Quality-of-life measurement long-term after resection of colorectal liver metastases - is there an optimal assessment tool?

BACKGROUND: There is limited literature on health-related quality-of-life (HRQoL) in patients with colorectal liver metastases (CRLM). Furthermore, there is no consensus on which HRQoL tool is most appropriate. This study assessed the long-term HRQoL in patients who undergo liver resection for CRLM and assessed which HRQoL tool is most useful. METHODS: This was a cross-sectional study of patients who had curative resection for CRLM between 2010 and June 2021. Three validated instruments were used: The European Organisation for Research and Treatment of Cancer (EORTC), which consists of the QLQ-C30 (a generic questionnaire) and QLQ-LMC21 (CRLM specific); the EuroQol-5D (EQ-5D) and the 36-Item Short Form Survey. RESULTS: 121 patients underwent liver resection for CRLM, of which 85 were alive. There was a 61 % response rate (n = 52). The median post-operative time when the survey was completed was 4.0 years. Across all three questionnaires, patients performed exceptionally well in all domains, with median functional scores >90. The EQ-5D-5L VAS and the EROTC QLQ-C30 produced similar results. CONCLUSION: This study demonstrates excellent long-term HRQoL in patients who undergo resection for CRLM. The EQ-5D questionnaire is the preferred questionnaire because it is shorter and simpler to complete than the other tools without compromising accuracy.

The artery first technique: re-examining the critical view of safety during laparoscopic cholecystectomy.

INTRODUCTION: Significant discrepancies exist between surgeon-documented and actual rates of critical view of safety (CVS) achievement on retrospective review following laparoscopic cholecystectomy. This discrepancy may be due to surgeon utilisation of the artery first technique (AFT), an exception to the CVS first described by Strasberg et al. The present study aims to characterise the use of the AFT, hypothesising it is used as an adjunct in difficult dissections to maximise exposure of the hepato-cystic triangle ensuring safe cholecystectomy. METHODS: Prospective digital recording of the operative procedure of patients' undergoing laparoscopic cholecystectomy were undertaken at Christchurch Public Hospital, New Zealand and North Shore Private Hospital, Sydney, Australia. Videos were uploaded to Touch Surgery™ Enterprise. Difficulty was graded, annotated and indications for the AFT quantified using a standardised protocol. RESULTS: A total of 275 annotated procedures were included in this study. The AFT was employed in 54 (20%) patients; in 13 (24%) patients for bleeding, in 35 (65%) patients where windows one and two were visible, and in 6 (11%) patients no windows were visible within the hepato-cystic triangle. There were significant differences in utilisation across operative grade and by seniority of operator (p < 0.005). CONCLUSIONS: The data presented here demonstrate the AFT is frequently used, particularly with Grade 3 cholecystectomy. However, more data are needed to confirm the utility and safety of this approach. Analysis of the AFT shows that to understand and improve safety in laparoscopic cholecystectomy appreciating how the operation was undertaken and not just that the CVS was achieved is crucial.

Sociocultural and Demographic Factors Predict Readmissions for General Surgery Patients.

INTRODUCTION: Readmission is a poor outcome for both patients and healthcare systems. The association of certain sociocultural and demographic characteristics with likelihood of readmission is uncertain in general surgical patients. METHOD: A multi-centre retrospective cohort study of consecutive unique individuals who survived to discharge during general surgical admissions was conducted. Sociocultural and demographic variables were evaluated alongside clinical parameters (considered both as raw values and their proportion of change in the 1-2 days prior to admission) for their association with 7 and 30 days readmission using logistic regression. RESULTS: There were 12,701 individuals included, with 304 (2.4%) individuals readmitted within 7 days, and 921 (7.3%) readmitted within 30 days. When incorporating absolute values of clinical parameters in the model, age was the only variable significantly associated with 7-day readmission, and primary language and presence of religion were the only variables significantly associated with 30-day readmission. When incorporating change in clinical parameters between the 1-2 days prior to discharge, primary language and religion were predictive of 30-day readmission. When controlling for changes in clinical parameters, only higher comorbidity burden (represented by higher Charlson comorbidity index score) was associated with increased likelihood of 30-day readmission. CONCLUSIONS: Sociocultural and demographic patient factors such as primary language, presence of religion, age, and comorbidity burden predict the likelihood of 7 and 30-day hospital readmission after general surgery. These findings support early implementation a postoperative care model that integrates all biopsychosocial domains across multiple disciplines of healthcare.

