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.

Incidence and risk factors for anastomotic bile leakage in hepatic resection with bilioenteric reconstruction - A international multicenter study.

BACKGROUND: Anastomotic leak (AL) after bilioenteric reconstruction (BR) is a feared complication after bile duct resection, especially in combination with liver resection. Literature on surgical outcome is sparse. This study aimed to determine the incidence and risk factors for AL after combined liver and bile duct resection with a focus on operative or endoscopic reinterventions. METHODS: Data from consecutive patients who underwent liver resection and BR between 2004 and 2018 in 11 academic institutions in Europe were collected from prospectively maintained databases. RESULTS: Within 921 patients, AL rate was 5.4% with a 30d mortality of 9.6%. Pringle maneuver (p<0.001),postoperative external biliary (p=0.007) and abdominal drainage (p<0.001) were risk factors for clinically relevant AL. Preoperative biliary drainage (p<0.001) was not associated with a higher rate of AL. AL was more frequent in stented patients (76.5%) compared to PTCD (17.6%) or PTCD+stent (5.9%,p=0.017). AL correlated with increased incidence of postoperative liver failure (p=0.036), cholangitis, hemorrhage and sepsis (all p<0.001). CONCLUSION: This multicenter data provides the largest series to date of LR with BR and could help in the management of these patients which are often challenging and hampering the patients' postoperative course negatively.

Primary Tumor Resection is Associated with Improved Disease-Specific Mortality in Patients with Stage IV Small Intestinal Neuroendocrine Tumors (NETs): A Comparison of Upfront Surgical Resection Versus a Watch and Wait Strategy in Two Specialist NET Centers.

INTRODUCTION: Small intestinal neuroendocrine tumors (SI-NETs) often present with metastatic disease. An ongoing debate exists on whether to perform primary tumor resection (PTR) in patients with stage IV SI-NETs, without symptoms of the primary tumor and inoperable metastatic disease. OBJECTIVE: The aim of this study was to compare a treatment strategy of upfront surgical resection versus a surveillance strategy of watch and wait. METHODS: This was a retrospective cohort study of patients with stage IV SI-NETs at diagnosis, between 2000 and 2018, from two tertiary referral centers (Netherlands Cancer Institute [NKI] and Aintree University Hospital [AUH]) who had adopted contrasting treatment approaches: upfront surgical resection and watch and wait, respectively. Patients without symptoms related to the primary tumor were included. Multivariable intention-to-treat (ITT), per-protocol (PP), and instrumental variable (IV) analyses using 'institute' as an IV were performed to assess the influence of PTR on disease-specific mortality (DSM). RESULTS: A total of 557 patients were identified, with 145 patients remaining after exclusion of stage I-III disease or symptoms of the primary tumor (93 from the NKI and 52 from AUH). The cohorts differed in performance status (PS; p = 0.006) and tumor grade (p < 0.001). PTR was independently associated with reduced DSM irrespective of statistical methods employed: ITT hazard ratio [HR] 0.60, p = 0.005; PP HR 0.58, p < 0.001; and IV HR 0.07, p = 0.019. Other factors associated with DSM were age, PS, high chromogranin A, and somatostatin analog treatment. CONCLUSION: Taking advantage of contrasting institutional treatment strategies, this study identified PTR as an independent predictor of DSM. Future prospective studies should aim to validate these results.

Surgical management of suspected gallbladder cancer: The role of intraoperative frozen section for diagnostic confirmation.

