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Background and Aims: Metastases to the pancreas are rare and their surgical treatment is not well reported. We present a considerable experience from a single centre analysing various prognostic factors.Methods: Data were collected on 13 cases who underwent surgery between 1988 and 2002. Since 1997, data have been recorded prospectively on a dedicated database. Clinical and histopathological factors were reviewed.Results: There were two women and 11 men with a median age of 62 years (range 40-73). There were seven cases of renal cell carcinomas, three colorectal carcinomas, two sarcomas and one lung carcinoma. A prolonged disease-free interval from primary surgery was characteristic for renal cell carcinoma cases (median = 10.8 years). The operative procedures performed included seven pancreatoduodenectomies, four total and two distal pancreatectomies. The operative mortality and morbidity was 7.7% and 46.1% respectively. The overall one- and two-year survival was 78.8% and 54% respectively. Median survival for renal cell carcinoma was 30.5 months and for non-renal cell carcinoma was 26.4 months (p = 0.76).Conclusions: Pancreatectomy should be considered for metastases to the pancreas in the absence of generalised metastatic disease. However, decision making and experience should be concentrated in centres with significant familiarity of this approach. [ABSTRACT FROM AUTHOR]

The long-term (>5 y) outcomes following liver transplantation (LT) have not been extensively reported. The aim was to evaluate outcomes of LT recipients who have survived the first 5 years. A multicenter retrospective analysis of prospectively collected data from 3 high volume LT centers (Dallas-USA, Birmingham-UK, and Barcelona-Spain) was undertaken. All adult patients, who underwent LT since the inception of the program to December 31, 2010, and survived at least 5 years since their LT were included. Patient survival was the primary outcome. A total of 3682 patients who survived at least 5 years following LT (long-term survivors) were included. Overall, median age at LT was 52 years (IQR 44-58); 53.1% were males; and 84.6% were Caucasians. A total of 49.4% (n=1820) died during a follow-up period of 36,828 person-years (mean follow-up 10 y). A total of 80.2% (n=1460) of all deaths were premature deaths. Age-standardized all-cause mortality as compared to general population was 3 times higher for males and 5 times higher for females. On adjusted analysis, besides older recipients and older donors, predictors of long-term mortality were malignancy, cardiovascular disease, and dialysis. Implementation of strategies such as noninvasive cancer screening, minimizing immunosuppression, and intensive primary/secondary cardiovascular prevention could further improve survival., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Paediatric pancreatic pathology and its management is rarely described. We present our experience., Methods: A retrospective case-note review of all patients with pancreatic disease from 1995 to 2021 was completed. Data are quoted as median (range)., Results: Two hundred and twelve patients were identified with 75.9% presenting with pancreatitis. Referrals for pancreatitis increased during the study period and affected a wide age range (2 months-15.6 years). Acute pancreatitis (n = 118) (age 10.6 (0.18-16.3) years). The most common causes were idiopathic (n = 60, 50.8%) and biliary (n = 28, 23.8%). About 10% required treatment for complications or underlying biliary causes. Recurrent pancreatitis (n = 14) (11.6 (0.3-14.3) years). The most common cause was hereditary pancreatitis (n = 6, 42.9%). One patient required endoscopic drainage of pseudocyst. Chronic pancreatitis (n = 29) (16 (0.38-15.5) years). The underlying diagnosis was idiopathic (n = 14, 48.4%) or hereditary pancreatitis (n = 10, 34.5%). 13 patients required active management, including pancreaticojejunostomies (n = 5). Blunt Trauma (n = 34) was managed conservatively in 24 (70.5%). 6 patients required open surgery, but 4 were managed by either endoscopy or interventional radiology. Pancreatic tumours (n = 13) presented at 11.2 (2.3-16) years. Pathology included pancreaticoblastomas (n = 3), solid pseudopapillary tumours (n = 3), neuroendocrine tumours (n = 2), acinar cell cystadenoma (n = 1), intraductal papillary mucinous neoplasm (n = 1), pancreatic insulinoma (n = 1), pancreatic ductal adenocarcinoma (n = 1), and embryonal rhabdomyosarcoma (n = 1). OTHERS (N = 4): Pancreatic cyst (n = 3) and annular pancreas (n = 1)., Conclusion: Paediatric pancreatic disease spans a wide spectrum of both benign and malignant disease and benefits from access to specialist medical, surgical, endoscopic, and interventional radiology expertise. Referrals for paediatric pancreatitis are increasing, but aetiology is different to that seen in adults., Level of Evidence: IV., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Normothermic machine perfusion (NMP) enables pretransplant assessment of high-risk donor livers. The VITTAL trial demonstrated that 71% of the currently discarded organs could be transplanted with 100% 90-day patient and graft survivals. Here, we report secondary end points and 5-year outcomes of this prospective, open-label, phase 2 adaptive single-arm study. The patient and graft survivals at 60 months were 82% and 72%, respectively. Four patients lost their graft due to nonanastomotic biliary strictures, one caused by hepatic artery thrombosis in a liver donated following brain death, and 3 in elderly livers donated after circulatory death (DCD), which all clinically manifested within 6 months after transplantation. There were no late graft losses for other reasons. All the 4 patients who died during the study follow-up had functioning grafts. Nonanastomotic biliary strictures developed in donated after circulatory death livers that failed to produce bile with pH >7.65 and bicarbonate levels >25 mmol/L. Histological