Proteomic Profiling and Biomarker Discovery in Colorectal Liver Metastases.

Colorectal liver metastases (CRLM) are the leading cause of death among patients with metastatic colorectal cancer (CRC). As part of multimodal therapy, liver resection is the mainstay of curative-intent treatment for select patients with CRLM. However, effective treatment of CRLM remains challenging as recurrence occurs in most patients after liver resection. Proposed clinicopathologic factors for predicting recurrence are inconsistent and lose prognostic significance over time. The rapid development of next-generation sequencing technologies and decreasing DNA sequencing costs have accelerated the genomic profiling of various cancers. The characterisation of genomic alterations in CRC has significantly improved our understanding of its carcinogenesis. However, the functional context at the protein level has not been established for most of this genomic information. Furthermore, genomic alterations do not always result in predicted changes in the corresponding proteins and cancer phenotype, while post-transcriptional and post-translational regulation may alter synthesised protein levels, affecting phenotypes. More recent advancements in mass spectrometry-based technology enable accurate protein quantitation and comprehensive proteomic profiling of cancers. Several studies have explored proteomic biomarkers for predicting CRLM after oncologic resection of primary CRC and recurrence after curative-intent resection of CRLM. The current review aims to rationalise the proteomic complexity of CRC and explore the potential applications of proteomic biomarkers in CRLM.

Use of prospective video analysis to understand the impact of technical difficulty on operative process during laparoscopic cholecystectomy.

BACKGROUND: An understanding of the impact of operative difficulty on operative process in laparoscopic cholecystectomy is lacking. The aim of the present study was to prospectively analyse digitally recorded laparoscopic cholecystectomy to assess the impact of operative technical difficulty on operative process. METHODS: Video of laparoscopic cholecystectomy procedures performed at Christchurch Hospital, NZ and North Shore Private Hospital, Sydney Australia were prospectively recorded. Using a framework derived from a previously published standard process video was annotated using a standardized template and stratified by operative grade to evaluate the impact of grade on operative process. RESULTS: 317 patients had their laparoscopic cholecystectomy operations prospectively recorded. Seventy one percent of these videos (n = 225) were annotated. Single ICC of operative grade was 0.760 (0.663-0.842 p < 0.010). Median operative time, rate of operative errors significantly increased and rate of CVS decreased with increasing operative grade. Significant differences in operative anatomy, operative process and instrumentation were seen with increasing grade. CONCLUSION: Operative technical difficulty is accurately predicted by operative grade and this impacts on operative process with significant implications for both surgeons and patients. Consequently operative grade should be documented routinely as part of a culture of safe laparoscopic cholecystectomy.

Performance of prognostic models incorporating KRAS mutation status to predict survival after resection of colorectal liver metastases.

BACKGROUND: The Genetic And Morphologic Evaluation (GAME) score and modified clinical score (m-CS) are two novel prognostic models that incorporate KRAS mutation status to predict survival after resection of colorectal liver metastases (CRLM). This retrospective cohort study evaluated the performance of these two models. METHODS: A total of 103 patients who underwent resection of CRLM between 2007 and 2017 and had known KRAS mutation status were included, 39 (37.9%) of whom had KRAS mutated tumours. Complete case analysis of the patients was performed according to the Clinical Risk Score (CRS), m-CS, and GAME score. The primary outcome was overall survival stratified according to low-risk and high-risk scores. Harrell's C-index and Akaike information criterion (AIC) were used to compare the discrimination of the evaluated prognostic models. RESULTS: The GAME score demonstrated the largest difference in overall survival for patients stratified according to low-risk and high-risk groups. Harrell's C-index values for the CRS, m-CS, and GAME models were 0.583, 0.600, and 0.668, respectively. AIC values for the CRS, m-CS, and GAME models were 441, 439, and 427, respectively. CONCLUSION: The GAME score outperforms the CRS and m-CS in predicting overall survival after resection of CRLM in patients with known KRAS mutation status.

Management of disappearing colorectal liver metastases: an international survey.

