A multimodal atlas of hepatocellular carcinoma reveals convergent evolutionary paths and 'bad apple' effect on clinical trajectory.

BACKGROUND & AIMS: Hepatocellular Carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies. METHODS: Through the Asia-Pacific Hepatocellular Carcinoma (AHCC) trials group (NCT03267641), we recruited one of the largest prospective cohorts of HCC with over 600 whole genome and transcriptome samples from 123 treatment-naïve patients. RESULTS: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the 'bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival. CONCLUSIONS: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provided a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories. CLINICAL TRIAL NUMBER: NCT03267641 (Observational cohort) IMPACT AND IMPLICATIONS: This prospective study, utilizing comprehensive multi-sector, multi-omics sequencing and clinical data from surgically resected HCC, reveals critical insights into the role of tumor evolution and intra-tumor heterogeneity (ITH) in determining the prognosis of Hepatocellular Carcinoma (HCC). These findings are invaluable for oncology researchers and clinicians, as they underscore the influence of distinct evolutionary paths and the 'bad apple' effect, where the most aggressive tumor fraction dictates disease progression. These insights not only enhance prognostic accuracy post-surgical resection but also pave the way for developing personalized therapies tailored to specific tumor evolutionary and transcriptomic profiles. The co-existence of multiple sub-types within the same tumor prompts a re-appraisal of the utilities of depending on single samples to represent the entire tumor and suggests the need for clinical molecular imaging. This research thus marks a significant step forward in the clinical understanding and management of HCC, underscoring the importance of integrating tumor evolutionary dynamics and multi-omics biomarkers into therapeutic decision-making.

Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma.

BACKGROUND: Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC). METHODS: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples. RESULTS: Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate. DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.

Living donor hepatectomy in medium volume liver transplant centre has comparable outcomes to high volume centres: validation of donabedian quality assurance framework.

BACKGROUND: Given the complexity of living donor hepatectomy, it is expected that high hospital volume will better outcomes. This study aims to evaluate post-operative outcomes for living donor hepatectomy in a medium volume liver transplant centre and compare to outcomes in high volume centres. Also, it serves as a validation tool for framework of structure-process-outcome model for safe living donor hepatectomy program. METHODS: 204 donors who underwent donor hepatectomy between June 1996 to September 2019 were reviewed retrospectively and compared to outcomes in high volume centres. RESULTS: At 6 months, overall donor morbidity rate was 20/204 (9.8%). Wound complications were most common at 5/204 (2.5%). Majority of complications were either Clavien grade 1 or 2 and only 3 donors had Clavien grade 3 complications. There was zero donor mortality. DISCUSSION: Our centre's donor morbidity rate of 9.8% is the one of the lowest reported in the published literature. With increased experience, stringent donor selection and enhanced perioperative care by a multi-disciplinary team, outcomes in a medium volume centre can match the outcomes reported in high volume centres. The framework for quality in terms of structure, process and outcomes is presented which can be adopted for developing programs.

Presence of tumor cells in intra-operative blood salvage autotransfusion samples from hepatocellular carcinoma liver transplantation: analysis using highly sensitive microfluidics technology.

BACKGROUND: The application of intra-operative blood salvage autotransfusion(IBSA) in liver transplantation(LT) for hepatocellular carcinoma(HCC) remains controversial due to the theoretical risk of tumour cell(TC) reintroduction. Current studies evaluating for presence of TC are limited by suboptimal detection techniques. This study aims to analyze the presence of TC in HCC LT autologous blood using microfluidics technology. METHODS: A prospective study of HCC patients who underwent LT from February 2018-April 2019 was conducted. Blood samples were collected peri-operatively. TCs were isolated using microfluidics technology and stained with antibody cocktails for confirmation. RESULTS: A total of 15 HCC LT patients were recruited. All recipients had tumour characteristics within the University of California, San Francisco(UCSF) criteria pre-operatively. TC was detected in all of the autologous blood samples collected from the surgical field. After IOCS wash, five patients had no detectable TC, while 10 patients had detectable TC; of these two remained positive for TC after Leukocyte Depletion Filter(LDF) filtration. CONCLUSION: The risk of tumour cell reintroduction using IBSA in HCC LT patients can be reduced with a single LDF. Future studies should evaluate the proliferation capacity and tumorigenicity of HCC TC in IBSA samples, and the effects of TC reintroduction in patients with pre-existing HCC TCs.

