Hepatopancreaticobiliary Resection Arginine Immunomodulation (PRIMe) trial: protocol for a randomised phase II trial of the impact of perioperative immunomodulation on immune function following resection for hepatopancreaticobiliary malignancy.

INTRODUCTION: Surgical stress results in immune dysfunction, predisposing patients to infections in the postoperative period and potentially increasing the risk of cancer recurrence. Perioperative immunonutrition with arginine-enhanced diets has been found to potentially improve short-term and cancer outcomes. This study seeks to measure the impact of perioperative immunomodulation on biomarkers of the immune response and perioperative outcomes following hepatopancreaticobiliary surgery. METHODS AND ANALYSIS: This is a 1:1:1 randomised, controlled and blinded superiority trial of 45 patients. Baseline and perioperative variables were collected to evaluate immune function, clinical outcomes and feasibility outcomes. The primary outcome is a reduction in natural killer cell killing as measured on postoperative day 1 compared with baseline between the control and experimental cohorts. ETHICS AND DISSEMINATION: This trial has been approved by the research ethics boards at participating sites and Health Canada (parent control number: 223646). Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov (identifier: NCT04549662). Any modifications to the protocol will be communicated via publications and ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04549662.

Association Between Biliary Pathogens, Surgical Site Infection, and Pancreatic Fistula: Results of a Randomized Trial of Perioperative Antibiotic Prophylaxis in Patients Undergoing Pancreatoduodenectomy.

OBJECTIVE: To establish the association between bactibilia and postoperative complications when stratified by perioperative antibiotic prophylaxis. BACKGROUND: Patients undergoing pancreatoduodenectomy experience high rates of surgical site infection (SSI) and clinically relevant postoperative pancreatic fistula (CR-POPF). Contaminated bile is known to be associated with SSI, but the role of antibiotic prophylaxis in mitigation of infectious risks is ill-defined. METHODS: Intraoperative bile cultures (IOBCs) were collected as an adjunct to a randomized phase 3 clinical trial comparing piperacillin-tazobactam with cefoxitin as perioperative prophylaxis in patients undergoing pancreatoduodenectomy. After compilation of IOBC data, associations between culture results, SSI, and CR-POPF were assessed using logistic regression stratified by the presence of a preoperative biliary stent. RESULTS: Of 778 participants in the clinical trial, IOBC were available for 247 participants. Overall, 68 (27.5%) grew no organisms, 37 (15.0%) grew 1 organism, and 142 (57.5%) were polymicrobial. Organisms resistant to cefoxitin but not piperacillin-tazobactam were present in 95 patients (45.2%). The presence of cefoxitin-resistant organisms, 92.6% of which contained either Enterobacter spp. or Enterococcus spp., was associated with the development of SSI in participants treated with cefoxitin [53.5% vs 25.0%; odds ratio (OR)=3.44, 95% CI: 1.50-7.91; P =0.004] but not those treated with piperacillin-tazobactam (13.5% vs 27.0%; OR=0.42, 95% CI: 0.14-1.29; P =0.128). Similarly, cefoxitin-resistant organisms were associated with CR-POPF in participants treated with cefoxitin (24.1% vs 5.8%; OR=3.45, 95% CI: 1.22-9.74; P =0.017) but not those treated with piperacillin-tazobactam (5.4% vs 4.8%; OR=0.92, 95% CI: 0.30-2.80; P =0.888). CONCLUSIONS: Previously observed reductions in SSI and CR-POPF in patients that received piperacillin-tazobactam antibiotic prophylaxis are potentially mediated by biliary pathogens that are cefoxitin resistant, specifically Enterobacter spp. and Enterococcus spp.

Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial.

Importance: Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood. Objective: To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics. Design, Setting, and Participants: Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment. Intervention: The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care). Main Outcomes and Measures: The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program. Results: The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32). Conclusions and Relevance: In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT03269994.