assessment in these livers revealed high bile duct injury scores characterized by arterial medial necrosis. The quality of life at 6 months significantly improved in all but 4 patients suffering from nonanastomotic biliary strictures. This first report of long-term outcomes of high-risk livers assessed by normothermic machine perfusion demonstrated excellent 5-year survival without adverse effects in all organs functioning beyond 1 year (ClinicalTrials.gov number NCT02740608)., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Biliary atresia (BA) is rare liver disease of unknown etiology, and is a major indication for liver transplant (LT). Previous data indicate improved outcomes with early referral for Kasai portoenterostomy (KPE)., Objective: Evaluate the long-term outcomes in BA, with particular focus on those transitioned to adult care with native livers., Subjects and Methods: Patients with BA treated between1980 and 2012 were identified. Data were collected from the time of referral, transition to adult care, and the most recent clinic notes, from which patient and native liver survival were calculated., Results: Four hundred and fifty-four patients with BA were identified, who were followed up for median of 16.4 years from birth; 74 died (41 of whom had a LT), giving a 20-year survival rate of 83.6%. Two hundred and seventy-two patients received an LT, with the median native liver survival being 35 months. Of patients who transitioned to adult care, 54 of 180 (30.0%) retained their native liver. Of these, 72% (39 of 54) had evidence of chronic liver disease at transition, of whom 8 were subsequently lost to follow-up, 9 were transplanted, and 22 remained stable with compensated liver disease. Of the 15 of 54 patients (28%) with no evidence of chronic disease in their native liver disease at transition, 3 were subsequently lost to follow-up; none received transplants, although 3 patients developed new-onset liver disease. All patients transitioned to adult care completed secondary school education ( N  = 180), with 49% having attended college/university and 87% being in employment or education at the last follow-up. Of female patients, 34% had at least one pregnancy (27 children in 21 women), while 22% of males had fathered a child., Conclusion: Long-term outcomes in BA are good, with patients surviving into adult life. Progression of chronic liver disease and associated morbidity is common in those who retained their native livers, suggesting that these patients require monitoring of liver disease throughout adult life, and early recognition of the need for LT., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Bench liver reduction, with or without intestinal length reduction (LR) (coupled with delayed closure and abdominal wall prostheses), has been a strategy adopted by our program for small children due to the limited availability of size-matched donors. This report describes the short, medium, and long-term outcomes of this graft reduction strategy., Methods: A single-center, retrospective analysis of children that underwent intestinal transplantation (April 1993 to December 2020) was performed. Patients were grouped according to whether they received an intestinal graft of full length (FL) or following LR., Results: Overall, 105 intestinal transplants were performed. The LR group (n = 10) was younger (14.5 months vs. 40.0 months, p = .012) and smaller (8.7 kg vs. 13.0 kg, p = .032) compared to the FL group (n = 95). Similar abdominal closure rates were achieved after LR, without any increase in abdominal compartment syndrome (1/10 vs. 7/95, p = .806). The 90-day graft and patient survival were similar (9/10, 90% vs. 83/95, 86%; p = .810). Medium and long-term graft survival at 1 year (8/10, 80% vs. 65/90, 71%; p = .599), and 5 years (5/10, 50% vs. 42/84, 50%; p = 1.00) was similar., Conclusion: LR of intestinal grafts appears to be a safe strategy for infants and small children requiring intestinal transplantation. This technique should be considered in the situation of significant size mismatch of intestine containing grafts., (© 2023 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Introduction: Small superficial colorectal liver metastases (CLM) may be difficult to localise intraoperatively, especially during minimally invasive hepatectomy due to reduced tactile feedback and limitations of ultrasound (US). Near-infrared (NIRF) fluorescence imaging is an emerging technology that permits detection of liver tumours after systemic injection of indocyanine green (ICG). Our aim was to report our experience using NIRF to detect CLM., Patients and Methods: Patients with small, superficial resectable CLM received a 10-mg IV bolus of ICG the day before hepatectomy. All patients underwent preoperative liver-specific MRI. CLM were localised intraoperatively using a combination of white light/ultrasound (WL-US) and NIRF. Sensitivity and specificity of NIRF were compared with WL-US., Results: Between March 2019 and July 2021, NIRF was utilised in 15 patients who underwent hepatectomy (laparoscopic 13, open 2). Thirty-two lesions were detected by MRI (including 3 disappearing CLM), of which 2 were ICG-negative and not resected (1 haemangioma, 1 disappearing CLM). Of 30 resected lesions, the median tumour diameter was 11 mm (range 2-25), median distance from liver surface was 4.5 mm (range 0-20) and all were confirmed CLM on histology (R0 resection rate 71%). Twenty-three of thirty (77%) and twenty-seven of thirty (90%) resected CLM were detected by WL-US and NIRF, respectively. Of 7/30 (23%) resected CLM that were WL-US negative, 5 were ICG-positive. Two resected 'disappearing' CLM were ICG-positive, one of which contained viable cancer cells. Overall, NIRF influenced the operative strategy in 6 patients (43%)., Conclusion: Near-infrared fluorescence imaging allows detection of small, superficial colorectal liver metastases that are missed by conventional techniques and warrants further study., (© 2022. Crown.)