BACKGROUND: Preoperative diagnosis for suspected gallbladder cancers is challenging, with a risk of overtreating benign disease, for example, xanthogranulomatous cholecystitis, with radical cholecystectomies. We retrospectively evaluated the surgeon's intraoperative assessment alone, and with the addition of intraoperative frozen sections, for suspected gallbladder cancers from a tertiary hepatobiliary multidisciplinary team (MDT). METHODS: MDT patients with complex gallbladder disease were included. Collated data included demographics, MDT discussion, operative details, and patient outcomes. RESULTS: A total of 454 patients with complex gallbladder disease were reviewed, 48 (10.6%) were offered radical surgery for suspected cancer. Twenty-five underwent frozen section that led to radical surgery in 6 (25%). All frozen sections were congruent with final histopathology but doubled the operating time (p < 0.0001). Both the surgeon's subjective and additional frozen section's objective assessment, allowed for de-escalation of unnecessary radical surgery, comparing favourably to a 13.0% cancer diagnosis among radical surgery historically. CONCLUSIONS: The MDT process was highly sensitive in identifying gallbladder cancers but lacked specificity. The surgeon's intraoperative assessment is paramount in suspected cancers, and deescalated unnecessary radical surgery. Intraoperative frozen section was a safe and viable adjunct at a cost of resources and operative time.

Prognosis and Circumferential Margin in Patients with Resected Hilar Cholangiocarcinoma.

BACKGROUND: Resection margin status is a known prognosticator in patients who undergo resection for hilar cholangiocarcinoma. However, the influence of an isolated positive circumferential margin on clinical outcome is unclear. METHODS: Patients with resected de novo hilar cholangiocarcinoma from two European hepatobiliary centres (Medical University of Vienna and Aintree University Hospital, 2006-2016) were classified according to resection margin status (negative, surgically positive, isolated circumferentially positive) and investigated with respect to overall survival (OS), recurrence-free survival (RFS) and recurrence pattern. RESULTS: Eighty-three (48 male/35 female) patients were enrolled. The median age was 64 years (range 33-80). The median follow-up was 21.7 months (range 0.3-92.4). Forty (48%) patients had negative resection margins, 25 (30%) had an isolated positive circumferential margin and 18 (22%) had a positive surgical margin. The 5-year OS rates in patients with negative, isolated positive circumferential and positive surgical resection margins were 47%, 33% and 0%, respectively. Median OS was 45.6, 32.7 and 14.5 months, respectively (log rank, P = 0.011). Upon multivariable Cox regression analysis, resection margin status and lymph node status remained statistically significant (P < 0.05). No difference with respect to RFS and recurrence pattern was found between the groups (P > 0.05). CONCLUSION: Our data show that these three resection margin types were associated with different clinical outcomes. Circumferential margin status may therefore serve as a novel prognostic biomarker.

Exosomal Transport of Hepatocyte-Derived Drug-Modified Proteins to the Immune System.

Idiosyncratic drug-induced liver injury (DILI) is a rare, often difficult-to-predict adverse reaction with complex pathomechanisms. However, it is now evident that certain forms of DILI are immune-mediated and may involve the activation of drug-specific T cells. Exosomes are cell-derived vesicles that carry RNA, lipids, and protein cargo from their cell of origin to distant cells, and they may play a role in immune activation. Herein, primary human hepatocytes were treated with drugs associated with a high incidence of DILI (flucloxacillin, amoxicillin, isoniazid, and nitroso-sulfamethoxazole) to characterize the proteins packaged within exosomes that are subsequently transported to dendritic cells for processing. Exosomes measured between 50 and 100 nm and expressed enriched CD63. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) identified 2,109 proteins, with 608 proteins being quantified across all exosome samples. Data are available through ProteomeXchange with identifier PXD010760. Analysis of gene ontologies revealed that exosomes mirrored whole human liver tissue in terms of the families of proteins present, regardless of drug treatment. However, exosomes from nitroso-sulfamethoxazole-treated hepatocytes selectively packaged a specific subset of proteins. LC/MS-MS also revealed the presence of hepatocyte-derived exosomal proteins covalently modified with amoxicillin, flucloxacillin, and nitroso-sulfamethoxazole. Uptake of exosomes by monocyte-derived dendritic cells occurred silently, mainly through phagocytosis, and was inhibited by latrunculin A. An amoxicillin-modified 9-mer peptide derived from the exosomal transcription factor protein SRY (sex determining region Y)-box 30 activated naïve T cells from human leukocyte antigen A*02:01-positive human donors. Conclusion: This study shows that exosomes have the potential to transmit drug-specific hepatocyte-derived signals to the immune system and provide a pathway for the induction of drug hapten-specific T-cell responses.

