COVID-19 and liver cancer: lost patients and larger tumours.

BACKGROUND: Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region. OBJECTIVE: To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region. DESIGN: We prospectively audited our service for the first year of the pandemic (March 2020-February 2021), comparing mode of presentation, disease stage, treatments and outcomes to a retrospective observational consecutive cohort immediately prepandemic (March 2019-February 2020). RESULTS: We observed a marked decrease in HCC referrals compared with previous years, falling from 190 confirmed new cases to 120 (37%). Symptomatic became the the most common mode of presentation, with fewer tumours detected by surveillance or incidentally (% surveillance/incidental/symptomatic; 34/42/24 prepandemic vs 27/33/40 in the pandemic, p=0.013). HCC tumour size was larger in the pandemic year (60±4.6 mm vs 48±2.6 mm, p=0.017), with a higher incidence of spontaneous tumour haemorrhage. The number of new cases of intrahepatic cholangiocarcinoma (ICC) fell only slightly, with symptomatic presentation typical. Patients received treatment appropriate for their cancer stage, with waiting times shorter for patients with HCC and unchanged for patients with ICC. Survival was associated with stage both before and during the pandemic. 9% acquired COVID-19 infection. CONCLUSION: The pandemic-associated reduction in referred patients in our region was attributed to the disruption of routine healthcare. For those referred, treatments and survival were appropriate for their stage at presentation. Non-referred or missing patients are expected to present with more advanced disease, with poorer outcomes. While protective measures are necessary during the pandemic, we recommend routine healthcare services continue, with patients encouraged to engage.

Impact of prior biliary stenting on diagnostic performance of endoscopic ultrasound for mesenteric vascular staging in patients with head of pancreas and periampullary malignancy.

OBJECTIVE: The diagnostic performance of endoscopic ultrasound (EUS) for stratification of head of pancreas and periampullary tumours into resectable, borderline resectable and locally advanced tumours is unclear as is the effect of endobiliary stents. The primary aim of the study was to assess the diagnostic performance of EUS for resectability according to stent status. DESIGN: A retrospective study was performed. All patients presenting with a solid head of pancreas mass who underwent EUS and surgery with curative intent during an 8-year period were included. Factors with possible impact on diagnostic performance of EUS were analysed using logistic regression. RESULTS: Ninety patients met inclusion criteria and formed the study group. A total of 49 (54%) patients had an indwelling biliary stent at the time of EUS, of which 36 were plastic and 13 were self-expanding metal stents (SEMS). Twenty patients underwent venous resection and reconstruction (VRR). Staging was successfully performed in 100% unstented cases, 97% plastic stent and 54% SEMS, p<0.0001. In successfully staged patients, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for classification of resectability were 70%, 70%, 70%, 42% and 88%. For vascular involvement (VI), sensitivity, specificity, accuracy, PPV and NPV were 80%, 68%, 69%, 26% and 96%. Increasing tumour size OR 0.53 (95% CI, 0.30 to 0.95) was associated with a decrease in accuracy of VI classification. CONCLUSIONS: EUS has modest diagnostic performance for stratification of staging. Staging was less likely to be completed when a SEMS was in situ. Staging EUS should ideally be performed before endoscopic retrograde cholangiopancreatography and biliary drainage.

Comparative analysis of open, laparoscopic and robotic distal pancreatic resection: The United Kingdom's first single-centre experience.