Feasibility and Safety of a "Shared Care" Model in Complex Hepatopancreatobiliary Surgery: A 5-year Observational Study of Outcomes in Pancreaticoduodenectomy.

OBJECTIVE: To determine the safety of a fully functioning shared care model (SCM) in hepatopancreatobiliary surgery through evaluating outcomes in pancreaticoduodenectomy. BACKGROUND: SCMs, where a team of surgeons share in care delivery and resource utilization, represent a surgeon-level opportunity to improve system efficiency and peer support, but concerns around clinical safety remain, especially in complex elective surgery. METHODS: Patients who underwent pancreaticoduodenectomy between 2016 and 2020 were included. Adoption of shared care was demonstrated by analyzing shared care measures, including the number of surgeons encountered by patients during their care cycle, the proportion of patients with different consenting versus primary operating surgeon (POS), and the proportion of patients who met their POS on the day of surgery. Outcomes, including 30-day mortality, readmission, unplanned reoperation, sepsis, and length of stay, were collected from the institution's National Surgical Quality Improvement Program (NSQIP) database and compared with peer hospitals contributing to the pancreatectomy-specific NSQIP collaborative. RESULTS: Of the 174 patients included, a median of 3 surgeons was involved throughout the patients' care cycle, 69.0% of patients had different consenting versus POS and 57.5% met their POS on the day of surgery. Major outcomes, including mortality (1.1%), sepsis (5.2%), and reoperation (7.5%), were comparable between the study group and NSQIP peer hospitals. Length of stay (10 day) was higher in place of lower readmission (13.2%) in the study group compared with peer hospitals. CONCLUSIONS: SCMs are feasible in complex elective surgery without compromising patient outcomes, and wider adoption may be encouraged.

Phlebotomy resulting in controlled hypovolemia to prevent blood loss in major hepatic resections (PRICE-2): study protocol for a phase 3 randomized controlled trial.

INTRODUCTION: Blood loss and red blood cell (RBC) transfusion in liver surgery are areas of concern for surgeons, anesthesiologists, and patients alike. While various methods are employed to reduce surgical blood loss, the evidence base surrounding each intervention is limited. Hypovolemic phlebotomy, the removal of whole blood from the patient without volume replacement during liver transection, has been strongly associated with decreased bleeding and RBC transfusion in observational studies. This trial aims to investigate whether hypovolemic phlebotomy is superior to usual care in reducing RBC transfusions in liver resection. METHODS: This study is a double-blind multicenter randomized controlled trial. Adult patients undergoing major hepatic resections for any indication will be randomly allocated in a 1:1 ratio to either hypovolemic phlebotomy and usual care or usual care alone. Exclusion criteria will be minor resections, preoperative hemoglobin <100g/L, renal insufficiency, and other contraindication to hypovolemic phlebotomy. The primary outcome will be the proportion of patients receiving at least one allogeneic RBC transfusion unit within 30 days of the onset of surgery. Secondary outcomes will include transfusion of other allogeneic blood products, blood loss, morbidity, mortality, and intraoperative physiologic parameters. The surgical team will be blinded to the intervention. Randomization will occur on the morning of surgery. The sample size will comprise 440 patients. Enrolment will occur at four Canadian academic liver surgery centers over a 4-year period. Ethics approval will be obtained at participating sites before enrolment. DISCUSSION: The results of this randomized control trial will provide high-quality evidence regarding the use of hypovolemic phlebotomy in major liver resection and its effects on RBC transfusion. If proven to be effective, this intervention could become standard of care in liver operations internationally and become incorporated within perioperative patient blood management programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03651154 . Registered on August 29 2018.

