Baseline Albumin-Bilirubin grade as a predictor of response and outcome of regorafenib therapy in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The use of regorafenib in the treatment of hepatocellular carcinoma (HCC) is widespread. Albumin-Bilirubin (ALBI) has been shown to be a potential prognostic marker for regorafenib treatment, but its prognostic value remains controversial. Therefore, we conducted a meta-analysis to investigate the value of the baseline ALBI grade in predicting the efficacy and survival outcomes of HCC patients after regorafenib treatment. METHODS: PubMed, Embase, Cochrane library, Web of Science, CNKI, Wan Fang Data, and Vip Database were searched from January 2010 to October 2022. Studies treating HCC patients with regorafenib and with ALBI as a categorical variable, overall survival (OS) and progression-free survival (PFS) as outcome indicators were included. After applying Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included studies, Review Manager 5.4 was used to statistically analyze. Chi-square Q test and I2 statistics were used to detect heterogeneity. Funnel plot asymmetry, Egger's and Begg's test were used to evaluate publication bias. RESULTS: A total of 12 studies, comprising 1,918 patients, were included in the meta-analysis. The included studies were all evaluated as high quality. Compared to the high-grade baseline ALBI group, patients in the low-grade group had a longer survival time after receiving regorafenib and also more suitable for regorafenib treatment [odds ratio (OR) = 6.50, 95% confidence interval (CI): 2.22-18.96, P < 0.01]. The low-grade baseline ALBI group before sorafenib treatment was significantly correlated with better OS [hazard ratio (HR) = 2.36, 95% CI: 1.68-3.31, P < 0.00001] and PFS (HR = 1.56, 95% CI: 1.16-2.08, P = 0.003). Likewise, the low-grade baseline ALBI group before regorafenib was also significantly correlated with better OS (HR = 1.56, 95% CI: 1.15-2.13, P = 0.005) and PFS (HR = 2.06, 95% CI: 1.37-3.11, P = 0.0005). In addition, the ALBI grade was significantly correlated with disease control rate (DCR) (OR = 2.90, 95% CI: 1.45-5.79, P = 0.003), but not the objective response rate (OR = 1.98, 95% CI: 0.71-5.46, P = 0.19). CONCLUSIONS: The baseline ALBI grade could be a valuable prognostic indicator for predicting response and outcomes in HCC patients treated with regorafenib.

Obstacles for T-lymphocytes in the tumour microenvironment: Therapeutic challenges, advances and opportunities beyond immune checkpoint.

The tumour microenvironment (TME) imposes a major obstacle to infiltrating T-lymphocytes and suppresses their function. Several immune checkpoint proteins that interfere with ligand/receptor interactions and impede T-cell anti-tumour responses have been identified. Immunotherapies that block immune checkpoints have revolutionized the treatment paradigm for many patients with advanced-stage tumours. However, metabolic constraints and soluble factors that exist within the TME exacerbate the functional exhaustion of tumour-infiltrating T-cells. Here we review these multifactorial constraints and mechanisms - elevated immunosuppressive metabolites and enzymes, nutrient insufficiency, hypoxia, increased acidity, immense amounts of extracellular ATP and adenosine, dysregulated bioenergetic and purinergic signalling, and ionic imbalance - that operate in the TME and collectively suppress T-cell function. We discuss how scientific advances could help overcome the complex TME obstacles for tumour-infiltrating T-lymphocytes, aiming to stimulate further research for developing new therapeutic strategies by harnessing the full potential of the immune system in combating cancer.

The Impact of the COVID-19 Pandemic on Hepatobiliary and Pancreatic Surgical Services in Singapore: Retrospective Quantitative Study.