Preoperative Leucocyte-Based Inflammatory Scores in Patients with Colorectal Liver Metastases: Can We Count on Them?

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) have been identified as potential prognostic factors for overall survival (OS) in primary colorectal cancer, and there is a growing interest in their use in colorectal liver metastases (CLMs). However, optimal cut-off values for these ratios have not been defined by making comparison between series difficult. This study aimed to confirm the prognostic value of inflammatory scores in patients undergoing resection for CLM. METHODS: We retrospectively analysed data from 376 consecutive patients who underwent liver surgery for CLM between June 2010 and August 2015. We assessed the reproducibility of previously published ratios and determined new cut-off values using the Cut-off Finder web-based tool. Relations between cut-off values and OS were analysed with Kaplan-Meier log-rank survival analysis and multivariate Cox models. RESULTS: Three hundred and forty-three patients had full preoperative blood tests for calculation of NLR, PLR and LMR. The number of cut-off values which showed a significant discrimination for OS was 49/249 (19.7%) for NLR, 28/316 (8.9%) for PLR and 22/214 (10.3%) for LMR, all with a scattered nonlinear distribution. CONCLUSIONS: This study showed that inflammatory scores expressed as ratios do not seem to be consistently reliable prognostic markers in patients with resectable CLM.

A simple scoring model for predicting early graft failure and postoperative mortality after liver transplantation.

INTRODUCTION AND OBJECTIVES: Graft failure and postoperative mortality are the most serious complications after liver transplantation. The aim of this study is to establish a prognostic scoring system to predict graft and patient survival based on serum transaminases levels that are routinely used during the postoperative period in human cadaveric liver transplants. PATIENTS AND METHODS: Postoperative graft failure and patient mortality after liver transplant were analyzed from a consecutive series of 1299 patients undergoing cadaveric liver transplantation. This was correlated with serum liver function tests and the rate of reduction in transaminase levels over the first postoperative week. A cut-off transaminase level correlating with graft and patient survival was calculated and incorporated into a scoring system. RESULTS: Aspartate-aminotransferase (AST) on postoperative day one showed significant correlation with early graft failure for levels above 723U/dl and early postoperative mortality for levels above 750U/dl. AST reduction rate (day 1 to 3) greater than 1.8 correlated with reduced graft failure and greater than 2 with mortality. Alanine-aminotransferase (ALT) reduction in the first 48h post transplantation also correlated with outcomes. CONCLUSION: A scoring system with these three variables allowed us to classify our patients into three groups of risk for early graft failure and mortality.

Recipient body mass index and infectious complications following liver transplantation.

BACKGROUND: Nutritional problems are common in patients requiring liver transplantation. Recipient obesity or malnutrition are thought to increase postoperative complications. Body mass index (BMI) is commonly used prior to major surgery but its value specifically in liver transplant assessment has not been established. This is a retrospective study assessing the correlation between the BMI of individuals undergoing liver transplant and the development of postoperative infectious complications. METHODS: Data were collected from a prospectively maintained database regarding all consecutive patients over a period of 23 years. Preoperative recipient BMI was correlated with the number, nature and outcome of postoperative infective complications. RESULTS: Of a total of 1156 consecutive patients, 13.2% developed infectious complications. Thirty-day mortality was 7.2% and 90-day mortality was 10%. Higher BMI was associated with higher risk of infections (p = 0.002). Wound infections occurred predominantly in obese patients (p = 0.001) while other types of infections were more common in malnourished patients (p < 0.001). CONCLUSION: Extremes of BMI are associated with increased infectious complications following liver transplantation. Patients with lower BMI had a higher rate of overall infectious complications whereas those with a higher BMI had increased general and wound complications.

Validation of clinical prognostic scores for patients treated with curative-intent for recurrent colorectal liver metastases.