INTRODUCTION: Laparoscopic distal pancreatectomy (LDP) has potential advantages over its open equivalent open distal pancreatectomy (ODP) for pancreatic disease in the neck, body and tail. Within the United Kingdom (UK), there has been no previous experience describing the role of robotic distal pancreatectomy (RDP). This study evaluated differences between ODP, LDP and RDP. METHODS: Patients undergoing distal pancreatectomy performed in the Department of Hepatobiliary and Pancreatic Surgery at the Freeman Hospital between September 2007 and December 2018 were included from a prospectively maintained database. The primary outcome measure was length of hospital stay, and the secondary outcome measures were complication rates graded according to the Clavien-Dindo classification. RESULTS: Of the 125 patients, the median age was 61 years and 46% were male. Patients undergoing RDP (n = 40) had higher American Society of Anesthesiologists grading III compared to ODP (n = 38) and LDP (n = 47) (57% vs. 37% vs. 38%, P = 0.02). RDP had a slightly lower but not significant conversion rate (10% vs. 13%, P = 0.084), less blood loss (median: 0 vs. 250 ml, P < 0.001) and a higher rate of splenic preservation (30% vs. 2%, P < 0.001) and shorter operative time, once docking time excluded (284 vs. 300 min, P < 0.001) compared to LDP. RDP had a higher R0 resection rate than ODP and LDP (79% vs. 47% vs. 71%, P = 0.078) for neoplasms. RDP was associated with significantly shorter hospital stay than LDP and ODP (8 vs. 9 vs. 10 days, P = 0.001). While there was no significant different in overall complications across the groups, RDP was associated with lower rates of Grade C pancreatic fistula than ODP and LDP (2% vs. 5% vs. 6%, P = 0.194). CONCLUSION: Minimally invasive pancreatic resection offers potential advantages over ODP, with a trend showing RDP to be marginally superior when compared to conventional LDP, but it is accepted that that this is likely to be at greater expense compared to the other current techniques.

A retrospective cohort study of nutritional status, nutritional interventions and hospital admissions in patients with chronic pancreatitis managed at a tertiary referral centre.

PURPOSE: Chronic pancreatitis (CP) is a complex disease process causing abdominal pain, diarrhoea and weight loss. The long-term nutritional implications however are not well documented. The aim of this study was to evaluate nutritional status in patients with CP over an extended time period and assess frequency and duration of CP related hospitalisation. METHODS: Retrospective analysis of patients with known CP for nutritional status (weight, BMI, and weight changes), nutritional interventions and hospital admissions were recorded. Weight was recorded at 3 points; baseline consultation, first review and most recent consultations. Number of dietitian contacts and documented evidence of nutritional advice/interventions were recorded and grouped. Nutritional status was compared in those who had dietetic input with those who did not. RESULTS: 46 consecutive subjects (34/46 male, mean age 56.15 years, 26/46 alcohol aetiology) were followed up for a mean of 5.24 years. 38/46 lost weight from baseline to review with mean percentage weight change: baseline to review = -7.36, p < 0.0001, baseline to recent = -6.70, p = 0.003, review to recent = 1.47, p = 0.581. 23/46 were reviewed by dietitian (mean 4.65 reviews). The number of dietitian reviews were positively associated with weight gain; baseline to recent (p = 0.010) and review to recent (p = 0.011). 23/46 received nutritional advice/interventions with 11 requiring enteral feeding. 29/46 experienced unplanned CP related hospital admissions (median 3) comprising 30 median total admission days. CONCLUSION: Patients with CP lose a significant amount of weight in a short time period which plateaus. Dietitian review is associated with improved nutritional status in CP.

Novel multidisciplinary hub-and-spoke tertiary service for the management of severe acute pancreatitis.

OBJECTIVE: Severe acute pancreatitis (SAP) is associated with high mortality (15%-30%). Current guidelines recommend these patients are best managed in a multidisciplinary team setting. This study reports experience in the management of SAP within the UK's first reported hub-and-spoke pancreatitis network. DESIGN: All patients with SAP referred to the remote care pancreatitis network between 2015 and 2017 were prospectively entered onto a database by a dedicated pancreatitis specialist nurse. Baseline characteristics, aetiology, intensive care unit (ICU) stay, interventions, complications, mortality and follow-up were analysed. RESULTS: 285 patients admitted with SAP to secondary care hospitals during the study period were discussed with the dedicated pancreatitis specialist nurse and referred to the regional service. 83/285 patients (29%; 37 male) were transferred to the specialist centre mainly for drainage of infected pancreatic fluid collections (PFC) in 95% (n=79) of patients. Among the patients transferred; 29 (35%) patients developed multiorgan failure with an inpatient mortality of 14% (n=12/83). The median follow-up was 18.2 months (IQR=11.25-35.51). Multivariate analysis showed that transferred patients had statistically significant longer overall hospital stay (p<0.001) but less ICU stay (p<0.012). CONCLUSION: This hub-and-spoke model facilitates the management of the majority of patients with SAP in secondary care setting. 29% warranted transfer to our tertiary centre, predominantly for endoscopic drainage of PFCs. An evidence-based approach with a low threshold for transfer to tertiary care centre can result in lower mortality for SAP and fewer days in ICU.

