Extended distal pancreatectomy in pancreatic cancer: is it justified? A systematic review of literature.

Background: Extended distal pancreatectomy (EDP) is being increasingly performed for pancreatic cancers with suspected invasion into the adjacent organs. However, the perioperative safety and oncological efficacy of this procedure merit further elucidation. Methods: Major databases were searched for studies evaluating EDP, and a meta-analysis was performed using fixed- or random-effects models. Results: Fifteen studies were included in the analysis. EDP was found to be associated with significantly greater incidence of postoperative pancreatic fistula overall and with major complications, re-explorations, mortality and readmissions. However, on pooled analysis of 3- and 5-year survival, EDP was found to be noninferior to standard distal pancreatectomy. Conclusion: EDP is feasible and may offer equivalent survival in highly selected patients but carries a higher risk of perioperative morbidity and mortality.

Impact of Unplanned Intra-Operative Conversions on Outcomes in Minimally Invasive Pancreatoduodenectomy.

BACKGROUND: Minimally-invasive pancreatoduodenectomy (MIPD) is fraught with the risk of complication-related deaths (LEOPARD-2), a significant volume-outcome relationship and a long learning curve. With rates of conversion for MIPD approaching 40%, the impact of these on overall patient outcomes, especially, when unplanned, are yet to be fully elucidated. This study aimed to compare peri-operative outcomes of (unplanned) converted MIPD against both successfully completed MIPD and upfront open PD. METHODS: A systematic review of major reference databases was undertaken. The primary outcome of interest was 30-day mortality. Newcastle-Ottawa scale was used to judge the quality of the studies. Meta-analysis was performed using pooled estimates, derived using random effects model. RESULTS: Six studies involving 20,267 patients were included in the review. Pooled analysis demonstrated (unplanned) converted MIPD were associated with an increased 30-day (RR 2.83, CI 1.62- 4.93, p = 0.0002, I2 = 0%) and 90-day (RR 1.81, CI 1.16- 2.82, p = 0.009, I2 = 28%) mortality and overall morbidity (RR 1.41, CI 1.09; 1.82, p = 0.0087, I2 = 82%) compared to successfully completed MIPD. Patients undergoing (unplanned) converted MIPD experienced significantly higher 30-day mortality (RR 3.97, CI 2.07; 7.65, p < 0.0001, I2 = 0%), pancreatic fistula (RR 1.65, CI 1.22- 2.23, p = 0.001, I2 = 0%) and re-exploration rates (RR 1.96, CI 1.17- 3.28, p = 0.01, I2 = 37%) compared upfront open PD. CONCLUSIONS: Patient outcomes are significantly compromised following unplanned intraoperative conversions of MIPD when compared to successfully completed MIPD and upfront open PD. These findings stress the need for objective evidence-based guidelines for patient selection for MIPD.

Global Perceptions on ERAS® in Pancreatoduodenectomy.

BACKGROUND: Uptake of ERAS® pathways for pancreatic surgery have been slow and impacted by low compliance. OBJECTIVE: To explore global awareness, perceptions and practice of ERAS® peri-pancreatoduodenectomy (PD). METHODS: A structured, web-based survey (EPSILON) was administered through the ERAS® society and IHPBA membership. RESULTS: The 140 respondents included predominantly males (86.4%), from Europe (45%), practicing surgery (95%) at academic/teaching hospitals (63.6%) over a period of 10-20 years (38.6%). Most respondents identified themselves as general surgeons (68.6%) with 40.7% reporting an annual PD volume of 20-50 cases, practicing post-PD clinical pathways (37.9%), with 31.4% of respondents auditing their outcomes annually. Reduced medical complications, cost and hospital length of stay, and improved patient satisfaction were perceived benefits of compliance to enhancing-recovery. Multidisciplinary co-ordination was considered the most important factor in the implementation and sustainability of peri-PD ERAS® pathways, while reluctance to change among health care practitioners, difficulties in data collection and audit, lack of administrative support, and recruitment of an ERAS® dedicated nurse were reported to be important barriers. CONCLUSIONS: The EPSILON survey highlighted global clinician perceptions regarding the benefits of compliance to peri-PD ERAS®, the importance of individual components, perceived facilitators and barriers, to the implementation and sustainability of these pathways.