BACKGROUND: At the height of the COVID-19 pandemic, the hepatopancreatobiliary (HPB) unit had to reorganize its surgical case volume due to the rationing of health care resources. We report on a local audit evaluating the impact of COVID-19 on the HPB unit and the HPB surgical oncology practice. OBJECTIVE: The aim of this study was to review the impact of the COVID-19 pandemic on the HPB unit's elective and emergency surgical cases. The secondary aims were to investigate the impact on the HPB surgical oncology operative case volume. METHODS: We performed a comparative audit of the HPB unit surgical case volume for January-June 2019 (baseline) and 2020 (COVID-19). Elective and emergency cases performed under general anesthesia were audited. Elective cases included hernia and gallbladder operations and liver and pancreatic resections. Emergency cases included cholecystectomies and laparotomies performed for general surgical indications. We excluded endoscopies and procedures done under local anesthesia. The retrospective data collected during the 2 time periods were compared. This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000040265). RESULTS: The elective surgical case volume decreased by 41.8% (351 cases in 2019 compared to 204 cases in 2020) during the COVID-19 pandemic. The number of hernia operations decreased by 63.9% (155 in 2019 compared to 56 in 2020; P<.001) and cholecystectomies decreased by 40.1% (157 in 2019 compared to 94 in 2020; P=.83). The liver and pancreatic resection volume increased by 16.7% (30 cases in 2019 compared to 35 cases in 2020; P=.004) and 111.1% (9 cases in 2019 compared to 19 cases in 2020; P=.001), respectively. The emergency surgical workload decreased by 40.9% (193 cases in 2019 compared to 114 cases in 2020). The most significant reduction in the emergency workload was observed in March (41 to 23 cases, a 43.9% reduction; P=.94), April (35 to 8 cases, a 77.1% reduction; P=.01), and May (32 to 14 cases, a 56.3% reduction; P=.39); however, only April had a statistically significant reduction in workload (P=.01). CONCLUSIONS: The reallocation of resources due to the COVID-19 pandemic did not adversely impact elective HPB oncology work. With prudent measures in place, essential surgical services can be maintained during a pandemic. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000040265); https://tinyurl.com/ms9kpr6x.

Pancreaticoduodenectomy after Roux-en-Y Gastric Bypass: a novel reconstruction technique.

The obesity epidemic continues to increase around the world with its attendant complications of metabolic syndrome and increased risk of malignancies, including pancreatic malignancy. The Roux-en-Y gastric bypass (RYGB) is an effective bariatric procedure for obesity and its comorbidities. We describe a report wherein a patient with previous RYGB was treated with a novel reconstruction technique following a pancreaticoduodenectomy (PD). A 59-year-old male patient with previous history of RYGB was admitted with painless progressive jaundice. Imaging revealed a distal common bile duct stricture and he underwent PD. There are multiple options for reconstruction after PD in patients with previous RYGB. The two major decisions for pancreatic surgeon are: (I) resection/preservation of remnant stomach and (II) resection/preservation of original biliopancreatic limb. This has to be tailored to the patient based on the intraoperative findings and anatomical suitability. In our patient, the gastric remnant was preserved, and distal part of original biliopancreatic limb was anastomosed to the stomach as a venting anterior gastrojejunostomy. A distal loop of small bowel was used to reconstruct the pancreaticojejunostomy and hepaticojejunostomy and further distally a new jejunojejunostomy performed. The post-operative course was uneventful, and the patient was discharged on 7th day. With the increase in number of bariatric procedures performed worldwide, pancreatic surgeons should be aware of the varied surgical reconstruction options for PD following RYGB. This should be tailored to the patient and there is no "one-size-fits-all".

Role of social comparison in preparedness for practice as a junior doctor in Singapore: a longitudinal qualitative study.

OBJECTIVES: To date, most research on medical graduates' preparedness for practice has conceptualised preparedness as something possessed by the individual. However, new doctors work within social settings with other people and, given this, we argue that preparedness has a social and comparative dimension. The aim of this paper is to explore medical students'/graduates' self-assessments of their preparedness for practice using the lens of social comparison theory. SETTING: We invited medical students from one of Singapore's three medical schools who were in their final-year Student Assistantship Programme to participate in semi-structured interviews, and follow-up interviews 6 months later when they were working as junior doctors. Data was collected from two cohorts, in 2018 and 2019. Initial analysis of interview transcripts was inductive and thematic. Social comparison theory was used for subsequent theory-driven analysis. PARTICIPANTS: 31 participants took part, of whom 21 also engaged in follow-up interviews. RESULTS: We identified three uses of social comparison: as coping strategy to manage uncertainties in transitions where there was no formal, objective testing of their performance; as a means to confirm their self-perceived preparedness (upwards or downwards, eg, being better or worse prepared than comparator others); and as the basis for decision-making (eg, changing career choices). CONCLUSIONS: Senior medical students and newly-graduated doctors compare themselves with peers and near-peers in terms of prior learning and current performance to evaluate and understand their own performance at work. Future studies need to examine further how the feeling of preparedness or unpreparedness generated from social comparisons may affect subsequent clinical performance and professional development.

3D Laparoscopic common bile duct exploration with primary repair by absorbable barbed suture is safe and feasible.