An international multicenter study of protocols for liver transplantation during a pandemic: A case for quadripartite equipoise.

BACKGROUND & AIMS: The outbreak of COVID-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern. There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources. METHODS: We performed an international multicenter study of transplant centers to understand the evolution of policies for transplant prioritization in response to the pandemic in March 2020. To describe the ethical tension arising in this setting, we propose a novel ethical framework, the quadripartite equipoise (QE) score, that is applicable to liver transplantation in the context of limited national resources. RESULTS: Seventeen large- and medium-sized liver transplant centers from 12 countries across 4 continents participated. Ten centers opted to limit transplant activity in response to the pandemic, favoring a "sickest-first" approach. Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors - recipient outcome, donor/graft safety, waiting list mortality and healthcare resources - for 7 countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. CONCLUSIONS: This four-dimensional model of quadripartite equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems. LAY SUMMARY: There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources during the COVID-19 pandemic. We describe a four-dimensional model of quadripartite equipoise that models these ethical tensions and can guide the regulation of transplant activity in response to the increasing burden on healthcare systems.

Clinical management and outcomes of acute pancreatitis: Identifying areas for quality improvement in a tertiary Asian setting.

BACKGROUND: This study aims to review the clinical management of patients with acute pancreatitis in a tertiary institute in Singapore, and to identify areas qualiy improvement based on validation against the recommendations in the IAP/APA and the Japanese guidelines. METHODS: 391 patients from a prospective electronic database were included and reviewed for compliance to the International Association of Pancreatology (IAP)/American Pancreatic Association (APA) guidelines (2013) and the Japanase Guidelines (2015). RESULTS: The 90 day mortality was 8.4% for moderately severe and 11.9% for severe pancreatitis. The accuracy of SIRS in predicting severe acute pancreatitis on admission was 72.1% and at 48 h 80.8%. Only 61.1% patients had ultrasound scan during their admission of whom 32.9% had it within 24 h of admission. 18.3% patients with initial diagnosis of idiopathic pancreatitis had EUS. 50% received Ringer lactate for initial fluid resuscitation. 38.7% received antibiotics as prophylaxis. 21.4% with severe acute pancreatitis had early enteral nutrition. Only 21.4% patients with biliary pancreatitis had index admission cholecystectomy. CONCLUSION: The compliance to existing guidelines for management of acute pancreatitis is variable. Identifying gaps and implementing measures to address them allows for continued improvement in the management of patients with acute pancreatitis.

The influence of the middle hepatic vein and its impact on outcomes in right lobe living donor liver transplantation.

BACKGROUND: In adult right lobe living donor liver transplantation, the decision to include the middle hepatic vein (MHV) remains controversial. METHODS: A retrospective analysis of 50 R-LDLTs between January 2008 and June 2016 was performed. RESULTS: Twenty-one procedures were performed using a MHV+ graft (42.0%) and 29 procedures using a MHV- graft (58%). MHV- donors were taller (173 vs 166 cm, p = 0.004) with a larger standard liver volume (1351 vs 1245 mls, p = 0.014) compared to MHV+ donors. The duration of operation for donors was significantly longer in the MHV+ group (530 (313-975) mins) compared to the MHV- group (489 (336-708) mins) (p = 0.029). Similarly, the operative time for recipients was longer in the MHV+ group (660 (428-831) mins) compared to MHV- (579 (359-1214) mins) (p = 0.023). MHV- grafts were heavier compared to MHV+ grafts (918 vs 711 g, p = 0.017). Recipient mortality rates and Kaplan-Meier survival analysis were comparable (p = 0.411). All donors were well at last review. CONCLUSION: Both MHV+ and MHV- grafts are safe for the donor and recipient. The decision to take the MHV should be based on specific donor-recipient characteristics.

A predictive nomogram to identify factors influencing the success of a concomitant laparoscopic cholecystectomy with common bile duct exploration for choledocholithiasis.

