-
Frontiers in Oncology 2021To compare perioperative and oncological outcomes of pancreatic duct adenocarcinoma (PDAC) after laparoscopic open pancreaticoduodenectomy (LPD OPD), we performed a...
BACKGROUND
To compare perioperative and oncological outcomes of pancreatic duct adenocarcinoma (PDAC) after laparoscopic open pancreaticoduodenectomy (LPD OPD), we performed a meta-analysis of currently available propensity score matching studies and large-scale retrospective cohorts to compare the safety and overall effect of LPD to OPD for patients with PDAC.
METHODS
A meta-analysis was registered at PROSPERO and the registration number is CRD42021250395. PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched based on a defined search strategy to identify eligible studies before March 2021. Data on operative times, blood loss, 30-day mortality, reoperation, length of hospital stay (LOS), overall morbidity, Clavien-Dindo ≥3 complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0 resection, lymph node dissection, overall survival, and long-term survival) were subjected to meta-analysis.
RESULTS
Overall, we identified 10 retrospective studies enrolling a total of 11,535 patients (1,514 and 10,021 patients underwent LPD and OPD, respectively). The present meta-analysis showed that there were no significant differences in overall survival time, 1-year survival, 2-year survival, 30-day mortality, Clavien-Dindo ≥3 complications, POPF, DGE, PPH, and lymph node dissection between the LPD and OPD groups. Nevertheless, compared with the OPD group, LPD resulted in significantly higher rate of R0 resection (OR: 1.22; 95% CI 1.06-1.40; = 0.005), longer operative time (WMD: 60.01 min; 95% CI 23.23-96.79; = 0.001), lower Clavien-Dindo grade ≥III rate ( = 0.02), less blood loss (WMD: -96.49 ml; 95% CI -165.14 to -27.83; = 0.006), lower overall morbidity rate (OR: 0.65; 95% CI 0.50 to 0.85; = 0.002), shorter LOS (MD = -2.73; 95% CI -4.44 to -1.03; = 0.002), higher 4-year survival time ( = 0.04), 5-year survival time ( = 0.001), and earlier time to starting adjuvant chemotherapy after surgery (OR: -10.86; 95% CI -19.42 to -2.30; = 0.01).
CONCLUSIONS
LPD is a safe and feasible alternative to OPD for patients with PDAC, and compared with OPD, LPD seemed to provide a similar OS.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/#recordDetails.
PubMed: 34778064
DOI: 10.3389/fonc.2021.749140 -
European Journal of Surgical Oncology :... Mar 2022It is unclear whether patients with intraductal papillary mucinous neoplasia harbor a higher risk of developing extrapancreatic malignancies. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is unclear whether patients with intraductal papillary mucinous neoplasia harbor a higher risk of developing extrapancreatic malignancies.
AIMS
We performed a pooled estimate of the incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasia, with a particular focus on the comparison to the general population.
METHODS
Computerized bibliographic search of main databases was performed through February 2021. The primary endpoint was the pooled incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasms. Additional outcome was the comparison between intraductal papillary mucinous neoplasia patients and the general population, expressed in terms of standardized incidence ratio along with 95% confidence intervals.
RESULTS
Eighteen studies with 8709 patients were included. The pooled rate of metachronous extrapancreatic malignancies was 10 (6-13)/1000 persons-year. No difference was observed according to intraductal papillary mucinous neoplasia histology and sex, whereas a significantly superior incidence of extrapancreatic malignancies was observed in patients with main-duct (36.7%, 25.4%-48%) as compared to branch-duct intraductal papillary mucinous neoplasia (26.2%, 17.6%-34.8%; p = 0.03). Pooled standardized incidence ratio comparing expected rates in the general population was 1.01 (0.79-1.29); no difference was observed concerning rates of metachronous gastric cancer (standardized incidence ratio 1.60, 0.72-3.54) and colorectal cancer (1.29, 0.92-1.18), whereas biliary cancer was observed more frequently in intraductal papillary mucinous neoplasia patients (2.29, 1.07-4.93).
CONCLUSION
Patients with intraductal papillary mucinous neoplasia harbor an overall rate of extrapancreatic malignancies as high as 27.3%. The rate of metachronous extrapancreatic malignancies is not superior to the general population.
Topics: Adenocarcinoma, Mucinous; Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; Humans; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms
PubMed: 34620511
DOI: 10.1016/j.ejso.2021.09.018 -
Modern Pathology : An Official Journal... Jan 2022The literature is highly conflicted on what percentage of pancreatic ductal adenocarcinomas (PDACs) arise in association with intraductal papillary mucinous neoplasms... (Comparative Study)
Comparative Study
Pancreatic ductal adenocarcinomas associated with intraductal papillary mucinous neoplasms (IPMNs) versus pseudo-IPMNs: relative frequency, clinicopathologic characteristics and differential diagnosis.