Fluid resuscitation in the early management of acute pancreatitis - evidence from a systematic review and meta-analysis.

BACKGROUND: Third space fluid loss is one of the hallmarks of the pathophysiology of acute pancreatitis (AP) contributing to complications, including organ failure and death. We conducted a systematic review of literature to determine the ideal fluid resuscitation in the early management of AP, primarily comparing aggressive versus moderate intravenous fluid resuscitation (AIR vs MIR). METHODS: A systematic review of major reference databases was undertaken. Meta-analysis was performed using random-effects model. Bias was assessed using Cochrane risk of bias and ROBINS-I tools for randomized and non-randomised studies, respectively. RESULTS: Twenty studies were included in the analysis. Though there was no significant difference in mortality between AIR and MIR groups (8.3% versus 6.0%; p = 0.3), AIR cohort had significantly higher rates of organ failure (p = 0.009), including pulmonary (p = 0.02) and renal (p = 0.01) complications. Similarly, there was no difference in mortality between normal saline (NS) and Ringer's lactate (RL) (3.17% versus 3.01%; p = 0.23), though patients treated with NS had a significantly longer length of hospital stay (LOS) (p = 0.009). CONCLUSIONS: Current evidence appears to support moderate intravenous resuscitation (level of evidence, low) with RL (level of evidence, moderate) in the early management of AP.

Post-hepatectomy venous thromboembolism: a systematic review with meta-analysis exploring the role of pharmacological thromboprophylaxis.

PURPOSE: Patients undergoing hepatectomy are at moderate-to-high risk of venous thromboembolism (VTE). This study critically examines the efficacy of combining pharmacological (PTP) and mechanical thromboprophylaxis (MTP) versus only MTP in reducing VTE events against the risk of hemorrhagic complications. METHODS: A systematic review of major reference databases was undertaken, and a meta-analysis was performed using common-effects model. Risk of bias assessment was performed using Newcastle-Ottawa scale. Trial sequential analysis (TSA) was used to assess the precision and conclusiveness of the results. RESULTS: 8 studies (n = 4238 patients) meeting inclusion criteria were included in the analysis. Use of PTP + MTP was found to be associated with significantly lower VTE rates compared to only MTP (2.5% vs 5.3%; pooled RR 0.50, p = 0.03, I2 = 46%) with minimal type I error. PTP + MTP was not associated with an increased risk of hemorrhagic complications (3.04% vs 1.9%; pooled RR 1.54, p = 0.11, I2 = 0%) and had no significant impact on post-operative length of stay (12.1 vs 10.8 days; pooled MD - 0.66, p = 0.98, I2 = 0%) and mortality (2.9% vs 3.7%; pooled RR 0.73, p = 0.33, I2 = 0%). CONCLUSION: Despite differences in the baseline patient characteristics, extent of hepatectomy, PTP regimens, and heterogeneity in the pooled analysis, the current study supports the use of PTP in post-hepatectomy patients (grade of recommendation: strong) as the combination of PTP + MTP is associated with a significantly lower incidence of VTE (level of evidence, moderate), without an increased risk of post-hepatectomy hemorrhage (level of evidence, low).

Enhancing the cost-effectiveness of surgical care in pancreatic cancer: a systematic review and cost meta-analysis with trial sequential analysis.

BACKGROUND: Clinical pathways (CP) based on Enhanced recovery after surgery (ERAS®) are increasingly utilised in patients undergoing pancreatoduodenectomy (PD). This systematic review aimed to compare the impact of CPs versus conventional care (CC) on peri-PD costs. METHODS: A systematic review of major reference databases was undertaken. Quality assessment was performed using the CHEERS checklist. Incremental cost-effectiveness ratios were calculated as part of the cost-effectiveness analysis. A meta-analysis was performed using random-effects models and Trial sequential analysis (TSA) was used to assess the precision and conclusiveness of the results. RESULTS: 14 studies meeting inclusion criteria were included for full qualitative synthesis. All studies reported a reduction in overall costs, length of stay and overall complication rates for CPs when compared to CC. Meta-analysis performed on nine studies demonstrated significantly reduced costs in the CP group, with considerable heterogeneity (Pooled mean difference of $ 4.28 × 103, p < 0.01, I2 = 95%). Cost-effectiveness analysis in relation to complications demonstrated dominance of CPs over CC in being cheaper as well as more effective. TSA supported the cost benefit of enhanced-recovery CPs, displaying minimal type 1 error. CONCLUSION: Peri-PD CPs result in significant cost-reduction in comparison to CC.

