestinal tract. The diagnosis is usually late and most patients presented with the advanced stage. Because of this rarity, there is limited data when making decisions for treatment and biological behavior. Most forms of the cancer occur in the duodenum with surgery being the treatment of choice if the cancer is operable. Chemotherapy has an accepted role in duodenal cancer, with the best form being regimen, which yields the best result in combination with capecitabin and oxaliplatin. Our case patient was present with liver metastasis and a huge mass in her first duodenal region so we were required to use chemotherapy and radiotherapy. Like other duodenal cancers, the metastasis decreased her survival and she died about 13 months after diagnosis.
Collapse
Affiliation(s)
- Pedram Fadavi
- Department of Radiation Oncology, Hafte Tir Hospital, Iran University of Medical Science , Tehran, Iran
| | - Mahkameh Zare
- Department of Radiation Oncology, Hafte Tir Hospital, Iran University of Medical Science , Tehran, Iran
| |
Collapse
|
|
43
|
Yhim HY, Cho SH, Kim SY, Cho IS, Lee KT, Lee WS, Lee SI, Park MR, Park SG, Han HS, Choi YS, Chung IJ, Shim HJ, Lee NR, Song EK, Kim HS, Yim CY. Prognostic implications of thymidylate synthase gene polymorphisms in patients with advanced small bowel adenocarcinoma treated with first-line fluoropyrimidine-based chemotherapy. Oncol Rep 2015; 34:155-64. [PMID: 25955097 DOI: 10.3892/or.2015.3954] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Accepted: 04/17/2015] [Indexed: 11/06/2022] Open
Abstract
Thymidylate synthase (TS) gene polymorphisms such as tandem repeat (TR) polymorphisms and single-nucleotide polymorphisms (SNPs) affect transcriptional efficiency of the TS gene and may be prognostic markers for fluoropyrimidine-based therapy in various gastrointestinal cancers. However, data for TS polymorphisms on clinical outcomes in advanced small bowel adenocarcinoma (SBA) are limited. We retrospectively enrolled 58 locally advanced/metastatic SBA patients treated with first-line fluoropyrimidine-based chemotherapy and analyzed the relationship between TS genotypes and clinical outcomes in 30 patients who were available for tumor tissue. Based on TR polymorphisms and a G>C SNP in the promoter region of the TS gene, 74% of patients had high TS expression genotypes (2R/3RG, 3RG/3RC, 3RG/3RG); the remainder had low TS expression genotypes (2R/2R, 2R/3RC, 3RC/3RC). After a median follow-up of 48.8 months, median progression-free survival (PFS) and overall survival (OS) in all patients were 6.0 and 11.3 months, respectively. However, patients with low TS expression genotypes had better median PFS (12.8 vs. 4.3 months, P=0.027) and OS (28.8 vs. 8.9 months, P=0.025) than those with high TS expression genotypes. In multivariate analysis, poor Eastern Cooperative Oncology Group performance status [hazard ratio (HR), 2.85; 95% CI, 1.02-7.93] and high TS expression genotypes (HR, 3.49; 95% CI, 1.13-10.78) were independent prognostic factors for worse OS. Therefore, TS genotypes, based on a G>C SNP in the TR sequence of the TS gene, may be a useful biomarker for predicting outcomes for fluoropyrimidine-based chemotherapy in patients with locally advanced/metastatic SBA.
