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Introduction: Medical students have long provided informal, structured academic support for their peers in parallel with the institution’s formal curriculum, demonstrating a high degree of motivation and engagement for peer teaching. This qualitative descriptive study aimed to examine the perspectives of participants in a pilot peer teaching programme on the effectiveness and feasibility of adapting existing student-initiated peer bedside teaching into formal bedside teaching. Methods: Study participants were senior medical students who were already providing self-initiated peer-led bedside clinical teaching, clinicians who co-taught bedside clinical skills teaching sessions with the peer teachers and junior students allocated to the bedside teaching sessions led by peer teachers. Qualitative data were gathered via evaluation form, peer teacher and clinician interviews, as well as the observational field notes made by the research assistant who attended the teaching sessions as an independent observer. Additionally, a single Likert-scale question on the evaluation form was used to rate teaching effectiveness. Results: All three peer teachers, three clinicians and 12 students completed the interviews and/or questionnaires. The main themes identified were teaching effectiveness, teaching competency and feasibility. Teaching effectiveness related to the creation of a positive learning environment and a tailored approach. Teaching competency reflected confidence or doubts about peer-teaching, and feasibility subthemes comprised barriers and facilitators. Conclusion: Students perceived peer teaching effectiveness to be comparable to clinicians’ teaching. Clinical peer teaching in the formal curriculum may be most feasible in a hybrid curriculum that includes both peer teaching and clinician-led teaching with structured training and coordinated timetabling.

Summary: Background/objective: Complete resection is the most effective treatment of hilar cholangiocarcinoma (HC) but may result in high morbidity and mortality. Most HC patients have jaundice, and preoperative biliary drainage may reduce their risk of obstructive jaundice. ERCP and PTBD have been advocated for this purpose. This retrospective study investigated the influence of ERCP versus PTBD versus their combination on the short-term outcomes of curative HC resection. Methods: Patients having curative HC resection with preoperative biliary drainage in a span of 26 years were reviewed and divided into groups according to drainage modality. Drainage-related and surgical complications and hospital mortality were compared between groups. Intention-to-treat analysis using a separate set of initial drainage data was performed. Results: Eighty-six patients were divided into: Group A, ERCP only, n = 32 (32/86 = 37.2%); Group B, PTBD only, n = 10 (10/86 = 11.6%); Group C, ERCP + PTBD, n = 44 (44/86 = 51.2%). International normalized ratio was significantly higher in Group B (p = 0.008). The three groups were comparable in operative details, hospital stay, and mortality. Fifty-two patients had postoperative complications. Significantly more patients in Groups A and C had subphrenic abscess (A: 25%, B: 0%, C: 9.1%; p = 0.035) and subsequent radiological drainage. Group A had insignificantly more patients with wound infection (31.3% vs 10% vs 22.7%, p = 0.334), chest infection (28.1% vs 20% vs 11.4%, p = 0.178), and urinary tract infection (6.3% vs 0% vs 0%, p = 0.133). The three groups had similar rates of major complications (p = 0.501). They also had comparable survival outcomes (overall, p = 0.370; disease-free, p = 0.569). Fifteen and 71 patients received PTBD and ERCP respectively as first drainage mode. These two groups were comparable in liver function, preoperative comorbidity, intraoperative details, and postoperative outcomes. Conclusion: In the preoperative management of HC, the use of ERCP, PTBD or their combination is acceptable and can optimize patients’ condition for curative HC resection.

