Does Pancreatic Fistula Affect Long-Term Survival after Resection for Pancreatic Cancer? A Systematic Review and Meta-Analysis.
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ABSTRACT: Background
The impact of postoperative pancreatic fistula (POPF) on survival after resection for pancreatic ductal adenocarcinoma (PDAC) remains unclear.Methods
The MEDLINE, Scopus, Embase, Web of Science, and Cochrane Library databases were searched for studies reporting on survival in patients with and without POPF. A meta-analysis was performed to investigate the impact of POPF on disease-free survival (DFS) and overall survival (OS).Results
Sixteen retrospective cohort studies concerning a total of 5019 patients with an overall clinically relevant POPF (CR-POPF) rate of 12.63% (n = 634 patients) were considered. Five of eleven studies including DFS data reported higher recurrence rates in patients with POPF, and one study showed a higher recurrence rate in the peritoneal cavity. Six of sixteen studies reported worse OS rates in patients with POPF. Sufficient data for a meta-analysis were available in 11 studies for DFS, and in 16 studies for OS. The meta-analysis identified a shorter DFS in patients with CR-POPF (HR 1.59, p = 0.0025), and a worse OS in patients with POPF, CR-POPF (HR 1.15, p = 0.0043), grade-C POPF (HR 2.21, p = 0.0007), or CR-POPF after neoadjuvant therapy.Conclusions
CR-POPF after resection for PDAC is significantly associated with worse overall and disease-free survival.
SUBMITTER: Grego A
PROVIDER: S-EPMC8616191 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe short-term morbidity associated with post-operative pancreatic fistula (POPF) is well established, however data regarding the long-term impact are lacking. We aim to characterize long-term oncologic outcomes of POPF after pancreatic resection through a single institution, retrospective study of pancreatic resections performed for adenocarcinoma from 2009 to 2016.MethodsKaplan-Meier survival analysis, logistic regression, and multivariate analysis (MVA) were used to evaluate impact of POPF on overall survival (OS), disease free survival (DFS), and receipt of adjuvant chemotherapy (AC).Results767 patients were included. 82 (10.6%) developed grade B (n = 67) or C (n = 15) POPF. Grade C POPF resulted in decreased OS when compared to no POPF (20.22 vs 26.33 months, p = 0.027) and to grade B POPF (20.22 vs. 26.87 months, p = 0.049). POPF patients were less likely to receive AC than those without POPF (59.5% vs 74.9%, p = 0.003) and grade C POPF were less likely to receive AC than all others (26.7% vs 74.2%, p = 0.0001).ConclusionPOPF patients are less likely to receive AC and more likely to have delay in time to AC. These factors are exacerbated in grade C POPF and likely contribute to decreased OS. These findings validate the clinical significance of the ISGPF definition of POPF.
| S-EPMC8282784 | biostudies-literature
Project description:Early detection of postoperative pancreatic fistula (POPF) may help to improve the outcome following pancreatic surgery, and exclusion of POPF may allow early drain removal which can accelerate recovery. The aim of this study was to evaluate the diagnostic accuracy of drain/plasma pancreatic amylase values on postoperative day 1 (DPA1/PPA1) in POPF by means of a systemic review and meta-analysis.Online journal databases and a manual search up to March 2015 were used. Studies clearly documenting DPA1 or PPA1 in predicting overall POPF (Grade 0 vs A+B+C) or clinically relevant POPF (Grade 0+A vs B+C) following pancreatic surgery were selected. Pooled predictive parameters were performed using STATA 12.0.Fifteen studies were finally identified with a total of 4331 patients. The pooled sensitivity and specificity of DPA1 were 0.92 (95% confidence interval (CI) 0.81-0.96) and 0.77 (95% CI 0.64-0.86) for predicting overall POPF and 0.79 (95% CI 0.61-0.90) and 0.83 (95% CI 0.74-0.89) for predicting clinically relevant POPF. The pooled sensitivity and specificity of PPA1 were 0.74 (95% CI 0.63-0.82) and 0.62 (95% CI 0.55-0.70) for overall POPF. After the DPA1 at/over cutoff values for overall POPF or clinically relevant POPF, corresponding post-test probability (Post-test (+)) (if pretest probability was 50%) was 80% and 82% respectively, while, if values were below the cutoff values, the post-test probability (Post-test (-)) was 10% and 20% respectively. Post-test (+) and Post-test (-) of PPA1 for overall POPF were 66% and 30% respectively. In subgroup analysis, the summary sensitivities of cutoff <1000 group and cutoff >1000 group were 0.96 (0.92-0.98) and 0.85 (0.64-0.95), respectively; the summary specificities were 0.59 (0.44-0.72) and 0.86 (0.80-0.91) respectively. Positive LR were 2.3 (1.7-3.3) and 6.2 (3.7-10.2) respectively. Negative LR were 0.06 (0.03-0.14) and 0.18 (0.07-0.47) respectively.DPA1 is a useful predictive test for overall POPF and clinically relevant POPF which has good sensitivity and specificity based on the current studies. Meanwhile, it should be cautiously applied to clinical practice because cutoffs had a wide range between studies.