Systematic review and meta-analysis of risk factors of postoperative pancreatic fistula after distal pancreatectomy in the era of 2016 International Study Group pancreatic fistula definition.

BACKGROUND: Risk factors for the development of clinically relevant POPF (CR-POPF) following distal pancreatectomy (DP) need clarification particularly following the 2016 International Study Group of Pancreatic Fistula (ISGPF) definition. METHODS: A systemic search of MEDLINE, Pubmed, Scopus, and EMBASE were conducted using the PRISMA framework. Studies were evaluated for risk factors for the development CR-POPF after DP using the 2016 ISGPF definition. Further subgroup analysis was undertaken on studies ≥10 patients in exposed and non-exposed subgroups. RESULTS: Forty-three studies with 8864 patients were included in the meta-analysis. The weighted rate of CR-POPF was 20.4% (95%-CI: 17.7-23.4%). Smoking (OR 1.29, 95%-CI: 1.08-1.53, p = 0.02) and open DP (OR 1.43, 95%-CI: 1.02-2.01, p = 0.04) were found to be significant risk factors of CR-POPF. Diabetes (OR 0.81, 95%-CI: 0.68-0.95, p = 0.02) was a significant protective factor against CR-POPF. Substantial heterogeneity was observed in the comparisons of pancreatic texture and body mass index. Seventeen risk factors achieved significance in a univariate or multivariate comparison as reported by individual studies in the narrative synthesis, however, they remain difficult to interpret as statistically significant comparisons were not uniform. CONCLUSION: This meta-analysis found smoking and open DP to be risk factors and diabetes to be protective factor of CR-POPF in the era of 2016 ISGPF definition.

Impact of pancreatic enzyme replacement therapy on short- and long-term outcomes in advanced pancreatic cancer: meta-analysis of randomized controlled trials.

Objectives: We analyzed randomized controlled trials (RCTs) to assess the impact of PERT on weight change, quality of life, and overall survival (OS) in patients with advanced pancreatic cancer (APC).Methods: All RCTs indexed in PubMed, Medline and Scopus, databases reporting PEI in APC and the effect of PERT were included up to August 2020. The primary outcome measure was OS and the secondary outcome measures were weight change and quality of life.Results: Four RCTs including 194 patients (107 males) were analyzed. Ninety-eight (50.5%) patients received PERT treatment. Treatment with PERT did not show a significant effect on OS (SMD 0.12, 95% confidence interval -0.46-0.70, p = 0.46). There was no difference in change in body weight (SMD 0.53, 95% confidence interval -0.72-1.77, p = 0.21). Quality of life was not significantly different in those taking PERT compared to controls.Conclusions: This meta-analysis found no significant difference in OS, change in weight or quality of life with use of PERT in APC. However, non-uniform designs and different end points , along with smaller number of patients, limit a more in-depth analysis of outcomes. Further, RCTs are warranted to support evidence of routine use of PERT in APC.

Endoscopic transmural drainage is associated with improved outcomes in disconnected pancreatic duct syndrome: a systematic review and meta-analysis.