Primary nonfunction (PNF) is a life-threatening complication of liver transplantation (LT), but in the early postoperative period, it can be difficult to differentiate from early allograft dysfunction (EAD). The aim of this study was to determine if serum biomarkers can distinguish PNF from EAD in the initial 48 h following LT., Materials and Methods: A retrospective study of adult patients that underwent LT between January 2010 and April 2020 was performed. Clinical parameters, absolute values and trends of C-reactive protein (CRP), blood urea, creatinine, liver function tests, platelets, and international normalized ratio in the initial 48 h after LT were compared between the EAD and PNF groups., Results: There were 1937 eligible LTs, with PNF and EAD occurring in 38 (2%) and 503 (26%) patients, respectively. A low serum CRP and urea were associated with PNF. CRP was able to differentiate between the PNF and EAD on postoperative day (POD)1 (20 versus 43 mg/L; P < 0.001) and POD2 (24 versus 77; P < 0.001). The area under the receiver operating characteristic curve (AUROC) of POD2 CRP was 0.770 (95% confidence interval [CI] 0.645-0.895). The urea value on POD2 (5.05 versus 9.0 mmol/L; P = 0.002) and trend of POD2:1 ratio (0.71 versus 1.32 mmol/L; P < 0.001) were significantly different between the groups. The AUROC of the change in urea from POD1 to 2 was 0.765 (95% CI 0.645-0.885). Aspartate transaminase was significantly different between the groups, with an AUROC of 0.884 (95% CI 0.753-1.00) on POD2., Discussion: The biochemical profile immediately following LT can distinguish PNF from EAD; CRP, urea, and aspartate transaminase are more effective than ALT and bilirubin in distinguishing PNF from EAD in the initial postoperative 48 h. Clinicians should consider the values of these markers when making treatment decisions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Introduction: Future liver remnant volume (FLRV), a risk factor for liver failure (PHLF) after major hepatectomy (MH), is not routinely measured. This study aimed to evaluate the association between FLRV and PHLF., Patients and Methods: All patients undergoing MH (4 + segments) between 2011 and 2018 were identified from a prospectively maintained single-centre database. Perioperative data were collected for patients with PHLF, who were matched (1:2) with non-PHLF controls. FLRV and FLRV % (i.e., % of total liver volume) were calculated retrospectively from preoperative CT scans using Synapse-3D software, and compared between the PHLF and matched control groups., Results: Of 711 patients undergoing MH, PHLF occurred in 27 (3.8%), of whom 24 had preoperative CT scans available. These patients were matched to 48 non-PHLF controls, 98% of whom were classified as being at high risk of PHLF on preoperative risk scoring. FLRV % was significantly lower in the PHLF group, compared to matched controls (median: 28.7 vs. 35.2%, p  = 0.010), with FLRV% < 30% in 58% and 29% of patients, respectively. Assessment of the ability of FLRV % to differentiate between PHLF and matched controls returned an area under the ROC curve of 0.69, and an optimal cut-off value of FLRV %  < 31.5%, which yielded 79% sensitivity and 67% specificity., Conclusions: FLRV % is significantly predictive of PHLF after MH, with over half of patients with PHLF having FLRV %  < 30%. In light of this, we propose that all patients should undergo risk stratification prior to MH, with the high risk patients additionally being assessed with CT volumetry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Piccus, Joshi, Hodson, Bartlett, Chatzizacharias, Dasari, Isaac, Marudanayagam, Mirza, Roberts and Sutcliffe.)

