Meta-analysis and trial sequential analysis of randomized controlled trials comparing aggressive versus non-aggressive intravenous fluid therapy in acute pancreatitis: an insight into the existence of type 2 error.

BACKGROUND AND AIM: We aimed to evaluate comparative outcomes of aggressive versus non-aggressive intravenous fluid (IVF) therapy in patients with acute pancreatitis. METHODS: A systematic search of electronic data sources and bibliographic reference lists were conducted. All randomized controlled trials (RCTs) reporting outcomes of aggressive versus non-aggressive IVF therapy in acute pancreatitis were included and their risk of bias were assessed. Effect sizes were determined for overall mortality, systemic inflammatory response syndrome (SIRS), sepsis, respiratory failure, pancreatic necrosis, severe pancreatitis, clinical improvement, AKI, and length of stay using random-effects modeling. Trial sequential analysis was conducted to determine risk of types 1 or 2 errors. RESULTS: We included 10 RCTs reporting 993 patients with acute pancreatitis who received aggressive (n = 475) or non-aggressive (n = 518) IVF therapy. Aggressive IVF therapy was associated with significantly higher rate of sepsis (OR: 2.68, P = 0.0005) and longer length of stay (MD: 0.94, P < 0.00001) compared with the non-aggressive approach. There was no statistically significant difference in mortality (RD: 0.02, P = 0.31), SIRS (OR: 0.93, P = 0.89), respiratory failure (OR: 2.81, P = 0.07), pancreatic necrosis (OR: 1.98, P = 0.06), severe pancreatitis (OR: 1.31, P = 0.38), clinical improvement (OR: 1.12, P = 0.83) or AKI (OR: 1.06, P = 0.91) between the two groups. Sub-group analysis demonstrated higher morbidity and mortality associated with the aggressive approach in more severe disease. Trial sequential analysis detected risk of type 2 error. CONCLUSIONS: Aggressive IVF therapy may be associated with higher morbidity in patients with acute pancreatitis compared with the non-aggressive approach, particularly in patients with more severe disease. It may also prolong length of hospital stay. The available evidence is subject to type 2 error indicating the need for adequately powered RCTs.

Meta-analysis of pancreatic re-resection for locally recurrent pancreatic cancer following index pancreatectomy.

The role of surgical resection in patients with recurrent pancreatic cancer is unclear. We aimed to evaluate the survival outcomes of pancreatic re-resection for locally recurrent pancreatic cancer following index pancreatectomy. A literature search was carried out in CENTRAL, EMBASE, MEDLINE, CINAHL, and Web of Science. Proportion meta-analysis model was constructed to quantify 1 to 5-year survival after pancreatic re-resection for locally recurrent pancreatic cancer. Random-effects modelling was applied to calculate pooled outcome data. Fifteen retrospective studies were included, reporting a total of 250 patients who underwent pancreatic re-resection for locally recurrent pancreatic cancer following their index pancreatectomy. Pancreatic re-resection was associated with 1-year survival 70.6% (95% confidence interval [CI], 65.0-76.2), 2-year survival 38.8% (95% CI, 28.6-49.0), 3-year survival 20.2% (95% CI, 13.8-26.7), and 5-year survival 9.2% (95% CI, 5.5-12.8). The between-study heterogeneity was insignificant in all outcome syntheses. Repeat pancreatectomy for local recurrence of pancreatic cancer in the remnant pancreas following the index pancreatectomy is associated with acceptable overall patient survival. We recommend selective re-resection of such recurrences in younger patients with favorable tumor size and location. Our findings may encourage more robust studies to be conducted in this context to provide stronger evidence.

Meta-analysis of laparoscopic spleen-preserving distal pancreatectomy versus laparoscopic distal pancreatectomy with splenectomy: An insight into confounding by indication.

AIMS: To evaluate comparative outcomes of laparoscopic spleen-preserving distal pancreatectomy (LSPDP) and laparoscopic distal pancreatectomy with splenectomy (LDPS). METHODS: A systematic search of multiple electronic data sources and bibliographic reference lists were conducted. Comparative studies reporting outcomes of LSPDP and LDPS were considered followed by evaluation of the associated risk of bias according to ROBINS-I tool. Perioperative complications, clinically important postoperative pancreatic fistula (POPF), infectious complications, blood loss, conversion to open, operative time and duration of hospital stay were the investigated outcome parameters. RESULTS: Nineteen studies were identified enrolling 3739 patients of whom 1860 patients underwent LSPDP and the remaining 1879 patients had LDPS. The patients in the LSPDP and LDPS groups were of comparable age (p = 0.73), gender (p = 0.59), and BMI (p = 0.07). However, the patient in the LDPS group had larger tumour size (p = 0.0004) and more malignant lesions (p = 0.02). LSPDP was associated with significantly lower POPF (OR:0.65, p = 0.02), blood loss (MD:-28.30, p = 0.001), and conversion to open (OR:0.48, p < 0.0001) compared to LDPS. Moreover, it was associated with significantly shorter procedure time (MD: -22.06, p = 0.0009) and length of hospital stay (MD: -0.75, p = 0.005). However, no significant differences were identified in overall perioperative (OR:0.89, p = 0.25) or infectious (OR:0.67, p = 0.05) complications between two groups. CONCLUSIONS: LSPDP seems to be associated with lower POPF, bleeding and conversion to open compared to LDPS in patients with small-sized benign tumours. Moreover, it may be quicker and reduce hospital stay. Nevertheless, such advantages are of doubtful merit about large-sized or malignant tumours. The available evidence is subject to confounding by indication.