BACKGROUND: Disconnected pancreatic duct syndrome (DPDS) is a complication of acute necrotizing pancreatitis in the neck and body of the pancreas often manifesting as persistent pancreatic fluid collection (PFC) or external pancreatic fistula (EPF). This systematic review and pairwise meta-analysis aimed to review the definitions, clinical presentation, intervention, and outcomes for DPDS. METHODS: The PubMed, EMBASE, MEDLINE, and SCOPUS databases were systematically searched until February 2020 using the PRISMA framework. A meta-analysis was performed to assess the success rates of endoscopic and surgical interventions for the treatment of DPDS. Success of DPDS treatment was defined as long-term resolution of symptoms without recurrence of PFC, EPF, or pancreatic ascites. RESULTS: Thirty studies were included in the quantitative analysis comprising 1355 patients. Acute pancreatitis was the most common etiology (95.3%, 936/982), followed by chronic pancreatitis (3.1%, 30/982). DPDS commonly presented with PFC (83.2%, 948/1140) and EPF (13.4%, 153/1140). There was significant heterogeneity in the definition of DPDS in the literature. Weighted success rate of endoscopic transmural drainage (90.6%, 95%-CI 81.0-95.6%) was significantly higher than transpapillary drainage (58.5%, 95%-CI 36.7-77.4). Pairwise meta-analysis showed comparable success rates between endoscopic and surgical intervention, which were 82% (weighted 95%-CI 68.6-90.5) and 87.4% (95%-CI 81.2-91.8), respectively (P = 0.389). CONCLUSIONS: Endoscopic transmural drainage was superior to transpapillary drainage for the management of DPDS. Endoscopic and surgical interventions had comparable success rates. The significant variability in the definitions and treatment strategies for DPDS warrant standardisation for further research.

Meta-analysis of survival outcomes following surgical and non surgical treatments for colorectal cancer metastasis to the lung.

BACKGROUND: Controversy exists regarding the optimal management of colorectal lung metastases (CRLM). This meta-analysis compared surgical (Surg) versus interventional (chemotherapy and/or radiotherapy) and observational non-surgical (NSurg) management of CRLM. METHODS: A systematic review of the major databases including Medline, Embase, SCOPUS and the Cochrane library was performed. RESULTS: One randomized and nine observational studies including 2232 patients: 1551 (69%) comprised the Surg cohort, 521 (23%) the interventional NSurg group and 160 (7%) the observational NSurg group. A significantly higher overall survival (OS) was observed when Surg was compared to interventional NSurg at 1 year (Surg 88%, 310/352; interventional NSurg 64%, 245/383; odds ratio (OR) 2.77 (confidence interval (CI) 1.94-3.97), P = 0.001), at 3 years (Surg 59%, 857/1444; interventional NSurg 26%, 138/521; OR 2.61 (CI 1.65-4.15), P = 0.002), at 5 years (Surg 47%, 533/1144; interventional NSurg 23%, 45/196; OR 3.24 (CI 1.42-7.39), P = 0.009) and at 10 years (Surg 27%, 306/1122; interventional NSurg 1%, 2/168; OR 15.64 (CI 1.87-130.76), P = 0.031). Surg was associated with a greater OS than observational NSurg at only 1 year (Surg 92%, 98/107; observational NSurg 83%, 133/160; OR 6.69 (CI 1.33-33.58), P = 0.037) and was similar to observational NSurg at all other OS time points. Comparable survival was observed among Surg and overall NSurg cohorts at 3- and 5-year survival in articles published within the last 3 years. CONCLUSIONS: Recent evidence suggests comparable survival with Surg and NSurg modalities for CRLM, contrasting to early evidence where Surg had an improved survival. Significant selection bias contributes to this finding, prompting the need for high powered randomized controlled trials and registry data.

Therapeutic Strategies Toward Lactate Dehydrogenase Within the Tumor Microenvironment of Pancreatic Cancer.

OBJECTIVES: Pancreatic stellate cells (PSCs) play a key metabolic role within the tumor microenvironment (stroma) of pancreatic ductal adenocarcinoma (PDAC), being glycolytic and associated with protumorigenic acidification from excess lactate. This study investigates the clinical significance of glycolytic enzyme lactate dehydrogenase (LDH) and determines efficacy of the novel pan-LDH inhibitor Galloflavin. METHODS: An in vitro Transwell system was adopted for coculture of PSCs and 3 PDAC cell lines (MIA PaCa-2, PANC-1, and BxPC-3). Cells were treated with Galloflavin, and outcomes were analyzed regarding proliferation, apoptosis, lactate production, and glycolytic enzyme protein expression. Immunohistochemical staining for lactate dehydrogenase B (LDHB) was performed on 59 resected PDAC tumors annotated for clinical outcome. RESULTS: Galloflavin reduced PDAC proliferation in monoculture (P < 0.01); however, in co-culture with PSCs, an antiproliferative effect was only evident in PANC-1 (P = 0.001). An apoptotic effect was observed in MIA PaCa-2 and BxPC-3 in coculture (P < 0.05). A reduction in media lactate was observed in coculture (P < 0.01) with PSCs. Immunohistochemistry revealed stromal and tumoral LDHB expression had no impact on survival. CONCLUSIONS: Galloflavin has the potential to neutralize the acidic PDAC microenvironment and thereby reduce tumor invasiveness and metastasis. Patients with lower LDHB expression are more likely to be beneficial responders.

