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.

Minimally invasive pancreatoduodenectomy is associated with a higher incidence of postoperative venous thromboembolism when compared to the open approach: A systematic review and meta-analysis.

BACKGROUND: Despite the increased use of minimally invasive approaches for pancreatoduodenectomy (PD), the association between surgical approach and venous thromboembolism (VTE) risk is still unknown. This study aims to compare VTE rates following open (OPD) and minimally invasive pancreatoduodenectomy (MIPD). METHOD: MEDLINE, Web of Sciences and EMBASE databases were searched to identify eligible studies. Studies were considered suitable if the incidence of postoperative VTE in open and minimally invasive (laparoscopic or robotic) pancreatic surgery was reported. The review was conducted following the PRISMA guidelines. RESULTS: Five studies including 12 984 patients met the inclusion criteria and were considered for meta-analysis. A total of 11 060 patients underwent OPD and 1924 MIPD. Overall, patients who underwent OPD had a lower rate of VTE compared to MIPD (3.6 % vs 4.6 %, OR (95 % CI) = 0.66 (0.52-0.85), p < 0.001). Subgroup analysis showed similar results for pulmonary embolism (PE) (1.1 % in OPD vs 1.9 % in MIPD, OR (95 % CI) = 0.54 (0.36-0.80), p 0.002) and deep venous thrombosis (DVT) (1.3 % in OPD vs 3.1 % in MIPD, OR (95 % CI) = 0.48 (0.29-0.79), p 0.004). CONCLUSION: Patients who undergo minimally invasive pancreatoduodenectomy have a higher incidence of postoperative VTE when compared to open pancreatoduodenectomy.

Perioperative outcomes of utilizing infrahepatic inferior vena cava clamping and Pringle maneuver during hepatectomy: a meta-analysis.

PURPOSE: Intraoperative bleeding during hepatectomy is primarily controlled through anaesthesiological interventions or surgical techniques such as Pringle maneuver (PM). Infrahepatic IVC clamping (IIVCC) is an alternative surgical technique to reduce central venous pressure and prevent retrograde hepatic venous bleeding. The aim of the meta-analysis was to compare IIVCC+PM with PM alone in terms of intraoperative outcomes and perioperative complications. METHODS: Medline, Cochrane Library, Scopus, Web of Science, and EMBASE were searched for comparative studies till 16.04.2024, resulting in 679 articles, of which eight studies met inclusion criteria. Data on patient demographics, surgical technique, and perioperative outcomes was assessed. Cochrane Risk of Bias 2.0 (RoB 2.0) Tool and Newcastle-Ottawa Scale (NOS) were used for risk of bias assessment. RESULTS: Two randomized controlled trials, one prospective, and five retrospective cohort studies with 358 patients in IIVCC+PM and 397 patients in PM alone group were included. IIVCC+PM resulted in significantly greater CVP reduction, less intraoperative blood loss (MD (95% CI) = - 233.03 (- 360.48 to - 105.58), P < 0.001), and less intraoperative blood transfusion (OR (95% CI) = 0.38 (0.25 to 0.57), P < 0.001) compared to PM alone. The two groups had comparable total operative time, transection time and total intraoperative fluid infusion. Patients undergoing IIVCC+PM had significantly shorter length of stay (MD (95% CI) = - 0.63 days (- 1.21 to - 0.05 days), P = 0.03) and overall complication rates (OR (95% CI) = 0.63 (0.43-0.92), P = 0.02) compared to PM alone group. CONCLUSION: The utilization of IIVCC along with PM during liver resection may be beneficial in reducing intraoperative bleeding and blood transfusion without adversely influencing operative times or perioperative outcomes compared to PM alone.

Low versus standard central venous pressure during laparoscopic liver resection: A systematic review, meta-analysis and trial sequential analysis.