Collapse
Affiliation(s)
- Ho-Young Yhim
- Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea
| | - Sang-Hee Cho
- Department of Internal Medicine, Chonnam National University Medical School, Jeollanam-do, Republic of Korea
| | - Sam Yong Kim
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - In Sung Cho
- Department of Internal Medicine, Eulji University Hospital, Daejeon, Republic of Korea
| | - Kyu Taek Lee
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
| | - Won Sup Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - Soon Il Lee
- Department of Medicine, Dankook University Hospital, Cheonan, Republic of Korea
| | - Moo Rim Park
- Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Republic of Korea
| | - Sang-Gon Park
- Department of Internal Medicine, Chosun University Hospital, Gwangju, Republic of Korea
| | - Hye-Suk Han
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea
| | - Yoon Seok Choi
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Ik-Joo Chung
- Department of Internal Medicine, Chonnam National University Medical School, Jeollanam-do, Republic of Korea
| | - Hyun-Jeong Shim
- Department of Internal Medicine, Chonnam National University Medical School, Jeollanam-do, Republic of Korea
| | - Na-Ri Lee
- Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea
| | - Eun-Kee Song
- Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea
| | - Hee Sun Kim
- Department of Nursing, Wonkwang University School of Medicine, Iksan, Republic of Korea
| | - Chang-Yeol Yim
- Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea
| |
Collapse
|
|
44
|
Khan K, Peckitt C, Sclafani F, Watkins D, Rao S, Starling N, Jain V, Trivedi S, Stanway S, Cunningham D, Chau I. Prognostic factors and treatment outcomes in patients with Small Bowel Adenocarcinoma (SBA): the Royal Marsden Hospital (RMH) experience. BMC Cancer 2015; 15:15. [PMID: 25603878 PMCID: PMC4305243 DOI: 10.1186/s12885-015-1014-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 01/07/2015] [Indexed: 02/06/2023] Open
Abstract
Background SBA is a rare tumour which carries a poor prognosis. Very few data on prognostic factors and treatment outcomes are available. We conducted a retrospective analysis of patients treated for SBA at our institution. Methods Clinico-pathological characteristics, treatments and outcomes of all the SBA patients treated consecutively from 1996 to 2011 were retrospectively collected. The prognostic value of baseline factors was assessed using the Cox regression model. The Kaplan-Meier method was used to estimate the survival outcomes. Results Eighty-four patients with SBA were treated during the study period. Of these, 48 presented with early stage SBA, while 36 had unresectable disease. All early stage SBA patients (58.3% males; median age, 59 years) underwent resection (R0 in 44/48) and 27 (56%) received adjuvant chemotherapy. Median relapse-free survival and overall survival (OS) were 31.1 months (95% CI: 8.0-54.3) and 42.9 (95% CI: 0–94.9), respectively. In univariate analyses, poor histological differentiation (p = 0.025) and lymphovascular invasion (p = 0.003) were prognostic for OS. In the group of patients with relapsed, unresectable or metastatic disease (n = 59), systemic chemotherapy was administered in 46 cases (78%). The response rate to first line chemotherapy was 50%. Median progression-free survival and OS were 8.8 (95% CI: 5.5-12.3) and 12.8 months (95% CI: 8.4-17.2), respectively. In univariate analyses, low albumin (p = 0.041) and high platelet count (p = 0.007) were prognostic for OS. Conclusion Prospective clinical trials are needed to inform the management of SBA patients. Prognostic factors evaluated in our series may be useful for patient stratification and treatment selection in future studies.
