Long-term Outcomes following Resection of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasm (A-IPMN) versus Pancreatic Ductal Adenocarcinoma (PDAC): A Propensity-score Matched Analysis.

OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

Discarded livers tested by normothermic machine perfusion in the VITTAL trial: Secondary end points and 5-year outcomes.

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).

Precursor Epithelial Subtypes of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasms (A-IPMN): Clinicopathological Features, Recurrence and Response to Adjuvant Chemotherapy.

BACKGROUND: The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown. METHODS: Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010-2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis. RESULTS: In total, 297 patients were included (median age, 70 years; male, 78.9%), including 54 (18.2%) gastric, 111 (37.3%) pancreatobiliary, 80 (26.9%) intestinal and 52 (17.5%) mixed subtypes. Gastric, pancreaticobiliary and mixed subtypes had comparable clinicopathological features, yet the outcomes were significantly less favourable than the intestinal subtype. The median time to recurrence in gastric, pancreatobiliary, intestinal and mixed subtypes were 32, 30, 61 and 33 months. Gastric and pancreatobiliary subtypes had worse overall recurrence (p = 0.048 and p = 0.049, respectively) compared with the intestinal subtype but gastric and pancreatobiliary subtypes had comparable outcomes. Adjuvant chemotherapy was associated with improved survival in the pancreatobiliary subtype (p = 0.049) but not gastric (p = 0.992), intestinal (p = 0.852) or mixed subtypes (p = 0.723). In multivariate survival analysis, adjuvant chemotherapy was associated with a lower likelihood of death in pancreatobiliary subtype, albeit with borderline significance [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.31-1.01; p = 0.058]. CONCLUSIONS: Gastric, pancreatobiliary and mixed subtypes have comparable recurrence and survival outcomes, which are inferior to the more indolent intestinal subtype. Pancreatobiliary subtype may respond to adjuvant chemotherapy and further research is warranted to determine the most appropriate adjuvant chemotherapy regimens for each subtype.

Invasive intraductal oncocytic papillary neoplasms (IOPN) and adenocarcimoma arising from intraductal papillary mucinous neoplasms (A-IPMN) of the pancreas: comparative analysis of clinicopathological features, patterns of recurrence and survival: a multicentre study.

BACKGROUND: Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas are now considered a separate entity to intraductal papillary mucinous neoplasms (IPMN). Invasive IOPNs are extremely rare, and their recurrence patterns, response to adjuvant chemotherapy and long-term survival outcomes are unknown. METHODS: Consecutive patients undergoing pancreatic resection (2010-2020) for invasive IOPNs or adenocarcinoma arising from IPMN (A-IPMN) from 18 academic pancreatic centers worldwide were included. Outcomes of invasive IOPNs were compared with A-IPMN invasive subtypes (ductal and colloid A-IPMN). RESULTS: 415 patients were included: 20 invasive IOPN, 331 ductal A-IPMN and 64 colloid A-IPMN. After a median follow-up of 6-years, 45% and 60% of invasive IOPNs had developed recurrence and died, respectively. There was no significant difference in recurrence or overall survival between invasive IOPN and ductal A-IPMN. Overall survival of invasive IOPNs was inferior to colloid A-IPMNs (median time of survival 24.4 months vs. 86.7, months, p = 0.013), but the difference in recurrence only showed borderline significance (median time to recurrence, 22.5 months vs. 78.5 months, p = 0.132). Adjuvant chemotherapy, after accounting for high-risk features, did not reduce rates of recurrence in invasive IOPN (p = 0.443), ductal carcinoma (p = 0.192) or colloid carcinoma (p = 0.574). CONCLUSIONS: Invasive IOPNs should be considered an aggressive cancer with a recurrence rate and prognosis consistent with ductal type A-IPMN.

Intraductal papillary neoplasms of the bile ducts: a comparative study of a rare disease in Europe and Nagoya, Japan.