BACKGROUND: Single-staged laparoscopic common bile duct exploration (LCBDE) offers clear benefits in terms of cost and shorter hospitalization stays. However, a failed LCBDE requiring conversion to open surgery is associated with increased morbidity. This study reviewed the factors determining success of LCBDE, and created a predictive nomogram to stratify patients for the procedure. METHODS: A retrospective analysis of 109 patients who underwent LCBDE was performed. A nomogram was developed from factors significantly associated with conversion to open surgery and validated. RESULTS: Sixty-two patients underwent a successful LCBDE, while 47 patients required a conversion to open CBDE. The presence of underlying cholangitis (crude OR 2.70, 95% CI: 1.12-6.56, p = 0.017), together with its subsequent interventions, seemed to adversely increase the rate of conversion to open surgery. The predictive factors included in the nomogram for a failed laparoscopic CBDE included prior antibiotic use (adjusted OR (AOR) 2.98, 95% CI: 1.17-7.57, p = 0.022), previous ERCP (AOR 4.99, 95% CI: 2.02-12.36, p = 0.001) and abnormal biliary anatomy (AOR 9.37, 95% CI: 2.18-40.20, p = 0.003). CONCLUSION: LCBDE is useful for the treatment of choledocholithiasis. However, patients who were predicted to have an elevated risk for open conversion might not be ideal candidates for the procedure.

Same admission laparoscopic cholecystectomy for acute cholecystitis: is the "golden 72 hours" rule still relevant?

BACKGROUND: Studies have shown that same admission laparoscopic cholecystectomy (SALC) is superior to delayed laparoscopic cholecystectomy for acute cholecystitis (AC). While some proposed a"golden 72-hour" for SALC, the optimal timing remains controversial. The aim of the study was to compare the outcomes of SALC in AC patients with different time intervals from symptom onset. METHODS: A retrospective analysis of 311 patients who underwent SALC for AC from June 2010-June 2015 was performed. Patients were divided into three groups based on the time interval between symptom onset and surgery: <4 days (E-SALC), 4-7 days (M-SALC), >7 (L-SALC). RESULTS: The mean duration of symptoms was 2(1-3), 5(4-7) and 9 (8-13) days for E-SALC, M-SALC and L-SALC, respectively (p < 0.001). Conversion rates were higher in the L-SALC group [E-SALC, 8.2% vs M-SALC, 9.6% vs L-SALC, 21.4%] (p = 0.048). The total length of stay was longer in patients with longer symptom duration [E-SALC, 4 (2-33) vs M-SALC, 2 (2-23) vs L-SALC, 7 (2-49)] (p < 0.001). CONCLUSION: Patients with AC presenting beyond 7 days of symptoms have higher conversion rates and longer length of stay associated with SALC. However, patients with less than a week of symptoms should be offered SALC.

Outcomes of Percutaneous Cholecystostomy for Acute Cholecystitis.

BACKGROUND: Acute cholecystitis (AC) is an important cause of emergency admissions among the elderly. The use of percutaneous cholecystostomy (PC) as bridging therapy among high-risk patients is widely accepted. However, the use of PC as definitive treatment is controversial. AIM: To determine the characteristics, clinical outcomes and predictors of recurrence of AC among patients who underwent PC. METHODS: A retrospective case series of 71 consecutive patients [73 (38-96) years, 43/71 males] treated with PC for AC at a tertiary hospital from 2007 to 2013, with data collected from case records. RESULTS: Patients were followed up for 37.0 (0.1-110.8) months after PC. Mortality rate was 8.5 % (6/71) during the index admission and 32.4 % (23/71) at the end of follow-up. Recurrence rate for AC was 11.9 % (7/59). Median time to recurrence was 62 (13-464) days. PC was definitive treatment in 33/59. Predictors of recurrence were higher serum alkaline phosphatase (ALP) at diagnosis (OR = 1.01, 95 % CI 1.00-1.02, p = 0.021) and acute myocardial infarction (AMI) during index admission (OR = 8.00, 95 % CI 1.19-54.0, p = 0.033). Fifteen patients (26.3 %, 15/71) had post-procedural complications including dislodgement (14 %, 10/71), tube obstruction (7.0 %, 5/71), bile leaks (2.8 %, 2/71), gallbladder perforation (1.4 %, 1/71), bowels perforation (1.4 %, 1/71) and severe post-procedural haemorrhage (1.4 %, 1/71). CONCLUSION: PC is effective and relatively safe in high-risk patients with AC. However, patients with higher ALP or AMI during index admission have higher risk of recurrence and might benefit from definitive cholecystectomy.