To compare the outcomes of low central venous pressure (CVP) to standard CVP during laparoscopic liver resection. The study design was a systematic review following the PRISMA statement standards. The available literature was searched to identify all studies comparing low CVP with standard CVP in patients undergoing laparoscopic liver resection. The outcomes included intraoperative blood loss (primary outcome), need for blood transfusion, mean arterial pressure, operative time, Pringle time, and total complications. Random- effects modelling was applied for analyses. Type I and type II errors were assessed by trial sequential analysis (TSA). A total of 8 studies including 682 patients were included (low CVP group, 342; standard CVP group, 340). Low CVP reduced intraoperative blood loss during laparoscopic liver resection (mean difference [MD], -193.49 mL; 95% confidence interval [CI], -339.86 to -47.12; p = 0.01). However, low CVP did not have any effect on blood transfusion requirement (odds ratio [OR], 0.54; 95% CI, 0.28-1.03; p = 0.06), mean arterial pressure (MD, -1.55 mm Hg; 95% CI, -3.85-0.75; p = 0.19), Pringle time (MD, -0.99 minutes; 95% CI, -5.82-3.84; p = 0.69), operative time (MD, -16.38 minutes; 95% CI, -36.68-3.39; p = 0.11), or total complications (OR, 1.92; 95% CI, 0.97-3.80; p = 0.06). TSA suggested that the meta-analysis for the primary outcome was not subject to type I or II errors. Low CVP may reduce intraoperative blood loss during laparoscopic liver resection (moderate certainty); however, this may not translate into shorter operative time, shorter Pringle time, or less need for blood transfusion. Randomized controlled trials with larger sample sizes will provide more robust evidence.

Outcomes of metachronous para-aortic lymphadenectomy in colorectal cancer: a systematic review of the literature.

INTRODUCTION AND AIM: Para-aortic lymph node metastasis associated with colorectal cancer is a very rare occurrence, but at the same time an important predictor of survival. Despite its importance, there is still no gold standard management strategy, particularly for lymph nodes detected during follow-up, after resection of the primary tumour. Therefore, this review was undertaken to examine the evidence available on the surgical and non-surgical management of metachronous para-aortic lymph node metastasis (m-PALNM) in colorectal cancer treatment. METHODS: This is a systematic review using the patient, intervention, comparison, outcome and study strategy. The literature search was undertaken using Cochrane, MEDLINE, EMBASE and PubMed databases with the following MeSH terms: lymph node excision, para-aortic lymph node, metastasis, metachronous and colorectal neoplasms. RESULTS: Five original papers met the study criteria including 188 patients in total (55.3% male, 44.7% female). Surgical resection of the m-PALND was the management of choice in 64% of patients. Reporting styles on survival outcomes were heterogeneous. However, patients undergoing surgical management for m-PALNM had longer disease-free survival and overall survival rates. CONCLUSION: There is significant paucity in the evidence available on the management of m-PALNM. However, the evidence reported by this review suggests that surgical management should be considered whenever possible, with the aim of prolonging survival. Future randomised trials are needed in order to provide further high-level evidence on m-PALNM management.

Accuracy of the END-PAC Model in Predicting the Risk of Developing Pancreatic Cancer in Patients with New-Onset Diabetes: A Systematic Review and Meta-Analysis.

OBJECTIVES: To investigate the performance of the END-PAC model in predicting pancreatic cancer risk in individuals with new-onset diabetes (NOD). METHODS: The PRISMA statement standards were followed to conduct a systematic review. All studies investigating the performance of the END-PAC model in predicting pancreatic cancer risk in individuals with NOD were included. Two-by-two tables, coupled forest plots and summary receiver operating characteristic plots were constructed using the number of true positives, false negatives, true negatives and false positives. Diagnostic random effects models were used to estimate summary sensitivity and specificity points. RESULTS: A total of 26,752 individuals from four studies were included. The median follow-up was 3 years and the pooled risk of pancreatic cancer was 0.8% (95% CI 0.6-1.0%). END-PAC score ≥ 3, which classifies the patients as high risk, was associated with better predictive performance (sensitivity: 55.8% (43.9-67%); specificity: 82.0% (76.4-86.5%)) in comparison with END-PAC score 1-2 (sensitivity: 22.2% (16.6-29.2%); specificity: 69.9% (67.3-72.4%)) and END-PAC score < 1 (sensitivity: 18.0% (12.8-24.6%); specificity: 50.9% (48.6-53.2%)) which classify the patients as intermediate and low risk, respectively. The evidence quality was judged to be moderate to high. CONCLUSIONS: END-PAC is a promising model for predicting pancreatic cancer risk in individuals with NOD. The score ≥3 should be considered as optimum cut-off value. More studies are needed to assess whether it could improve early pancreatic cancer detection rate, pancreatic cancer re-section rate, and pancreatic cancer treatment outcomes.