Should Cell Salvage Be Used in Liver Resection and Transplantation? A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effect of intraoperative blood cell salvage and autotransfusion (IBSA) use on red blood cell (RBC) transfusion and postoperative outcomes in liver surgery. BACKGROUND: Intraoperative RBC transfusions are common in liver surgery and associated with increased morbidity. IBSA can be utilized to minimize allogeneic transfusion. A theoretical risk of cancer dissemination has limited IBSA adoption in oncologic surgery. METHODS: Electronic databases were searched from inception until May 2021. All studies comparing IBSA use with control in liver surgery were included. Screening, data extraction, and risk of bias assessment were conducted independently, in duplicate. The primary outcome was intraoperative allogeneic RBC transfusion (proportion of patients and volume of blood transfused). Core secondary outcomes included: overall survival and disease-free survival, transfusion-related complications, length of hospital stay, and hospitalization costs. Data from transplant and resection studies were analyzed separately. Random effects models were used for meta-analysis. RESULTS: Twenty-one observational studies were included (16 transplant, 5 resection, n=3433 patients). Seventeen studies incorporated oncologic indications. In transplant, IBSA was associated with decreased allogeneic RBC transfusion [mean difference -1.81, 95% confidence interval (-3.22, -0.40), P =0.01, I 2 =86%, very-low certainty]. Few resection studies reported on transfusion for meta-analysis. No significant difference existed in overall survival or disease-free survival in liver transplant [hazard ratio (HR)=1.12 (0.75, 1.68), P =0.59, I 2 =0%; HR=0.93 (0.57, 1.48), P =0.75, I 2 =0%] and liver resection [HR=0.69 (0.45, 1.05), P =0.08, I 2 =0%; HR=0.93 (0.59, 1.45), P =0.74, I 2 =0%]. CONCLUSION: IBSA may reduce intraoperative allogeneic RBC transfusion without compromising oncologic outcomes. The current evidence base is limited in size and quality, and high-quality randomized controlled trials are needed.

The impact of prophylactic negative pressure wound therapy on surgical site infections in pancreatic resection: A systematic review and meta-analysis.

BACKGROUND: Surgical site infections (SSI) cause significant morbidity. Prophylactic negative pressure wound therapy (NPWT) may promote wound healing and decrease SSI. The objective is to evaluate the effect of prophylactic NPWT on SSI in patients undergoing pancreatectomy. METHODS: Electronic databases were searched from inception until April 2022. Randomized controlled trials (RCTs) comparing prophylactic NPWT to standard dressings in patients undergoing pancreatectomy were included. The primary outcome was the risk of SSI. Secondary outcomes included the risk of superficial and deep SSI and organ space infection (OSI). Random effects models were used for meta-analysis. RESULTS: Four single-centre RCTs including 309 patients were identified. Three studies were industry-sponsored, and two were at high risk of bias. There was no significant difference in the risk of SSI in patients receiving NPWT vs. control (14% vs. 21%, RR = 0.72, 95%CI = 0.32-1.60, p = 0.42, I2 = 53%). Likewise, there was no significant difference in the risk of superficial and deep SSI or OSI. No significant difference was found on subgroup analysis of patients at high risk of wound infection or on sensitivity analysis of studies at low risk of bias. CONCLUSION: Prophylactic NPWT does not significantly decrease the risk of SSI among patients undergoing pancreatectomy. Insufficient evidence exists to justify the routine use of NPWT.

Does Caudate Resection Improve Outcomes of Patients Undergoing Curative Resection for Perihilar Cholangiocarcinoma? A Systematic Review and Meta-Analysis.

