-
Annals of Surgical Oncology Sep 2018Duodenal adenocarcinoma (DA) is a rare tumor for which survival data per treatment modality and disease stage are unclear. This systematic review and meta-analysis aims... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Duodenal adenocarcinoma (DA) is a rare tumor for which survival data per treatment modality and disease stage are unclear. This systematic review and meta-analysis aims to summarize the current literature on patient outcome after surgical, (neo)adjuvant, and palliative treatment in patients with DA.
METHODS
A systematic search was performed according to the preferred reporting items for systematic reviews and meta-analyses guidelines, to 25 April 2017. Primary outcome was overall survival (OS), specified for treatment strategy or disease stage. Random-effects models were used for the calculation of pooled odds ratios per treatment modality. Included papers were also screened for prognostic factors.
RESULTS
A total of 26 observational studies, comprising 6438 patients with DA, were included. Of these, resection with curative intent was performed in 71% (range 53-100%) of patients, and 29% received palliative treatment (range 0-61%). The pooled 5-year OS rate was 46% after curative resection, compared with 1% in palliative-treated patients (OR 0.04, 95% confidence interval [CI] 0.02-0.09, p < 0.0001). Both segmental resection and pancreaticoduodenectomy allowed adequate assessment of lymph node involvement and resulted in similar OS. Lymph node involvement correlated with worse OS (pooled 5-year survival rate 21% for nodal metastases vs. 65% for node-negative disease; OR 0.17, 95% CI 0.11-0.27, p < 0.0001). In the current literature, no survival benefit for adjuvant therapy after curative resection was found.
CONCLUSION
Resection with curative intent, either pancreaticoduodenectomy or segmental resection, and lack of nodal metastases, favors survival for DA. Further studies exploring multimodality (neo)adjuvant therapy are warranted to investigate their benefit.
Topics: Adenocarcinoma; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Duodenal Neoplasms; Humans; Lymphatic Metastasis; Metastasectomy; Neoadjuvant Therapy; Palliative Care; Pancreaticoduodenectomy; Survival Rate; Treatment Outcome
PubMed: 29946997
DOI: 10.1245/s10434-018-6567-6 -
Asian Journal of Surgery Jan 2019Primary duodenal adenocarcinoma (PDAC) is a rare malignancy. The aim of this study was to evaluate the published evidence for resection with curative intent in patients... (Meta-Analysis)
Meta-Analysis
Primary duodenal adenocarcinoma (PDAC) is a rare malignancy. The aim of this study was to evaluate the published evidence for resection with curative intent in patients with PDAC. A literature search was conducted in PubMed and EMBASE databases for eligible studies that reported 5-year overall survival (OS) after surgical resection of PDAC from January 1990 to January 2018. Independent prognostic factors related to OS were evaluated using meta-analytical techniques. Odds ratio (OR) and hazard ratio (HR) with their 95% confidence interval (CI) were calculated as appropriate. Thirty-seven observational studies comprising a total of 1728 patients who underwent resection for PDAC were reviewed. The overall 30-day postoperative mortality was 3.2% (range, 0-16.0%) and the median 5-year OS was 46.4% (range, 16.6-71.1%). Surgical resection significantly improved the prognosis as compared with the palliative therapy (OR 15.76, P < 0.001). Lymph node metastasis (HR 2.58, P < 0.001), poor tumor differentiation (HR 1.43, P = 0.05), perineural invasion (HR 2.21, P = 0.002), and lymphovascular invasion (HR 2.18, 95% CI 1.18-4.03; P = 0.01) were found to be independently associated with decreased OS after surgical resection. The present study provides evidence that surgical resection can be performed safely for PDAC patients and offers a favorable long-term outcome. Tumor-specific factors have prognostic significance.
Topics: Adenocarcinoma; Confidence Intervals; Databases, Bibliographic; Digestive System Surgical Procedures; Duodenal Neoplasms; Humans; Lymphatic Metastasis; Observational Studies as Topic; Odds Ratio; Prognosis; Proportional Hazards Models; Survival Rate; Time Factors; Treatment Outcome
PubMed: 29802028
DOI: 10.1016/j.asjsur.2018.04.005 -
The Cochrane Database of Systematic... Apr 2018Biliary tract cancers are a group of rare heterogeneous malignant tumours. They include intrahepatic and extrahepatic cholangiocarcinomas, gallbladder carcinomas, and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Biliary tract cancers are a group of rare heterogeneous malignant tumours. They include intrahepatic and extrahepatic cholangiocarcinomas, gallbladder carcinomas, and ampullary carcinomas. Surgery remains the optimal modality of therapy leading to long-term survival for people diagnosed with resectable biliary tract carcinomas. Unfortunately, most people with biliary tract carcinomas are diagnosed with either unresectable locally-advanced or metastatic disease, and they are only suitable for palliative chemotherapy or supportive care.