Collapse
Affiliation(s)
- Khurum Khan
- Department of Medicine, GI and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
| | - Clare Peckitt
- Department of Medicine, GI and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
| | - Francesco Sclafani
- Department of Medicine, GI and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
| | - David Watkins
- Department of Medicine, GI and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
| | - Sheela Rao
- Department of Medicine, GI and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
| | - Naureen Starling
- Department of Medicine, GI and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
| | - Vikram Jain
- Department of Medicine, GI and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
| | - Sachin Trivedi
- Department of Medicine, GI and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
| | - Susannah Stanway
- Department of Medicine, GI and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
| | - David Cunningham
- Department of Medicine, GI and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
| | - Ian Chau
- Department of Medicine, GI and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
| |
Collapse
|
|
45
|
Suh CH, Tirumani SH, Shinagare AB, Kim KW, Rosenthal MH, Ramaiya NH, Baheti AD. Diagnosis and management of duodenal adenocarcinomas: a comprehensive review for the radiologist. ACTA ACUST UNITED AC 2014; 40:1110-20. [DOI: 10.1007/s00261-014-0309-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
|
|
46
|
Bandyopadhyay A, Das M, Kundu SK. Metastatic primary duodenal adeno-carcinoma responding to metronomic oral cyclophosphamide chemotherapy. Indian J Palliat Care 2014; 20:239-42. [PMID: 25191014 PMCID: PMC4154174 DOI: 10.4103/0973-1075.138402] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Primary adenocarcinoma of duodenum is a very rare tumour with a prevalence of only 0.3 to 1% of among all the tumours of gastrointestinal tracts. Localised tumours, if resected have good prognosis but those with metastates entails a poor prognosis, where generally palliation may be the only feasible option. Low dose continous cytotoxic treatment or metronomic chemotherapy prevents neoangiogenesis and chemoresistance thereby, provides excellent symptom relief and palliation in many advanced heavily pretreated solid malignancies. It offers as an affordable, less toxic therapy with moderate to good efficacy. Here we report a case of a 52 year female who, presented with history of maleana, pallor and pedal edema for last 2 months. Her performance status was poor (KPS 40) and she had enlarged left supraclavicular lymph node, palpable liver and vague mass in paraumbilical region. Upper GI endoscopy revealed large ulceroproliferative growth in the D2 segment and HPE showed moderately differentiated adenocarcinoma. CT scan revealed paratracheal and retroperitoneal lymphadenopathy and bone scan revealed vertebral metastasis. Patient received oral cyclophosphamide and hematinic and vitamin support, along with radiation to spine. There was near complete clinical response, and progression free period of about 32 weeks. Thus, single agent cyclophosphamide in the present case provided near total clinical response and prolonged period of freedom from disease progression with excellent palliation of symptoms. Hence in patient of advanced and metastatic small bowel cancer, with poor performance status metronomic therapy with single agent cyclophosphamide may provide viable option both for treatment and palliation.
Collapse
Affiliation(s)
- Anis Bandyopadhyay
- Department of Radiotherapy, Medical College and Hospital, Kolkata, West Bengal, India
| | - Mou Das
- Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
| | - Subhra Kanti Kundu
- Department of Radiotherapy, Medical College and Hospital, Kolkata, West Bengal, India
| |
Collapse
|
|
47
|
Kim HS, Shin SJ, Kim JH, Kim H, Choi HJ. Better outcome of XELOX chemotherapy in patients with advanced intestinal-type adenocarcinoma of the ampulla of Vater. TOHOKU J EXP MED 2014; 231:21-8. [PMID: 23994910 DOI: 10.1620/tjem.231.21] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Adenocarcinoma arising from the ampulla of Vater is a rare disease and has limited data regarding outcome of chemotherapy. The ampulla of Vater is a heterogeneous junctional structure located at the union of the common bile duct, the pancreatic duct, and the small intestine. Thus, ampullary adenocarcinoma is classified as either intestinal type or pancreatobiliary type. We investigated the efficacy of the XELOX (capecitabine plus oxaliplatin) chemotherapy in patients with recurrent or metastatic ampullary adenocarcinoma, and analyzed the histopathologic features and outcomes. From November 2009 to December 2011, 21 patients were treated with XELOX regimen. XELOX was administered in outpatient clinic every 3 weeks according to the following protocol: oral administration of capecitabine 750 mg/m² twice a day on days 1-14 and intravenous injection of oxaliplatin 130 mg/m² on day 1. With follow-up of median 16.6 months, median time to progression (TTP) was 7.6 months (95% confidence interval [CI], 6.7-8.5), and median overall survival was 19.7 months (95% CI, 14.8-23.6). Two patients (9%) achieved complete response and 6 patients (29%) showed partial response. In subgroup analysis with tissue specimens obtained from 17 patients, median TTP was longer among patients with the intestinal-type adenocarcinoma (n = 7), compared to those with the pancreatobiliary type (n = 10) (13.1 vs. 6.4 months, P = 0.038). The most common grade 3-4 adverse event was neutropenia (27%), and most events were mild. XELOX chemotherapy shows favorable efficacy with manageable toxicity for advanced intestinal-type ampullary adenocarcinoma.