BACKGROUND: Improved chemotherapy response rates have lead to "disappearing" colorectal liver metastases (dCRLM). We aim to assess management patterns of dCRLM from an international body of hepatobiliary surgeons. METHODS: A survey was designed, tested for item relevance, readability and content validity, and distributed to the AHPBA, IHPBA and ANZHPBA. RESULTS: The majority of 226 respondents were <15 years from training (69%), practiced in academia (82%) and devoted >50% of their practice to hepatobiliary (75%). Surgeons utilize CT(45%) or MRI(47%) for preoperative planning with a preferred imaging interval of <6 weeks. Nearly all have experienced dCRLM (99%) and 63% of surgeons have waited a few months to assess for durability of response prior to definitive surgical/ablative therapy. Only 24% place fiducial markers for lesions <1-cm prior to neoadjuvant chemotherapy. Intra-operatively, 97% of surgeons perform ultrasound, and 71% ablation. When a tumor has "disappeared," 49% elect for observation and 31% resect if the dCRLM is superficial. Of those electing observation, 87% believe there is effective treatment with progression on surveillance imaging. CONCLUSIONS: Nearly all surgeons have experienced dCRLM with half choosing observation over intervention due to the belief that these lesions may be re-addressed in the future.

Minimally Invasive Versus Open Liver Resection for Hepatocellular Carcinoma in the Setting of Portal Vein Hypertension: Results of an International Multi-institutional Analysis.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) and portal vein hypertension assessed with platelet count (PVH-PLT; platelet count < 100,000/mL) are often denied surgery even when the disease is technically resectable. Short- and long-term outcomes of patients undergoing minimally invasive surgery (MIS) versus open resection for HCC and PVH-PLT were compared. METHODS: Propensity score matching (PSM) was used to balance the clinicopathological differences between MIS and non-MIS patents. Univariate comparison and standard survival analyses were utilized. RESULTS: Among 1974 patients who underwent surgery for HCC, 13% had a PVH-PLT and 33% underwent MIS. After 1:1 PSM, 407 MIS and 407 non-MIS patients were analyzed. Incidence of complications and length-of-stay (LoS) were higher among non-MIS versus MIS patients (both p ≤ 0.002). After PSM, among 178 PVH-PLT patients (89 MIS and 89 non-MIS), patients who underwent a non-MIS approach had longer LoS (> 7 days; non-MIS: 55% vs. MIS: 29%), as well as higher morbidity (non-MIS: 42% vs. MIS: 29%) [p <0.001]. In contrast, long-term oncological outcomes were comparable, including 3-year overall survival (non-MIS: 66.2% vs. MIS: 72.9%) and disease-free survival (non-MIS: 47.3% vs. MIS: 50.2%) [both p ≥ 0.08]. CONCLUSION: An MIS approach was associated with improved short-term outcomes, but similar long-term outcomes, compared with open liver resection for patients with HCC and PVH-PLT. An MIS approach for liver resection should be considered for patients with HCC, even those individuals with PVH-PLT.

SELDI-TOF MS Analysis of Hepatocellular Carcinoma in an Australian Cohort.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cause of cancer death worldwide. Resection offers the best chance of long-term survival, but a consistent adverse prognostic factor is the presence of microvascular invasion (MVI). In this study, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), a high throughput method of analyzing complex samples, was used to explore differentially expressed proteins between HCC and adjacent nontumour liver tissue (ANLT). These findings were correlated with clinical outcomes. MATERIALS AND METHODS: From 2002 to 2011, tumor and ANLT were collected from patients who underwent liver resection and these samples were later prepared for SELDI-TOF MS. Output data were then used to identify proteins capable of discriminating HCC from ANLT. Proteins from the multivariate analysis were then analyzed to determine prognostic factors and the m/z ratios of these proteins were entered into the ExPASy database to infer potential candidates. RESULTS: During the study period, 30 patients had SELDI-TOF MS performed on their HCC and ANLT samples. On multivariate analysis, a panel of four proteins-m/z 5840, m/z 8921, m/z 9961, and m/z 25,872-discriminated HCC from ANLT with an area under the ROC curve of 0.954 (P < 0.001). On prognostic factor assessment, decreased m/z 9961 was significantly associated with the presence of MVI (P = 0.025) and shorter disease-free survival (P = 0.045) in our patients. A potential candidate for this protein was coxsackievirus and adenovirus receptor, isoform 3 (CAR 3/7), which helps maintain tight junction integrity. CONCLUSIONS: Using SELDI TOF-MS, we identified a panel of four proteins with excellent discriminative capacity between HCC and ANLT. Of these, m/z 9961 was the only protein significantly associated with a known poor prognostic factor (presence of MVI) and survival (shorter disease-free survival). While loss of CAR 3/7 could lead to MVI, further research is warranted to validate the identity of protein m/z 9961.