Introduction While combination of stereotactic body radiotherapy (SBRT) and immunotherapy are promising, their efficacy and safety have not been compared with SBRT-alone in patients with unresectable HCC. Methods This retrospective study included 100 patients with non-metastatic, unresectable HCC in two hospitals. Eligible patients had tumor nodules ≤ 3 and Child-Pugh liver function score of A5 to B7. Seventy patients received SBRT-alone, and 30 patients underwent combined SBRT and immunotherapy (SBRT-IO). Overall survival (OS), time to progression (TTP), overall response rate (ORR), and toxicity were analyzed. We adjusted for the potential confounding factors using propensity score matching. Results The median tumor size was 7.3 cm (range, 2.6 – 18 cm). Twenty-five (25%) of patients had vascular invasion. Before propensity score matching, the 1-year and 3-year OS rate was 89.9% and 59.8% in the SBRT-IO group and 75.7% and 42.3% in SBRT-alone group (p=0.039). After propensity score matching (1:2), 25 and 50 patients were selected from the SBRT-IO and SBRT-alone group. The 1-year and 3-year OS was 92.0% and 63.9% in the SBRT-IO group versus 74.0% and 43.3% in the SBRT-alone group (p=0.034). The 1-year and 3-year TTP was better in SBRT-IO group (1-year: 68.9% versus 58.9% and 3-year: 61.3% versus 32.5%, p=0.057). The ORR of 88% (CR: 56%, PR: 22%) in SBRT-IO arm was significantly better than 50% (CR: 20%, PR: 30%) in the SBRT-alone arm (p=0.006). Three patients (12%) developed ≥ grade 3 immune-related treatment adverse events (n=2 hepatitis, n=1 dermatitis) leading to permanent treatment discontinuation. Discussion / Conclusion Adding immunotherapy to SBRT resulted in better survival with manageable toxicities. Prospective randomized trial is warranted.

Abstract We present a 37 years’ experience in the management of biliary atresia (BA) and discuss long-term complications after Kasai portoenterostomy (KPE). A retrospective territory-wide study from 1980 to 2017 on 231 patients with open KPE from three tertiary paediatric surgical centres was performed. Outcome parameters were clearance of jaundice (COJ), native liver survival (NLS) and long-term complications. Factors affecting the operative outcomes were analyzed. The median duration of follow up was 17.5 (IQR: 13.5–22) years. Over 66% of patients became jaundice-freed at 1 year after KPE. Seventy patients (30.3%) received liver transplant (LT) at a median age of 6.2 (IQR: 4.3–8.4) years. The NLS rates at 10 and 20 years were 70.7% and 61.5% respectively with no significant change over the study period. The median age at KPE was 59 (IQR: 49–67) days. KPE performed before 70 days was associated with higher odd ratios for successful drainage but the age of KPE did not have an impact on the long-term NLS. Among all native liver survivors (n = 153), the median bilirubin level was 24 (IQR: 16–36) µmol/L. Portal hypertension (PHT) and recurrent cholangitis were found in 51.6% and 27.5% of them respectively. With a vigilant follow up program, more than 60% of BA patients could remain stable with the disease and achieve long-term survival without LT. Although cholestasis, portal hypertension and recurrent cholangitis are common in long-term NLS, with a comprehensive follow management strategy, they do not always necessitate LT. Our study serves as an example for countries where deceased donor organs are scarce due to very low donation rate.

Summary: Background/Objective: Hepatectomy is the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). The relationship between postoperative complication and oncological outcome has not been defined. We aimed to elucidate the effect of postoperative complication on long-term survival of ICC patients after curative resection. Methods: Data of consecutive patients who had curative resection for ICC at our hospital from 1991 to 2013 were reviewed. Patients with cholangiohepatocellular carcinoma, metastatic adenocarcinoma or Klaskin tumor were excluded. Clinicopathological data and postoperative events were extracted from database for survival analysis. Results: There were 107 patients in our series. Their median age was 61 years. The median follow-up time was 24 months. The median tumor size was 6 cm. Major hepatectomy was required in 52.3% of them. The median operation time and blood loss was 439 minutes and 0.9L respectively. R0 resection was achieved in 88.8% of them. The median length of stay was 11 days. The 30-day and 90-day mortality was 2.5% and 6.8% respectively. Major complications were found in 20.6% of them. Patients with postoperative complications had significantly inferior survival than patients without (3-yr DFS 38% vs. 27%, P = 0.001; 3-yr overall: 51% vs. 27%, P