Meta-Analysis and Meta-Regression of Risk Factors for Surgical Site Infections in Hepatic and Pancreatic Resection.

BACKGROUND: The risk factors for surgical site infection (SSI) after HPB surgery are poorly defined. This meta-analysis aimed to quantify the SSI rates and risk factors for SSI after pancreas and liver resection. METHODS: The PUBMED, MEDLINE and EMBASE databases were systematically searched using the PRISMA framework. The primary outcome measure was pooled SSI rates. The secondary outcome measure was risk factor profile determination for SSI. RESULTS: The overall rate of SSI after pancreatic and liver resection was 25.1 and 10.4%, respectively (p < 0.001). 32% of pancreaticoduodenectomies developed SSI vs 23% after distal pancreatectomy (p < 0.001). The rate of incisional SSI in the pancreatic group was 9% and organ/space SSI 16.5%. Biliary resection during liver surgery was a risk factor for SSI (25.0 vs 15.7%, p = 0.002). After liver resection, the incisional SSI rate was 7.6% and the organ space SSI rate was 10.2%. Pancreas-specific SSI risk factors were pre-operative biliary drainage (p < 0.001), chemotherapy (p < 0.001) and radiotherapy (p = 0.007). Liver-specific SSI risk factors were smoking (p = 0.046), low albumin (p < 0.001) and significant blood loss (p < 0.001). The rate of organ/space SSI in patients with POPF was 47.7% and in patients without POPF 7.3% (p < 0.001). Organ/space SSI rate was 43% in patients with bile leak and 10% in those without (p < 0.001). CONCLUSIONS: The risk factors for SSI following pancreatic and liver resections are distinct from each other, with higher SSI rates after pancreatic resection. Pancreaticoduodenectomy has increased risk of SSI compared to distal pancreatectomy. Similarly, biliary resections during liver surgery increase the rates of SSI.

A Network Meta-analysis of Surgery for Chronic Pancreatitis: Impact on Pain and Quality of Life.

BACKGROUND: The surgical operation associated with improved pain and quality of life (QoL) in patients with chronic pancreatitis (CP) is unknown. METHOD: The Scopus, EMBASE, Medline and Cochrane databases were systematically searched until May 2019, and all randomised trials (RCTs) comparing surgical operations for CP pain were included in a network meta-analysis (NMA). RESULTS: Four surgical operations for treating CP were directly compared in eight RCTs including 597 patients. Patients were mainly male (79%, 474/597) with alcoholic CP (85%, 382/452). Surgical operations included were pancreatoduodenectomy (224, 38%), Berne procedure (168, 28%), Beger procedure (133, 22%) and Frey procedure (72, 12%). The NMA revealed that the Beger procedure ranked best for pain relief, whilst the Frey procedure ranked best for postoperative QoL, postoperative pancreatic fistula rate and postoperative exocrine insufficiency rate during a median follow-up of 26 months (reported range 6-58 months). Overall the Frey procedure ranked best for the combination of primary outcome measures based on surface under cumulative ranking curve scores. CONCLUSIONS: Overall the Frey procedure may perform the best for both pain relief and postoperative QoL in patients with CP. Further trials are warranted in defining the role of surgery in relation to endotherapy.

Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis.