BACKGROUND: Intraductal papillary neoplasm of the bile ducts (IPNB) is a rare disease in Western countries. The aim of this study was to compare tumor characteristics, management strategies, and outcomes between Western and Eastern patients who underwent surgical resection for IPNB. METHODS: A multi-institutional retrospective series of patients with IPNB undergoing surgery between January 2010 and December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), and at Nagoya University Hospital, Japan. RESULTS: A total of 85 patients (51% male; median age 66 years) from 28 E-AHPBA centers were compared to 91 patients (64% male; median age 71 years) from Nagoya. Patients in Europe had more multiple lesions (23% vs 2%, P < .001), less invasive carcinoma (42% vs 85%, P < .001), and more intrahepatic tumors (52% vs 24%, P < .001) than in Nagoya. Patients in Europe experienced less 90-day grade >3 Clavien-Dindo complications (33% vs 68%, P < .001), but higher 90-day mortality rate (7.0% vs 0%, P = .03). R0 resections (81% vs 82%) were similar. Overall survival, excluding 90-day postoperative deaths, was similar in both regions. DISCUSSION: Despite performing more extensive resections, the low perioperative mortality rate observed in Nagoya was probably influenced by a combination of patient-, tumor-, and surgery-related factors.

Multisocietal European consensus on the terminology, diagnosis, and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE.

BACKGROUND: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management. METHODS: This project was a multiorganizational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis, and management. Statements were refined during an online Delphi process, and those with 70 per cent agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising 12 key statements. RESULTS: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term 'early metachronous metastases' applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour, the term 'late metachronous metastases' applies to those detected after 12 months. 'Disappearing metastases' applies to lesions that are no longer detectable on MRI after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards, and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways, including systemic chemotherapy, synchronous surgery, and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. CONCLUSION: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.

E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment. METHODS: A modified Delphi approach was used to achieve consensus. The expert panel consisted of hepatobiliary surgeons, radiologists, nuclear medicine specialists, and hepatologists. The guideline process was supervised by a methodologist and reviewed by a patient representative. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane library, and the WHO International Clinical Trials Registry. Evidence assessment and statement development followed Scottish Intercollegiate Guidelines Network methodology. RESULTS: Based on 271 publications covering 4 key areas, 21 statements (at least 85 per cent agreement) were produced (median level of evidence 2- to 2+). Only a few systematic reviews (2++) and one RCT (1+) were identified. Preoperative liver function assessment should be considered before complex resections, and in patients with suspected or known underlying liver disease, or chemotherapy-associated or drug-induced liver injury. Clinical assessment and blood-based scores reflecting liver function or portal hypertension (for example albumin/bilirubin, platelet count) aid in identifying risk of PHLF. Volumetry of the future liver remnant represents the foundation for assessment, and can be combined with indocyanine green clearance or LiMAx® according to local expertise and availability. Functional MRI and liver scintigraphy are alternatives, combining FLR volume and function in one examination. CONCLUSION: These guidelines reflect established methods to assess preoperative liver function and PHLF risk, and have uncovered evidence gaps of interest for future research.

Liver surgery is an effective treatment for liver tumours. Liver failure is a major problem in patients with a poor liver quality or having large operations. The treatment options for liver failure are limited, with high death rates. To estimate patient risk, assessing liver function before surgery is important. Many methods exist for this purpose, including functional, blood, and imaging tests. This guideline summarizes the available literature and expert opinions, and aids clinicians in planning safe liver surgery.

Where Are We Now with Liver Transplantation in Neuroendocrine Neoplasms? The Place of Liver Transplantation for Grades 1 and 2 Well-Differentiated Unresectable Liver Metastatic Neuroendocrine Tumours.

PURPOSE OF REVIEW: This review outlines the role of liver transplantation in selected patients with unresectable neuroendocrine tumour liver metastases. It discusses the international consensus on eligibility criteria and outlines the efforts taking place in the UK and Ireland to develop effective national liver transplant programmes for neuroendocrine tumour patients. RECENT FINDINGS: In the early history of liver transplantation, indications included cancer metastases to the liver as well as primaries of liver origin. Often, liver transplantation was a salvage procedure. The early results were disappointing, including in patients with neuroendocrine tumours. These data discouraged the widespread adoption of liver transplantation for neuroendocrine tumour liver metastases (NET LM). A few centres persisted in performing liver transplantation for patients with NET LM and in determining parameters predictive of good outcomes. Their work has provided evidence for benefit of liver transplantation in a selected group of patients with NET LM. Liver transplantation for NET LM is now accepted as a valid indication by many professional bodies, including the European Neuroendocrine Tumour Society (ENETS) and the United Network for Organ Sharing (UNOS). It is nevertheless rarely utilised. The UK and the Republic of Ireland are commencing a pilot programme of liver transplantation in selected patients. This programme will help develop the expertise and infrastructure to make liver transplantation for NET LM a routine procedure.