Using patient-derived xenograft models of colorectal liver metastases to predict chemosensitivity.

BACKGROUND: Few in vivo models for colorectal cancer have been demonstrated to show external validity by accurately predicting clinical patient outcomes. Patient-derived xenograft (PDX) models of cancer have characteristics that might provide a form of translational research leading to personalized cancer care. The aim of this pilot study was to assess the feasibility of using PDXs as a platform for predicting patient colorectal liver metastases responses, in this case by correlating PDX and patient tumor responses to either folinic acid, fluorouracil plus oxaliplatin or folinic acid, fluorouracil plus irinotecan-based regimens. METHODS: Sixteen patients underwent potentially curative resection of colorectal liver metastases, and tumors were grafted into NOD.CB17-Prkdcscid/Arc mice. Mice were divided into groups to determine relative tumor growth in response to treatment. Tumors were analyzed by immunohistochemistry for Ki67 and Excision repair cross-complementation group 1. RESULTS: An engraftment rate of 81% was achieved. Overall, there was a 67% positive match rate between eligible patient and PDX chemosensitivity profiles. There was a significant difference in relative decrease in Ki67 expression between sensitive/stable versus resistant PDXs for both treatment regimens. There was no statistically significant correlation between baseline ERCC1 expression and response to Oxaliplatin + 5-Fluorouracil in the PDXs. CONCLUSIONS: This pilot study supports the feasibility of using PDX models of advanced colorectal cancer in larger studies to potentially predict patient chemosensitivity profiles.

Challenges in chemotherapy delivery: comparison of standard chemotherapy delivery to locoregional vascular mass fluid transfer.

Standard intravenous chemotherapy delivery to neoplasms relies on simple diffusion gradients from the intravascular to the interstitial space. Systemic perfusion creates untoward effects on normal tissue limiting both concentration and exposure times. Regional intra-arterial therapy is limited by drug recirculation and vascular isolation repeatability and does not address the interstitial microenvironment. Barriers to delivery relate to chaotic vascular architecture, heterogeneous fluid flux, increased interstitial and variable solid tumor pressure and ischemia. To address these difficulties, a delivery system was developed allowing mass fluid transfer of chemotherapeutic agents into the interstitium. This implantable, reusable system is comprised of multiple independently steerable balloons and catheters capable of controlling the locoregional hydraulic and oncotic forces across the vascular endothelium.

Long-term outcomes and quality of life after surgical or conservative treatment of benign simple liver cysts.

BACKGROUND: Benign liver cysts are common and are often detected incidentally. Most patients do not require intervention. Occasionally, large dominant or multifocal small cysts cause symptoms as a result of rapid growth, secondary infection, intra-cystic bleeding or compression of adjacent organs. AIM: To compare presenting symptoms and outcomes of a consecutive series of patients with benign liver cysts treated either conservatively or by surgical intervention. Long-term quality of life (QoL) was also assessed. METHODS: Retrospective analysis of prospectively collected data was conducted. Long-term general and disease-specific quality of life was also documented. RESULTS: Ninety-five patients were included in the study (46 treated operatively, 49 treated conservatively). 80% were female, and the mean age of the cohort was 58 years. Those who had surgical intervention were older (62 vs 55 years, p = 0.004), were more likely to have shortness of breath at presentation (11 vs 5%, p = 0.018) and had larger cysts (12 vs 4 cm, p < 0.001) compared with those offered conservative treatment. Laparoscopic stapled excision was the most common operative procedure (70%) and the overall complication rate was 20%. At a median follow-up of 64 months, 17% (8/46) of the surgically treated patients had radiological evidence of cyst recurrence but only 9% (4/46) were symptomatic. At median follow-up of 71 months, 37% (14/38) of conservatively treated patients had unchanged or new symptoms compared to the first presentation. Furthermore, 10% (4/38) of this group had additional radiological or surgical intervention for persistent symptoms during the follow-up period. Overall, there was no difference in long-term QoL between the two groups. CONCLUSION: Surgical intervention for selected patients with symptomatic benign liver cysts results in low long-term recurrence rates and excellent patient-reported outcomes and quality of life. Laparoscopic-stapled excision can be done safely and reliably in carefully selected patients.