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP), with interval laparoscopic cholecystectomy (LC), is the most common treatment approach for common bile duct (CBD) stones. However, recent studies show that single-stage laparoscopic CBD exploration (LCBDE) is safe and feasible. Three-dimensional (3D) laparoscopy enhances depth perception and facilitates intracorporeal suturing. The application of 3D technology for LCBDE is emerging, and we report our case series of 3D LCBDE. METHODS: We audited the 27 consecutive 3D LCBDE performed from July 2017 to January 2020. We have a liberal policy for magnetic resonance cholangiopancreatography (MRCP) in patients with deranged liver function tests (LFT). All CBD explorations were done through choledochotomy with a 5 mm flexible choledochoscope and primarily repaired with an absorbable barbed suture without a stent or T-tube. RESULTS: The mean age of patients was 68 (range 44-91) years, and 12 (44%) were male. The indications for surgery were choledocholithiasis 67% (n=18), cholangitis 22% (n=6), and gallstone pancreatitis 11% (n=3). About 67% (n=18) had pre-operative ERCP. About 37% (n=10) had pre-operative biliary stent. Pre-operative MRCP was done in 74% (n=20), and the mean diameter of CBD was 14.5 mm (range 7-30). The median operative time was 160 (range 80-265) min. The operative drain was inserted in 18 patients. One patient each (4%) had a bile leak and a retained stone. There was no open conversion, readmission, or mortality. CONCLUSION: 3D LCBDE with primary repair by an absorbable barbed suture is safe and feasible. RELEVANCE FOR PATIENTS: This paper emphasized that one stage LCBDE should be a treatment option which is comparable with two stage ERCP followed by LC to treat CBD stones. In addition, 3D technology and barbed sutures use in LCBDE are safe and useful.

A study of 3013 cases of hepatocellular carcinoma: Etiology and therapy before and during the current decade.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a significant global problem. With advances in HCC diagnosis and therapy, our hypothesis is that there are significant differences in the clinical characteristics and treatment of HCC over the years. METHODS: Patients with HCC between 1980 and 2018 from three major tertiary hospitals in Singapore were enrolled into a Research Electronic Data Capture database. Clinical characteristics and treatment of HCC were compared between those diagnosed before 2008 (cohort A) and during the current decade (ie from 2008 onwards) (cohort B). RESULTS: There were 3013 patients. Mean age of HCC diagnosis was significantly older in cohort B (68.6 vs 61.2 years, P < 0.001). The most common etiology remained as chronic hepatitis B infection but the proportion due to hepatitis B was significantly lower in cohort B (46.6% vs 57.2%, P < 0.0001). The prevalence of cryptogenic/non-alcoholic steatohepatitis was significantly higher in cohort B than cohort A (27.1% vs 18.6%, P < 0.0001). More patients received curative therapy in cohort B (43.7% vs 27.1%, P < 0.0001. CONCLUSION: In this largest collection of HCC patients in Singapore, patients are diagnosed with HCC at an older age and cryptogenic/non-alcoholic steatohepatitis is becoming more important as an etiology of HCC in the current decade. More patients also received curative therapy in the current decade.

Helicobacter pylori knowledge and perception among multi-ethnic Asians.

BACKGROUND: Helicobacter pylori (HP) infection is endemic and causes peptic ulcer disease and gastric cancer. There is a lack of data related to awareness of the general public about HP and associated health risks. The objective of this study was to investigate the awareness and public perceptions about HP and the attitudes towards screening. METHODS: This cross-sectional study included a structured 19-item questionnaire targeting members of the general public at a restructured acute hospital in Singapore. RESULTS: Out of 504 participants, 152 (30.2%) were aware of HP. Higher education was associated with HP awareness (p < 0.001, OR 7.4, 95% CI 1.6-32.6). A third, 175 (34.7%) of the respondents identified the stomach as the primary site of infection. 131 (26.0%) respondents identified the fecal-oral route as a mode of transmission. 178 (35.3%) respondents were aware of available screening modalities, with around half of them willing to be screened with blood (n = 256, 50.8%) or breath tests (n = 265, 52.6%). 430 (85.3%) participants were keen to learn more about HP, and this was associated with age (p < 0.05, OR 3.9, 95% CI 2.1-7.1). CONCLUSION: Awareness about HP infection is low, and acceptance of screening tests is high. Educational efforts are needed to improve awareness.

Improving postoperative mobilisation rates in patients undergoing elective major hepatopancreatobiliary surgery.