BACKGROUND: Margin-negative (R0) resection is the strongest positive prognostic factor in perihilar cholangiocarcinoma (PHC). Due to its anatomic location, the caudate lobe is frequently involved in PHC. This review aimed to examine the impact of caudate lobe resection (CLR) in addition to hepatectomy and bile duct resection for patients with PHC. METHODS: The MEDLINE, EMBASE, and Cochrane databases were systematically reviewed from inception to October 2021 to identify studies comparing patients undergoing surgical resection with hepatectomy and bile duct resection with or without CLR for treatment of PHC. Outcomes included the proportion of patients achieving R0 resection, overall survival (OS), and perioperative morbidity. RESULTS: Altogether, 949 studies were screened. The review included eight observational studies reporting on 1137 patients. The patients who underwent CLR had a higher likelihood of R0 resection (odds ratio [OR], 5.85; 95% confidence interval [CI], 2.64-12.95) and a better OS (hazard ratio [HR], 0.65; 95% CI, 0.54-0.79) than those who did not. The use of CLR did not increase the risk of perioperative morbidity (OR, 1.03; 95% CI, 0.65-1.63). CONCLUSIONS: Given the higher likelihood of R0 resection, improved OS, and no apparent increase in perioperative morbidity, this review supports routine caudate lobectomy in the surgical management of PHC. These results should be interpreted with caution given the lack of high-quality prospective data and the high probability of selection bias.

Does Intraoperative Frozen Section and Revision of Margins Lead to Improved Survival in Patients Undergoing Resection of Perihilar Cholangiocarcinoma? A Systematic Review and Meta-analysis.

BACKGROUND: Perihilar cholangiocarcinoma (PHC) is a rare malignancy that arises at the biliary confluence. Achieving a margin-negative resection (R0) is challenging given the anatomic location of tumors and remains the most important prognostic indicator of long-term survival. The objective of this study is to review the impact of intraoperative revision of positive biliary margins in PHC on oncologic outcomes. PATIENTS AND METHODS: Electronic databases were searched from inception to October 2021. Studies comparing three types of patients undergoing resection of PHC with intraoperative frozen section of the proximal and/or distal bile ducts were identified: those who were margin-negative (R0), those with an initially positive margin who had revised negative margins (R1R0), and those with a persistently positive margin with or without revision of a positive margin (R1). The primary outcome was overall survival (OS). Secondary outcomes included risk of postoperative complication. RESULTS: A total of 449 studies were screened. Ten retrospective observational studies reporting on 1955 patients were included. Patients undergoing successful revision of a positive proximal and/or distal bile duct margin (R1R0) had similar OS to those with a primary margin-negative resection (R0) [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.72-1.19, p = 0.56, I2 = 84%], and significantly better OS than patients with a positive final bile duct margin (R1) (HR 0.52, 95% CI 0.34-0.79, p = 0.002, I2 = 0%). There was no increase in the risk of postoperative complications associated with additional resection, although postoperative morbidity was inconsistently reported. CONCLUSIONS: This review supports routine intraoperative biliary margin evaluation during resection of PHC with revision if technically feasible.

Prognostic factors associated with development of infected necrosis in patients with acute necrotizing or severe pancreatitis-A systematic review and meta-analysis.

PURPOSE: Acute pancreatitis is a potentially life-threatening condition with a wide spectrum of clinical presentation and illness severity. An infection of pancreatic necrosis (IPN) results in a more than twofold increase in mortality risk as compared with patients with sterile necrosis. We sought to identify prognostic factors for the development of IPN among adult patients with severe or necrotizing pancreatitis. METHODS: We conducted this prognostic review in accordance with systematic review methodology guidelines. We searched six databases from inception through March 21, 2021. We included English language studies describing prognostic factors associated with the development of IPN. We pooled unadjusted odds ratio (uOR) and adjusted odds ratios (aOR) for prognostic factors using a random-effects model. We assessed risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the GRADE approach. RESULTS: We included 31 observational studies involving 5,210 patients. Factors with moderate or higher certainty of association with increased IPN risk include older age (uOR, 2.19; 95% confidence interval [CI], 1.39-3.45, moderate certainty), gallstone etiology (aOR, 2.35; 95% CI, 1.36-4.04, high certainty), greater than 50% necrosis of the pancreas (aOR, 3.61; 95% CI, 2.15-6.04, high certainty), delayed enteral nutrition (aOR, 2.09; 95% CI, 1.26-3.47, moderate certainty), multiple or persistent organ failure (aOR, 11.71; 95% CI, 4.97-27.56, high certainty), and invasive mechanical ventilation (uOR, 12.24; 95% CI, 2.28-65.67, high certainty). CONCLUSION: This meta-analysis confirms the association between several clinical early prognostic factors and the risk of IPN development among patients with severe or necrotizing pancreatitis. These findings provide the foundation for the development of an IPN risk stratification tool to guide more targeted clinical trials for prevention or early intervention strategies. LEVEL OF EVIDENCE: Systematic review and meta-analysis, Level IV.

