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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 -
Journal of Vascular and Interventional... May 2018To compare postoperative complications in patients who underwent pancreatoduodenectomy after either endoscopic or percutaneous biliary drain (BD). (Meta-Analysis)
Meta-Analysis Review
Is Percutaneous Transhepatic Biliary Drainage Better than Endoscopic Drainage in the Management of Jaundiced Patients Awaiting Pancreaticoduodenectomy? A Systematic Review and Meta-analysis.
PURPOSE
To compare postoperative complications in patients who underwent pancreatoduodenectomy after either endoscopic or percutaneous biliary drain (BD).
MATERIAL AND METHODS
Data from studies comparing the rate of postoperative complications in patients who underwent endoscopic BD or percutaneous BD before pancreatoduodenectomy were extracted independently by 2 investigators. The primary outcome compared in the meta-analysis was the risk of postoperative complications. Secondary outcomes were the risks of procedure-related complications, postoperative mortality, postoperative pancreatic fistula, severe complications, and wound infection. For dichotomous variables, the odds ratio (OR) with 95% confidence interval (CI) was calculated.
RESULTS
Thirteen studies, including 2334 patients (501 in the percutaneous BD group and 1833 in the endoscopic group), met the inclusion criteria. Postoperative and procedure-related complication rates were significantly lower in the percutaneous BD group (OR = .7, 95% CI = .52-.94, P = .02 and OR = .44, 95% CI = .23-.84, P = .01, respectively). No significant differences were observed when severe postoperative complications, postoperative mortality, postoperative pancreatic fistula, and wound infection rates were compared.
CONCLUSIONS
In patients awaiting pancreatoduodenectomy, preoperative percutaneous BD is associated with fewer procedure-related or postoperative complications than endoscopic drain.
Topics: Bile Duct Neoplasms; Cholangiocarcinoma; Cholangiopancreatography, Endoscopic Retrograde; Drainage; Duodenal Neoplasms; Endoscopy; Humans; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications
PubMed: 29548873
DOI: 10.1016/j.jvir.2017.12.027 -
Langenbeck's Archives of Surgery Mar 2018Predicting the biologic behavior of intraductal papillary mucinous neoplasm (IPMN) remains challenging. Current guidelines utilize patient symptoms and imaging... (Review)
Review
Can we better predict the biologic behavior of incidental IPMN? A comprehensive analysis of molecular diagnostics and biomarkers in intraductal papillary mucinous neoplasms of the pancreas.
PURPOSE
Predicting the biologic behavior of intraductal papillary mucinous neoplasm (IPMN) remains challenging. Current guidelines utilize patient symptoms and imaging characteristics to determine appropriate surgical candidates. However, the majority of resected cysts remain low-risk lesions, many of which may be feasible to have under surveillance. We herein characterize the most promising and up-to-date molecular diagnostics in order to identify optimal components of a molecular signature to distinguish levels of IPMN dysplasia.
METHODS
A comprehensive systematic review of pertinent literature, including our own experience, was conducted based on the PRISMA guidelines.
RESULTS
Molecular diagnostics in IPMN patient tissue, duodenal secretions, cyst fluid, saliva, and serum were evaluated and organized into the following categories: oncogenes, tumor suppressor genes, glycoproteins, markers of the immune response, proteomics, DNA/RNA mutations, and next-generation sequencing/microRNA. Specific targets in each of these categories, and in aggregate, were identified by their ability to both characterize a cyst as an IPMN and determine the level of cyst dysplasia.
CONCLUSIONS
Combining molecular signatures with clinical and imaging features in this era of next-generation sequencing and advanced computational analysis will enable enhanced sensitivity and specificity of current models to predict the biologic behavior of IPMN.
Topics: Adenocarcinoma, Mucinous; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Pancreatic Ductal; Female; Humans; Immunohistochemistry; Incidental Findings; Male; MicroRNAs; Needs Assessment; Pancreatic Neoplasms; Pathology, Molecular; Practice Guidelines as Topic; Predictive Value of Tests; Prognosis; Risk Factors
PubMed: 29218397
DOI: 10.1007/s00423-017-1644-z -
Journal of Gastroenterology and... Aug 2021Gastric intestinal metaplasia (GIM), a precursor of gastric adenocarcinoma, is challenging to diagnose with white light endoscopy (WLE) and can be missed by random... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Gastric intestinal metaplasia (GIM), a precursor of gastric adenocarcinoma, is challenging to diagnose with white light endoscopy (WLE) and can be missed by random gastric biopsies. Narrowband imaging (NBI) may potentially improve the detection of GIM. However, pooled estimates from prospective studies are lacking.