Surgery for pancreatic cancer: current controversies and challenges.

Two areas that remain the focus of improvement in pancreatic cancer include high post-operative morbidity and inability to uniformly translate surgical success into long-term survival. This narrative review addresses specific aspects of pancreatic cancer surgery, including neoadjuvant therapy, vascular resections, extended pancreatectomy, extent of lymphadenectomy and current status of minimally invasive surgery. R0 resection confers longer disease-free survival and overall survival. Vascular and adjacent organ resections should be undertaken after neoadjuvant therapy, only if R0 resection can be ensured based on high-quality preoperative imaging, and that too, with acceptable post-operative morbidity. Extended lymphadenectomy does not offer any advantage over standard lymphadenectomy. Although minimally invasive distal pancreatectomies offers some short-term benefits over open distal pancreatectomy, safety remains a concern with minimally invasive pancreatoduodenectomy. Strict adherence to principles and judicious utilization of surgery within a multimodality framework is the way forward.

Lay abstract Two main areas of focus in pancreatic cancer research are the high rates of post-surgery complications and poor survival despite completely removing the tumor. Complete, margin-negative resection (where some healthy tissue is removed to ensure the whole tumor is cut out) is the only way to ensure long-term survival. However, such extensive resections, especially when they involve nearby blood vessels and/or organs, should only be undertaken if the imaging done pre-surgery indicates the possibility that a complete, margin-negative resection can be achieved. It should be noted that the removal of lymph nodes, in addition to the ones normally removed during a pancreatic resection, does not confer a survival benefit. Distal pancreatectomy (performed for tumors involving the body or tail of the pancreas) is safe and feasible using minimal access methods; however, the safety of minimally-invasive pancreatoduodenectomy (performed for tumors of the head of the pancreas) remains to be proven. The oncological benefit of minimally-invasive distal pancreatectomy over open surgery has not been established.

Outcomes of level of ligation of inferior mesenteric artery in colorectal cancer: a systematic review and meta-analysis.

The level of ligation of the inferior mesenteric artery (IMA) is a critical factor that can influence outcomes. The aim of this meta-analysis was to compare outcomes following high or low ligation of IMA. A systematic search was performed for relevant articles published between 2000 and 2020. Meta-analysis was performed using fixed-effects or random-effects models; 31 studies were included. Results show significantly lower rates of anastomotic leak, postoperative morbidity and urinary dysfunction with low ligation compared with high ligation. Though recurrence rates were similar, 5-year overall survival was longer in the low ligation group. Low ligation of IMA decreases anastomotic leak rates and overall morbidity. Addition of IMA nodal clearance to low ligation appears to improve overall survival in colorectal cancer.

Deviations from a clinical pathway post pancreatoduodenectomy predict 90-day unplanned re-admission.

Aim: To determine the frequency and relevance of deviations from a post pancreatoduodenectomy (PD) clinical care pathway. Materials & methods: A retrospective analysis using a prospectively maintained database of a post-PD clinical care pathway was carried out between May 2016 and March 2018. Patients were divided based on the number of factors deviating from the clinical care pathway (Group I: no deviation; Group II: deviation in 1-4 factors; Group III: deviation in 5-8 factors). The analysis included profiling of patients on different demographic and clinical as well as medical and surgical outcome parameters (discharge by postoperative day 8 and 90-day unplanned re-admission rate). Results: Post-PD clinical care pathways are feasible but deviations from the pathway are frequent (91%). An increase in frequency of deviations from the pathway was significantly associated with increased risk of POPF and delayed gastric emptying, delayed discharge, risk of mortality and 90-day unplanned re-admission rate. Conclusion: Deviations from a post-PD clinical care pathway are common. Poor nutrition and cardiac co-morbidities are associated with an increased likelihood of deviation. As the number of deviations increase, so does the risk of significant complications and interventions, delayed discharge and 90-day re-admission rate.