A randomized controlled trial comparing post-operative pain in single-incision laparoscopic cholecystectomy versus conventional laparoscopic cholecystectomy.

INTRODUCTION: An increasing body of evidence is being published about single-incision laparoscopic cholecystectomy (SILC), but there are no well-powered trials with an adequate evaluation of post-operative pain. This randomized trial compares SILC against four-port laparoscopic cholecystectomy (LC) with post-operative pain as the primary endpoint. METHODS: Hundred patients were randomized to either SILC (n = 50) or LC (n = 50). Exclusion criteria were (1) Acute cholecystitis; (2) ASA 3 or above; (3) Bleeding disorders; and (4) Previous open upper abdominal surgery. Patients and post-operative assessors were blinded to the procedure performed. The site and severity of pain were compared at 4 h, 24 h, 14 days and 6 months post-procedure using the visual analog scale; non-inferiority was assumed when the lower boundary of the 95% confidence interval of the difference was above -1 and superiority when p ≤ 0.05. RESULTS: The study arms were demographically similar. At 24 h post-procedure, SILC was associated with less pain at extra-umbilical sites (rest: p = 0.004; movement: p = 0.008). Pain data were inconclusive at 24 h at the umbilical site on movement; SILC was otherwise non-inferior for pain at all other points. Operating duration was longer in SILC (79.46 vs 58.88 min, p = 0.003). 8% of patients in each arm suffered complications (p = 1.000). Re-intervention rates, analgesic use, return to function, and patient satisfaction did not differ significantly. CONCLUSIONS: SILC has improved short-term pain outcomes compared to LC and is not inferior in both short-term and long-term pain outcomes. The operating time is longer, but remains feasible in routine surgical practice.

Banking of cryopreserved iliac artery and vein homografts: clinical uses in transplantation.

Iliac artery and vein homografts are critical for revascularization in living-donor liver transplantation. Since 2010, National Cardiovascular Homograft Bank and National University Hospital have collaborated in the pioneer endeavor of banking iliac vessel homografts for such surgeries in Singapore. This article aims to demonstrate that the processing, decontamination and cryopreservation techniques that our bank follow, help preserve iliac vessel homografts for a longer duration as compared to homografts preserved using short-term preservation techniques. This paper reports the first 4 years of post-operative outcome for recipients as a preliminary report for a longer-term outcome study. Criteria for donor assessment, techniques of iliac vessel homograft recovery, processing, decontamination, cryopreservation and storage according to the American Association of Tissue Banks standards are also described. From 2010 until 2013, we discovered of the iliac vessel homografts processed, 17 (94.4 %) were suitable for clinical use. Nine iliac artery grafts (64 %) and one iliac vein graft (14 %) were implanted. Irrespective of vessel type, homografts <90 mm in length were of little use. Of the nine current iliac vessel homograft recipients, eight patients (89 %) had living-donor liver transplantation and one patient (11 %) had reconstruction of the right internal carotid artery after resection of an aneurysm. Our preliminary results supports existing literatures that suggest cryopreserved iliac vessel homografts can be successfully used for revascularization in liver transplantation and reconstruction of carotid artery. Encouraging short-term post-operative patient outcomes have been achieved, with no report of adverse event attributed to implanted homografts. We believe that our processing, decontamination and cryopreservation techniques have helped preserve the homografts for longer duration as compared to homografts preserved using short-term preservation techniques.

Outcomes of resection of giant hepatocellular carcinoma in a tertiary institution: does size matter?