Meta-analysis of fenestrating versus reconstituting subtotal cholecystectomy in the management of difficult gallbladder.

AIMS: To evaluate comparative outcomes of fenestrating and reconstituting subtotal cholecystectomy (STC) in patients with difficult gallbladder. METHODS: A systematic search of electronic data sources and bibliographic reference lists were conducted. All comparative studies reporting outcomes of laparoscopic fenestrating and reconstituting STC were included and their risk of bias were assessed using ROBINS-I tool. RESULTS: Seven comparative studies were included enrolling 590 patients undergoing laparoscopic STC using either fenestrating (n = 353) or reconstituting (n = 237) approaches. Although fenestrating STC was associated with a significantly higher rate of bile leak (OR: 2.47, p = 0.007) compared to reconstituting STC, both approaches were comparable in terms of resolution of bile leak without (RD: -0.02, p = 0.86) or with (OR: 1.84, p = 0.40) postoperative ERCP. Moreover, there was no significant difference in development of bile duct injury (RD: -0.02, p = 0.16), need for postoperative ERCP (OR: 1.36, p = 0.49), wound infection (RD: 0.03, p = 0.27), re-operation (OR: 0.95, p = 0.95), gallbladder remnant cholecystitis (OR: 0.21, p = 0.09) or need for completion cholecystectomy (RD: 0.01, p = 0.59) between two groups. CONCLUSIONS: Fenestrating STC is associated with a higher risk of bile leak than the reconstructing technique. This issue can be mitigated by routine use of drains, delayed drain removal, and in selected cases endoscopic therapy. We encourage the fenestrating approach considering trends in improved short- and long-term outcomes.

Pancreatic resection for metastasis from renal cell carcinoma: A single institution experience and meta-analysis of survival outcomes.

AIMS: To evaluate short-term clinical and long-term survival outcomes of pancreatic resection for pancreatic metastasis from renal cell carcinoma (RCC). METHODS: A retrospective evaluation of patients undergoing pancreatic resection for metastasis from RCC over a 12-years period was conducted. Furthermore, a systematic search of electronic data sources and bibliographic reference lists were conducted to identify studies investigating the same clinical question. Short-term clinical and long-term survival outcomes were evaluated. Kaplan-Meier survival plots were constructed for survival outcomes. Cox-proportional regression analysis was performed to determine factors associated with survival. Finally, meta-analysis of survival outcomes was conducted using random-effects modelling. RESULTS: Eighteen patients underwent pancreatic resections for RCC pancreatic metastasis within the study period. The mean age of the included patients was 63.8 ± 8.0 years. There were 10(55.6 %) male and 8(44.4 %) female patients. Pancreatectomy was associated with 4(25.0 %) Clavien-Dindo (C-D) I, 5(31.3 %) C-D II, and 7(43.7 %) C-D III complications, 7(38.8 %) pancreatic fistula, 3(16.7 %) post-pancreatectomy acute pancreatitis, 1(5.6 %) delayed gastric emptying, and 1(5.6 %) chyle leak. The mean length of hospital stay was 18 ± 16.3 days. The median survival was 64 months (95 % CI 60-78). The 3-and 5-year disease-free survival rates were 83.3 % and 55.5 %, respectively. The 3-and 5-year survival rates were 100 % and 55.6 %, respectively. The pooled analyses of 553 patients demonstrated 3-and 5-year survival rates of 77.6 % and 60.7 %, respectively. CONCLUSIONS: Pancreatectomy for RCC metastasis is associated with acceptable short-term clinical and promising long-term survival outcomes. Considering the rarity of the entity, escalation of level of evidence in this context is challenging.

Meta-analysis of adjuvant chemotherapy versus no adjuvant chemotherapy for resected stage I pancreatic cancer.