METHODS
Electronic databases were searched for studies comparing NBI and WLE alone for detection of GIM and synchronous dysplasia. Primary outcome was pooled detection rate of GIM by NBI compared with WLE in prospective studies. The secondary outcome was concurrent dysplasia detection.
RESULTS
Ten studies were found eligible from 306 articles screened. Eight prospective studies were found eligible for primary endpoint of GIM detection. Two other retrospective studies were included for dysplasia detection. A total of 1366 subjects (694 males, 54.4 ± 5.08 years) underwent upper endoscopy. GIM was detected in 482 (35.3%) subjects. NBI detected GIM in 32% additional subjects (70% vs 38%, RR 1.79; 95% CI 1.34-2.37; P < 0.01). Subgroup analysis revealed newer NBI scopes (GIF260) detected significantly more GIM than WLE (RR 2.47; 95% CI 1.63-3.76; P < 0.01) but not the older (H180) NBI endoscopes (RR 1.33; 95% CI 0.93-1.88; P = 0.11). There was moderate heterogeneity between the studies (I = 63%). In five studies (n = 628) that reported dysplasia, there was no significant difference between NBI and WLE in dysplasia detection (RR 1.09; 95% CI 0.81-1.47; P = 0.58).
CONCLUSION
Narrowband imaging can significantly increase the detection of GIM when used in addition to standard white light exam during an upper endoscopy.
Topics: Female; Gastroscopy; Humans; Hyperplasia; Male; Metaplasia; Middle Aged; Narrow Band Imaging; Precancerous Conditions; Prospective Studies; Retrospective Studies; Stomach Neoplasms
PubMed: 34090306
DOI: 10.1111/jgh.15564 -
Surgery Oct 2021Ampullary carcinoma patients require radical resection for optimal survival; however, the outcomes are often unsatisfactory. The utility of adjuvant therapy among such... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ampullary carcinoma patients require radical resection for optimal survival; however, the outcomes are often unsatisfactory. The utility of adjuvant therapy among such patients is unclear, probably owing to its potential side effects. Therefore, this study investigated the benefits and safety of adjuvant therapy in resected ampullary carcinoma.
METHODS
Cochrane, Embase, Medline, and PubMed databases were systematically searched for eligible studies, and those comparing adjuvant therapy and surgical treatment alone were included. Hazard ratios for survival outcomes and the number of adverse events for safety endpoints were extracted and subjected to pooled analyses through a random-effects model.
RESULTS
In total, 27 studies involving 3,538 patients were included. Adjuvant therapy was significantly associated with decreased mortality risk (hazard ratio, 0.58; 95% confidence interval 0.40-0.84), especially for chemoradiotherapy (hazard ratio, 0.42; 95% confidence interval 0.28-0.62). Furthermore, adjuvant therapy was significantly associated with increased overall survival among high-risk patients (hazard ratio, 0.63; 95% confidence interval 0.48-0.82) or those with the pancreaticobiliary subtype (hazard ratio, 0.53; 95% confidence interval 0.32-0.85). By contrast, adjuvant therapy was not associated with improved overall survival among low-risk patients (hazard ratio, 0.93; 95% confidence interval 0.52-1.68) or those with the intestinal subtype (hazard ratio, 1.06; 95% confidence interval 0.57-1.95). Regarding the safety of adjuvant therapy, no intervention-related mortality occurred, and severe adverse events were within the acceptable range (risk difference, 0.04; 95% confidence interval 0.01-0.08).
CONCLUSION
The present results suggest that adjuvant therapy is safe and extends survival in high-risk patients or those with the pancreaticobiliary subtype of ampullary carcinoma.
Topics: Ampulla of Vater; Antineoplastic Agents; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Humans; Pancreatectomy; Pancreatic Neoplasms; Postoperative Care; Treatment Outcome
PubMed: 33902926
DOI: 10.1016/j.surg.2021.03.046 -
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 -
Minerva Chirurgica Jun 2019Once liver metastases in pancreatic and periampullary carcinoma are diagnosed, guidelines do not recommend resection of the primary tumor. In this stage of the disease,...
INTRODUCTION
Once liver metastases in pancreatic and periampullary carcinoma are diagnosed, guidelines do not recommend resection of the primary tumor. In this stage of the disease, therapeutic regimes with chemotherapy are the standard treatment. However, it is unclear whether combinations of extensive surgery and novel chemotherapy treatments confer a survival benefit in selected patients.
EVIDENCE ACQUISITION
We provide a systematic review about liver metastases in pancreatic and periampullary carcinoma treated by surgery utilizing EMBASE, Medline/PubMed, Cochrane and Scopus databases according to PRISMA guidelines.