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.

Venous thromboembolism (VTE) after open hepatectomy compared to minimally invasive liver resection: a systematic review and meta-analysis.

BACKGROUND: Even though the risk of postoperative venous thromboembolism (VTE) after liver resection is well recognized, the association between surgical approach and VTE risk is unknown. This study aims to compare VTE rates following open liver resection (OLR) and minimally invasive liver resection (MILR). METHODS: MEDLINE, Web Of Sciences and EMBASE databases were interrogated to identify eligible studies published between February 2016 and August 2022. Studies were considered suitable if they reported a comparison between OLR and MILR (including laparoscopic liver resection [LLR] or robotic liver resection [RLR]). RESULTS: Fourteen studies including 11 356 patients met the inclusion criteria. 5622 patients underwent OLR and 5734 patients underwent MILR. The VTE rate was higher among patients who underwent OLR compared to MILR (2.8% vs 1.4%, OR (95% CI) = 1.84, p=<00001). Similarly, the subgroup analysis showed a higher rate of deep venous thrombosis (DVT) (1.4% vs 0.7%, OR (95% CI) = 1.98, p = 0.02) and pulmonary embolism (PE) (1.3% vs 0.7%, OR (95% CI) = 1.88, p = 0.002) in patients who underwent OLR compared to MILR. DISCUSSION: Patients who undergo open hepatectomy have a higher incidence of postoperative VTE when compared to those undergoing minimally invasive liver resection. This finding was consistent for both DVT and PE.

Neoadjuvant chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: Meta-analysis and trial sequential analysis of randomized controlled trials.

We aimed to compare resection and survival outcomes of neoadjuvant chemoradiotherapy (CRT) and immediate surgery in patients with resectable pancreatic cancer (RPC) or borderline resectable pancreatic cancer (BRPC). In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards, a systematic review of randomized controlled trials (RCTs) was conducted. Random effects modeling was applied to calculate pooled outcome data. Likelihood of type 1 or 2 errors in the meta-analysis model was assessed by trial sequential analysis. A total of 400 patients from four RCTs were included. When RPC and BRPC were analyzed together, neoadjuvant CRT resulted in a higher R0 resection rate (risk ratio [RR]: 1.55, p = 0.004), longer overall survival (mean difference [MD]: 3.75 years, p = 0.009) but lower overall resection rate (RR: 0.83, p = 0.008) compared with immediate surgery. When RPC and BRPC were analyzed separately, neoadjuvant CRT improved R0 resection rate (RR: 3.72, p = 0.004) and overall survival (MD: 6.64, p = 0.004) of patients with BRPC. However, it did not improve R0 resection rate (RR: 1.18, p = 0.13) or overall survival (MD: 0.94, p = 0.57) of patients with RPC. Neoadjuvant CRT might be beneficial for patients with BRPC, but not for patients with RPC. Nevertheless, the best available evidence does not include contemporary chemotherapy regimens. Patients with RPC and those with BRPC should not be combined in the same cohort in future studies.

Procedural outcomes of laparoscopic caudate lobe resection: A systematic review and meta-analysis.

A systematic review was conducted in compliance with PRISMA statement standards to identify all studies reporting outcomes of laparoscopic resection of benign or malignant lesions located in caudate lobe of liver. Pooled outcome data were calculated using random-effects models. A total of 196 patients from 12 studies were included. Mean operative time, volume of intraoperative blood loss, and length of hospital stay were 225 minutes (95% confidence interval [CI], 181-269 minutes), 134 mL (95% CI, 85-184 mL), and 7 days (95% CI, 5-9 days), respectively. The pooled risk of need for intraoperative transfusion was 2% (95% CI, 0%-5%). It was 3% (95% CI, 1%-6%) for conversion to open surgery, 6% (95% CI, 0%-19%) for need for intra-abdominal drain, 1% (95% CI, 0%-3%) for postoperative mortality, 2% (95% CI, 0%-4%) for biliary leakage, 2% (95% CI, 0%-4%) for intra-abdominal abscess, 1% (95% CI, 0%-4%) for biliary stenosis, 1% (95% CI, 0%-3%) for postoperative bleeding, 1% (95% CI, 0%-4%) for pancreatic fistula, 2% (95% CI, 1%-5%) for pulmonary complications, 1% (95% CI, 0%-4%) for paralytic ileus, and 1% (95% CI, 0%-4%) for need for reoperation. Although the available evidence is limited, the findings of the current study might be utilized for hypothesis synthesis in future studies. They can be used to inform surgeons and patients about estimated risks of perioperative complications until a higher level of evidence is available.