The literature is highly conflicted on what percentage of pancreatic ductal adenocarcinomas (PDACs) arise in association with intraductal papillary mucinous neoplasms (IPMNs). Some studies have claimed that even small (Sendai-negative) IPMNs frequently lead to PDAC. Recently, more refined pathologic definitions for mucin-lined cysts were provided in consensus manuscripts, but so far there is no systematic analysis regarding the frequency and clinicopathologic characteristics of IPMN-mimickers, i.e., pseudo-IPMNs. In this study, as the first step in establishing frequency, we performed a systematic review of the pathologic findings in 501 consecutive ordinary PDACs, which disclosed that 10% of PDACs had associated cysts ≥1 cm. While 31 (6.2%) of these were IPMN or mucinous cystic neoplasm (MCN), 19 (3.8%) were other cyst types that mimicked IPMN (pseudo-IPMNs) per recent WHO/consensus criteria. As the second step of the study, we performed a comparative clinicopathologic analysis by also including our entire surgical pathology/consultation databases that was comprised of 60 IPMN-associated PDACs, 30 MCN-associated PDACs and 40 pseudo-IPMN-associated PDACs. We found that 84% of true IPMNs were pre-operatively recognized, whereas IPMN was considered in differential diagnosis of 33% of pseudo-IPMNs. Of the 40 pseudo-IPMNs, there were 15 secondary duct ectasias; 6 large-duct-type PDACs; 5 pseudocysts; 5 cystic tumor necrosis; 4 simple mucinous cysts; 3 groove pancreatitis-associated paraduodenal wall cysts; and 2 congenital cysts. Microscopically, pseudo-IPMNs had at least partial mucinous-lining mimicking IPMN but had smaller cystic (mean = 1.9 cm) and larger PDAC (mean = 3.8 cm) components compared to true IPMNs (cyst = 5.7 cm; PDAC = 2.0 cm). In summary, in this pathologically verified analysis that utilized refined criteria, 10% of PDACs were discovered to have cysts ≥1 cm, about two-thirds of which were IPMN/MCN but about one-third were pseudo-IPMNs. True IPMNs underlying the PDACs are often large and are already diagnosed pre-operatively as having an IPMN component, whereas only a third of the pseudo-IPMNs receive IPMN diagnosis by imaging and their cysts are smaller. At the histopathologic level, pseudo-IPMNs are highly prone to misdiagnosis as IPMN, which presumably accounts for much higher association of IPMNs with PDAC as reported in some studies. The subtle but salient characteristics of pseudo-IPMNs elucidated in this study should be combined with careful radiological/clinical correlation in order to exclude pseudo-IPMNs.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Carcinoma, Pancreatic Ductal; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms
PubMed: 34518632
DOI: 10.1038/s41379-021-00902-x -
World Journal of Gastrointestinal... Aug 2021Pancreatic endotherapy provides treatment options for the management of chronic pancreatitis-related structural complications such as pancreatic duct stones, strictures,...
BACKGROUND
Pancreatic endotherapy provides treatment options for the management of chronic pancreatitis-related structural complications such as pancreatic duct stones, strictures, and pancreatic fluid collections. Most studies detailing endotherapy, however, have focused on technical success outcomes such as stone clearance or stricture resolution.
AIM
To review the effect of pancreatic endotherapy on patient-centered outcomes.
METHODS
Systematic review of studies examining pancreatic endotherapy.
RESULTS
A total of 13 studies including 3 randomized clinical trials were included. The majority of studies found an improvement in quality of life with pancreatic endotherapy.
CONCLUSION
While pancreatic endotherapy does appear to improve quality of life, there are clear gaps in knowledge regarding many pancreatic endotherapy modalities. Furthermore, qualitative analysis is lacking in these studies and further work is needed to elucidate the patient experience with pancreatic endotherapy.
PubMed: 34512881
DOI: 10.4253/wjge.v13.i8.336 -
Annals of Gastroenterology 2021The American Gastroenterological Association recommends endoscopic ultrasound (EUS) for evaluating pancreatic cystic lesions (PCL) with ≥2 high-risk features (HRF),...
BACKGROUND
The American Gastroenterological Association recommends endoscopic ultrasound (EUS) for evaluating pancreatic cystic lesions (PCL) with ≥2 high-risk features (HRF), whereas the American College of Gastroenterology recommends EUS for ≥1 HRF. This systematic review and meta-analysis compared the diagnostic accuracy of using ≥1 vs. ≥2 HRF for assessing the risk of advanced neoplasia (AN) and performing EUS in PCL.