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Project description:While curative resection is the only chance of cure in pancreatic cancer, controversies exist about the impact of surgical margin status on survival. Non-standardized pathologic report and different criteria on the R1 status made it difficult to implicate adjuvant therapy after resection based on the margin status. We evaluated the influence of resection margins on survival by meta-analysis.We thoroughly searched electronic databases of PubMed, EMBASE, and Cochrane Library. We included studies reporting survival outcomes with different margin status: involved margin (R0 mm), margin clearance with ≤ 1 mm (R0-1 mm), and margin with > 1 mm (R>1 mm). Hazard ratio (HR) for overall survival was extracted, and a random-effects model was used for pooled analysis.A total of eight retrospective studies involving 1,932 patients were included. Pooled HR for overall survival showed that patients with R>1 mm had reduced risk of death than those with R0-1 mm (HR, 0.74; 95% confidence interval [CI], 0.61 to 0.88; p=0.001). In addition, patients with R0-1 mm had reduced risk of death than those with R0 mm (HR, 0.81; 95% CI, 0.72 to 0.91; p < 0.001). There was no heterogeneity between the included studies (I2 index, 42% and 0%; p=0.10 and p=0.82, respectively).Our results suggest that stratification of the patients based on margin status is warranted in the clinical trials assessing the role of adjuvant treatment for pancreatic cancer.
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Project description:ObjectiveTo compare the intraoperative and postoperative outcomes of central pancreatectomy (CP) with distal pancreatectomy (DP).MethodsA systematic literature search was performed on electronic databases from MEDLINE, Embase, and PubMed from 1998 to 2018. Statistical analysis and meta-analysis were performed using statistics/data analysis (Stata®) software, version 12.0 (StataCorp LP, College Station, Texas 77845, USA). Dichotomous variables were analyzed by estimation of relative risk (RR) with a 95 percent (%) confidence interval (CI) and continuous variables were analyzed by standardized mean differences (SMD) with 95% CI.ResultsTwenty-four studies with 593 CP and 1226 DP were included in the meta-analysis. CP had significantly longer operation time (SMD: 1.03; 95% CI 0.62 to 1.44; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.01). Estimated blood loss was significantly lower in CP (SMD: -0.34; 95% CI -0.58 to -0.09; P = 0.007). Overall postoperative morbidity (RR: 1.30; 95% CI: 1.13 to 1.50; P < 0.001), overall pancreatic fistula (RR: 1.41; 95% CI: 1.20 to 1.66; P < 0.001), clinically relevant fistula (RR: 1.64; 95% CI: 1.25 to 2.16; P < 0.001), and postoperative hemorrhage (RR: 1.90; 95% CI: 1.18 to 3.06; P < 0.05) were all significantly higher after CP. On long-term follow-up, DP patients were more likely to have postoperative exocrine (RR: 0.56; 95% CI: 0.37 to 0.84; P < 0.05) and endocrine (RR: 0.27; 95% CI: 0.18 to 0.40; P < 0.001) insufficiency. There was no statistically significant difference in transfusion requirement, postoperative mortality, reoperation, and tumor recurrence.ConclusionCP is associated with significantly higher morbidity and clinically relevant pancreatic fistula. CP should only be reserved for selected patients who require postoperative pancreatic function preservation.
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Project description:BackgroundPancreatic cancer (PC) continues to rank as one of the deadliest forms of cancer, with the majority of patients being diagnosed with unresectable disease. The implementation of cryoablation-based comprehensive treatment is expected to lead to a reduction in tumor size and potentially achieve complete resection. However, the availability of systematic and evidence-based treatment guidelines for cryoablation in pancreatic cancer is currently limited.Materials and methodsA computerized search was conducted in the Medline, Embase, Cochrane Library databases, and Clinicaltrials to retrieve studies published from August 1987 to June 2023. The perioperative outcomes and long-term survival of patients with locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (mPC) who underwent cryosurgery were systematically collected. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. Data were pooled and analyzed using Stata 14.0 software. The Newcastle-Ottawa Quality Assessment Form tool was employed for quality evaluation.Results9 studies including 368 patients were identified. The pooled overall incidence rate was 4% (95%CI: 0-14%; I²=54.06%) for acute pancreatitis, 0% (95%CI: 0-0%; I²=0.0%) for delayed gastric emptying, 0% (95%CI: 0-1%; I²=0.0%) for postoperative pancreatic fistula (POPF) or bile leakage, 2% (95%CI:0-5%; I²=0.0%) for bleeding, and 4% (95%CI: 0-12%; I²=70.46%) for fever. Our subgroup analysis revealed that the percutaneous treatment group had a lower incidence of complications compared to laparotomy, but had higher incidences of POPF, bleeding, and pancreatitis than the intraoperative group. Median overall survival (OS) varied from 5 to 16.2 months. The median survival rates at 6, 12, 24, and 36 months for patients who underwent cryosurgery were as follows: 94.9%, 64.8% (range: 4.8%-63.1%), 22.80%, and 9.5%, respectively.ConclusionWith the advancements in cryoablation and anti-tumor therapy, cryoablation emerges as a promising treatment modality for patients with unresectable pancreatic cancer. According to existing literature, the combination of cryoablation with radioactive particle implantation or immunotherapy has demonstrated considerable efficacy and safety. However, while the majority of included data is derived from retrospective studies, it is imperative to conduct larger sample sizes or prospective trials for further validation.