Hajibandeh Index versus NELA score in predicting mortality following emergency laparotomy: A retrospective Cohort Study.

OBJECTIVES: To compare performance of the Hajibandeh Index (HI) and National Emergency Laparotomy Audit (NELA) score in predicting postoperative mortality in patients undergoing emergency laparotomy. METHODS: In compliance with STROCSS guidelines for observational studies a cohort study was conducted. All patients aged over 18 who underwent emergency laparotomy between January 2014 and January 2021 in our centre were considered eligible for inclusion. The HI and NELA indices in predicting 30-day and 90-day postoperative mortality were compared. The discrimination of each test was evaluated using Receiver Operating Characteristic (ROC) curve analysis, classification using the classification table and calibration using a plotted diagram of the expected versus observed mortality rates. RESULTS: Analysis of 700 patients showed that the predictive performance of the HI and NELA models were comparable (30-day mortality: AUC: 0.86 vs 0.87, P = 0.557; 90-day mortality: AUC: 0.81 vs 0.84, P = 0.0607). In terms of 30-day mortality, HI was significantly better than the NELA model in predicting postoperative mortality in patients aged over 80 (AUC: 0.85 vs 0.72, P = 0.0174); however, the performances of both tools were comparable in patients with ASA status above 3 (AUC: 0.82 vs 0.82, P = 0.9775), patients with intraperitoneal contamination (AUC: 0.77 vs 0.85, P = 0.0728) and patients who needed a bowel resection (AUC: 0.85 vs 0.88, P = 0.2749). In terms of 90-day mortality, HI was significantly better than the NELA model in predicting mortality in patients aged over 80 (AUC: 0.82 vs 0.71, P = 0.0214); however, NELA had better predictive value in patients with intraperitoneal contamination (AUC: 0.76 vs 0.85, P = 0.0268); the performances of both tools were comparable in patients with ASA status above 3 (AUC: 0.77 vs 0.80, P = 0.2582), and patients who needed a bowel resection (AUC: 0.81 vs 0.86, P = 0.05). Both tools were comparable in terms of classification and calibration. CONCLUSIONS: Hajibandeh index was better than the NELA score in predicting postoperative 30-day and 90-day mortality in patients aged over 80 undergoing emergency laparotomy. Its performance in predicting 30-day and 90-day mortality was comparable with NELA score in other subgroups except 90-day mortality in patients with intraperitoneal contamination where the performance of NELA was better. We encourage other researchers to validate HI in predicting mortality following emergency laparotomy.

Selective Hepatic Vascular Exclusion versus Pringle Maneuver in Major Hepatectomy: A Systematic Review and Meta-Analysis.

Objectives: Mortality and morbidity following hepatic resection is significantly affected by major intra-operative blood loss. This systematic review and meta-analysis evaluates whether selective hepatic vascular exclusion (SHVE) compared to a Pringle maneuver in hepatic resection reduces rates of morbidity and mortality. Methods: A systematic review and meta-analysis were conducted according to the PRISMA guidelines by screening EMBASE, MEDLINE/PubMed, CENTRAL and SCOPUS for comparative studies meeting the inclusion criteria. Pooled odds ratios or mean differences were calculated for outcomes using either fixed- or random-effects models. Results: Six studies were identified: three randomised controlled trials and three observational studies reporting a total of 2,238 patients. Data synthesis showed significantly decreased rates of mortality, overall complications, blood loss, transfusion requirements, air embolism, liver failure and multi-organ failure in the SHVE group. Rates of hepatic vein rupture, post-operative hemorrhage, operative and warm ischemia time, length of stay in hospital and intensive care unit were not statistically significant between the two groups. Conclusion: Performing SHVE in major hepatectomy may result in reduced rates of morbidity and mortality when compared to a Pringle maneuver. The results of this meta-analysis are based on studies where tumors were adjacent to major vessels. Further RCTs are required to validate these results. Clinical Trial Registration: PROSPERO (CRD42020212372) https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=212372.