METHODS
An electronic database search was performed for eligible studies. AN was defined as pancreatic adenocarcinoma, intraductal papillary mucinous neoplasm or mucinous cystadenoma with high-grade dysplasia, pancreatic intraepithelial neoplasia and pancreatic neuroendocrine tumors. HRF included cyst size ≥3 cm, solid component, and dilated pancreatic duct ≥5 mm. The primary outcome was the sensitivity and specificity of using ≥1 vs. ≥2 HRF as an indication for EUS to detect AN in PCL.
RESULTS
Of 38 studies initially screened, 8 were included in the final analysis. Seven studies assessed the accuracy of ≥2 HRF and 4 studies assessed ≥1 HRF. The pooled sensitivity, specificity, positive and negative predictive values of EUS for detecting AN were 41.7% (95% confidence interval 19.5-67.8%), 90.8% (81.9-95.5%), 30.4% (19.4-44.2%) and 94.3% (89.6-97.0%) with ≥2HRFs, and 77.1% (66.1-85.3%), 72.7% (50.4-87.5%), 17.95% (10.3-29.4%), 98.1% (90.8-99.6%), respectively, with ≥1 HRF.
CONCLUSION
Performing EUS for PCL with ≥1 HRF could offer greater sensitivity in detecting AN compared to ≥2 HRF, with a similar negative predictive value.
PubMed: 34475747
DOI: 10.20524/aog.2021.0630 -
Polski Przeglad Chirurgiczny Jun 2021Postoperative pancreatic fistula (POPF) is a potentially life-threatening complication after pancreaticoduodenectomy (PD). It is observed when the amylase activity in... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Postoperative pancreatic fistula (POPF) is a potentially life-threatening complication after pancreaticoduodenectomy (PD). It is observed when the amylase activity in the drain fluid exceeds three times the normal upper value. Grades B and C of POPF are considered as clinically relevant. Fistula might originate due to failure of healing of a pancreatic anastomosis or from raw pancreatic surface.
MATERIALS AND METHODS
18 retrospective and prospective studies published between 2015 and 2020 were included in this meta-analysis. Total number of patients was 5836. To investigate potential risk factors associated with the occurrence of POPF, odds ratios (OR) with 95% confidence intervals (CI) were calculated. To compare discontinuous data, mean differences (MD) were calculated.
RESULTS
13 factors were divided into preoperative and intraoperative groups. Male sex, higher BMI, soft pancreatic texture and small pancreatic duct were considered as significant risk factors while vascular resection lowered the risk of development pancreatic fistula.
DISCUSSION
It is considered that the development of POPF is associated with intrapancreatic fat. More severe infiltration with fat tissue is responsible for soft texture of the gland, while higher BMI is one of the risk factors of increased pancreatic fat. On the contrary, diabetes is associated with fibrotic pancreas which could lower the risk of developing POPF.
Topics: Amylases; Anastomosis, Surgical; Humans; Male; Pancreas; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Prospective Studies; Retrospective Studies; Risk Factors
PubMed: 36169536
DOI: 10.5604/01.3001.0014.9659 -
World Journal of Gastrointestinal... Jun 2021Hepatopancreatoduodenectomy (HPD) is the simultaneous combination of hepatic resection, pancreaticoduodenectomy, and resection of the entire extrahepatic biliary system....
BACKGROUND
Hepatopancreatoduodenectomy (HPD) is the simultaneous combination of hepatic resection, pancreaticoduodenectomy, and resection of the entire extrahepatic biliary system. HPD is not a universally accepted due to high mortality and morbidity rates, as well as to controversial survival benefits.
AIM
To evaluate the current role of HPD for curative treatment of gallbladder cancer (GC) or extrahepatic cholangiocarcinoma (ECC) invading both the hepatic hilum and the intrapancreatic common bile duct.
METHODS
A systematic literature search using the PubMed, Web of Science, and Scopus databases was performed to identify studies reporting on HPD, using the following keywords: 'Hepatopancreaticoduodenectomy', 'hepatopancreatoduodenectomy', 'hepatopancreatectomy', 'pancreaticoduodenectomy', 'hepatectomy', 'hepatic resection', 'liver resection', 'Whipple procedure', 'bile duct cancer', 'gallbladder cancer', and 'cholangiocarcinoma'.
RESULTS
This updated systematic review, focusing on 13 papers published between 2015 and 2020, found that rates of morbidity for HPD have remained high, ranging between 37.0% and 97.4%, while liver failure and pancreatic fistula are the most serious complications. However, perioperative mortality for HPD has decreased compared to initial experiences, and varies between 0% and 26%, although in selected center it is well below 10%. Long term survival outcomes can be achieved in selected patients with R0 resection, although 5-year survival is better for ECC than GC.