Background: Early stratification of postoperative pancreatic fistula according to severity and/or need for invasive intervention may improve outcomes after pancreaticoduodenectomy. This study aimed to identify the early postoperative variables that may predict postoperative pancreatic fistula severity., Methods: All patients diagnosed with biochemical leak and clinically relevant-postoperative pancreatic fistula based on drain fluid amylase >300 U/L on the fifth postoperative day after pancreaticoduodenectomy were identified from a consecutive cohort from Birmingham, UK. Demographics, intraoperative parameters, and postoperative laboratory results on postoperative days 1 through 7 were retrospectively extracted. Independent predictors of clinically relevant-postoperative pancreatic fistula were identified using multivariable binary logistic regression and converted into a risk score, which was applied to an external cohort from Verona, Italy., Results: The Birmingham cohort had 187 patients diagnosed with postoperative pancreatic fistula (biochemical leak: 99, clinically relevant: 88). In clinically relevant-postoperative pancreatic fistula patients, the leak became clinically relevant at a median of 9 days (interquartile range: 6-13) after pancreaticoduodenectomy. Male sex (P = .002), drain fluid amylase-postoperative day 3 (P < .001), c-reactive protein postoperative day 3 (P < .001), and albumin-postoperative day 3 (P = .028) were found to be significant predictors of clinically relevant-postoperative pancreatic fistula on multivariable analysis. The multivariable model was converted into a risk score with an area under the receiver operating characteristic curve of 0.78 (standard error: 0.038). This score significantly predicted the need for invasive intervention (postoperative pancreatic fistula grades B3 and C) in the Verona cohort (n = 121; area under the receiver operating characteristic curve: 0.68; standard error = 0.06; P = .006) but did not predict clinically relevant-postoperative pancreatic fistula when grades B1 and B2 were included (area under the receiver operating characteristic curve 0.52; standard error = 0.07; P = .802)., Conclusion: We developed a novel risk score based on early postoperative laboratory values that can accurately predict higher grades of clinically relevant-postoperative pancreatic fistula requiring invasive intervention. Early identification of severe postoperative pancreatic fistula may allow earlier intervention., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Background: The shortage of donors' livers for pediatric recipients inspired the search for alternatives including donation after cardiac death (DCD)., Methods: Retrospective review of pediatric liver transplant (PLT) using DCD grafts. Patients were divided into either FLG or RLG recipients. Pre-transplant recipient parameters, donor parameters, operative parameters, post-transplant recipient parameters, and outcomes were compared., Results: Overall, 14 PLTs from DCD donors between 2005 and 2018 were identified; 9 FLG and 5 RLG. All donors were Maastricht category III. Cold ischemia time was significantly longer in RLG (8.2 h vs. 6.2 h; p = .038). Recipients of FLG were significantly older (180 months vs. 7 months; p = .012) and waited significantly longer (168 days vs. 22 days; p = .012). Recipients of RLG tended to be sicker in the immediate pre-transplant period and this was reflected by the need for respiratory or renal support. There was no significant difference between groups regarding long-term complications. Three patients in each group survived more than 5 year post-transplant. One child was re-transplanted in the RLG due to portal vein thrombosis but failed to survive after re-transplant. One child from FLG also died from a non-graft-related cause., Conclusions: Selected DCD grafts are an untapped source to widen the donor pool, especially for sick recipients. In absence of agreed criteria, graft and recipient selection for DCD grafts should be undertaken with caution., (© 2022 Wiley Periodicals LLC.)

In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial., (© 2022 The Authors. Liver Transplantation published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: To determine whether the short-term benefits associated with an enhanced recovery after surgery programme (ERAS) following pancreaticoduodenectomy (PD) vary with age., Methods: 830 consecutive patients who underwent PD between January 2009 and March 2019 were divided according to age: elderly (≥75 years) vs. non-elderly patients (<75 years). Within each age group, cohort characteristics and outcomes were compared between patients treated pre- and post-ERAS (ERAS was systematically introduced in December 2012). Univariable and multivariable analysis were then performed, to assess whether ERAS was independently associated with length of hospital stay (LOS)., Results: Of the entire cohort, 577 of 830 patients (69.5%) were managed according to an ERAS protocol, and 170 patients (20.5%) were aged ≥75 years old. Patients treated post-ERAS were significantly more comorbid than those pre-ERAS, with a mean Charlson Comorbidity Index of 4.6 vs. 4.1 (p < 0.001) and 6.0 vs. 5.7 (p = 0.039) for the non-elderly and elderly subgroups, respectively. There were significantly fewer medical complications in non-elderly patients treated post-ERAS compared to pre-ERAS (12.4% vs. 22.4%; p = 0.002), but not in elderly patients (23.6% vs. 14.0%; p = 0.203). On multivariable analysis, ERAS was independently associated with reduced LOS in both elderly (14.8% reduction, 95% CI: 0.7-27.0%, p = 0.041) and non-elderly patients (15.6% reduction, 95% CI: 9.2-21.6%, p < 0.001), with the effect size being similar in each group., Conclusion: ERAS protocols can be safely applied to patients undergoing pancreaticoduodenectomy irrespective of age. Implementation of an ERAS protocol was associated with a significant reduction in postoperative LOS in both elderly and non-elderly patients, despite higher comorbidity in the post-ERAS period., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Although laparoscopic hepatectomy (LH) is associated with improved short-term outcomes compared to open hepatectomy (OH), it is unknown whether frail patients also benefit from LH. The aim of this study was to evaluate the impact of frailty on post-operative outcomes after LH and OH., Patients and Methods: Consecutive patients who underwent LH and OH between January 2011 and December 2018 were identified from a prospective database. Frailty was assessed using the modified Frailty Index (mFI), with patients scoring mFI ≥ 1 deemed to be frail., Results: Of 1826 patients, 34.7% (N = 634) were frail and 18.6% (N = 340) were elderly (≥ 75 years). Frail patients had significantly higher 90-day mortality (6.6% vs. 2.9%, p < 0.001) and post-operative complications (36.3% vs. 26.1%, p < 0.001) than those who were not frail, effects that were independent of patient age on multivariate analysis. For those undergoing minor resections, the benefits of LH vs. OH were similar for frail and non-frail patients. Length of hospital stay was 53% longer in OH (vs. LH) in frail patients, compared to 58% longer in the subgroup of non-frail patients., Conclusions: Frailty is independently associated with inferior post-operative outcomes in patients undergoing hepatectomy. However, the benefits of laparoscopic (compared to open) hepatectomy are similar for frail and non-frail patients. Frailty should not be a contraindication to laparoscopic minor hepatectomy in carefully selected patients., (© 2022. The Author(s).)

Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes.

Aims: To compare outcomes of interrupted (IS) and continuous (CS) suturing techniques for Roux-en-Y hepaticojejunostomy and duct-to-duct choledochocholedochostomy., Methods: The study protocol was prospectively registered in PROSPERO (registration number: CRD42021286294). A systematic search of MEDLINE, CENTRAL, and Web of Science and bibliographic reference lists were conducted (last search: 14th March 2022). All comparative studies reporting outcomes of IS and CS in hepaticojejunostomy and choledochocholedochostomy were included and their risk of bias was assessed using ROBINS-I tool. Overall biliary complications, bile leak, biliary stricture, cholangitis, liver abscess, and anastomosis time were the evaluated outcome parameters., Results: Ten comparative studies (2 prospective and 8 retrospective) were included which reported 1617 patients of whom 1186 patients underwent Roux-en-Y hepaticojejunostomy (IS: 789, CS: 397) and the remaining 431 patients underwent duct-to-duct choledochocholedochostomy (IS: 168, CS: 263). Although use of IS for hepaticojejunostomy was associated with significantly longer anastomosis time (MD: 14.15 min, p=0.0002) compared to CS, there was no significant difference in overall biliary complications (OR: 1.34, p=0.11), bile leak (OR: 1.64, p=0.14), biliary stricture (OR: 0.84, p=0.65), cholangitis (OR: 1.54, p=0.35), or liver abscess (OR: 0.58, p=0.40) between two groups. Similarly, use of IS for choledochocholedochostomy was associated with no significant difference in risk of overall biliary complications (OR: 0.92, p=0.90), bile leak (OR: 1.70, p=0.28), or biliary stricture (OR: 1.07, p=0.92) compared to CS., Conclusions: Interrupted and continuous suturing techniques for Roux-en-Y hepaticojejunostomy or duct-to-duct choledochocholedochostomy seem to have comparable clinical outcomes. The available evidence may be subject to confounding by indication with respect to diameter of bile duct. Future high-quality research is encouraged to report the outcomes with respect to duct diameter and suture material., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Persistent ascites after orthotropic liver transplantation has numerous causes and can be challenging to manage. This study aimed to determine the outcomes associated with conservative and endovascular intervention of posttransplant ascites after deceased donor liver transplantation., Methods: Adult (≥18 y) liver transplant recipients (between 2006 and 2019) who underwent hepatic venous pressure studies to investigate posttransplant ascites were included in this retrospective study. Comparisons were made between those who were managed with conservative therapy versus endovascular intervention and were also based on hepatic venous wedge pressure gradient (normal [≤10 mm Hg] versus elevated [>10 mm Hg])., Results: A total of 30 patients underwent hepatic venography to investigate ascites during the study period. The median time from transplant to venography was 70 d. At least 1 endovascular intervention was performed in 18 of 30 patients (62%), and 12 of 30 patients (38%) were managed conservatively. Endovascular interventions included angioplasty (n = 4), hepatic vein stenting (n = 9), or a transjugular intrahepatic portosystemic shunt (n = 7). The mean (range) hepatic venous wedge pressure gradient for the conservative and endovascular intervention groups was 12 mm Hg (3-23) and14 mm Hg (2-35), respectively. At a 6-mo follow-up, ascites resolved in 6 of 12 patients (50%) and 11 of 18 patients (61%) in the medical management and endovascular groups, respectively. The graft survival rates at 6 and 12 mo were (7/12 [58%] versus 17/18 [94%], P = 0.02) and (7/12 [58%] versus 14/18 [78%], P = 0.25), respectively., Conclusions: Despite medical or endovascular intervention, resolution of ascites is achieved in <60% of patients with persistent ascites. Biopsy findings and venographic pressure studies should be carefully integrated into the management of posttransplant ascites., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Infants with intestinal failure associated liver disease (IFALD) requiring liver and bowel transplant have a high mortality on the transplant waiting list due to the scarcity of the size-matched donor organs. Bridging liver transplantation has been used to allow the children to grow to a reasonable size so that a combined liver and small bowel transplant could be performed in the future. We report on two children with irreversible intestinal failure (ultra-short bowel syndrome secondary to gastroschisis and microvillous inclusion disease) with IFALD who underwent bridging liver transplantation at our institution. Both patients made a good recovery from their initial surgery. One patient died 6 months following surgery from generalized sepsis, and the other patient survived in good condition to undergo a combined liver and small bowel transplant but died a few days post-transplant. In the current era of scarcity of donor organs, this raises an ethical dilemma for the team involved regarding appropriate utilisation of a scarce resource.