Prospective evaluation of the International Study Group for Liver Surgery definition of post hepatectomy liver failure after liver resection: an international multicentre study.

BACKGROUND: The International Study Group for Liver Surgery (ISGLS) definition of post hepatectomy liver failure (PHLF) was developed to be consistent, widely applicable, and to include severity stratification. This international multicentre collaborative study aimed to prospectively validate the ISGLS definition of PHLF. METHODS: 11 HPB centres from 7 countries developed a standardised reporting form. Prospectively acquired anonymised data on liver resections performed between 01 July 2010 and 30 June 2011 was collected. A multivariate analysis was undertaken of clinically important variables. RESULTS: Of the 949 patients included, 86 (9%) met PHLF requirements. On multivariate analyses, age ≥70 years, pre-operative chemotherapy, steatosis, resection of >3 segments, vascular reconstruction and intraoperative blood loss >300 ml significantly increased the risk of PHLF. Receiver operator curve (ROC) analysis of INR and serum bilirubin relationship with PHLF demonstrated post-operative day 3 and 5 INR performed equally in predicting PHLF, and day 5 bilirubin was the strongest predictor of PHLF. Combining ISGLS grades B and C groups resulted in a high sensitivity for predicting mortality compared to the 50-50 rule and Peak bilirubin >7 mg/dl. CONCLUSIONS: The ISGLS definition performed well in this prospective validation study, and may be the optimal definition for PHLF in future research to allow for comparability of data.

Resection of colorectal liver metastases and extra-hepatic disease: a systematic review and proportional meta-analysis of survival outcomes.

BACKGROUND: Colorectal cancer (CRC) accounts for 9.7% of all cancers with 1.4 million new cases diagnosed each year. 19-31% of CRC patients develop colorectal liver metastases (CRLM), and 23-38% develop extra-hepatic disease (EHD). The aim of this systematic review was to determine overall survival (OS) in patients resected for CRLM and known EHD. METHODS: A systematic review was undertaken to identify studies reporting OS after resection for CRLM in the presence of EHD. Proportional meta-analyses and relative risk of death before five years were assessed between patient groups. RESULTS: A total of 15,144 patients with CRLM (2308 with EHD) from 52 studies were included. Three and 5-year OS were 58% and 26% for lung, 37% and 17% for peritoneum, and 35% and 15% for lymph nodes, respectively. The combined relative risk of death by five years was 1.49 (95% CI = 1.34-1.66) for lung, 1.59 (95% CI = 1.16-2.17) for peritoneal and 1.70 (95% CI = 1.57-1.84) for lymph node EHD, in favour of resection in the absence of EHD. CONCLUSION: This review supports attempts at R0 resection in selected patients and rejects the notion that EHD is an absolute contraindication to resection.

Intra-operative amylase in peri-pancreatic fluid independently predicts for pancreatic fistula post pancreaticoduodectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) is a common and potentially life-threatening complication following pancreaticoduodectomy. The aim of this study was to assess the predictive value of intra-operative amylase concentration (IOAC) in peri-pancreatic fluid after resection for the diagnosis of POPF. METHODS: Consecutive patients who underwent a pancreaticoduodectomy between September 2014 and October 2015 were included in the analysis. IOAC was measured intraoperatively followed by drain fluid analysis for amylase on post-operative days (POD) 1, 3 and 5. Receiver operator characteristic (ROC) analysis was performed to evaluate the discriminative capacity of IOAC as a predictor of POPF. RESULTS: IOAC was measured after pancreaticoduodectomy in 62 patients. The IOAC correlated significantly with i) POD 1 and 3 drain amylase (p < 0.01), ii) the development of POPF (p < 0.01), iii) the development of clinically relevant fistula (Type B, C) (p < 0.01), iv) delayed gastric emptying (p < 0.01), and v) grade of complication as per the Clavien-Dindo definition (p = 0.02). ROC curve analysis confirmed the predictive relationship of IOAC and POPF as a good test with an area under the curve of 0.93, 95% CI 0.87-0.99, p < 0.01. In patients with IOAC of 200 U/L or higher the POPF rate was 80% (OR = 50.1, p < 0.0001). DISCUSSION: Measurement of IOAC allows early and accurate categorization of patients at risk for POPF.