BACKGROUND: Scoring systems were developed to stratify patients with colorectal liver metastases considered for liver resection into different risk groups. Such scores have never been evaluated in recurrent liver metastases. The aim of this study was to evaluate whether these scores are applicable to patients with recurrent colorectal liver metastases and treated with curative intent. METHODS: We retrospectively analyzed data from 375 consecutive patients who underwent liver surgery for colorectal liver metastases between June 2010 and August 2015. Seventy-three patients developed liver-limited recurrence treated with curative intent. The predictive value of 6 scores (Fong, Sofocleous, Nagashima, Nordlinger, Konopke, and the Basingstoke index) was assessed in this set of patients. RESULTS: Median follow-up was 36.2 months. Overall survival and progression-free survival were 33.6 and 5.6 months, respectively. When scores were applied for OS, none showed a significant stratification between patients, although Nagashima's score showed a significant difference in overall survival between patients from the low-risk group and those from the intermediate- and high-risk groups (40.8 vs 30.5 months, P = 0.039). For PFS, only Fong's score showed a statistically significant stratification (6.6 vs 4.7 months, P = 0.027). CONCLUSION: Scoring systems are of limited-value in stratifying patients operated on for recurrent colorectal liver metastases.

Defining the Optimal Use of Ablation for Metastatic Colorectal Cancer to the Liver Without High-Level Evidence.

OPINION STATEMENT: The role of physical interventions (surgical resection and surgical/radiological ablation) for liver metastases of colorectal cancer has changed dramatically over the last 10-15 years. Whereas in the 1990s, when only those patients with up to three unilobar metastases were considered for any form of such intervention, our present approach to these physical interventions is determined by how much viable disease-free liver can be preserved (most authorities accepting 25-30% disease-free future remnant liver volume) and the possibility of further such interventions if the disease recurs in the liver. There is increasing evidence that for smaller tumours (<3 cm diameter), ablation therapy may be therapeutically the equivalent of surgical resection and possibly safer in high-risk patients with multiple comorbidities. Therefore, we now consider the use of such ablation therapies (with or without surgical resection) to be clinically effective when treating patients with multiple bilobar metastases that have shown good radiologic response to prior systemic therapy.

High serum Aspartate transaminase levels on day 3 postliver transplantation correlates with graft and patient survival and would be a valid surrogate for outcome in liver transplantation clinical trials.

Aspartate transaminase, a liver specific enzyme released into serum following acute liver injury, is used in experimental organ preservation studies as a measure of liver IR injury. Whether post-operative serum transaminases are a good indicator of IR injury and subsequent graft and patient survival in human liver transplantation remains controversial. A single centre prospectively collected liver transplant database was analysed for the period 1988-2012. All patients were followed up for 5 years or until graft failure. Transaminase levels on the 1st, 3rd and 7th post-operative days were correlated with the patient demographics, operative outcomes, post-operative complications and both graft and patient survival via a binary logistic regression analysis. Graft and patient survival at 3 months was 80.3% and 87.5%. AST levels on the 3rd (P = 0.005) and 7th (P = 0.001) post-operative days correlated with early graft loss. Patients were grouped by their AST level (day 3): <107iU, 107-1213iU, 1213-2744iU and >2744iU. The incidence of graft loss at 3 months was 10%, 12%. 27% and 59% and 1-year patient mortality was 12%, 14%, 27% and 62%. Day 3 AST levels correlate with patient and graft outcome post-liver transplantation and would be a suitable surrogate endpoint for clinical trials in liver transplantation.

Ectopic pancreas in gallbladder. Clinical significance, diagnostic and therapeutic implications.

Ectopic or heterotopic pancreas is defined as the presence of pancreatic tissue in an anatomical place not related to the pancreas, being it most frequent locations the stomach and small bowel. Its finding in the gallbladder is exceptional. Since the first case was reported by Otschkin in 1916, about 30 cases have been described in literature. We report the case of a 43 years-old male patient who had an urgent laparoscopic cholecystectomy with the diagnosis of acute cholecystitis, which pathological study showed the existence of chronic cholecystitis with heterotopic pancreatic tissue in the gallbladder wall.