Normothermic machine perfusion (NMP) allows objective assessment of donor liver transplantability. Several viability evaluation protocols have been established, consisting of parameters such as perfusate lactate clearance, pH, transaminase levels, and the production and composition of bile. The aims of this study were to assess 3 such protocols, namely, those introduced by the teams from Birmingham (BP), Cambridge (CP), and Groningen (GP), using a cohort of high-risk marginal livers that had initially been deemed unsuitable for transplantation and to introduce the concept of the viability assessment sensitivity and specificity. To demonstrate and quantify the diagnostic accuracy of these protocols, we used a composite outcome of organ use and 24-month graft survival as a surrogate endpoint. The effects of assessment modifications, including the removal of the most stringent components of the protocols, were also assessed. Of the 31 organs, 22 were transplanted after a period of NMP, of which 18 achieved the outcome of 24-month graft survival. The BP yielded 94% sensitivity and 50% specificity when predicting this outcome. The GP and CP both seemed overly conservative, with 1 and 0 organs, respectively, meeting these protocols. Modification of the GP and CP to exclude their most stringent components increased this to 11 and 8 organs, respectively, and resulted in moderate sensitivity (56% and 44%) but high specificity (92% and 100%, respectively) with respect to the composite outcome. This study shows that the normothermic assessment protocols can be useful in identifying potentially viable organs but that the balance of risk of underuse and overuse varies by protocol., (© 2021 The Authors. Liver Transplantation published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: Retransplantation candidates are disadvantaged owing to lack of good-quality liver grafts. Strategies that can facilitate transplantation of suboptimal grafts into retransplant candidates require investigation. The aim was to determine whether late liver retransplantation can be performed safely with suboptimal grafts, following normothermic machine perfusion., Methods: A prospectively enrolled group of patients who required liver retransplantation received a suboptimal graft preserved via normothermic machine perfusion. This group was compared with both historical and contemporaneous cohorts of patient who received grafts preserved by cold storage. The primary outcome was 6-month graft and patient survival., Results: The normothermic machine perfusion group comprised 26 patients. The historical (cold storage 1) and contemporaneous (cold storage 2) groups comprised 31 and 25 patients respectively. The 6-month graft survival rate did not differ between groups (cold storage 1, 27 of 31, cold storage 2, 22 of 25; normothermic machine perfusion, 22 of 26; P = 0.934). This was despite the normothermic machine perfusion group having significantly more steatotic grafts (8 of 31, 7 of 25, and 14 of 26 respectively; P = 0.006) and grafts previously declined by at least one other transplant centre (5 of 31, 9 of 25, and 21 of 26; P < 0.001)., Conclusion: In liver retransplantation, normothermic machine perfusion can safely expand graft options without compromising short-term outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Ex vivo normothermic machine liver perfusion (NMLP) involves artificial cannulation of vessels and generation of flow pressures. This could lead to shear stress-induced endothelial damage, predisposing to vascular complications, or improved preservation of donor artery quality. This study aims to assess the spatial donor hepatic artery (HA) endothelial quality downstream of the cannulation site after end-ischaemic NMLP., Methods: Remnant HA segments from the coeliac trunk up to the gastroduodenal artery branching were obtained after NMLP (n = 15) and after static cold storage (SCS) preservation (n = 15). Specimens were fixed in 10% neutral buffered formalin and sectioned at pre-determined anatomical sites downstream of the coeliac trunk. CD31 immunohistostaining was used to assess endothelial integrity by a 5-point ordinal scale (grade 0: intact endothelial lining, grade 5: complete denudation). Endothelial integrity after SCS was used as a control for the state of the endothelium at commencement of NMP., Results: In the SCS specimens, regardless of the anatomical site, near complete endothelial denudation was present throughout the HA (median scores 4.5-5). After NMLP, significantly less endothelial loss in the distal HA was present compared to SCS grafts (NMLP vs. SCS: median grade 3 vs. 4.5; p = 0.042). In NMLP specimens, near complete endothelial denudation was present at the cannulation site in all cases (median grade: 5), with significantly less loss of the endothelial lining the further from the cannulation site (proximal vs. distal, median grade 5 vs. 3; p = 0.005)., Conclusion: Loss of endothelial lining throughout the HA after SCS and at the cannulation site after NMLP suggests extensive damage related to surgical handling and preservation injury. Gradual improved endothelial lining along more distal sites of the HA after NMLP indicates potential for re-endothelialisation. The regenerative effect of NMLP on artery quality seems to occur to a greater extent further from the cannulation site. Therefore, arterial cannulation for machine perfusion of liver grafts should ideally be as proximal as possible on the coeliac trunk or aortic patch, while the site of anastomosis should preferentially be attempted distal on the common HA., (© 2021. Crown.)