Systematic review and meta-analysis of cost-effectiveness of minimally invasive versus open pancreatic resections.

BACKGROUND: The systematic review is aimed to evaluate the cost-effectiveness of minimally invasive surgery (MIS) and open distal pancreatectomy and pancreaticoduodenectomy. METHOD: The MEDLINE, CENTRAL, EMBASE, Centre for Reviews and Dissemination, and clinical trial registries were systematically searched using the PRISMA framework. Studies of adults aged ≥ 18 year comparing laparoscopic and/or robotic versus open DP and/or PD that reported cost of operation or index admission, and cost-effectiveness outcomes were included. The risk of bias of non-randomised studies was assessed using the Newcastle-Ottawa Scale, while the Cochrane Risk of Bias 2 (RoB2) tool was used for randomised studies. Standardised mean differences (SMDs) with 95% confidence intervals (CI) were calculated for continuous variables. RESULTS: Twenty-two studies (152,651 patients) were included in the systematic review and 15 studies in the meta-analysis (3 RCTs; 3 case-controlled; 9 retrospective studies). Of these, 1845 patients underwent MIS (1686 laparoscopic and 159 robotic) and 150,806 patients open surgery. The cost of surgical procedure (SMD 0.89; 95% CI 0.35 to 1.43; I2 = 91%; P = 0.001), equipment (SMD 3.73; 95% CI 1.55 to 5.91; I2 = 98%; P = 0.0008), and operating room occupation (SMD 1.17, 95% CI 0.11 to 2.24; I2 = 95%; P = 0.03) was higher with MIS. However, overall index hospitalisation costs trended lower with MIS (SMD - 0.13; 95% CI - 0.35 to 0.06; I2 = 80%; P = 0.17). There was significant heterogeneity among the studies. CONCLUSION: Minimally invasive major pancreatic surgery entailed higher intraoperative but similar overall index hospitalisation costs.

Hepatobiliary scintigraphy to predict postoperative liver failure after major liver resection; a multicenter cohort study in 547 patients.

BACKGROUND: This study aimed to analyze the predictive value of Hepatobiliary scintigraphy (HBS) for posthepatectomy liver failure (PHLF) after major liver resection with a comparison to assessment of liver volume in a multicenter cohort. METHODS: Patients who underwent liver resection after HBS were included from six centers. Remnant liver volume was calculated from CT images. PHLF was scored and graded according to the grade B/C ISGLS criteria. RESULTS: In 547 patients PHLF incidence was 10% (56/547) and 90-day mortality rate 8% (42/547). Overall predictive value of remnant liver function was 0.66 (0.58-0.74) and similar to that of remnant volume (0.63 (0.72). For biliary tumors, a function cut-off of 2.7%/min/m2 and 30% volume cut-off resulted in a PHLF rate 12% and 13%, respectively. While an 8.5%/min (4.5%/min/m2) function cut-off resulted in 7% PHLF for those with a function above the cutoff while a 40% volume cutoff still resulted in 14% PHLF rate. In the multivariable analyses for PHLF, liver function was predictive but liver volume was not. CONCLUSION: The current study shows that preoperative liver function assessment using HBS is at least as predictive for PHLF as liver volume assessment, and likely has several advantages, particularly in the high-risk sub-group of biliary tumors.

The multi-societal European consensus on the terminology, diagnosis and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE.

BACKGROUND: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management. METHODS: This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements. RESULTS: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term "early metachronous metastases" applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with "late metachronous metastases" applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. CONCLUSIONS: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.

Adjuvant Chemotherapy in the Treatment of Intraductal Papillary Mucinous Neoplasms of the Pancreas: Systematic Review and Meta-Analysis.

BACKGROUND: The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy. METHOD: A systematic search of MEDLINE, PubMed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy. RESULTS: Eleven studies and 3393 patients with IIPMNs were included in the meta-analysis. Adjuvant chemotherapy significantly reduced the risk of death in the overall cohort (HR 0.57, 95% CI 0.38-0.87, p = 0.009) and node-positive patients (HR 0.29, 95% CI 0.13-0.64, p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node-positive patients was 11.6 months (95% CI 3.83-19.38, p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node-negative patients (HR 0.53, 95% CI 0.20-1.43, p = 0.209). High heterogeneity (I2 > 75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy was reported for patients with stage III/IV disease, tumour size > 2 cm, node-positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion. CONCLUSION: Adjuvant chemotherapy was associated with improved OS in node-positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.