A patient-derived subrenal capsule xenograft model can predict response to adjuvant therapy for cancers in the head of the pancreas.

BACKGROUND: Although gemcitabine is commonly used as adjuvant therapy for pancreatic adenocarcinoma and pancreaticobiliary-type periampullary cancers, not all patients appear to benefit. This translational study evaluates the potential of a patient-derived subrenal capsule pancreatic cancer xenograft (SRCPCX) model to identify within eight weeks after surgery those tumours which will respond to gemcitabine. METHODS: SRCPCXs from 32 pancreatectomy patients were established in six to ten NOD/SCID mice per patient. After four weeks the mice were randomly assigned to receive gemcitabine or saline for four more weeks. After eight weeks, gemcitabine response in the grafts was evaluated by the percentage of tumour growth inhibition (%TGI), histological morphology and immunohistochemical markers (Ki-67, CK7 and cleaved caspase-3). These were collated into an Overall Response. Survival was assessed by Kaplan-Meier and Cox multivariate analyses. RESULTS: 375 of 450 pieces of tissue from 27 of 31 patients were evaluable. In 90% of patients, histopathological and immunostaining features of saline-treated control grafts were concordant with their original tumours. At follow up, six of 15 patients whose tumours had an Overall Response to gemcitabine died, compared with ten of 12 whose tumours did not respond (P = 0.025, Fisher's exact test). This was associated with improved survival on Kaplan-Meier analysis (P = 0.013). Cox multivariate analysis indicated that Overall Response, stage and grade were independent predictors of survival. CONCLUSION: This SRCPCX model retains major histopathological and immunohistochemical characteristics of the original tumour and when a combination of measures is used, enables early assessment of tumour sensitivity to gemcitabine in pancreatic cancers.

Complications following liver resection for colorectal metastases do not impact on longterm outcome.

BACKGROUND: It has been suggested that adverse postoperative outcomes may have a negative impact on longterm survival in patients with colorectal liver metastases. OBJECTIVES: This study was conducted to evaluate the prognostic impact of postoperative complications in patients submitted to a potentially curative resection of colorectal liver metastases. METHODS: A retrospective analysis of outcomes in 199 patients submitted to hepatic resection with curative intent for metastatic colorectal cancer during 1999-2008 was conducted. RESULTS: The overall complication rate was 38% (n = 75). Of all complications, 79% were minor (Grades I or II). There were five deaths (3%). The median length of follow-up was 39 months. Rates of 5-year overall and disease-free survival were 44% and 27%, respectively. Univariate analysis demonstrated that an elevated preoperative level of carcinoembryonic antigen (CEA), intraoperative blood loss of > 300 ml, multiple metastases, large (≥ 35 mm) metastases and resection margins of < 1 mm were associated with poor overall and disease-free survival. In addition, male sex and synchronous metastases were associated with poor disease-free survival. Postoperative complications did not have an impact on either survival measure. The multivariate model did not include complications as a predictive factor. CONCLUSIONS: Postoperative complications were not found to influence overall or disease-free survival in the present series. The number and size of liver metastases were confirmed as significant prognostic factors.

Prospective evaluation of the International Study Group for Liver Surgery definition of bile leak after a liver resection and the role of routine operative drainage: an international multicentre study.

BACKGROUND: The International Study Group for Liver Surgery (ISGLS) proposed a definition for bile leak after liver surgery. A multicentre international prospective study was designed to evaluate this definition. METHODS: Data collected prospectively from 949 consecutive patients on specific datasheets from 11 international centres were collated centrally. RESULTS: Bile leak occurred in 69 (7.3%) of patients, with 31 (3.3%), 32 (3.4%) and 6 (0.6%) classified as grade A, B and C, respectively. The grading system of severity correlated with the Dindo complication classification system (P < 0.001). Hospital length of stay was increased when bile leak occurred, from a median of 7 to 15 days (P < 0.001), as was intensive care stay (P < 0.001), and both correlated with increased severity grading of bile leak (P < 0.001). 96% of bile leaks occurred in patients with intra-operative drains. Drain placement did not prevent subsequent intervention in the bile leak group with a 5-15 times greater risk of intervention required in this group (P < 0.001). CONCLUSION: The ISGLS definition of bile leak after liver surgery appears robust and intra-operative drain usage did not prevent the need for subsequent drain placement.