BACKGROUND: Early mobilisation reduces postoperative complications such as pneumonia, deep vein thrombosis and hospital length of stay. Many authors have reported poor compliance with early mobilisation within Enhanced Recovery After Surgery initiatives. OBJECTIVES: The primary objective was to increase postoperative day (POD) 2 mobilisation rate from 23% to 75% in patients undergoing elective major hepatopancreatobiliary (HPB) surgery within 6 months. METHODS: We report a multidisciplinary team clinical practice improvement project (CPIP) to improve postoperative mobilisation of patients undergoing elective major HPB surgery. We identified the common barriers to mobilisation and analysed using the fishbone or cause-and-effect diagram and Pareto chart. A series of Plan-Do-Study-Act cycles followed this. We tracked the rate of early mobilisation and mean distance walked. In the post hoc analysis, we examined the potential cost savings based on reduced hospital length of stay. RESULTS: Mobilisation rate on POD 2 following elective major HPB surgery improved from 23% to 78.9%, and this sustained at 6 months after the CPIP. Wound pain was the most common reason for failure to ambulate on POD 2. Hospital length of stay reduced from a median of 8 days to 6 days with an estimated cost saving of S$2228 per hospital stay. CONCLUSION: Multidisciplinary quality improvement intervention effort resulted in an improved POD 2 mobilisation rate for patients who underwent elective major HPB surgery. This observed outcome was sustained at 6 months after completion of the CPIP with potential cost savings.

Perceived Stress, Stigma, Traumatic Stress Levels and Coping Responses amongst Residents in Training across Multiple Specialties during COVID-19 Pandemic-A Longitudinal Study.

This study aimed to explore changes in psychological responses (perceived stress, traumatic stress, stigma, coping) over time in residents, as well as their predictors. The level of perceived stress, traumatic stress, stigma, and coping responses were assessed using the Perceived Stress Scale, Impact of Event-Revised, Healthcare Workers Stigma Scale, and Brief Coping Orientation to Problems Experienced (COPE) Inventory, respectively. We collected responses from 274 residents at baseline and 221 residents at 3 months follow-up (timepoint 2) from the National Healthcare Group (NHG) residency programs in Singapore. All residents reported lower perceived stress and lower perceived stigma compared to baseline. Use of avoidance coping was associated with all three psychological responses (perceived stress, traumatic stress, and stigma) across the two timepoints. Compared to baseline, specific factors associated with perceived stress and traumatic stress at timepoint 2 were living alone, less problem solving, and seeking social support. Residency programs should encourage active coping strategies (e.g., seeking social support, positive thinking, problem solving) among residents, and proactively identify residents who may be at higher risk of psychological sequelae due to circumstances that contribute to isolation.

Prehabilitation Program Improves Outcomes of Patients Undergoing Elective Liver Resection.

BACKGROUND: Preoperative phase can be effectively used by multidisciplinary teams to optimize the surgical candidate to improve perioperative outcomes. The aim of our study was to evaluate the impact of prehabilitation program (PP) in patients undergoing elective liver resection (LR). METHODS: This was a prospective study including patients undergoing elective LR from February 2016 to October 2017. Outcomes of patients enrolled into PP were compared with patients receiving standard care. PP involved physiotherapist, dietitian, and case managers along with surgical and anesthetic services. Postoperative morbidity, length of stay, 90-day mortality, readmission rate, quality of life, and cost were measured. RESULTS: Seventy patients were enrolled into PP and compared with 34 patients receiving standard care. Median Charlson comorbidity index was higher in PP group (4 versus 3, P = 0.03). PP showed reduction in overall morbidity (30% versus 52.9%, P = 0.02) and social issues (nil versus 3, P = 0.03). Quality of life survey showed improved social well-being. A tendency to cost savings was observed in prehabilitation group with 16.5% ($1359) cost reduction (median cost $6892 versus $8251, P = 0.07). CONCLUSIONS: PP improves outcomes in patients undergoing elective LR.

Subtotal cholecystectomy: early and long-term outcomes.

BACKGROUND: In difficult gallbladders, partial or subtotal cholecystectomy (SC) has been described as a reasonable procedure with safe outcomes. Our aim was to look at our data on SC with respect to safety, morbidity and long-term outcome. METHODS: A retrospective analysis was performed for 3560 patients undergoing cholecystectomy from January 2010 to June 2016. For patients who underwent SC, demographics, intra-operative and follow-up details were analysed. RESULTS: A total of 168 SC patients were included. 102 (60.7%) were male while 66 (39.3%) were female. The median age was 63 years (31-87). These patients were on follow-up for a median of 29 months (1.7-80). 153 were attempted laparoscopically and there were 25 (16.3%) patients which had open conversion. The rest of the 15 patients had open SC. Mean operative time 150 min (70-315) and average blood loss was 170 ml (50-1500). Median length of stay for these patients was 4 days (1-68). There were no common bile duct (CBD) injuries. We had 12 (7.1%) post-operative collections, 4 (2.4%) wound infections, 1 (0.6%) bile leak and 7 (4.2%) retained stones. Post-operative endoscopic retrograde cholangiopancreatography (ERCP) was performed on 4 (2.4%) patients with successful retrieval of CBD stones. One patient has spontaneous passage of CBD stone. The rest of the two patients with very small retained stones in remnant gallbladder were successfully managed conservatively. There was no 30-day or operation-related mortality. No patient required a second operation. CONCLUSIONS: SC is safe and feasible when encountering a difficult gallbladder.