Meta-analysis of interrupted versus continuous suturing for Roux-en-Y hepaticojejunostomy and duct-to-duct choledochocholedochostomy.

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.

A scoring system for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: a multicenter EUROPEAN validation.

PURPOSE: A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort. METHODS: An observational multicenter European study from 2010 to 2015. All consecutive patients undergoing surgery for IPMN at 35 hospitals with histological-confirmed IPMN were included. RESULTS: A total of 567 patients were included. The score was significantly associated with the presence of malignancy (p < 0.001). In all, 64% of the patients with benign IPMN had a Shin score < 3 and 57% of those with a diagnosis of malignancy had a score ≥ 3. The relative risk (RR) with a Shin score of 3 was 1.37 (95% CI: 1.07-1.77), with a sensitivity of 57.1% and specificity of 64.4%. CONCLUSION: Patients with a Shin score ≤ 1 should undergo surveillance, while patients with a score ≥ 4 should undergo surgery. Treatment of patients with Shin scores of 2 or 3 should be individualized because these scores cannot accurately predict malignancy of IPMNs. This score should not be the only criterion and should be applied in accordance with agreed clinical guidelines.

Early postoperative arterial lactate concentrations to stratify risk of post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) represents the major determinant for death after liver resection. Early recognition is essential. Perioperative lactate dynamics for risk assessment of PHLF and associated morbidity were evaluated. METHODS: This was a multicentre observational study of patients undergoing hepatectomy with validation in international high-volume units. Receiver operating characteristics analysis and cut-off calculation for the predictive value of lactate for clinically relevant International Study Group of Liver Surgery grade B/C PHLF (clinically relevant PHLF (CR-PHLF)) were performed. Lactate and other perioperative factors were assessed in a multivariable CR-PHLF regression model. RESULTS: The exploratory cohort comprised 509 patients. CR-PHLF, death, overall morbidity and severe morbidity occurred in 7.7, 3.3, 40.9 and 29.3 per cent of patients respectively. The areas under the curve (AUCs) regarding CR-PHLF were 0.829 (95 per cent c.i. 0.770 to 0.888) for maximum lactate within 24 h (Lactate_Max) and 0.870 (95 per cent c.i. 0.818 to 0.922) for postoperative day 1 levels (Lactate_POD1). The respective AUCs in the validation cohort (482 patients) were 0.812 and 0.751 and optimal Lactate_Max cut-offs were identical in both cohorts. Exploration cohort patients with Lactate_Max 50 mg/dl or greater more often developed CR-PHLF (50.0 per cent) than those with Lactate_Max between 20 and 49.9 mg/dl (7.4 per cent) or less than 20 mg/dl (0.5 per cent; P < 0.001). This also applied to death (18.4, 2.7 and 1.4 per cent), severe morbidity (71.1, 35.7 and 14.1 per cent) and associated complications such as acute kidney injury (26.3, 3.1 and 2.3 per cent) and haemorrhage (15.8, 3.1 and 1.4 per cent). These results were confirmed in the validation group. Combining Lactate_Max with Lactate_POD1 further increased AUC (ΔAUC = 0.053) utilizing lactate dynamics for risk assessment. Lactate_Max, major resections, age, cirrhosis and chronic kidney disease were independent risk factors for CR-PHLF. A freely available calculator facilitates clinical risk stratification (www.liver-calculator.com). CONCLUSION: Early postoperative lactate values are powerful, readily available markers for CR-PHLF and associated complications after hepatectomy with potential for guiding postoperative care.Presented in part as an oral video abstract at the 2020 online Congress of the European Society for Surgical Research and the 2021 Congress of the Austrian Surgical Society.

Liver failure represents a major complication after liver resection and determines the risk of postoperative death, therefore early anticipation and risk stratification are highly relevant. This study, of 991 patients in three international centres, shows that the maximum lactate blood level within 24 h after surgery is a very strong factor predicting the further course after liver operations. Lactate could potentially aid in clinical decision making such as prophylactic treatment, intensified observation or early discharge of patients.