BACKGROUND: To evaluate comparative outcomes of pancreatic cancer resection with or without adjuvant chemotherapy in patients with stage I pancreatic cancer. METHODS: A systematic search of MEDLINE, CENTRAL, and Web of Science and bibliographic reference lists were conducted. All comparative studies reporting outcomes of pancreatic cancer resection for stage I cancer with or without adjuvant chemotherapy were included, and their risk of bias was assessed using the Risk Of Bias In Non-randomized Studies-of Interventions tool. Survival outcomes were analyzed using the hazard ratio and odds ratio for the time-to-event and dichotomous outcomes, respectively. RESULTS: We included 6 comparative studies reporting a total of 6,874 patients with resected stage 1 pancreatic cancer, of whom 3,951 patients had no adjuvant chemotherapy, and the remaining 2,923 patients received adjuvant chemotherapy. The use of adjuvant chemotherapy was associated with significantly higher overall survival (hazard ratio 0.71, 95% confidence interval 0.62-0.82, P < .00001) and 2-year survival (65.1% vs 57.4%, odds ratio 1.99; 95% confidence interval 1.01-1.41, P = .04) compared to no use of adjuvant chemotherapy. However, there was no statistically significant difference in 1-year (86.8% vs 78.4%, odds ratio 1.60; 95% confidence interval 0.72-3.57, P = .25), 3-year (46.0% vs 44.0%, odds ratio 1.07; 95% confidence interval 0.90-1.29, P = .43), or 5-year survival (24.8% vs 23.3%, odds ratio 1.03; 95% confidence interval 0.80-1.33, P = .81) between the 2 groups. CONCLUSION: Meta-analysis of best available evidence (level 2a with low to moderate certainty) demonstrates that adjuvant chemotherapy may confer survival benefits for stage I pancreatic cancer when compared to the use of surgery alone. Randomized control trials are required to escalate the level of evidence and confirm these findings with consideration of contemporary chemotherapy agents and regimens.

Preoperative C-Reactive Protein-to-Albumin Ratio and Its Ability to Predict Outcomes of Pancreatic Cancer Resection: A Systematic Review.

OBJECTIVES: To evaluate the ability of the c-reactive protein-to-albumin ratio (CAR) in predicting outcomes in patients undergoing pancreatic cancer resection. METHODS: A systematic search of electronic information sources and bibliographic reference lists was conducted. Survival outcomes and perioperative morbidity were the evaluated outcome parameters. RESULTS: Eight studies reporting a total of 1056 patients undergoing pancreatic cancer resection were identified. The median cut-off value for CAR was 0.05 (range 0.0003-0.54). Using multivariate analysis, all studies demonstrated that a higher CAR value was an independent and significant predictor of poor overall survival in patients undergoing pancreatic cancer resection. The estimated hazard ratio (HR) ranged from 1.4 to 3.6. Although there was a positive correlation between the reported cut-off values for CAR and HRs for overall survival, it was weak and non-significant (r = 0.36, n = 6, p = 0.480). There was significant between-study heterogeneity. CONCLUSIONS: Preoperative CAR value seems to be an important prognostic score in predicting survival outcomes in patients undergoing pancreatic cancer resection. However, the current evidence does not allow the determination of an optimal cut-off value for CAR, considering the heterogeneous reporting of cut-off values by the available studies and the lack of knowledge of their sensitivity and specificity. Future research is required.

Short and long term outcomes of laparoscopic fenestrating or reconstituting subtotal cholecystectomy versus laparoscopic total cholecystectomy in the management of acute cholecystitis.

BACKGROUND: Strasberg proposed classifying subtotal cholecystectomy techniques into fenestrating (fSC) and reconstituting (rSC) subtypes. The aim of this study is to compare our outcomes of laparoscopic subtotal cholecystectomies of both subtypes against laparoscopic total cholecystectomy (TC) in difficult emergency laparoscopic cholecystectomies. METHODS: Patients undergoing emergency laparoscopic cholecystectomy were identified over 2 years and all Nassar scale 3 and 4 cholecystectomies were included for analysis. RESULTS: 108 fSC and 24 rSC were compared against 317 TC. Patients undergoing fSC and rSC were older and more likely to be male. fSC (128 min) and rSC (141 min) recorded longer median operative times than TC (109). Post-operative ERCP was more common after rSC (16.7%). Patients undergoing fSC (2 days) and rSC (3.5 days) had longer post-operative stays. Bile leaks were more likely in fSC (9.3%) and rSC (8.3%) compared to TC (1.9%), Long term morbidity was higher in the rSC group (12.5% vs 10%). And these were solely due to gallbladder remnant complications. CONCLUSION: Laparoscopic fSC and rSC techniques are associated with a higher rate of bile leaks and rSC has more long term morbidty as compared to TC.