OBJECTIVES
To assess the benefits and harms of intravenous administration of gemcitabine monotherapy or gemcitabine-based chemotherapy versus placebo, or no intervention, or other treatments (excluding gemcitabine) in adults with advanced biliary tract carcinomas.
SEARCH METHODS
We performed electronic searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science up to June 2017. We also checked reference lists of primary original studies and review articles manually, for further related articles (cross-references).
SELECTION CRITERIA
Eligible studies include randomised clinical trials, irrespective of language or publication status, comparing intravenous administration of gemcitabine monotherapy or gemcitabine-based combination to placebo, to no intervention, or to treatments other than gemcitabine.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We assessed risks of bias of the included trials using definitions of predefined bias risk domains, and presented the review results incorporating the methodological quality of the trials using GRADE.
MAIN RESULTS
We included seven published randomised clinical trials with 600 participants. All included trials were at high risk of bias, and we rated the evidence as very low quality. Cointerventions were equally applied in three trials (gemcitabine plus S-1 (a combination of tegafur, gimeracil, and oteracil) versus S-1 monotherapy; gemcitabine plus S-1 versus gemcitabine monotherapy versus S-1 monotherapy; and gemcitabine plus vandetanib versus gemcitabine plus placebo versus vandetanib monotherapy), while four trials compared gemcitabine plus cisplatin versus S-1 plus cisplatin; gemcitabine plus mitomycin C versus capecitabine plus mitomycin C; gemcitabine plus oxaliplatin versus chemoradiotherapy; and gemcitabine plus oxaliplatin versus 5-fluorouracil plus folinic acid versus best supportive care. The seven trials were conducted in India, Japan, France, China, Austria, South Korea, and Italy. The median age of the participants in the seven trials was between 50 and 60 years, and the male/female ratios were comparable in most of the trials. Based on these seven trials, we established eight comparisons. We could not perform all planned analyses in all comparisons because of insufficient data.Gemcitabine versus vandetanibOne three-arm trial compared gemcitabine versus vandetanib versus both drugs in combination. It reported no data for mortality, health-related quality of life, or tumour progression outcomes. We rated the increased risk of serious adverse events, anaemia, and overall response rate as very low-certainty evidence.Gemcitabine plus cisplatin versus S-1 plus cisplatinFrom one trial of 96 participants, we found very low-certainty evidence that gemcitabine can lower the risk of mortality at one year when used with cisplatin versus S-1 plus cisplatin (risk ratio (RR) 0.76, 95% confidence interval (CI) 0.58 to 0.98; P = 0.04; participants = 96). The trial did not report data for serious adverse events, quality of life, or tumour response outcomes. There is very low-certainty evidence that gemcitabine plus cisplatin combination leads to a higher risk of high-grade thrombocytopenia compared with S-1 plus cisplatin combination (RR 5.28, 95% CI 1.23 to 22.55; P = 0.02; participants = 96).Gemcitabine plus S-1 versus S-1From two trials enrolling 151 participants, we found no difference between the two groups in terms of risk of mortality at one year or risk of serious adverse events. Gemcitabine plus S-1 combination was associated with a higher overall response rate compared with S-1 alone (RR 2.46, 95% CI 1.27 to 4.75; P = 0.007; participants = 140; trials = 2; I = 0%; very low certainty of evidence). Neither of the trials reported data for health-related quality of life or time to progression of the tumour.Gemcitabine plus oxaliplatin versus 5-fluorouracil plus folinic acid versus best supportive careOne three-arm trial compared gemcitabine plus oxaliplatin versus 5-fluorouracil plus folinic acid versus best supportive care. It reported no data for serious adverse events, health-related quality of life, or tumour progression. We rated the evidence for mortality and for overall response rate as of very low certainty.Gemcitabine plus oxaliplatin versus 5-fluorouracil plus cisplatin plus radiotherapyOne trial of 34 participants compared gemcitabine plus oxaliplatin versus 5-fluorouracil plus cisplatin plus radiotherapy. It reported no data for quality of life, overall response rate, or tumour progression outcomes. We rated the evidence for mortality and serious adverse events as of very low certainty.Gemcitabine plus mitomycin C versus capecitabine plus mitomycin COne trial of 51 participants compared gemcitabine plus mitomycin C versus capecitabine plus mitomycin C. It reported no data for serious adverse events, quality of life, or tumour progression. We rated the evidence for mortality, overall response rate and thrombocytopenia as of very low certainty.We also identified three ongoing trials evaluating outcomes of interest for our review, which we can incorporate in future updates.For-profit bias: there was a high risk of for-profit bias in two trials (because of industry sponsorship) while there was a low risk of for-profit bias in another three trials, and unclear risk in two trials.