BACKGROUND:Patients receiving total intravenous anesthesia (TIVA) with propofol have been shown to experience less postoperative pain. We evaluated the post-operative analgesic effects of propofol compared with sevoflurane maintenance of anesthesia in liver surgery. This study was registered at ClinicalTrials.gov (NCT02179437). METHODS:In this retrospective study, records of patients who underwent liver surgery between 2010 and 2013 were reviewed. Ninety-five patients anesthetized with propofol TIVA were matched with 95 patients anesthetized with sevoflurane. Numeric pain rating scale (NRS) pain scores, postoperative morphine consumption, side effects and patients' satisfaction with pain relief were evaluated. RESULTS:The TIVA group reported lower NRS pain scores during coughing on postoperative days 1 and 2 but not 3 (p = 0.0127, p = 0.0472, p = 0.4556 respectively). They also consumed significantly less daily (p = 0.001 on day 1, p = 0.0231 on day 2, p = 0.0004 on day 3), accumulative (p = 0.001 on day 1, p

Background & Aims: Combined 18F-fluorodeoxyglucose (FDG) and 11C-acetate (dual-tracer) positron-emission tomography/computed tomography (PET/CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels. Methods: We retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET/CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET/CT in diagnosing HCC were evaluated. A multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed. Results: Dual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n = 273, κ = 0.822; 95% CI 0.803-0.864). Conclusions: Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP. Impact and implications: Compared to CT or MRI, dual-tracer positron-emission tomography/computed tomography (PET/CT) led to upstaging in 12% of patients with hepatocellular carcinoma (HCC) undergoing staging, resulting in treatment modification in 8% of cases and a cost saving of US$495 per patient. It also accurately detected HCC in high-risk cases where CT or MRI were equivocal or normal. Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

Background & Aims: Hepatocellular carcinoma (HCC) is a heterogeneous cancer with varying levels of liver tumor initiating or cancer stem cells in the tumors. We aimed to investigate the expression of different liver cancer stem cell (LCSC) markers in human HCCs and identify their regulatory mechanisms in stemness-related cells. Methods: We used an unbiased, single-marker sorting approach by flow cytometry, fluorescence-activated cell sorting, and transcriptomic analyses on HCC patients’ resected specimens. Knockdown approach was used, and relevant functional assays were conducted on the identified targets of interest. Results: Flow cytometry on a total of 60 HCC resected specimens showed significant heterogeneity in the expression of LCSC markers, with CD24, CD13, and EpCAM mainly contributing to this heterogeneity. Concomitant expression of CD24, CD13, and EpCAM was detected in 32 HCC samples, and this was associated with advanced tumor stages. Transcriptomic sequencing on the HCC cells sorted for these individual markers identified epidermal growth factor receptor kinase substrate 8-like protein 3 (EPS8L3) as a common gene associated with the 3 markers and was functionally validated in HCC cells. Knocking down EPS8L3 suppressed the expression of all 3 markers. To search for the upstream regulation of EPS8L3, we found SP1 bound to EPS8L3 promoter to drive EPS8L3 expression. Furthermore, using Akt inhibitor MK2206, we showed that Akt signaling–driven SP1 drove the expression of the 3 LCSC markers. Conclusions: Our findings suggest that Akt signaling–driven SP1 promotes EPS8L3 expression, which is critical in maintaining the downstream expression of CD24, CD13, and EpCAM. The findings provide insight into potential LCSC-targeting therapeutic strategies.

Different cells of the tumour microenvironment in HBV-associated human hepatocellular carcinoma (HCC) interact to promote tumour immunity. Here the authors use single cell RNA sequencing to identify TIGIT-NECTIN2 as a pathway by which tumour-associated macrophages reduce intratumour T cell activation.

Background. Precise staging is essential in the management of patients with recurrent hepatocellular carcinoma (HCC) after liver transplantation. There is no current consensus on the optimal staging strategy. We conducted this study to evaluate the performance of dual-tracer positron emission tomography-computed tomography (PET-CT) for this purpose and to investigate whether the results of dual-tracer PET-CT affected patient management. Methods. A retrospective study was conducted. Patients who underwent dual-tracer PET-CT for suspected or confirmed HCC recurrence after liver transplant were included. The lesion-based sensitivity and positive predictive value of dual-tracer PET-CT were determined. Results. Fifty-six patients and 189 recurrent tumors were included. The lesion-based sensitivity and positive predictive value of dual-tracer PET-CT were 94.7% and 90.4%, respectively. The sensitivity of dual-tracer PET-CT was better than the standard imaging in the surveillance protocol (82.5% versus 94.7%, P < 0.001), especially for detecting liver recurrence (71.0% versus 96.8%, P < 0.001). Half of the dual-tracer PET-CT detected additional recurrence (n = 26, 46.4%) and one-third led to a change in management (n = 19, 33.9%). Ten patients (17.9%) with inconclusive standard imaging had metabolic recurrence confirmed on PET-CT and treatment was commenced early. Four patients (7.1%) had revised locoregional treatment, and 5 (8.9%) had to withdraw from locoregional treatment after the detection of additional metastatic disease. Conclusions. Dual-tracer PET-CT is effective for staging posttransplant HCC recurrence. It often provides valuable information to guide clinical management.