BACKGROUND: Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT. METHODS: The EMBASE, SCOPUS, PubMed, and Cochrane library databases were systematically searched to identify eligible studies that compare recurrence patterns between patients who had NAT (followed by resection) with those that had US. The primary outcome included site-specific recurrence. RESULTS: 26 articles were identified including 4986 patients who underwent resection. Borderline resectable pancreatic cancer (BRPC, 47% 1074/2264) was the most common, followed by resectable pancreatic cancer (RPC 42%, 949/2264). The weighted overall recurrence rates were lower among the NAT group, 63.4% vs. 74% (US) (OR 0.67 (CI 0.52-0.87), p = 0.006). The overall weighted locoregional recurrence rate was lower amongst patients who received NAT when compared to US (12% vs 27% OR 0.39 (CI 0.22-0.70), p = 0.004). In BRPC, locoregional recurrence rates improved with NAT (NAT 25.8% US 37.7% OR 0.62 (CI 0.44-0.87), p = 0.007). NAT was associated with a lower weighted liver recurrence rate (NAT 19.4% US 30.1% OR 0.55 (CI 0.34-0.89), p = 0.023). Lung and peritoneal recurrence rates did not differ between NAT and US cohorts (p = 0.705 and p = 0.549 respectively). NAT was associated with a significantly longer weighted mean time to first recurrence 18.8 months compared to US (15.7 months) (OR 0.18 (CI 0.05-0.32), p = 0.015). CONCLUSION: NAT was associated with lower overall recurrence rate and improved locoregional disease control particularly for those with BRPC. Although the burden of liver metastases was less, there was no overall effect upon distant metastatic disease.

Haemostatic Efficacy of Topical Agents During Liver Resection: A Network Meta-Analysis of Randomised Trials.

BACKGROUND: Hepatic resection carries a high risk of parenchymal bleeding both intra- and post-operatively. Topical haemostatic agents are frequently used to control bleeding during hepatectomy, with multiple products currently available. However, it remains unknown which of these is most effective for achieving haemostasis and improving peri-operative outcomes. METHODS: A systematic review and random-effects Bayesian network meta-analysis of randomised trials investigating topical haemostatic agents in hepatic resection was performed. Interventions were analysed by grouping into similar products; fibrin patch, fibrin glue, collagen products, and control. Primary outcomes were the rate of haemostasis at 4 and 10 min. RESULTS: Twenty randomized controlled trials were included in the network meta-analysis, including a total of 3267 patients and 7 different interventions. Fibrin glue and fibrin patch were the most effective interventions for achieving haemostasis at both 4 and 10 min. There were no significant differences between haemostatic agents with respect to blood loss, transfusion requirements, bile leak, post-operative complications, reoperation, or mortality. CONCLUSIONS: Amongst the haemostatic agents currently available, fibrin patch and fibrin glue are the most effective methods for reducing time to haemostasis during liver resection, but have no effect on other peri-operative outcomes. Topical haemostatic agents should not be used routinely, but may be a useful adjunct to achieve haemostasis when needed.

A Systematic Review and Network-Meta-Analysis of Gastro-Enteric Reconstruction Techniques Following Pancreatoduodenectomy to Reduce Delayed Gastric Emptying.

INTRODUCTION: This network meta-analysis aimed to identify the reconstruction technique associated with lowest rates of DGE following pancreatoduodenectomy (PD) from randomised controlled trials (RCTs). METHODS: A systematic literature search of PubMed, Embase and MEDLINE databases was carried out using the PRISMA framework to identify all RCTs comparing reconstruction techniques of gastrojejunostomy after PD, with overall DGE as the primary endpoint. The primary outcome measure was overall DGE. Secondary outcomes were grade B/C DGE, duration of nasogastric tube, time to solid food intake, overall and grade B/C pancreatic fistula, bile leaks, reoperation, length of hospital stay and in-hospital mortality. RESULTS: The search strategy identified eight RCTs including 761 patients. Six RCTs compared antecolic (n = 291 patients) and retrocolic Billroth II (n = 289 patients) reconstruction (n = 6 studies), and two RCTs compared antecolic Billroth II (n = 92 patients) and Roux-en-Y (n = 89 patients) reconstruction. Overall, antecolic Billroth II ranked best for overall and grade B/C DGE, bile leak, surgical site infection, length of stay and in-hospital mortality. Roux-en-Y was best for overall and grade B/C pancreatic fistula. CONCLUSION: Antecolic Billroth II gastroenteric reconstruction is associated with the lowest rates of delayed gastric emptying after PD amongst the currently available techniques of gastrojejunostomy reconstructions.