AUTHORS' CONCLUSIONS
In adults with advanced biliary tract carcinomas, the effects of gemcitabine or gemcitabine-based chemotherapy are uncertain on mortality and overall response compared with a range of inactive or active controls. The very low certainty of evidence is due to risk of bias, lack of information in the analyses and hence large imprecision, and possible publication bias. The confidence intervals do not rule out meaningful benefits or lack of effect of gemcitabine in all comparisons but one on mortality where gemcitabine plus cisplatin is compared with S-1 plus cisplatin. Gemcitabine-based regimens showed an increase in non-serious adverse events (particularly haematological toxicities). Further randomised clinical trials are mandatory, to further explore the best therapeutic options for adults with advanced biliary tract carcinomas.
Topics: Ampulla of Vater; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Capecitabine; Cholangiocarcinoma; Cisplatin; Deoxycytidine; Drug Combinations; Female; Gallbladder Neoplasms; Humans; Male; Mitomycin; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Piperidines; Quinazolines; Randomized Controlled Trials as Topic; Tegafur; Gemcitabine
PubMed: 29624208
DOI: 10.1002/14651858.CD011746.pub2 -
The British Journal of Surgery Jun 2017Periampullary cancers are uncommon malignancies, often amenable to surgery. Several studies have suggested a role for adjuvant chemotherapy and chemoradiotherapy in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periampullary cancers are uncommon malignancies, often amenable to surgery. Several studies have suggested a role for adjuvant chemotherapy and chemoradiotherapy in improving survival of patients with periampullary cancers, with variable results. The aim of this meta-analysis was to determine the survival benefit of adjuvant therapy for periampullary cancers.
METHODS
A systematic review was undertaken of literature published between 1 January 2000 and 31 December 2015 to elicit and analyse the pooled overall survival associated with the use of either adjuvant chemotherapy or chemoradiotherapy versus observation in the treatment of surgically resected periampullary cancer. Included articles were also screened for information regarding stage, prognostic factors and toxicity-related events.
RESULTS
A total of 704 titles were screened, of which 93 full-text articles were retrieved. Fourteen full-text articles were included in the study, six of which were RCTs. A total of 1671 patients (904 in the control group and 767 who received adjuvant therapy) were included. The median 5-year overall survival rate was 37·5 per cent in the control group, compared with 40·0 per cent in the adjuvant group (hazard ratio 1·08, 95 per cent c.i. 0·91 to 1·28; P = 0·067). In 32·2 per cent of patients who had adjuvant therapy, one or more WHO grade 3 or 4 toxicity-related events were noted. Advanced T category was associated worse survival (regression coefficient -0·14, P = 0·040), whereas nodal status and grade of differentiation were not.
CONCLUSION
This systematic review found no associated survival benefit for adjuvant chemotherapy or chemoradiotherapy in the treatment of periampullary cancer.
Topics: Adenocarcinoma; Ampulla of Vater; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Common Bile Duct Neoplasms; Duodenal Neoplasms; Humans; Survival Rate
PubMed: 28518410
DOI: 10.1002/bjs.10563 -
HPB : the Official Journal of the... Jul 2016Hepatic-artery and para-aortic lymph node metastases (LNM) may be detected during surgical exploration for pancreatic (PDAC) or periampullary cancer. Some surgeons will... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatic-artery and para-aortic lymph node metastases (LNM) may be detected during surgical exploration for pancreatic (PDAC) or periampullary cancer. Some surgeons will continue the resection while others abort the exploration.
METHODS
A systematic search was performed in PubMed, EMBASE and Cochrane Library for studies investigating survival in patients with intra-operatively detected hepatic-artery or para-aortic LNM. Survival was stratified for node positive (N1) disease.
RESULTS
After screening 3088 studies, 13 studies with 2045 patients undergoing pancreatoduodenectomy were included. No study reported survival data after detection of LNM and aborted surgical exploration. In 110 patients with hepatic-artery LNM, median survival ranged between 7 and 17 months. Estimated pooled mean survival in 84 patients with hepatic-artery LNM was 15 [95%CI 12-18] months (13 months in PDAC), compared to 19 [16-22] months in 270 patients with N1-disease without hepatic-artery LNM (p = 0.020). In 192 patients with para-aortic LNM, median survival ranged between 5 and 32 months. Estimated pooled mean survival in 169 patients with para-aortic LNM was 13 [8-17] months (11 months in PDAC), compared to 17 (6-27) months in 506 patients with N1-disease without para-aortic LNM (p < 0.001). Data on the impact of (neo)adjuvant therapy on survival were lacking.