BACKGROUND: The surgical management of giant hepatocellular carcinoma (G-HCC), or HCC of ≥10 cm in diameter, remains controversial. The aim of this study was to compare the outcomes of surgical resection of, respectively, G-HCC and small HCC (S-HCC), or HCC measuring <10 cm. METHODS: A retrospective review of all patients (n = 86) diagnosed with HCC and submitted to resection in a tertiary hospital during the period from January 2007 to June 2012 was conducted. Overall survival (OS), recurrence rates and perioperative mortality at 30 days were compared between patients with, respectively, G-HCC and S-HCC. Prognostic factors for OS were analysed. RESULTS: The sample included 23 patients with G-HCC (26.7%) and 63 with S-HCC (73.3%) based on histological tumour size. Patient demographics and comorbidities were comparable. Median OS was 39.0 months in patients with G-HCC and 65.0 months in patients with S-HCC (P = 0.213). Although size did not affect OS in this cohort, the presence of satellite lesions [hazard ratio (HR) 3.70, P = 0.012] and perioperative blood transfusion (HR 2.85, P = 0.015) were negative predictors for OS. CONCLUSIONS: Surgical resection of G-HCC provides OS comparable with that after resection of S-HCC.

Metabolic syndrome after a liver transplantation in an Asian population.

BACKGROUND: With improvements in patient survival after a liver transplantation (LT), long-term sequelae such as metabolic syndrome (MS) have become increasingly common. This study aims to characterize the prevalence, associations and long-term outcomes of post-LTMS and its components in an Asian population. METHODS: A retrospective review of all adult patients who underwent LT at the National University Health System Singapore between December 1996 and May 2012 was performed. MS was defined using the Adult Treatment Panel (ATP) III criteria modified for an Asian population. RESULTS: The median age of this cohort of 90 patients was 50.0 (16.0-67.0) years, with a median follow-up duration of 60.0 (7.0-192.0) months. The prevalence of post-LTMS was 35.6%, diabetes mellitus (DM) 51.1%, hypertension 60.0%, obesity 26.7% and dyslipidaemia 46.7%. On univariate analysis, factors significantly associated with post-LT MS include female gender (P = 0.066), pre-LT respiratory comorbidities (P = 0.038), pre-LT obesity (P = 0.014), pre-LTDM (P < 0.001), pre-LT hypertension (P = 0.039), pre-LTMS (P < 0.001), prednisolone use ≥24 months (P = 0.005) and mycophenolate mofetil use ≥24 months (P = 0.035). On multivariate analysis, independent associations of post-LT MS were pre-LTDM (P = 0.011) and pre-LTMS (P = 0.024). There was no difference in long-term survival of patients with and without post-LTMS (P = 0.425). CONCLUSION: In conclusion, pre-LT components of the MS and the use of certain immunosuppressants are related to developing post-LTMS.

Laparoscopic drainage of cryptogenic liver abscess.

BACKGROUND: To retrospectively compare the outcomes of percutaneously drained and laparoscopically drained liver abscesses. METHODS: Eight-five consecutive patients with radiological evidence of liver abscess were treated at National University Hospital of Singapore from 2005 to 2011. Multivariable logistic regression was used to identify failures of intervention. This was defined as persistent objective signs of sepsis. Complications, length of antibiotic therapy, and hospital stay were recorded but not used as indicators for failure of intervention. A propensity score analysis was used to adjust for possible confounders. RESULTS: Twenty-seven (40.3%) patients in the percutaneous group did not respond to primary intervention compared to 2 patients (11.1%) in the laparoscopic group (p = 0.020). Two patients within the percutaneous group died from progression of sepsis despite intervention. In the multivariate model with propensity score, laparoscopic drainage had a protective effect against failure compared to percutaneous drainage of liver abscess (odds ratio [OR], 0.03; 95% confidence interval [CI], [0-0.4]; p = 0.008). There were no differences in complications related to the intervention (p = 0.108). Mean duration of antibiotics (p = 0.437) and hospital stay (p = 0.175) between the groups was similar. CONCLUSIONS: Laparoscopic drainage of cryptogenic liver abscesses should be considered as an option for drainage of liver abscess.

A genomic enhancer signature associates with hepatocellular carcinoma prognosis.