A systematic review and network meta-analysis of parenchymal transection techniques during hepatectomy: an appraisal of current randomised controlled trials.

BACKGROUND: Major liver resection can lead to significant morbidity and mortality. Blood loss is one of the most important factors predicting a good outcome. Although various transection methods have been reported, there is no consensus on the best technique. This systematic review and network meta-analysis aims to characterise and identify the best reported technique for elective parenchymal liver transection based on published randomised controlled trials (RCT's). METHODS: A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Central to identify RCT's up to 5th June 2019 that examined parenchymal transection for liver resection. Data including study characteristics and outcomes including intraoperative (blood loss, operating time) and postoperative measures (overall and major complications, bile leaks) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) which maintains randomisation within trials. RESULTS: This study identified 22 RCT's involving 2360 patients reporting ten parenchymal transection techniques. Bipolar cautery has lower blood loss and shorter operating time than stapler (mean difference: 85 mL; 22min) and Tissue Link (mean difference: 66 mL; 29min). Bipolar cautery was ranked first for blood loss and operating time followed by stapler and TissueLink. Harmonic scalpel is associated with lower overall complications than Hydrojet (Odds ratio (OR): 0.48), BiClamp forceps (OR: 0.46) and clamp crushing (OR: 0.41). CONCLUSION: Bipolar cautery techniques appear to best at reducing blood loss and associated with shortest operating time. In contrast, Harmonic scalpel appears best for overall and major complications. Given the paucity of data and selective outcome reporting, it is still hard to identify what is the best technique for liver resection. Therefore, further high-quality large-scale RCT's are still needed.

Critical appraisal of the techniques of pancreatic anastomosis following pancreaticoduodenectomy: A network meta-analysis.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains a major cause of morbidity following pancreaticoduodenectomy (PD). This network meta-analysis (NMA) compared techniques of pancreatic anastomosis following PD to determine the technique with the best outcome profile. METHODS: A systematic literature search was performed on the Scopus, EMBASE, Medline and Cochrane databases to identify RCTs employing the international study group of pancreatic fistula (ISGPF) definition of POPF. The primary outcome was clinically relevant POPF. RESULTS: Five techniques of pancreatic anastomosis following PD were directly compared in 15 RCTs comprising 2428 patients. Panreatojejunostomy (PJ) end-to-side invagination vs. PJ end-to-side duct-to-mucosa was the most frequent comparison (n = 7). Overall, 971 patients underwent PJ end-to-side duct-to-mucosa, 791 patients PJ end-to-side invagination, 505 patients pancreatogastrostomy (PG) end-to-side invagination, 98 patients PG end-to-side duct-to-mucosa, and 63 patients PJ end-to-side single layer. PG duct-to-mucosa was associated with the lowest rates of clinically relevant POPF, delayed gastric emptying, intra-abdominal abscess, all postoperative morbidity and postoperative mortality, the shortest operative time and postoperative hospital stay and the lowest volume of intra-operative blood loss. CONCLUSION: Duct-to-mucosa pancreaticogastrostomy was associated with the lowest rates of clinically relevant POPF and had the best outcome profile among all techniques of pancreatico-anastomosis following PD.

The association of pregnane X receptor activation with outcomes after liver transplantation-A retrospective study.

BACKGROUND: Many complications following liver transplantation are linked to ischemia-reperfusion injury. Activation of the pregnane X receptor (PXR) has been shown to alleviate this process in animal models. The aim of this retrospective study was to investigate the effect of early activation of human PXR (hPXR) on postoperative complications and survival following liver transplantation. METHODS: The study included deceased donor liver transplants at a single center over 6 years. Estimated hPXR activation value on day 7 (EPAV7 ) was calculated per patient based on potency/total dose of known hPXR-activating drugs administered in the first week post-transplantation. Patients were divided into low and high hPXR activation groups based on EPAV7 . RESULTS: Overall, 240 liver transplants were included. Average EPAV7 was significantly lower in patients who developed anastomotic biliary strictures (17.7 ± 5.5 vs 35.1 ± 5.7 in stricture-free patients; P = .03) and sepsis (16.4 ± 7.1 vs 34.9 ± 5.5; P = .04). Patient survival was significantly improved in the high hPXR group (5-year survival: 88.7% ± 3.8% versus 70.7% ± 5.8% [low hPXR]; P = .023). Regression analysis identified EPAV7 as a significant independent predictor of patient survival. CONCLUSION: hPXR activation within the first week of liver transplantation is a prognostic indicator of patient survival, possibly due to the associated lower biliary stricture and infection rates.