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Project description:PurposeNonsurgical therapies, including biotherapy, chemotherapy, and liver-directed therapy, provided a limit survival benefit for PNET patients with hepatic metastases. With the development of liver resection technique, there was a controversy on whether to perform a liver resection for these patients.MethodsA computerized search was made of the Medline/PubMed, EMbase, Cochrane Library, and SinoMed (CBM) before March 2018. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and nonliver resection treatments based on the evaluation of morbidity, 30-day mortality, symptom relief rate, and 1-, 3-, and 5-year survival. Two investigators reviewed all included articles and extracted the data of them. The meta-analysis was performed via Review Manager 5.3 software.ResultsA total of 13 cohort studies with 1524 patients were included in this meta-analysis. Compared with the nonliver resection group, liver resection group had a longer 1-, 3-, and 5-year survival time and a higher symptom relief with an acceptable mortality and morbidity.ConclusionsLiver resection is a safe treatment and could significantly prolong the long-term prognosis for highly selected patients with resectable liver metastases from PNET. Further randomized, controlled trials are needed.
| S-EPMC6261248 | biostudies-literature
Project description:ImportanceIn the past decade, the use of neoadjuvant therapy (NAT) has increased for patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Data on pancreatic fistula and related overall survival (OS) in this setting are limited.ObjectiveTo compare postoperative complications in patients undergoing either upfront resection or pancreatectomy following NAT, focusing on clinically relevant postoperative pancreatic fistula (CR-POPF) and potential associations with OS.Design, setting, and participantsThis retrospective cohort study was conducted on data from patients who underwent pancreatic resection for PDAC at the Massachusetts General Hospital from January 1, 2007, to December 31, 2017.ExposuresPancreatic cancer surgery with or without NAT.Main outcomes and measuresOverall morbidity and CR-POPF rates were compared between NAT and upfront resection. Factors associated with CR-POPF were assessed with univariate and multivariate analysis. Survival data were analyzed by Kaplan-Meier curves and a Cox proportional hazards regression model.ResultsOf 753 patients, 364 were men (48.3%); median (interquartile range) age was 68 (61-75) years. A total of 346 patients (45.9%) received NAT and 407 patients (54.1%) underwent upfront resection. At pathologic examination, NAT was associated with smaller tumor size (mean [SD], 26.0 [15.3] mm vs 32.7 [14.4] mm; P < .001), reduced nodal involvement (102 [25.1%] vs 191 [55.2%]; P < .001), and higher R0 rates (257 [74.3%] vs 239 [58.7%]; P < .001). There were no significant differences in severe complication rate or 90-day mortality. The rate of CR-POPF was 3.6-fold lower in patients receiving NAT vs upfront resection (13 [3.8%] vs 56 [13.8%]; P < .001). In addition, factors associated with CR-POPF changed after NAT, and only soft pancreatic texture was associated with a higher risk of CR-POPF (38.5% vs 6.3%; P < .001). Survival analysis showed no differences between patients with or without CR-POPF after upfront resection (26 vs 25 months; P = .66), but after NAT, a worse overall survival rate was observed in patients with CR-POPF (17 vs 34 months; P = .002). This association was independent of other established predictors of overall survival by multivariate analysis (hazard ratio, 2.80; 95% CI, 1.44-5.45; P < .002).Conclusions and relevanceNeoadjuvant therapy may be associated with a significant reduction in the rate of CR-POPF. In addition, standard factors associated with CR-POPF appear to be no longer applicable following NAT. However, once CR-POPF occurs, it is associated with a significant reduction in long-term survival. Patients with CR-POPF may require closer follow-up and could benefit from additional therapy.