Does perioperative hydrocortisone or indomethacin improve pancreatoduodenectomy outcomes? A triple arm, randomized placebo-controlled trial.

Backgrounds/Aims: This trial evaluated whether anti-inflammatory agents hydrocortisone (H) and indomethacin (I) could reduce major complications after pancreatoduodenectomy (PD). Methods: Between June 2018 and June 2020, 105 patients undergoing PD with > 40% of acini on the intraoperative frozen section were randomized into three groups (35 patients per group): 1) intravenous H 100 mg 8 hourly, 2) rectal I suppository 100 mg 12 hourly, and 3) placebo (P) from postoperative day (POD) 0-2. Participants, investigators, and outcome assessors were blinded. The primary outcome was major complications (Clavien-Dindo grades 3-5). Secondary outcomes were overall complications (Clavien-Dindo grades 1-5), Clinically relevant postoperative pancreatic fistula (CR-POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), surgical site infections (SSI), length of stay, POD-3 serum amylase, readmission rate, and mortality. Results: Major complications were comparable (8.6%, 5.7%, and 8.6% in groups H, I, and P, respectively). However, overall complications were significantly lower in group H than in group P (45.7% vs. 80.0%, p = 0.006). CR-POPF (14.3% vs. 25.7%, p = 0.371), PPH (8.6% vs. 14.3%, p = 0.710), DGE (8.6% vs. 22.9%, p = 0.188), and SSI (14.3% vs. 25.7%, p = 0.371) were comparable between groups H and P. Major complications and overall complications in group I were 5.7% and 60.0%, respectively, which were comparable to those in groups P and H. CR-POPF rates in groups H, I, and P were 14.3%, 17.1%, and 25.7%, respectively, which was comparable. Conclusions: H and I did not decrease major complications in PD.

Cholangioscopic classification of post-living donor liver transplantation biliary strictures can predict their natural history and response to therapy.

BACKGROUND: The study aimed to assess the morphology of post-living donor liver transplant (LDLT) anastomotic biliary strictures using cholangioscopy and assess the impact of morphology on its prognosis. METHODS: A single centre, prospective, observational study was conducted at a tertiary care teaching hospital from August 2014 to July 2016. Single operator cholangioscopy (SOC) was used to assess post-LDLT anastomotic biliary strictures at presentation in 24 patients. Analysis included demographic and biochemical characteristics, time to stricture development, endoscopic procedural details, time to remodelling and development of recurrence on follow-up. RESULTS: Two distinct patterns of strictures were identified, type I with minimal inflammatory changes and type II with severe inflammatory changes. Guidewire cannulation was successful in 23 out of 24 (95.8%) patients. There was no significant difference between the two types of strictures based on aetiology of liver disease, CTP and MELD scores, time taken for the development or laboratory parameters at presentation. However, type II strictures required more sessions of dilatation (4 vs. 2; P = 0.002), longer duration for resolution (282.5 vs. 201.5 days, P = 0.095) and more number of stents. CONCLUSIONS: Addition of cholangioscopy tends to improve stricture cannulation rates at ERCP. It offers a useful classification of post-LDLT strictures with prognostic and therapeutic significance. Type II strictures tend to require more sessions of endotherapy than type I strictures over a longer duration for remodelling.

The influence of socioeconomic status on access to cancer care and survival in resectable pancreatic cancer: a systematic review and meta-analysis.