A prospective validation of Sepsis-3 guidelines in acute hepatobiliary sepsis: qSOFA lacks sensitivity and SIRS criteria lacks specificity (Cohort Study).

BACKGROUND: Since its introduction in 2016, the Sepsis-3 guidelines, with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score, have generated much debate and controversy. It is recognised that the new definitions require validation in specific clinical settings and have yet to be universally adopted. We aim to validate new Sepsis-3 guidelines in acute hepatobiliary infection. MATERIAL AND METHODS: A prospective cohort of patients admitted with acute hepatobiliary infection from the emergency department from July 2016 to June 2017 was studied. The Systemic Inflammatory Response Syndrome (SIRS) criteria, SOFA and qSOFA scores were calculated and predictive performance evaluated with area under the receiver operating characteristic (AUROC) curves for predictive ability of these indices for critical care unit admission and morbidity. RESULTS: 124 patients with a median age of 64.5 years and majority males (n = 75, 60.5%) were admitted with acute hepatobiliary infection during the study period. Acute cholecystitis was the most common admission diagnosis (n = 83, 66.9%) and most patients were managed in general ward (n = 91, 73.3%) with median length of stay of 6 days (range 1-40). On multivariate analysis, diabetes mellitus (p = 0.003) predicted high dependency unit (HDU) admission, while age (p = 0.001), positive blood culture (p = 0.012), positive fluid culture (p = 0.015) and SOFA score (p = 0.002) predicted length of hospital stay. The sensitivity of SIRS in predicting HDU admission (60% vs. 4%), intensive care unit (ICU) admission (62.5% vs. 0%) and morbidity (66.7% vs. 0%) was higher than qSOFA score. The specificity of qSOFA in predicting HDU admission (100% vs. 49.5%), ICU admission (99.1% vs. 53.3%) and morbidity (99.2% vs. 47.9%) was higher than SIRS criteria. CONCLUSION: The SIRS criteria has high sensitivity and the qSOFA score has high specificity in predicting outcomes of patients with acute hepatobiliary infection.

Inferior vena cava leiomyosarcoma in an octogenerian.

Inferior Vena Cava (IVC) leiomyosarcoma (LM) is a rare malignancy of mesenchymal origin with an incidence of 1/100,000. We present an 82-year-old lady with a past history of open cholecystectomy who presented with a large indeterminate mass on abdominal imaging. Open resection of the mass was performed and histology with immunohistochemical staining revealed leiomyosarcoma. She received adjuvant radiotherapy and remained disease free 4 years after.

Patient reported outcomes in elective laparoscopic cholecystectomy.

BACKGROUNDS/AIMS: Traditional outcome measures (e.g., length of hospital stay, morbidity, and mortality) are used to determine the quality of care, but these may not be most important to patients. It is unclear which outcomes matter to patients undergoing elective laparoscopic cholecystectomy (ELC). We aim to identify patient-reported outcome measures (PROM) which patients undergoing ELC valued most. METHODS: A 45-item questionnaire with Four-point Likert-type questions developed from prior literature review, prospectively administered to patients treated with ELC at a tertiary institution in Singapore. RESULTS: Seventy-five patients participated. Most essential factors were technical skill and experience level of a surgeon, long-term quality of life (QoL), patient involvement in decision-making, communication skill of a surgeon, cleanliness of the ward environment, and standards of nursing care. Least important factors were hospitalization leave duration, length of hospital stay, a family's opinion of the hospital, and scar cosmesis. Employed patients were more likely to find hospitalization leave duration (p<0.001) and procedure duration (p=0.042) important. Younger patients (p=0.048) and female gender (p=0.003) were more likely to perceive scar cosmesis as important. CONCLUSIONS: Patients undergoing ELC value long-term QoL, surgeon technical skill and experience level, patient involvement in decision-making, surgeon communication skill, cleanliness of the ward environment, and nursing care standards. Day-case surgery, medical leave, family opinion of hospital, and scar cosmesis were least important. Understanding what patients value will help guide patient-centric healthcare delivery.