| S-EPMC6694396 | biostudies-literature
Project description:BackgroundEsophagectomy is still advised as an additional treatment for patients with superficial esophageal cancer (EC, T1a-T1b) after endoscopic resection (ER). However, esophagectomy often deteriorates the general condition of EC patients. In recent years, adjuvant chemoradiotherapy (CRT) has been recognized as a reliable, non-surgical treatment that can improve the prognosis. How to combine ER with adjuvant therapy to bring maximal benefits to patients has become a hot clinical research hot topic. However, the current studies have mostly been conducted retrospectively, in single centers, and with small clinical samples; there have been few prospective and large sample size randomized controlled trials (RCTs). The aim of this systematic review and meta-analysis was to compare the outcomes of adjuvant CRT versus esophagectomy in the treatment of early EC, and to provide a reference for clinical research and practice.MethodsA comprehensive and extensive literature search was performed via the databases of PubMed, Cochrane Library, Embase, and Web of Science online and all randomized cohort studies and retrospective cohort studies were collected. The quality of research was evaluated according to Cochrane's quality standards, and statistical analysis was conducted with Stata 13.0 and RevMan 5.3 software and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).ResultsA total of 9 cohort studies, including 790 patients, were included for meta-analysis. The long term effects of the esophagectomy group were better than those of the CRT after ER group [odds ratio (OR) =6.08, 95% confidence interval (CI): 1.96 to 18.84, P=0.002] in disease-free survival (DFS) [hazard ratio (HR) =0.24, 95% CI: 0.07 to 0.85, P=0.03] and overall survival (OS) (HR =1.02, 95% CI: 0.57 to 1.82, P=0.94). Other survival indicators showed no significant difference (P>0.05).ConclusionsThe 2 groups showed no significant results in OS. Although we found that CRT may be suitable for patients with high-risk of relapse or unable to tolerate surgery, it cannot totally replace surgical treatment; further randomized trials are required to verify this view.
| S-EPMC10482624 | biostudies-literature
Project description:BackgroundA large proportion of patients with uveal melanoma develop metastases and succumb to their disease. Reports on the size of this proportion vary considerably.MethodsPubMed, Web of Science and Embase were searched for articles published after 1980. Studies with ≥100 patients reporting ≥five-year relative survival rates were included. Studies solely reporting Kaplan-Meier estimates and cumulative incidences were not considered, due to risk for competing risk bias and classification errors. A meta-analysis was performed using random-effects and weighted averages models, as well as a combined estimate based on curve fitting.ResultsNine studies and a total of 18 495 patients are included. Overall, the risk of selective reporting bias is low. Relative survival rates vary across the population of studies (I2 48 to 97% and Q p < 0.00001 to 0.15), likely due to differences in baseline characteristics and the large number of patients included (τ2 < 0.02). The 30-year relative survival rates follow a cubic curve that is well fitted to data from the random-effects inverse-variance and weighted average models (R 2 = 0.95, p = 7.19E-7). The estimated five, ten, 15, 20, 25 and 30-year relative survival rates are 79, 66, 60, 60, 62 and 67%, respectively.ConclusionsThe findings suggest that about two in five of all patients with uveal melanoma ultimately succumb to their disease. This indicates a slightly better prognosis than what is often assumed, and that patients surviving 20 years or longer may have a survival advantage to individuals of the same sex and age from the general population.
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Project description:BackgroundA greater than 1 mm tumour-free resection margin (R0 >1 mm) is a prognostic factor in upfront-resected pancreatic ductal adenocarcinoma. After neoadjuvant treatment (NAT); however, the prognostic impact of resection margin (R) status remains controversial.MethodsRandomised and non-randomised studies assessing the association of R status and survival in resected pancreatic ductal adenocarcinoma after NAT were sought by systematic searches of MEDLINE, Web of Science and CENTRAL. Hazard ratios (HR) and their corresponding 95% CI were collected to generate log HR using the inverse-variance method. Random-effects meta-analyses were performed and the results presented as weighted HR. Sensitivity and meta-regression analyses were conducted to account for different surgical procedures and varying length of follow-up, respectively.ResultsTwenty-two studies with a total of 4929 patients were included. Based on univariable data, R0 greater than 1 mm was significantly associated with prolonged overall survival (OS) (HR 1.76, 95% CI 1.57-1.97; P<0.00001) and disease-free survival (DFS) (HR 1.66, 95% CI 1.39-1.97; P<0.00001). Using adjusted data, R0 greater than 1 mm was significantly associated with prolonged OS (HR 1.65, 95% CI 1.39-1.97; P<0.00001) and DFS (HR 1.76, 95% CI 1.30-2.39; P=0.0003). Results for R1 direct were comparable in the entire cohort; however, no prognostic impact was detected in sensitivity analysis including only partial pancreatoduodenectomies.ConclusionAfter NAT, a tumour-free margin greater than 1 mm is independently associated with improved OS as well as DFS in patients undergoing surgical resection for pancreatic cancer.
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