Background & Aims: Lifestyle and environmental-related exposures are important risk factors for hepatocellular carcinoma (HCC), suggesting that epigenetic dysregulation significantly underpins HCC. We profiled 30 surgically resected tumours and the matched adjacent normal tissues to understand the aberrant epigenetic events associated with HCC. Methods: We identified tumour differential enhancers and the associated genes by analysing H3K27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) and Hi-C/HiChIP data from the resected tumour samples of 30 patients with early-stage HCC. This epigenome dataset was analysed with previously reported genome and transcriptome data of the overlapping group of patients from the same cohort. We performed patient-specific differential expression testing using multiregion sequencing data to identify genes that undergo both enhancer and gene expression changes. Based on the genes selected, we identified two patient groups and performed a recurrence-free survival analysis. Results: We observed large-scale changes in the enhancer distribution between HCC tumours and the adjacent normal samples. Many of the gain-in-tumour enhancers showed corresponding upregulation of the associated genes and vice versa, but much of the enhancer and gene expression changes were patient-specific. A subset of the upregulated genes was activated in a subgroup of patients' tumours. Recurrence-free survival analysis revealed that the patients with a more robust upregulation of those genes showed a worse prognosis. Conclusions: We report the genomic enhancer signature associated with differential prognosis in HCC. Findings that cohere with oncofoetal reprogramming in HCC were underpinned by genome-wide enhancer rewiring. Our results present the epigenetic changes in HCC that offer the rational selection of epigenetic-driven gene targets for therapeutic intervention or disease prognostication in HCC. Impact and Implications: Lifestyle and environmental-related exposures are the important risk factors of hepatocellular carcinoma (HCC), suggesting that tumour-associated epigenetic dysregulations may significantly underpin HCC. We profiled tumour tissues and their matched normal from 30 patients with early-stage HCC to study the dysregulated epigenetic changes associated with HCC. By also analysing the patients' RNA-seq and clinical data, we found the signature genes - with epigenetic and transcriptomic dysregulation - associated with worse prognosis. Our findings suggest that systemic approaches are needed to consider the surrounding cellular environmental and epigenetic changes in HCC tumours.

Laparoendoscopic single-site minor hepatectomy for liver tumors.

BACKGROUND: Laparoscopic liver surgery is gaining increasing acceptance worldwide, but its frontiers are constantly challenged. Laparoendoscopic single-site surgery (LESS) has been performed for various organs, but the feasibility of LESS hepatectomies has yet to be explored fully. METHODS: From May 2010 to March 2011, seven patients underwent LESS minor hepatectomies. Patient demographic, operative, and clinical data were reviewed. RESULTS: Five left lateral sectionectomies, one segment 3, and one segment 5 resection were performed. The median operative time was 142 min (range, 104-171 min), and the median blood loss was 200 ml (range, 100-450 ml). The median hospital stay was 3 days (range, 1-11 days). For all the patients, the indications for surgery were suspected malignant tumors, and the surgical resection margins were clear for every patient. CONCLUSIONS: Laparoendoscopic single-site minor hepatectomy is a novel modification to traditional laparoscopic surgery. The method is safe and feasible without any compromise to oncologic safety for selected patients with hepatocellular carcinoma (HCC) and colorectal liver metastases that are peripheral and smaller than 5 cm in size.

Impact of donor age on recipient morbidity and mortality after living donor liver transplantation.

BACKGROUND: Evidence for use of graft from older donors in living donor liver transplantation (LDLT) has been conflicting. This study aims to clarify the impact of donor age on recipient morbidity and mortality after adult LDLT. METHODS: A total of 90 live liver donors and recipients who underwent primary adult-to-adult LDLT were divided into three groups according to donor age: donors in 20s (D-20s) group, donors in 30s and 40s (D-30s and 40s) group and donors in 50s & 60s (D-50s and 60s) group. Multivariate analyses were conducted to look for independent risk/prognostic factors. Donor age was analysed as a continuous variable to determine an optimal cut off. RESULTS: Overall donor morbidity was 4/90 (4.44%), major donor morbidity was 1/90 (1.11%) and there was no donor mortality. Recipients in the D-20s group had better 1-, 3- and 5-year recipient survival than recipients in the D-50s and 60s group (96%, 91%, 91% versus 73%, 58%, 58%, respectively) (P = 0.020). Donor age was identified to be an independently significant risk factor for increased major complications (P = 0.007) and prognostic factor for reduced overall survival (P = 0.014). The optimal donor age cut off was determined to be 46.5 years old. CONCLUSION: Older donors are associated with poorer recipient outcomes after adult-to-adult LDLT. Usage of liver grafts from older donors should be carefully considered when choosing liver grafts for patients undergoing LDLT.