Competing Interests: Conflict of interests disclosure DFM holds shares in the OrganOx Limited company. None of the other authors have any conflict of interest to disclose.

Background: Delayed biliary strictures (DBS) after cholecystectomy are uncommon and little is known of their aetiology or long-term consequences. The aims of this study were to investigate the clinical and economic impact of DBS after cholecystectomy., Methods: Patients who developed DBS after cholecystectomy were identified from a prospectively collected and maintained database. Risk factors for stricture development, quality of life (QoL) and long-term biliary complication rates were explored. Costs of treatment and follow up were determined. The same outcomes among patients with minor or major bile duct injury (BDI) were used as a comparison., Results: Among 44 patients, a laparoscopic converted to open procedure or post cholecystectomy bile leak affected some 18 and 12 patients respectively. Most DBS required surgical treatment (40). Over a median follow-up of 8.9 years after DBS treatment, 16 (36%) patients developed biliary complications (similar to minor, 26%, and major BDI, 40%) and 1 patient died of causes related to the biliary stricture. Costs of treating DBS and its follow up (£14,309.26 per patient), were similar to previously reported costs for major BDI (£15,784)., Conclusion: DBS typically occur after a technically and/or complicated cholecystectomy. Clinical, economic and QoL outcomes are similar to patients with major BDI., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach., Methods: Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis., Results: Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003)., Conclusion: In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard., (© 2021. The Author(s).)

Full-left-full-right split liver transplantation (FSLT) for adult recipients, may increase the availability of liver grafts, reduce waitlist time, and benefit recipients with below-average body weight. However, FSLT may lead to impaired graft and patient survival. This study aims to assess outcomes after FSLT. Five databases were searched to identify studies concerning FSLT. Incidences of complications, graft- and patient survival were assessed. Discrete data were pooled with random-effect models. Graft and patient survival after FSLT were compared with whole liver transplantation (WLT) according to the inverse variance method. Vascular complications were reported in 25/273 patients after FSLT (Pooled proportion: 6.9%, 95%CI: 3.1-10.7%, I 2 : 36%). Biliary complications were reported in 84/308 patients after FSLT (Pooled proportion: 25.6%, 95%CI: 19-32%, I 2 : 44%). Pooled proportions of graft and patient survival after 3 years follow-up were 72.8% (95%CI: 67.2-78.5, n = 231) and 77.3% (95%CI: 66.7-85.8, n = 331), respectively. Compared with WLT, FSLT was associated with increased graft loss (pooled HR: 2.12, 95%CI: 1.24-3.61, P = 0.006, n = 189) and patient mortality (pooled HR: 1.81, 95%CI: 1.17-2.81, P = 0.008, n = 289). FSLT was associated with high incidences of vascular and biliary complications. Nevertheless, long-term patient and graft survival appear acceptable and justify transplant benefit in selected patients., (© 2021 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Background: The aim of the current study is to investigate the variations of anatomical (LV Rem %) and functional remnant volumes (fLV Rem %) and the dynamic uptake of Technetium-Mebrofinate (FRLF) measured from 99 m Technetium-Mebrofinate SPECT-CT scan (TMSCT) in patients at high risk of post-hepatectomy liver failure (PHLF)., Methods: Variations in the measures of LV Rem % and fLV Rem % were assessed. The predictive accuracies of LV Rem %, fLV Rem % and FRLF with respect to PHLF were reported., Results: From the N = 92 scans performed, LV Rem % and fLV Rem % returned identical results in 15% of cases, and ±10 percentage points in 79% of cases. Some patients had larger discrepancies, with difference of >10 percentage points in 21% of cases. The difference was significant in those with primary liver cancers (-4.4 ± 9.2, p = 0.002). For the N = 29 patients that underwent surgery as planned on TMSCT, FRLF was a strong predictor of PHLF, with an AUROC of 0.83 (p = 0.005)., Conclusion: TMSCT is emerging as a useful modality in pre-operative assessment of patients undergoing major liver resection. For those with primary liver cancer, there is a significant variation in the anatomical and functional distributions that needs considered in surgical planning. Reduced FRLF, measured as the dynamic uptake in the future liver remnant, is a strong predictor of PHLF., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: After major bile duct injury, hepaticojejunostomy can result in good long-term patency, but anastomotic stricture is a common cause of long-term morbidity. There is a need to assimilate high-level evidence to establish risk factors for development of anastomotic stricture after hepaticojejunostomy for bile duct injury., Methods: A systematic review of studies reporting the rate of anastomotic stricture after hepaticojejunostomy for bile duct injury was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analyses of proposed risk factors were then performed., Results: Meta-analysis included 5 factors (n = 2,155 patients, 17 studies). Concomitant vascular injury (odds ratio 4.96; 95% confidence interval 1.92-12.86; P = .001), postrepair bile leak (odds ratio: 8.03; 95% confidence interval 2.04-31.71; P = .003), and repair by nonspecialist surgeon (odds ratio 11.29; 95% confidence interval 5.21-24.47; P < .0001) increased the rate of anastomotic stricture of hepaticojejunostomy after bile duct injury. Level of injury according to the Strasberg Grade did not significantly affect the rate of anastomotic stricture (odds ratio: 0.97; 95% confidence interval 0.45-2.10; P = .93). Owing to heterogeneity of reporting, it