CONCLUSION
Survival after pancreatoduodenectomy in patients with intra-operatively detected hepatic-artery and especially para-aortic LNM is inferior to patients undergoing pancreatoduodenectomy with other N1 disease. It remains unclear what the consequence of this should be since data on (neo-)adjuvant therapy and survival after aborted exploration are lacking.
Topics: Ampulla of Vater; Carcinoma, Pancreatic Ductal; Common Bile Duct Neoplasms; Hepatic Artery; Humans; Kaplan-Meier Estimate; Lymph Node Excision; Lymphatic Metastasis; Neoplasm Staging; Pancreatic Neoplasms; Pancreaticoduodenectomy; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 27346135
DOI: 10.1016/j.hpb.2016.05.001 -
World Journal of Surgical Oncology Jan 2014Metastases from breast cancer cause the frequent involvement of lung, bone, liver, and brain, while the occurrence of metastases to the gastrointestinal tract is rare,... (Review)
Review
BACKGROUND
Metastases from breast cancer cause the frequent involvement of lung, bone, liver, and brain, while the occurrence of metastases to the gastrointestinal tract is rare, and more frequently discovered after a primary diagnosis of breast cancer. Solitary pancreatic metastases from breast cancer, without widespread disease, are actually unusual, and only 19 cases have been previously described; truly exceptional is a solitary pancreatic metastasis becoming evident together with the primary breast cancer.
CASE PRESENTATION
A 68-year-old woman reported general fatigue, lethargy, and jaundice. Abdominal ultrasound (US) and magnetic resonance imaging (MRI) showed an ampulloma of Vater's papilla; moreover, a neoplastic nodule in the left breast was diagnosed. She underwent surgery for both breast cancer and ampulloma of Vater's papilla. Pathological examination of pancreatic specimen, however, did not confirm primary carcinoma of the duodenal papilla, but showed a metastatic involvement of pancreas from lobular breast cancer. Immunohistochemistry has been essential to confirm the origin of the malignancy: hormone receptors and mammaglobin were expressed in both the primary breast tumor and the pancreatic metastasis.
CONCLUSIONS
This is one of the few reported cases in literature of an isolated and synchronous pancreatic metastasis from breast cancer, where the definitive diagnosis was obtained only after surgery. We discuss the controversies in this diagnosis and the choice of correct treatment. The surgical resection of solitary metastases can be performed in the absence of disseminated disease.
Topics: Aged; Breast Neoplasms; Carcinoma, Lobular; Combined Modality Therapy; Female; Humans; Pancreatic Neoplasms; Prognosis
PubMed: 24387226
DOI: 10.1186/1477-7819-12-2 -
HPB : the Official Journal of the... Nov 2013Ampullary adenocarcinoma is considered to have a better prognosis than either pancreatic or bile duct adenocarcinoma. Pancreaticoduodenectomy is associated with... (Review)
Review
BACKGROUND
Ampullary adenocarcinoma is considered to have a better prognosis than either pancreatic or bile duct adenocarcinoma. Pancreaticoduodenectomy is associated with significant mortality and morbidity. Some recent publications have advocated the use of endoscopic papillectomy for the treatment of early ampullary adenocarcinoma. This article reviews investigations and surgical treatment options of ampullary tumours.
METHODS
A systematic review of English-language articles was carried out using an electronic search of the Ovid MEDLINE (from 1996 onwards), PubMed and Cochrane Database of Systematic Reviews databases to identify studies related to the investigation and management of ampullary tumours.
RESULTS
Distinguishing between ampullary adenoma and adenocarcinoma is challenging given the inaccuracy of endoscopic biopsy, for which high false negative rates of 25-50% have been reported. Endoscopic ultrasound is the most accurate method for local staging of ampullary lesions, but distinguishing between T1 and T2 adenocarcinomas is difficult. Lymph node metastasis occurs early in the disease process; it is lowest for T1 tumours, but the risk is still high at 8-45%. Case reports of successful endoscopic resection and transduodenal ampullectomy of T1 adenocarcinomas have been published, but their duration of follow-up is limited.
CONCLUSIONS
Optimal staging should be used to distinguish between ampullary adenoma and adenocarcinoma. Pancreaticoduodenectomy remains the treatment of choice for all ampullary adenocarcinomas.
Topics: Adenocarcinoma; Ampulla of Vater; Biopsy; Cholangiopancreatography, Endoscopic Retrograde; Common Bile Duct Neoplasms; Endosonography; Humans; Image-Guided Biopsy
PubMed: 23458317
DOI: 10.1111/hpb.12038