BACKGROUND: Socioeconomic status (SES) is an important factor affecting access to cancer care and survival. Its role in pancreatic cancer warrants scrutiny. METHODS: A systematic review of major reference databases was undertaken. Categorization of the study population into low SES (LSES) and high SES (HSES) was based on the criteria employed in the individual studies. The outcome measures studied were stage of cancer presentation, access to care and overall survival. Meta-analysis was performed using random-effects models and trial sequential analysis (TSA) was used to assess the precision and conclusiveness of the results. RESULTS: Thirteen studies meeting inclusion criteria were included in the meta-analysis, which demonstrated that LSES was associated with significantly lower rates of presentation at a non-metastatic stage and poorer access to cancer care, viz. surgery, chemotherapy and radiation therapy. Despite heterogeneity, TSA supported the findings, displaying minimal type I error. CONCLUSION: As LSES is associated with delayed presentation, poorer access to care and poorer survival, SES should be considered a modifiable risk factor for poor outcomes in pancreatic cancer.

Is enhancing recovery after pancreatic cancer surgery even possible?-a narrative review.

OBJECTIVE: This narrative review traces the evolutionary journey of ERAS® with emphasis on challenges specific to pancreatic cancer. This article will also attempt to explore the barriers to routine ERAS® implementation and offers possible solutions to increasing its uptake and compliance rates. BACKGROUND: Enhanced Recovery After Surgery (ERAS®) represents a paradigm shift in the perioperative management of surgical patients using a multi-modality approach each of which is based on best available evidence. ERAS® has come a long way since its inception and can now be regarded as one of the promising ways forward in the perioperative management of patients undergoing pancreatic surgery. METHODS: We identified 37 studies on the impact of ERAS® in pancreatic surgery, published over the last 2 decades. Implementation of ERAS® helped in shortening the length of stay without an increase in hospital re-admissions, morbidity, or mortality. Compliance to ERAS® is relatively low following pancreatic surgery, with a reported median compliance of 52%. Elderly patients or those with higher BMI, higher ASA scores, hypoalbuminemia, cardiac comorbidities or longer operative duration are more prone for deviations. CONCLUSIONS: ERAS pathways have been successful in achieving their intended outcomes, despite low compliance. Complementing existing ERAS® pathways with prehabilitation measures, risk-stratified clinical pathways and the accessibility to step-down care facilities following discharge may facilitate its wider utilisation.

Systematic review and meta-analysis of the impact of deviations from a clinical pathway on outcomes following pancreatoduodenectomy.

BACKGROUND: Enhanced recovery after surgery is steadily gaining importance in patients undergoing pancreatic surgery, including pancreatoduodenectomy (PD). While clinical pathways targeting enhanced-recovery can achieve their intended outcome in reducing length of stay, compliance to these pathways, and their relevance is poorly understood. The aim of this systematic review was to assess the impact of deviations from/non-compliance to a clinical pathway on post-PD outcomes. AIM: To assess the impact of deviations from/non-compliance to a clinical pathway on post-PD outcomes. METHODS: A systematic review of major reference databases was undertaken, according to preferred reporting items for systematic reviews and meta-analysis guidelines, between January 2000 and November 2020 relating to compliance with clinical pathways and its impact on outcomes in patients undergoing PD. A meta-analysis was performed using fixed-effects or random-effects models. RESULTS: Eleven studies including 1852 patients were identified. Median overall compliance to all components of the clinical pathway was 65.7% [interquartile range (IQR): 62.7%-72.3%] with median compliance to post-operative parameters of the clinical pathway being 44% (IQR: 34.5%-52.25%). Meta-analysis using a fixed-effects model showed that ≥ 50% compliance to a clinical pathway predicted significantly fewer post-operative complications [pooled odds ratio (OR): 9.46, 95% confidence interval (CI): 5.00-17.90; P < 0.00001] and a significantly shorter length of hospital stay [pooled mean difference (MD): 4.32, 95%CI: -3.88 to -4.75; P < 0.0001]. At 100% compliance which was associated with significantly fewer post-operative complications (pooled OR: 11.25, 95%CI: 4.71-26.84; P < 0.00001) and shorter hospital stay (pooled MD of 4.66, 95%CI: 2.81-6.51; P < 0.00001). CONCLUSION: Compliance to post-PD clinical pathways remains low. Deviations are associated with an increased risk of complications and length of hospital stay. Under-standing the relevance of deviations to clinical pathways post-PD presents pancreatic surgeons with opportunities to actively pursue an enhanced-recovery of their patients.