Biliary tract cancer.

BACKGROUND: Biliary tract cancers comprise a heterogeneous collection of malignancies usually described as cholangiocarcinoma of the intra- or extrahepatic bile duct, including perihilar cholangiocarcinoma and gallbladder cancer. METHODS: A review of pertinent parts of the ESSO core curriculum for the UEMS diploma targets (Fellowships exam, EBSQ), based on updated and available guidelines for diagnosis, surgical treatment and oncological management of cholangiocarcinoma. RESULTS: Following the outline from the ESSO core curriculum we present the epidemiology and risk factors for cholangiocarcinoma, as well as the rationale for the current diagnosis, staging, (neo-)adjuvant treatment, surgical management, and short- and long-term outcomes. The available guidelines and consensus reports (i.e. NCCN, BGS and ESMO guidelines) are referred to. Recognition of biliary tract cancers as separate entities of the intrahepatic biliary ducts, the perihilar and distal bile duct as well as the gallbladder is important for proper management, as they each provide distinct clinical, molecular and treatment profiles to consider. CONCLUSION: Core competencies in knowledge to the diagnosis, management and outcomes of biliary tract cancers are presented.

Hepatocellular carcinoma.

An update on the management of Hepatocellular carcinoma (HCC) is provided in the present article for those interested in the UEMS/EBSQ exam in Surgical Oncology. The most recent publications in HCC, including surveillance, guidelines, and indications for liver resection, liver transplantation, and locoregional or systemic therapies, are summarised. The objective is to yield a set of main points regarding HCC that are required in the core curriculum of hepatobiliary oncological surgery.

Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial.

PURPOSE: To compare outcomes after laparoscopic versus open major liver resection (hemihepatectomy) mainly for primary or metastatic cancer. The primary outcome measure was time to functional recovery. Secondary outcomes included morbidity, quality of life (QoL), and for those with cancer, resection margin status and time to adjuvant systemic therapy. PATIENTS AND METHODS: This was a multicenter, randomized controlled, patient-blinded, superiority trial on adult patients undergoing hemihepatectomy. Patients were recruited from 16 hospitals in Europe between November 2013 and December 2018. RESULTS: Of the 352 randomly assigned patients, 332 patients (94.3%) underwent surgery (laparoscopic, n = 166 and open, n = 166) and comprised the analysis population. The median time to functional recovery was 4 days (IQR, 3-5; range, 1-30) for laparoscopic hemihepatectomy versus 5 days (IQR, 4-6; range, 1-33) for open hemihepatectomy (difference, -17.5% [96% CI, -25.6 to -8.4]; P < .001). There was no difference in major complications (laparoscopic 24/166 [14.5%] v open 28/166 [16.9%]; odds ratio [OR], 0.84; P = .58). Regarding QoL, both global health status (difference, 3.2 points; P < .001) and body image (difference, 0.9 points; P < .001) scored significantly higher in the laparoscopic group. For the 281 (84.6%) patients with cancer, R0 resection margin status was similar (laparoscopic 106 [77.9%] v open 122 patients [84.1%], OR, 0.60; P = .14) with a shorter time to adjuvant systemic therapy in the laparoscopic group (46.5 days v 62.8 days, hazard ratio, 2.20; P = .009). CONCLUSION: Among patients undergoing hemihepatectomy, the laparoscopic approach resulted in a shorter time to functional recovery compared with open surgery. In addition, it was associated with a better QoL, and in patients with cancer, a shorter time to adjuvant systemic therapy with no adverse impact on cancer outcomes observed.

Post-surgical chemotherapy versus surgery alone for resectable gastric cancer.