Passive Versus Active Intra-Abdominal Drainage Following Pancreatic Resection: Does A Superior Drainage System Exist? A Systematic Review and Meta-Analysis.

Postoperative pancreatic fistula (POPF) is a major source of morbidity following pancreatic resection. Surgically placed drains under suction or gravity are routinely used to help mitigate the complications associated with POPF. Controversy exists as to whether one of these drain management strategies is superior. The objective was to identify and compare the incidence of POPF, adverse events, and resource utilization associated with passive gravity (PG) versus active suction (AS) drainage following pancreatic resection. MEDLINE, EMBASE, CINAHL, and Cochrane Library databases were searched from inception to May 18, 2020. Outcomes of interest included POPF, post-pancreatectomy hemorrhage (PPH), surgical site infection (SSI), other major morbidity, and resource utilization. Descriptive qualitative and pooled quantitative meta-analyses were performed. One randomized control trial and five cohort studies involving 10 663 patients were included. Meta-analysis found no difference in the odds of developing POPF between AS and PG (p = 0.78). There were no differences in other endpoints including PPH (p = 0.58), SSI (wound p = 0.21, organ space p = 0.05), major morbidity (p = 0.71), or resource utilization (p = 0.72). The risk of POPF or other adverse outcomes is not impacted by drain management following pancreatic resection. Based on current evidence, a suggestion cannot be made to support the use of one drain over another at this time. There is a trend toward increased intra-abdominal wound infections with AS drains (p = 0.05) that merits further investigation.

Passive Versus Active Intra-Abdominal Drainage Following Pancreaticoduodenectomy: A Retrospective Study Using The American College of Surgeons NSQIP Database.

BACKGROUND: Prophylactic drainage following pancreaticoduodenectomy (PD) reduces morbidity and mortality. Little evidence exists to advise on whether passive gravity (PG) or active suction (AS) drainage systems result in superior outcomes. This study examines the relationship between drainage system and morbidity following PD. METHODS: All patients undergoing elective PD with an operatively placed drain in the 2016 ACS-NSQIP database were included. Pre- and intra-operative factors were examined. Multivariable logistic regression and coarsened exact matching (CEM) were used to assess for an association between drainage system (PG vs. AS) and morbidity. The primary outcome was postoperative pancreatic fistula (POPF). RESULTS: In total, 3430 patients were included: 563 (16.4%) with PG and 2867 (83.6%) with AS drainage system. On multivariable regression, 1787 patients were included. Drainage type was not associated with POPF, surgical site infection, delayed gastric emptying, or re-operation. AS drainage was protective against percutaneous drain insertion (OR 0.65, 95% CI 0.44-0.96, p = 0.033). In the CEM cohort (n = 268), superficial SSI was higher in the AS group (0.8% vs. 6.0%, p = 0.036). There was a trend toward higher rates of composite total SSI (PG 15.7%, AS 23.9%, p = 0.092) and organ space SSI (PG 14.2%, AS 20.2%, p = 0.195) in the AS group; this did not demonstrate statistical significance. CONCLUSIONS: The findings of this study suggest that AS drainage is protective against percutaneous drain insertion, but may be associated with increased risk of SSI. There was no relation between drainage type and POPF. A prospective, randomized controlled trial is warranted to further explore these findings.