EVIDENCE SYNTHESIS
In pancreatic and periampullary carcinoma, the number of lesions that can be resected includes a mean or median of 1-3; the size of the lesions should not exceed 3 cm and the most frequent surgical technique used were wedge or atypical resections. Overall morbidity and mortality after liver resection from pancreatic tumors were 0-68% and 0-9.1%, respectively, and from periampullary carcinomas were 0-82% and 0-21%, respectively. Considering both types of carcinomas, the rate of recurrence was up to 91%. Median overall survival ranged from 5.5 to 16.6 months for liver metastases from pancreas carcinoma, and from 5 to 23 months for periampullary carcinoma, with better prognosis for duodenal carcinomas.
CONCLUSIONS
Perioperative chemotherapy is the cornerstone of treatment in patients with liver metastasis from pancreatic and periampullary carcinoma. Liver resection from early liver metastases could be acceptable in selected patients with oligometastatic disease and small single lesions taking into account the individual risk of complications.
Topics: Ampulla of Vater; Carcinoma, Pancreatic Ductal; Disease-Free Survival; Duodenal Neoplasms; Humans; Liver Neoplasms; Neoplasm Recurrence, Local; Pancreatic Neoplasms
PubMed: 30600968
DOI: 10.23736/S0026-4733.18.07972-5 -
Perineural Invasion is a Strong Prognostic Moderator in Ampulla of Vater Carcinoma: A Meta-analysis.Pancreas Jan 2019Ampulla of Vater carcinoma (AVC) has a broad spectrum of different prognoses. As such, new moderators of survival are urgently needed. We aimed at clarifying the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Ampulla of Vater carcinoma (AVC) has a broad spectrum of different prognoses. As such, new moderators of survival are urgently needed. We aimed at clarifying the prognostic role of perineural invasion in AVC.
METHODS
Using PubMed and SCOPUS databases, we conducted the first systematic review and meta-analysis on this topic.
RESULTS
Analyzing 29 articles for a total of 2379 patients, we found that the presence of perineural invasion increased the risk of all-cause mortality more than 2 times (relative risk [RR], 2.07; 95% confidence interval [CI], 1.78-2.42 [P < 0.0001]; hazard ratio [HR], 2.72; 95% CI, 1.86-3.97 [P < 0.0001]), of cancer-specific mortality more than 6 times (RR, 6.12; 95% CI, 3.25-11.54 [P < 0.0001]; HR, 6.59; 95% CI, 2.29-3.49 [P < 0.0001]), and of recurrence more than 2 times (RR, 2.63; 95% CI, 1.89-3.67 [P < 0.0001]; HR, 2.54; 95% CI, 1.24-5.21 [P = 0.01]).
CONCLUSIONS
Perineural invasion is strongly associated with a poorer prognosis in AVC, influencing both survival and risk of recurrence. It should be reported in the final pathology report and should be taken into account by future oncologic staging systems, identifying a group of AVC with a more malignant biological behavior.
Topics: Ampulla of Vater; Carcinoma, Pancreatic Ductal; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Perineum; Prognosis; Risk Factors
PubMed: 30451797
DOI: 10.1097/MPA.0000000000001194 -
Clinical & Translational Oncology :... Aug 2020Given the lack of evidence on the best adjuvant approach, this review closely examines optimal adjuvant management for resected true ampullary cancer and its...
BACKGROUND
Given the lack of evidence on the best adjuvant approach, this review closely examines optimal adjuvant management for resected true ampullary cancer and its histological subtypes.
MATERIALS AND METHODS
A comprehensive literature search of PubMed was performed to identify studies on resected true ampullary cancers, published between January 2010 and December 2018. Data including the use of radiation, chemotherapy or chemoradiation and the outcomes were extracted.
RESULTS
A total of 116 records were identified, of which 65 screened were selected. Finally, nine studies were included. Only two of the studies reported separately the outcomes of pancreatobiliary and intestinal subtypes. Patients in the selected studies were treated with a pancreaticoduodenectomy with negative margins. Patients treated with adjuvant therapy were more likely to be pT3-4 and have positive nodes; median survival ranged from 30 to 47 months. A significant benefit for adjuvant treatment was observed in four of the studies, restricted to patients at stage IIB or higher. Likewise, patients with positive nodes may have a longer median survival with adjuvant chemoradiation compared to observation.
CONCLUSIONS
The present review suggests a benefit for adjuvant treatment for patients with locally advanced tumors. Randomized trials are needed to ascertain the topic, as well as studies reporting toxicity and quality of life of resected true ampullary cancer patients.
Topics: Adenocarcinoma; Ampulla of Vater; Carcinoma; Carcinoma, Pancreatic Ductal; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Common Bile Duct Neoplasms; Duodenal Neoplasms; Humans; Pancreaticoduodenectomy; Radiotherapy, Adjuvant; Retrospective Studies; Treatment Outcome
PubMed: 31927720
DOI: 10.1007/s12094-019-02278-6