Objective: To derive and validate a scoring system for major complication after hepatectomy. Background: Complications after hepatectomy significantly compromise survival outcomes, method to predict such risk is lacking. A reliable scoring system is therefore awaited. Methods: Consecutive adult patients receiving hepatectomy for primary or secondary liver malignancy from 1995 to 2014 were recruited. After randomization, patients were allocated to derivation and validation group respectively. A scoring system predicting occurrence of major complication was developed. Results: There were 2613 patients eligible for the study. The overall complication rate for the series was 10%. Impaired performance status (p = 0.014), presence of pre-existing medical illness (p = 0.008), elevated ALP (p = 0.005), urea (p < 0.001), and hypoalbuminemia (p = 0.008), and major hepatectomy (p < 0.001) were found to be independently associated major complications. A score was assigned to each of these factors according to their respective odd ratio. A total score of 0-17 was calculated for all patients. This score was shown to discriminate well with complication rate in both derivation and validation group (c-statistic: 0.71, p < 0.001 and 0.74, p < 0.001 respectively). The complication rate for low (score 0-5), moderate (score 6-10) and high (score 10 or above) risk group were respectively 5%, 16% and 28%. This risk stratification model was tested and confirmed in the validation group using Chi-square goodness-of-fit test (p = 0.864). Conclusion: A validated risk stratification model provides an accurate and easy-to-use reference tool for patients and clinicians during the informed consent process. [ABSTRACT FROM AUTHOR]

Independent risk factors associated with hepatitis B (HBV)-related hepatocellular carcinoma (HCC) after resection remains unknown. An accurate risk score for HCC recurrence is lacking.We prospectively followed up 200 patients who underwent liver resection for HBV-related HCC for at least 2 years. Demographic, biochemical, tumor, virological and anti-viral treatment factors were analyzed to identify independent risk factors associated with recurrence after resection and a risk score for HCC recurrence formulated.Two hundred patients (80% male) who underwent liver resection for HBV-related HCC were recruited. The median time of recurrence was 184 weeks (IQR 52-207 weeks) for the entire cohort and 100 patients (50%) developed HCC recurrence. Stepwise Cox regression analysis identified that one-month post resection HBV DNA >20,000 IU/mL (p = 0.019; relative risk (RR) 1.67; 95% confidence interval (C.I.): 1.09-2.57), the presence of lymphovascular permeation (p100ng/mL before resection (p = 0.021; RR 1.63; 95% C.I.: 1.08-2.47) were independently associated with HCC recurrence. Antiviral treatment before resection (p = 0.024; RR 0.1; 95% C.I.: 0.01-0.74) was independently associated with reduced risk of HCC recurrence. A post-resection independent predictive score (PRIPS) was derived and validated with sensitivity of 75.3% and 60.6% and specificity of 55.7% and 79.2%, to predict the 1- and 3-year risks for the HCC recurrence respectively with the hazard ratio of 2.71 (95% C.I.: 2.12-3.48; p

Combined hepatocellular cholangiocarcinoma (cHCC-CC) is an uncommon histological variant of primary liver cancer. This combined type of tumour lesion follows an aggressive clinical course with an unfavourable prognosis. Although the role of orthotopic liver transplantation in the management for hepatocellular carcinoma is well defined, to date, there has been no report on its treatment value for cHCC-CC. We report our experience of orthotopic liver transplantation in three patients with cHCC-CC. One patient succumbed to distant metastases 16.5 months after liver transplantation whereas the other two patients continued to survive 35 and 25 months after transplantation, respectively.