Robotic versus conventional laparoscopic distal pancreatic resection: a systematic review and meta-analysis.

BACKGROUND: Robotic surgery offers theoretical advantages to conventional laparoscopic surgery including improved instrument dexterity, 3D visualization and better ergonomics. This review aimed to determine if these theoretical advantages translate into improved patient outcomes in patients undergoing distal pancreatectomy through laparoscopic (LDP) or robotic (RDP) approaches. METHOD: A systematic literature search was conducted for studies reporting minimally invasive surgery for distal pancreatectomy. Meta-analysis of intraoperative (blood loss, operating times, conversion and R0 resections) and postoperative outcomes (overall complications, pancreatic fistula, length of hospital stay) was performed using random effects models. RESULT: Twenty non-randomised studies including 3112 patients (793 robotic and 2319 laparoscopic) were considered appropriate for inclusion. LDP had significantly shorter operating time than RDP (mean: 28, p < 0.001) but no significant difference in blood loss (mean: 52 mL, p = 0.07). RDP was associated with significantly lower conversion rates than LDP (OR 0.48, p < 0.001), but no difference in spleen preservation rate and R0 resection. There were no significant differences in overall and major complications, overall and high-grade pancreatic fistula. However, RDP was associated with a shorter length of hospital stay (mean: 1, p < 0.001). CONCLUSION: Robotic distal pancreatectomy appears to offer some advantages compared to conventional laparoscopic surgery, although both techniques appear equivalent. Importantly, the quality of evidence is generally limited to cohort studies and a high-quality randomised trial comparing both techniques are needed.

Minimally invasive and endoscopic versus open necrosectomy for necrotising pancreatitis: a pooled analysis of individual data for 1980 patients.

OBJECTIVE: Minimally invasive surgical necrosectomy and endoscopic necrosectomy, compared with open necrosectomy, might improve outcomes in necrotising pancreatitis, especially in critically ill patients. Evidence from large comparative studies is lacking. DESIGN: We combined original and newly collected data from 15 published and unpublished patient cohorts (51 hospitals; 8 countries) on pancreatic necrosectomy for necrotising pancreatitis. Death rates were compared in patients undergoing open necrosectomy versus minimally invasive surgical or endoscopic necrosectomy. To adjust for confounding and to study effect modification by clinical severity, we performed two types of analyses: logistic multivariable regression and propensity score matching with stratification according to predicted risk of death at baseline (low: <5%; intermediate: ≥5% to <15%; high: ≥15% to <35%; and very high: ≥35%). RESULTS: Among 1980 patients with necrotising pancreatitis, 1167 underwent open necrosectomy and 813 underwent minimally invasive surgical (n=467) or endoscopic (n=346) necrosectomy. There was a lower risk of death for minimally invasive surgical necrosectomy (OR, 0.53; 95% CI 0.34 to 0.84; p=0.006) and endoscopic necrosectomy (OR, 0.20; 95% CI 0.06 to 0.63; p=0.006). After propensity score matching with risk stratification, minimally invasive surgical necrosectomy remained associated with a lower risk of death than open necrosectomy in the very high-risk group (42/111 vs 59/111; risk ratio, 0.70; 95% CI 0.52 to 0.95; p=0.02). Endoscopic necrosectomy was associated with a lower risk of death than open necrosectomy in the high-risk group (3/40 vs 12/40; risk ratio, 0.27; 95% CI 0.08 to 0.88; p=0.03) and in the very high-risk group (12/57 vs 28/57; risk ratio, 0.43; 95% CI 0.24 to 0.77; p=0.005). CONCLUSION: In high-risk patients with necrotising pancreatitis, minimally invasive surgical and endoscopic necrosectomy are associated with reduced death rates compared with open necrosectomy.