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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 -
Journal of Gastrointestinal and Liver... Dec 2022Somatostatinoma of the ampulla of Vater (SAV) is a rare neuroendocrine tumor that usually appears with atypical clinical manifestations and is associated with Von...
BACKGROUND AND AIMS
Somatostatinoma of the ampulla of Vater (SAV) is a rare neuroendocrine tumor that usually appears with atypical clinical manifestations and is associated with Von Recklinghausen's disease. The aims of this study were to systematically review the literature regarding SAV and to highlight the clinicopathological characteristics and optimal therapeutic management of this rare entity.
METHODS
A systematic search of the literature in PubMed/Medline and Scopus databases was performed by two independent investigators, including all case reports and case series concerning SAVs from 1980 until September 2021.
RESULTS
In total, 37 articles were retrieved, including 43 patients, with a male to female ratio of 1.8:1 and a mean age of 46.8 ± 11.3 years (mean, SD). For 23 out of 43 patients (53.5%), Von Recklinghausen's disease was proved. The main clinical manifestations were abdominal pain (41.9%), jaundice (27.9%), weight loss (20.9%) and bowel disorders (20.9%). Typical histological findings included psammoma bodies, nests or clusters of epithelial cells with eosinophilic cytoplasm, while somatostatin staining was positive in 35 patients (81.4%), chromogranin-A in 21 patients (48.8%) and synaptophysin in 18 patients (41.9%). Surgery was the initial therapeutic approach in 34 patients (79.1%), whereas Whipple's procedure was the preferred surgical approach in 23 patients (53.4%). The longest survival among included patients was 13 years and only two postoperative deaths (4.7%) were reported.
CONCLUSIONS
Somatostatinomas of the ampulla of Vater are rare malignancies that require increased physicians' suspicion and accurate surgical approach in order to achieve optimal therapeutic results.
Topics: Humans; Male; Female; Adult; Middle Aged; Somatostatinoma; Neurofibromatosis 1; Ampulla of Vater; Duodenal Neoplasms; Pancreatic Neoplasms
PubMed: 36535044
DOI: 10.15403/jgld-4383 -
Journal of B.U.ON. : Official Journal... 2018Pancreatic and periampullary adenocarcinoma have not generally been included in the tumour types considered for metastasectomy. However, there is an increasing interest... (Meta-Analysis)
Meta-Analysis
PURPOSE
Pancreatic and periampullary adenocarcinoma have not generally been included in the tumour types considered for metastasectomy. However, there is an increasing interest that metastasectomy in well-selected patients can prolong survival. This review aims to establish the recent evidence on the surgical management of oligometastatic disease and survival outcome in patients who underwent metastasectomy focusing on isolated hepatic and pulmonary metastases.
METHODS
A systematic search was performed in the PubMed database to identify all original articles on the role of metastasectomy for oligometastasis of pancreatic and periampullary adenocarcinoma. Data on methodologies used, 1,3,5 - year survival and median overall survival were summarized, and used to address relevant clinical questions related to the survival outcome in patients who underwent metastasectomy.
RESULTS
Sixteen studies were included in this review. All the studies included were retrospective and heterogenous in nature and did not have a uniform reporting on survival outcomes.
CONCLUSION
There is insufficient evidence to support a change of current practice in managing metastatic pancreatic and periampullary cancer. However, patients with ampullary cancer as the primary and any patients with first recurrence as isolated pulmonary metastases had better prognosis than patients with synchronous metastasis or metastases to the liver. This need to be explored in future studies.
Topics: Adenocarcinoma; Ampulla of Vater; Common Bile Duct Neoplasms; Humans; Metastasectomy; Neoplasms; Pancreatic Neoplasms; Prognosis; Survival Rate
PubMed: 30610789
DOI: No ID Found -
The Cochrane Database of Systematic... Jan 2021Pancreatic and periampullary adenocarcinomas account for some of the most aggressive malignancies, and the leading causes of cancer-related mortalities. Partial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatic and periampullary adenocarcinomas account for some of the most aggressive malignancies, and the leading causes of cancer-related mortalities. Partial pancreaticoduodenectomy (PD) with negative resection margins is the only potentially curative therapy. The high prevalence of lymph node metastases has led to the hypothesis that wider excision with the removal of more lymphatic tissue could result in an improvement of survival, and higher rates of negative resection margins.