Surgical Management of Genitourinary Cancer Liver Metastases.

Genitourinary cancers are common. Liver metastases from genitourinary cancers are uncommon; isolated liver metastasis is rare. Liver resection in select patients with metastatic renal cell carcinoma can lead to prolonged survival. Patients with metachronous and low-burden disease are most likely to benefit. Chemotherapy is first-line treatment of metastatic germ cell tumors. Liver resection is dependent on germ cell lineage and initial response to chemotherapy. Prognosis with liver metastases from prostate cancer is poor; liver-only lesions are rare. Liver resection generally is not indicated. Cumulative experience with liver resection for metastatic bladder cancer is limited. Liver metastases are poor prognostic indicators for metastasectomy.

Improving the treatment of pre-operative anemia in hepato-pancreato-biliary patients: a quality improvement initiative.

BACKGROUND: Pre-operative anemia is a common, but treatable, condition encountered by surgical patients. It has been associated with increased perioperative complications, length of stay, and blood transfusions. The aim of this project was to increase the treatment rate of pre-operative anemia to 75% of patients consented for major hepato-pancreato-biliary (HPB) surgery. METHODS: This was an interrupted time series study and a spread initiative from a similar project in a colorectal surgery population. Interventions included an anemia screening and treatment algorithm, standardized blood work, referral to a patient blood management program, and standardized oral iron prescriptions. The primary outcome measure was the change in pre-operative anemia treatment rate and the secondary outcome measure was the post treatment increase in hemoglobin. RESULTS: A total of 208 patients were included (n = 124 pre-intervention and n = 84 post-intervention). Anemia was present in 39.9% of patients. The treatment rate of pre-operative anemia increased to 44.1% from 28.6%. The mean hemoglobin increased from 110 g/L to 119 g/L in patients who were treated (p = 0.03). There was no significant increase or decrease in blood transfusions or mean number of red cell units transfused per patient. Screening rates for pre-operative anemia increased from 41.1 to 64.3% and appropriate referrals to the patient blood management program increased from 14.3 to 67.6%. CONCLUSIONS: This study demonstrates a small scale spread initiative focused on the treatment of pre-operative anemia. Although the goal to treat 75% of anemic patients was not reached, an effective referral pathway to an existing patient blood management program was developed, and a significant increase in the mean hemoglobin in anemic patients who have been treated pre-operatively was demonstrated.

Standardization of early drain removal following pancreatic resection: proposal of the "Ottawa pancreatic drain algorithm".

BACKGROUND: Early drain removal after pancreatic resection is encouraged for individuals with low postoperative day 1 drain amylase levels (POD1 DA) to mitigate associated morbidity. Although various protocols for drain management have been published, there is a need to assess the implementation of a standardized protocol. METHODS: The Ottawa pancreatic drain algorithm (OPDA), based on POD1 DA and effluent volume, was developed and implemented at our institution. A retrospective cohort analysis was conducted of all patients undergoing pancreatic resection January 1, 2016-October 30, 2017, excluding November and December 2016 (one month before and after OPDA implementation). RESULTS: 42 patients pre-implementation and 53 patients post-implementation were included in the analysis. The median day of drain removal was significantly reduced after implementation of the OPDA (8 vs. 5 days; p = 0.01). Early drain removal appeared safe with no difference in reoperation or readmission rate after protocol implementation (p = 0.39; p = 0.76). On subgroup analysis, median length of stay was significantly shorter following OPDA implementation for patients who underwent DP and did not develop a postoperative pancreatic fistula (POPF) (6 vs 10 days, p = 0.03). Although the incidence of both surgical site infection and POPF were reduced following the intervention, neither reached statistical significance (38.1 to 28.3%, p = 0.31; and 38.1 to 28.3%, p = 0.31 respectively). CONCLUSIONS: Implementing the OPDA was associated with earlier drain removal and decreased length of stay in patients undergoing distal pancreatectomy who did not develop POPF, without increased morbidity. Standardizing drain removal may help facilitate early drain removal after pancreatic resection at other institutions.