CONCLUSION
The present review supports the role of HPD in patients with GC and ECC with horizontal spread involving the hepatic hilum and the intrapancreatic bile duct, provided that it is performed in centers with high experience in hepatobiliary-pancreatic surgery. Extensive use of preoperative portal vein embolization, and preoperative biliary drainage in patients with obstructive jaundice, represent strategies for decreasing the occurrence and severity of postoperative complications. It is advisable to develop internationally-accepted protocols for patient selection, preoperative assessment, operative technique, and perioperative care, in order to better define which patients would benefit from HPD.
PubMed: 34163578
DOI: 10.4251/wjgo.v13.i6.625 -
BJS Open May 2021Postoperative pancreatic fistula (POPF) remains the main cause of morbidity in patients after distal pancreatectomy. The objective of this study was to investigate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative pancreatic fistula (POPF) remains the main cause of morbidity in patients after distal pancreatectomy. The objective of this study was to investigate whether an absorbable fibrin sealant patch could prevent POPF after distal pancreatectomy.
METHODS
A multicentre, patient-blinded, parallel-group randomized superiority trial was performed in seven Dutch hospitals. Allocation was done using a computer-generated randomization list with a 1 : 1 allocation ratio and concealed varying permuted block sizes. Pancreatic stump closure with a fibrin patch was compared with standard treatment in patients undergoing distal pancreatectomy. The primary endpoint was the development of grade B/C POPF. A systematic review and meta-analysis was performed which combined the present findings with all available evidence.
RESULTS
Between October 2010 and August 2017, 247 patients were enrolled. Fifty-four patients (22.2 per cent) developed a POPF, 25 of 125 patients in the patch group versus 29 of 122 in the control group (20.0 versus 23.8 per cent; P = 0·539). No related adverse effects were observed. In the meta-analysis, no significant difference was seen between the patch and control groups (19.7 versus 22.0 per cent; odds ratio 0.89, 95 per cent c.i. 0.60 to 1.32; P = 0·556).
CONCLUSION
Application of a fibrin patch to the pancreatic stump does not reduce the incidence of POPF in distal pancreatectomy. Future studies should focus on alternative fistula mitigation strategies, considering pancreatic neck thickness and duct size as risk factors. Trial registration number NL5876 (Netherlands Trial Registry).
Topics: Humans; Fibrin Tissue Adhesive; Multicenter Studies as Topic; Pancreas; Pancreatectomy; Pancreatic Fistula; Randomized Controlled Trials as Topic
PubMed: 34137446
DOI: 10.1093/bjsopen/zrab001 -
Journal of Hepatology Sep 2021Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS & AIMS
Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening.
METHODS
We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts.
RESULTS
We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57 genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (T)1 and T17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders.
CONCLUSIONS
This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders.
LAY SUMMARY
Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these 'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC.
Topics: Genome-Wide Association Study; Humans; Liver Cirrhosis, Biliary
PubMed: 34033851
DOI: 10.1016/j.jhep.2021.04.055 -
Gastroenterology Report Apr 2021Abdominal pain is a debilitating symptom affecting ∼80% of pancreatic cancer (PC) patients. Pancreatic duct (PD) decompression has been reported to alleviate this...
BACKGROUND
Abdominal pain is a debilitating symptom affecting ∼80% of pancreatic cancer (PC) patients. Pancreatic duct (PD) decompression has been reported to alleviate this pain, although this practice has not been widely adopted. We aimed to evaluate the role, efficacy, and safety of endoscopic PD decompression for palliation of PC post-prandial obstructive-type pain.
METHODS
A systematic review until 7 October 2020 was performed. Two independent reviewers selected studies, extracted data, and assessed the methodological quality.
RESULTS
We identified 12 publications with a total of 192 patients with PC presenting with abdominal pain, in whom PD decompression was attempted, and was successful in 167 patients (mean age 62.5 years, 58.7% males). The use of plastic stents was reported in 159 patients (95.2%). All included studies reported partial or complete improvement in pain levels after PD stenting, with an improvement rate of 93% (95% confidence interval, 79%-100%). The mean duration of pain improvement was 94 ± 16 days. Endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events (AEs) were post-sphincterotomy bleeding (1.8%), post-ERCP pancreatitis (0.6%), and hemosuccus pancreaticus (0.6%). AEs were not reported in two patients who underwent endoscopic ultrasound-guided PD decompression. In the 167 patients with technical success, the stent-migration and stent-occlusion rates were 3.6% and 3.0%, respectively. No AE-related mortality was reported. The methodological quality assessment showed the majority of the studies having low or unclear quality.
CONCLUSION
In this exploratory analysis, endoscopic PD drainage may be an effective and safe option in selected patients for the management of obstructive-type PC pain. However, a randomized-controlled trial is needed to delineate the role of this invasive practice.
PubMed: 34026217
DOI: 10.1093/gastro/goab001