was not possible to perform a meta-analysis for the impact of timing of repair on anastomotic stricture rate., Conclusion: The only modifiable risk factor, repair by a nonspecialist surgeon, demonstrates the importance of broad awareness of these data. Knowledge of these risk factors may permit risk stratification of follow-up, better informed consent, and understanding of prognosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Colorectal cancer is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Despite advances in improving resectability, most patients present with non-resectable colorectal liver metastases requiring palliative systemic therapy and locoregional disease control strategies. There is a growing interest in the use of liver transplantation to treat non-resectable colorectal liver metastases in well selected patients, leading to a surge in the number of studies and prospective trials worldwide, thereby fuelling the emerging field of transplant oncology. The interdisciplinary nature of this field requires domain-specific evidence and expertise to be drawn from multiple clinical specialities and the basic sciences. Importantly, the wider societal implication of liver transplantation for non-resectable colorectal liver metastases, such as the effect on the allocation of resources and national transplant waitlists, should be considered. To address the urgent need for a consensus approach, the International Hepato-Pancreato-Biliary Association commissioned the Liver Transplantation for Colorectal liver Metastases 2021 working group, consisting of international leaders in the areas of hepatobiliary surgery, colorectal oncology, liver transplantation, hepatology, and bioethics. The aim of this study was to standardise nomenclature and define management principles in five key domains: patient selection, evaluation of biological behaviour, graft selection, recipient considerations, and outcomes. An extensive literature review was done within the five domains identified. Between November, 2020, and January, 2021, a three-step modified Delphi consensus process was undertaken by the workgroup, who were further subgrouped into the Scientific Committee, Expert Panel, and Transplant Centre Representatives. A final consensus of 44 statements, standardised nomenclature, and a practical management algorithm is presented. Specific criteria for clinico-patho-radiological assessments with molecular profiling is crucial in this setting. After this, the careful evaluation of biological behaviour with bridging therapy to transplantation with an appropriate assessment of the response is required. The sequencing of treatment in synchronous metastatic disease requires special consideration and is highlighted here. Some ethical dilemmas within organ allocation for malignant indications are discussed and the role for extended criteria grafts, living donor transplantation, and machine perfusion technologies for non-resectable colorectal liver metastases are reviewed. Appropriate immunosuppressive regimens and strategies for the follow-up and treatment of recurrent disease are proposed. This consensus guideline provides a framework by which liver transplantation for non-resectable colorectal liver metastases might be safely instituted and is a meaningful step towards future evidenced-based practice for better patient selection and organ allocation to improve the survival for patients with this disease., Competing Interests: Declaration of interests PT receives honoraria from Astellas Pharma Europe, outside the current study. GS receives research grants from Bayer and Roche, and consulting fees from Astrazeneca, Novartis, and Roche, outside the current study. RA receives honoraria for symposia from Merck Serono and Sanofi, outside the current study. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The aim of this study is to assess the correlation between the margin status on the specimen side (Rs) and that from the patient side (base of resection) (Rp) and the influence of positive margins (R1s and R1p) on cancer related outcomes in patients with colorectal liver metastases (CRLM)., Methods: In this prospective study, patients undergoing non-anatomical resection (NAR) of multifocal CRLM, with suspected close resection margins were included. The primary outcome evaluated was the correlation of Rs and Rp., Results: Twenty-three patients had 89 NARs, and CUSA samples from the base of 36 specimens were analysed. Among 36 specimens where extended histology (EH) was performed, margin status on the specimen side (Rs) was positive in 69.4% (25/36), whereas on the patient side, the margin (Rp) was positive in only 8.3% (3/36) of specimens. On univariate analysis, there was no significant difference in the site-specific recurrence at previous resection with regards to Rs positivity (P = 0.56) and Rp positivity (P = 0.48)., Conclusion: There is a poor correlation between Rs and Rp and the local recurrence rates in the liver. These results might further support that tumour biology is more relevant than the margin status in patients with multifocal CRLM., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

High-risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end-stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0-10. Low-risk (0-3), medium-risk (4-5), and high-risk (6-10) groups were identified with significantly different 5-year survival rates ranging 56.9% (95% CI 52.8-60.7%), 46.3% (95% CI 41.1-51.4%), and 32.1% (95% CI 23.5-41.0%), respectively (P < 0.001). External validation showed that the expected survival rates were closely aligned with the observed mortality probabilities. The Retransplantation Risk Score identifies high-risk combinations of recipient- and graft-related factors prognostic for long-term graft survival after reLT. This tool may serve as a guidance for clinical decision-making on liver acceptance for reLT., (© 2021 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)