Work-Up and Outcome of Hepatic Resection for Peri-Hilar Cholangiocarcinoma (PH-CCA) without Staging Laparoscopy.

Background: This study reports the outcome of a work-up programme for resection of peri-hilar cholangiocarcinoma (PH-CCA) without the use of staging laparoscopy. Methods: This is a clinical case cohort series of patients undergoing surgical resection of PH-CCA without the use of staging laparoscopy in the work-up algorithm. During the 13 years from 1 January 2009 to 1 January 2022, 32 patients underwent laparotomy for planned surgical resection of PH-CCA. Data were collected on demographic profile, admission biochemistry, radiology, pre-operative intervention, operation and outcome, together with post-operative complications and disease-free and overall survival. Results: All patients underwent pre-operative contrast-enhanced CT. Twenty-four (75%) underwent pre-operative MR. Twenty-three (72%) underwent pre-operative biliary drainage. Twenty-nine patients (91%) had either type III or IV peri-hilar cholangiocarcinoma. One patient (3%) in this series underwent a non-resectional laparotomy. Twenty-nine (91%) had a final histopathological diagnosis of PH-CCA. One further patient had a final diagnosis of an intraductal papillary neoplasm of the biliary tree (IPNB) with high-grade dysplasia but no invasive cancer. Eleven patients (36%) received chemotherapy after surgery. The median (95% CI) time to recurrence was 14 (7-31) months. The median survival was 25 (18-upper limit not reached) months. Conclusion: This cohort of 32 patients undergoing attempted resection for PH-CCA without the use of staging laparoscopy in the work-up algorithm indicates that with careful attention to patient fitness and cross-sectional and interventional radiologic/endoscopic imaging, a very low non-therapeutic laparotomy rate of 3% can be achieved and sustained.

Level 2a evidence comparing robotic versus laparoscopic left lateral hepatic sectionectomy: a meta-analysis.

OBJECTIVES: To evaluate comparative outcomes of robotic and laparoscopic left lateral hepatic sectionectomy (LLS). METHODS: A systematic search of PubMed, Web of Science, EMBASE and bibliographic reference lists with application of a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators and limits was conducted. Overall, minor (Clavien-Dindo grade < III) and major (Clavien-Dindo grade > III) postoperative complications, mortality, volume of blood loss, conversion to an open procedure, procedure time, length of hospital stay, cost-effectiveness and R1 resection were the evaluated outcome measures. RESULTS: Seven comparative observational studies reporting a total of 319 patients of whom 150 underwent robotic LLS and the remaining 169 patients underwent laparoscopic LLS were included. The robotic approach was associated with significantly longer procedure time (MD: 29.40 min, p = 0.01) and higher cost (MD: $4170, p < 0.00001) compared to the laparoscopic approach. There was no significant difference in overall postoperative morbidity (OR: 1.29, p = 0.62), Clavien-Dindo grade < III (OR: 1.65, p = 0.49), Clavien-Dindo grade > III (OR: 1.18, p = 0.85), perioperative mortality (RD: 0.00, p = 1.00), volume of blood loss (MD: 1.96 mls, p = 0.91), conversion to an open procedure (RD: - 0.02, p = 0.46), length of hospital stay (MD: 0.22 day, p = 0.52) or R1 resection (RD:0.00, p = 1.00) between two groups. CONCLUSIONS: Meta-analysis of the best available evidence (level 2) demonstrated that robotic LLS is associated with significantly longer procedure time and higher cost and similar perioperative outcomes compared to the laparoscopic approach. Future randomised studies are required to evaluate short-term perioperative, long-term oncological and surgeon-centred outcomes.

A fast-track surgery programme leads to timelier treatment and higher resection rates in pancreatic cancer.