Passive versus active intra-abdominal drainage following pancreatic resection: does a superior drainage system exist? A protocol for systematic review.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most common cause of major morbidity following pancreatic resection. Intra-abdominal drains are frequently positioned adjacent to the pancreatic anastomosis or transection margin at the time of surgery to aid in detection and management of CR-POPF. Drains can either evacuate fluid by passive gravity (PG) or be attached to a closed suction (CS) system using negative pressure. There is controversy as to whether one of these two systems is superior. The objective of this review is to identify and compare the incidence of adverse events (AEs) and resource utilisation associated with PG and CS drainage following pancreatic resections. METHODS AND ANALYSIS: MEDLINE, EMBASE, CINAHL and Cochrane Central Registry of Controlled Trials will be searched from inception to April 2019, to identify interventional and observational studies comparing PG and CS drains following pancreatic resection. The primary outcome is POPF as defined by the International Study Group for Pancreatic Fistula in 2017. Secondary outcomes include postoperative AE, resource utilisation (length of stay, return to emergency department, readmission and reintervention), time to drain removal and quality of life. Study selection, data extraction and risk of bias assessment will be performed independently, by two reviewers. A meta-analysis will be conducted if deemed statistically appropriate. Subgroup analysis by study design will be performed. Study heterogeneity will be calculated with the χ2 test and reported as I2 statistics. Statistical analyses will be conducted and displayed using RevMan V.5.3 ETHICS AND DISSEMINATION: Ethics approval is not required. The results of this study will be submitted to relevant conferences for presentation and peer-reviewed journals for publication. PROSPERO REGISTRATION NUMBER: CRD42019123647.

Embryology, Anatomy, and Imaging of the Biliary Tree.

"The anatomy of the biliary tree is notoriously variable. This variation is the bane of the hepatobiliary surgeon, to whom an understanding of biliary anatomic variation is key to the planning and safe conduct of liver surgery, from oncological resections to split-liver transplantation. The hepatic diverticulum, also termed "the liver bud," is the first semblance of the biliary system in the human embryo. A variety of techniques used in the mid twentieth century for imaging the biliary tree have since been abandoned in favor of more practical, safer, less invasive, and more sensitive and specific contemporary methods."

Hypovolemic phlebotomy in liver surgery is associated with decreased red blood cell transfusion.

BACKGROUND: Perioperative red blood cell (RBC) transfusion is associated with poor outcomes in liver surgery. Hypovolemic phlebotomy (HP) is a novel intervention hypothesized to decrease transfusion requirements. The objective of this study was to examine this hypothesis. METHODS: Consecutive patients who underwent liver resection at one institution (2010-2016) were included. Factors found to be predictive of transfusion on univariate analysis and those previously published were modeled using multivariate logistic regression. RESULTS: A total of 361 patients underwent liver resection (50% major). HP was performed in 45 patients. Phlebotomized patients had a greater proportion of primary malignancy (31% vs 18%) and major resection (84% vs 45%). Blood loss was significantly lower with phlebotomy in major resections (400 vs 700 mL). Nadir central venous pressure was significantly lower with HP (2.5 vs 5 cm H2O). On multivariate logistic regression, HP (OR 0.20, 95% CI 0.068-0.57, p = 0.0029), major liver resection (OR 2.91, 95% CI 1.64-5.18, p = 0.0003), preoperative hemoglobin < 125 g/L (OR 6.02, 95% CI 3.44-10.56, p < 0.0001), and underlying liver disease (OR 2.24, 95% CI 1.27-3.95, p = 0.0051) were significantly associated with perioperative RBC transfusion. CONCLUSION: Hypovolemic phlebotomy appears to be strongly associated with a reduction in RBC transfusion requirements in liver resection, independent of other known risk factors.