Collapse
Affiliation(s)
- Han Sang Kim
- Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | | | | | | | | |
Collapse
|
|
48
|
Jabbour SK, Mulvihill D. Defining the role of adjuvant therapy: ampullary and duodenal adenocarcinoma. Semin Radiat Oncol 2014; 24:85-93. [PMID: 24635865 DOI: 10.1016/j.semradonc.2013.11.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Adenocarcinomas of the ampulla of Vater and duodenum are more rare than pancreatic cancer and have a better prognosis. However, studies conducted on the management of these cancers, such as adjuvant chemotherapy and radiation therapy, are limited by small sample sizes and series that are retrospective. This review evaluates ampullary and duodenal adenocarcinomas with regard to incidence, anatomy, prognostic features, patterns of failure, and the available literature studying adjuvant therapy.
Collapse
Affiliation(s)
- Salma K Jabbour
- Department of Radiation Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ.
| | - David Mulvihill
- Department of Radiation Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ
| |
Collapse
|
|
49
|
Reynolds I, Healy P, Mcnamara DA. Malignant tumours of the small intestine. Surgeon 2014; 12:263-70. [PMID: 24637026 DOI: 10.1016/j.surge.2014.02.003] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2013] [Accepted: 02/16/2014] [Indexed: 02/06/2023]
Abstract
Adenocarcinoma, neuroendocrine tumours, sarcomas and lymphomas are the four most common malignant tumours arising in the small intestine, although over forty different histological subtypes are described. Collectively these account for only 2% of cancers of the digestive system. The incidence of small bowel cancer has increased in recent decades with a four-fold increase in carcinoid tumours. Risk factors for small bowel tumours include coeliac disease, inflammatory bowel disease and a number of genetic abnormalities. The non-specific nature of their symptoms and the difficulty in visualising these tumours with normal endoscopic techniques often results in late diagnosis. Furthermore the paucity of literature on this topic has made it difficult to standardise management. There has however been marked improvement in imaging methods resulting in earlier diagnosis in many cases. As expected, early detection of localised, well differentiated tumours followed by surgical resection with negative margins offers the best chance of long term survival. Better adjuvant treatment, notably for gastrointestinal stromal tumours, has improved 5-year survival rates significantly. Development of surveillance guidelines for at risk populations may be a valuable way of improving early diagnosis of this challenging group of conditions.
Collapse
Affiliation(s)
- Ian Reynolds
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland
| | - Paul Healy
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland
| | | |
Collapse
|
|
50
|
Nagaraj G, Zarbalian Y, Flora K, Tan BR. Complete response and prolonged disease-free survival in a patient with recurrent duodenal adenocarcinoma treated with bevacizumab plus FOLFOX6. J Gastrointest Oncol 2014; 5:E1-6. [PMID: 24490045 DOI: 10.3978/j.issn.2078-6891.2013.038] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Accepted: 06/03/2013] [Indexed: 01/13/2023] Open
Abstract
Small bowel adenocarcinoma is an uncommon gastrointestinal malignancy with limited data on effective chemotherapy in the adjuvant setting, as well as for advanced disease. We present a case report of a patient with recurrent duodenal adenocarcinoma after resection and adjuvant chemotherapy who experienced a complete response to bevacizumab with oxaliplatin and 5FU (FOLFOX) followed by bevacizumab/capecitabine maintenance therapy for 2 years. The patient continues to be disease-free 8 years after his recurrence. This case highlights the potential of vascular endothelial growth factor (VEGF) inhibitors to enhance chemotherapeutic regimens for advanced small bowel adenocarcinoma.
Collapse
Affiliation(s)
- Gayathri Nagaraj
- Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri 63110, USA
| | - Yousef Zarbalian
- Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri 63110, USA
| | - Karin Flora
- Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri 63110, USA
| | - Benjamin R Tan
- Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri 63110, USA
| |
Collapse
|