BACKGROUND: The aim was to perform a propensity-matched comparison of patients with pancreatic cancer undergoing surgery, with and without biliary stenting and an intention to treat analysis of long-term survival between the two groups. METHODS: This was an observational study of a cohort of consecutive patients presenting with obstructive jaundice and undergoing pancreatoduodenectomy for pancreatic and periampullary malignancies between November 2015 and May 2019. RESULTS: In this study of 216 consecutive operable patients, 70 followed the fast-track pathway and 146 had pre-operative biliary drainage. All 70 patients in the FT group and 122 out of 146 in the PBD group proceeded to surgery (100% and 83.6% respectively, p = 0.001). Interval time from diagnostic CT scan to surgery and from MDT decision to treat to surgery was shorter in the FT group, (median 8 vs 43 days p < 0.001 and 3 vs 36 days p < 0.001 respectively) as was the overall time from diagnostic CT to adjuvant treatment (88 vs 121 days p < 0.001). Postoperative outcomes including complications, readmission and mortality rates were comparable in the two groups. There was no difference in survival. CONCLUSION: For a person with pancreatic cancer who is proceeding to surgery, the best approach is to avoid pre-operative biliary drainage.

Pancreatic Enzyme Replacement Therapy for Patients Diagnosed With Pancreaticobiliary Cancer: Validation of an Algorithm for Dose Escalation and Management.

OBJECTIVE: An algorithm was designed aiming to provide consistency of pancreatic enzyme replacement therapy (PERT) dosing/titration across healthcare professionals in pancreaticobiliary cancers (PBCs). This prospective observational study aimed to validate this algorithm. METHODS: Consecutive patients with inoperable or postoperative PBC with pancreatic exocrine insufficiency (PEI) symptoms, not taking PERT, or taking below the algorithm "starting dose," were eligible. A dietitian or clinical nurse specialist reviewed patients for up to 3 weeks, titrating PERT as per the algorithm. Feasibility of algorithm deliverability was assessed by the percentage of patients with successful completion (primary objective). RESULTS: Twenty-five patients were eligible (N = 25): at baseline, 22 took PERT (100% on suboptimal doses, 54.5% taking incorrectly) and 3 initiated PERT because of PEI symptoms. Algorithm completion (20 of 25, 80%) confirming deliverability by dietitians (11 of 12, 92%) and clinical nurse specialists (9 of 13, 69%). Symptom resolution occurred in 8 of 19 (42%), 3 of 7 (43%), and 1 of 3 (33%) patients at first, second, and third reviews, respectively; advice compliance was between 63% and 86%. CONCLUSIONS: This algorithm provides a structured method to titrate PERT. At diagnosis, all patients with PBC should be assessed for PEI and adequate PERT initiated. Regular reviews are required for timely symptom resolution and adequate escalation, facilitating differential diagnosis if refractory symptoms exist.

Liver Transplantation for Non-Resectable Liver Metastases from Colorectal Cancer: A Systematic Review and Meta-Analysis.

BACKGROUNDS: Colorectal liver metastases were historically considered a contraindication to liver transplantation, but dismal outcomes for those with metastatic colorectal cancer and advancements in liver transplantation (LT) have led to a renewed interest in the topic. We aim to compare the current evidence for liver transplantation for non-resectable colorectal liver metastases (NRCLM) with the current standard treatment of palliative chemotherapy. METHODS: A systematic review and meta-analysis of proportions was conducted following screening of MEDLINE, EMBASE, SCOPUS and CENTRAL for studies reporting liver transplantation for colorectal liver metastases. Post-operative outcomes measured included one-, three- and five-year survival, overall survival, disease-free survival and complication rate. RESULTS: Three non-randomised studies met the inclusion criteria, reporting a total of 48 patients receiving LT for NRCLM. Survival at one-, three- and five-years was 83.3-100%, 58.3-80% and 50-80%, respectively, with no significant difference detected (p = 0.22, p = 0.48, p = 0.26). Disease-free survival was 35-56% with the most common site of recurrence being lung. Thirteen out of fourteen deaths were due to disease recurrence. CONCLUSION: Although current evidence suggests a survival benefit conferred by LT in NRCLM compared to palliative chemotherapy, the ethical implications of organ availability and allocation demand rigorous justification. Concomitant improvements in the management of patients following liver resection and of palliative chemotherapy regimens is paramount.