OBJECTIVES
To compare overall survival following standard (SLA) versus extended lymph lymphadenectomy (ELA) for pancreatic head and periampullary adenocarcinoma. We also compared secondary outcomes, such as morbidity, mortality, and tumour involvement of the resection margins between the two procedures.
SEARCH METHODS
We searched CENTRAL, MEDLINE, PubMed, and Embase from 1973 to September 2020; we applied no language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCT) comparing PD with SLA versus PD with ELA, including participants with pancreatic head and periampullary adenocarcinoma.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened references and extracted data from study reports. We calculated pooled risk ratios (RR) for most binary outcomes except for postoperative mortality, for which we estimated a Peto odds ratio (Peto OR), and mean differences (MD) for continuous outcomes. We used a fixed-effect model in the absence of substantial heterogeneity (I² < 25%), and a random-effects model in cases of substantial heterogeneity (I² > 25%). Two review authors independently assessed risk of bias, and we used GRADE to assess the quality of the evidence for important outcomes.
MAIN RESULTS
We included seven studies with 843 participants (421 ELA and 422 SLA). All seven studies included Kaplan-Meier curves for overall survival. There was little or no difference in survival between groups (log hazard ratio (log HR) 0.12, 95% confidence interval (CI) -3.06 to 3.31; P = 0.94; seven studies, 843 participants; very low-quality evidence). There was little or no difference in postoperative mortality between the groups (Peto odds ratio (OR) 1.20, 95% CI 0.51 to 2.80; seven studies, 843 participants; low-quality evidence). Operating time was probably longer for ELA (mean difference (MD) 50.13 minutes, 95% CI 19.19 to 81.06 minutes; five studies, 670 participants; moderate-quality evidence). There was substantial heterogeneity between the studies (I² = 88%; P < 0.00001). There may have been more blood loss during ELA (MD 137.43 mL, 95% CI 11.55 to 263.30 mL; two studies, 463 participants; very low-quality evidence). There was substantial heterogeneity between the studies (I² = 81%, P = 0.02). There may have been more lymph nodes retrieved during ELA (MD 11.09 nodes, 95% CI 7.16 to 15.02; five studies, 670 participants; moderate-quality evidence). There was substantial heterogeneity between the studies (I² = 81%, P < 0.00001). There was little or no difference in the incidence of positive resection margins between groups (RR 0.81, 95% CI 0.58 to 1.13; six studies, 783 participants; very low-quality evidence).
AUTHORS' CONCLUSIONS
There is no evidence of an impact on survival with extended versus standard lymph node resection. However, the operating time may have been longer and blood loss greater in the extended resection group. In conclusion, current evidence neither supports nor refutes the effect of extended lymph lymphadenectomy in people with adenocarcinoma of the head of the pancreas.
Topics: Adenocarcinoma; Adult; Ampulla of Vater; Blood Loss, Surgical; Common Bile Duct Neoplasms; Confidence Intervals; Gastric Emptying; Humans; Kaplan-Meier Estimate; Lymph Node Excision; Margins of Excision; Operative Time; Pancreatic Fistula; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Postoperative Hemorrhage; Randomized Controlled Trials as Topic
PubMed: 33471373
DOI: 10.1002/14651858.CD011490.pub2 -
Annals of Surgical Oncology Jul 2024Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer...
Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review.
BACKGROUND
Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment.
METHODS
This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC.
RESULTS
The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015).
CONCLUSION
This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.
Topics: Humans; Lymphatic Metastasis; Retrospective Studies; Ampulla of Vater; Pancreaticoduodenectomy; Common Bile Duct Neoplasms; Duodenal Neoplasms; Male; Female; Pancreatic Neoplasms; Adenocarcinoma; Lymph Node Excision; Cholangiocarcinoma; Aged; Middle Aged; Prognosis; Follow-Up Studies; Lymph Nodes; Bile Duct Neoplasms; Carcinoma, Pancreatic Ductal
PubMed: 38602578
DOI: 10.1245/s10434-024-15213-z -
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