BACKGROUND: For gastric cancer surgery is the mainstay treatment. Chemotherapy seems to improve the survival results. But chemotherapy is not a complication-free therapy and its role has been questioned by some trials. OBJECTIVES: To determine whether post-surgical chemotherapy should be used routinely in resectable gastric cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded (July 2013). SELECTION CRITERIA: Randomised controlled trials (RCT) comparing post-surgical chemotherapy versus surgery alone for resectable gastric cancer. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for inclusion and independently extracted the data. We analysed the data with both the fixed-effect and the random-effects models using the RevMan analysis software. We calculated the hazard ratio (HR) with 95% confidence interval (CI) based on intention-to-treat or available case analysis. MAIN RESULTS: The authors identified 34 studies (7824 patients) reporting overall survival (OS) and only 15 reporting disease free survival (DFS) as well. Post-surgical chemotherapy showed an improvement in OS (HR 0.85; 95% CI 0.80 to 0.90) and an improvement in DFS (HR 0.79; 95% CI 0.72 to 0.87), although all the trials had a high risk of bias.The planned analysis of quality of life, return to work, and number of hospital admissions was impossible to complete as the outcome data for the analysis were not available from any trials. AUTHORS' CONCLUSIONS: Post-surgical chemotherapy should be used routinely for resectable gastric cancer where possible. Further RCTs are needed to determine the role at each stage of disease.

Genomic profiling of idiopathic peri-hilar cholangiocarcinoma reveals new targets and mutational pathways.

Peri-hilar cholangiocarcinoma (pCCA) is chemorefractory and limited genomic analyses have been undertaken in Western idiopathic disease. We undertook comprehensive genomic analyses of a U.K. idiopathic pCCA cohort to characterize its mutational profile and identify new targets. Whole exome and targeted DNA sequencing was performed on forty-two resected pCCA tumors and normal bile ducts, with Gene Set Enrichment Analysis (GSEA) using one-tailed testing to generate false discovery rates (FDR). 60% of patients harbored one cancer-associated mutation, with two mutations in 20%. High frequency somatic mutations in genes not typically associated with cholangiocarcinoma included mTOR, ABL1 and NOTCH1. We identified non-synonymous mutation (p.Glu38del) in MAP3K9 in ten tumors, associated with increased peri-vascular invasion (Fisher's exact, p < 0.018). Mutation-enriched pathways were primarily immunological, including innate Dectin-2 (FDR 0.001) and adaptive T-cell receptor pathways including PD-1 (FDR 0.007), CD4 phosphorylation (FDR 0.009) and ZAP70 translocation (FDR 0.009), with overlapping HLA genes. We observed cancer-associated mutations in over half of our patients. Many of these mutations are not typically associated with cholangiocarcinoma yet may increase eligibility for contemporary targeted trials. We also identified a targetable MAP3K9 mutation, in addition to oncogenic and immunological pathways hitherto not described in any cholangiocarcinoma subtype.

Long-term morbidity after surgery for perihilar cholangiocarcinoma: A cohort study.

BACKGROUND: Surgery for perihilar cholangiocarcinoma (pCCA) offers the only possibility of long-term survival, but remains a formidable undertaking. Traditionally, 90-day post-operative complications and death are used to define operative risk. However, there is concern that this metric may not accurately capture long-term morbidity after such complex surgery. METHODS: A retrospective review of a prospective database of patients undergoing surgery for pCCA at a Western centre between January 2009-2020. RESULTS: Eighty-five patients underwent surgical resection for pCCA with a median overall survival of 36.3 months. Post-op (<90day) morbidity rates were high with 46% of patients developing a major complication (Clavien-Dindo grade 3-4). Post-op mortality rate was 13%. In total 38% (28/74) of patients experienced at least 1 episode of delayed morbidity (>90-days of surgery) resulting in 53 separate admissions with a median LOS of 7 days (IQR 2-15). These episodes were predominately secondary to biliary obstruction with the majority requiring radiological intervention (Clavien-Dindo grade 3). The development of long-term morbidity was associated with increased recurrence rates and correlated with poorer OS (27.6 months vs. 65.7 months HR 2.2 CI 1.63-2.77). CONCLUSIONS: Routinely cited 90-day morbidity and mortality does not accurately capture the patient morbidity experienced following surgery for pCCA. Surgery clearly offers a survival benefit and should be pursued in selected patients, but they must be fully counselled on the potential for long-term morbidity before embarking on this strategy.