The effects of resection margin and KRAS status on outcomes after resection of colorectal liver metastases.

BACKGROUND: The aim of this study was to investigate the influence of resection margin status in patients with KRAS mutations (mt-KRAS) when compared to those with wild-type KRAS (wt-KRAS) on long-term outcomes in patients with resected CRLM. METHODS: All patients who underwent resection of CRLM with curative intent between January 2011 and December 2016 and had a KRAS type recorded were included in the study. Overall survival (OS), as well as death-censored overall (RFS) and liver-specific (LS-RFS) recurrence-free survival between KRAS types and the margin status within KRAS subgroups were compared using Cox regression models. RESULTS: Data were available for N = 500 patients (30.4% mt-KRAS). mt-KRAS status was independently associated with significantly shorter OS. Within the wt-KRAS subgroup, smaller margins were found to be associated with significantly shorter death-censored LS-RFS (p < 0.001), with HRs of 1.93 (p = 0.005) for 1-4 mm margins and 2.83 (p < 0.001) for <1 mm margins, relative to those with clear margins. No such association was observed in the mt-KRAS subgroup (p = 0.721). CONCLUSION: The resection margin status is of greater importance in patients with wt-KRAS. Such information could be useful in the operative planning, especially for those with multiple metastatic deposits, and also in the post-operative counselling and surveillance based on the margin and KRAS status.

Liver Resection and role of Extended Histology (LiREcH study) in patients with multifocal colorectal cancer liver metastases.

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.

Variations between the anatomical and functional distribution, based on 99m technetium -mebrofinate SPECT-CT scan, in patients at risk of post hepatectomy liver failure.

BACKGROUND: The aim of the current study is to investigate the variations of anatomical (LVRem%) and functional remnant volumes (fLVRem%) and the dynamic uptake of Technetium-Mebrofinate (FRLF) measured from 99m Technetium-Mebrofinate SPECT-CT scan (TMSCT) in patients at high risk of post-hepatectomy liver failure (PHLF). METHODS: Variations in the measures of LVRem% and fLVRem% were assessed. The predictive accuracies of LVRem%, fLVRem% and FRLF with respect to PHLF were reported. RESULTS: From the N = 92 scans performed, LVRem% and fLVRem% 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.

Critical Appraisal of the Impact of Oesophageal Stents in the Management of Oesophageal Anastomotic Leaks and Benign Oesophageal Perforations: An Updated Systematic Review.

INTRODUCTION: Endoscopic placement of oesophageal stents may be used in benign oesophageal perforation and oesophageal anastomotic leakage to control sepsis and reduce mortality and morbidity by avoiding thoracotomy. This updated systematic review aimed to assess the safety and effectiveness of oesophageal stents in these two scenarios. METHODS: A systematic literature search of all published studies reporting use of metallic and plastic stents in the management of post-operative anastomotic leaks, spontaneous and iatrogenic oesophageal perforations were identified. Primary outcomes were technical (deploying ≥ 1 stent to occlude site of leakage with no evidence of leakage of contrast within 24-48 h) and clinical success (complete healing of perforation or leakage by placement of single or multiple stents irrespective of whether the stent was left in situ or was removed). Secondary outcomes were stent migration, perforation and erosion, and mortality rates. Subgroup analysis was performed for plastic versus metallic stents and anastomotic leaks versus perforations separately. RESULTS: A total of 66 studies (n = 1752 patients) were included. Technical and clinical success rates were 96% and 87%, respectively. Plastic stents had significantly higher migration rates (24% vs 16%, p = 0.001) and repositioning (11% vs 3%, p < 0.001) and lower technical success (91% vs 95%, p = 0.032) than metallic stents. In patients with anastomotic leaks, plastic stents were associated with higher stent migration (26% vs 15%, p = 0.034), perforation (2% vs 0%, p = 0.013), repositioning (10% vs 0%, p < 0.001), and lower technical success (95% vs 100%, p = p = 0.002). In patients with perforations only, plastic stents were associated with significantly lower technical success (85% vs 99%, p < 0.001). CONCLUSIONS: Covered metallic oesophageal stents appear to be more effective than plastic stents in the management of oesophageal perforation and anastomotic leakage. However, quality of evidence of generally poor and high-quality randomised trial is needed to further evaluate best management option for oesophageal perforation and anastomotic leakage.