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.

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.

Predicting HCC Response to Multikinase Inhibitors With In Vivo Cirrhotic Mouse Model for Personalized Therapy.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) arises in a cirrhotic, pro-angiogenic microenvironment. Inhibiting angiogenesis is a key mode of action of multikinase inhibitors and current non-cirrhotic models are unable to predict treatment response. We present a novel mouse cirrhotic model of xenotransplant that predicts the natural biology of HCC and allows personalized therapy. METHODS: Cirrhosis was induced in NOD Scid gamma mice with 4 months of thioacetamide administration. Patient derived xenografts (PDXs) were created by transplant of human HCC subcutaneously into non-cirrhotic mice and intra-hepatically into both cirrhotic and non-cirrhotic mice. The applicability of cirrhotic PDXs for drug testing was tested with 16 days of either sorafenib or lenvatinib. Treatment response was evaluated by MRI. RESULTS: 8 out of 19 (42%) human HCC engrafted in the cirrhotic model compared with only 3 out of 19 (16%) that engrafted in the subcutaneous non-cirrhotic model. Tumor vasculature was preserved in the cirrhotic model but was diminished in the non-cirrhotic models. Metastasis developed in 3 cirrhotic PDX lines and was associated with early HCC recurrence in all 3 corresponding patients (100%), compared with only 5 out of 16 (31%) of the other PDX lines, P = .027. The cirrhotic model was able to predict response and non-response to lenvatinib and sorafenib respectively in the corresponding patients. Response to lenvatinib in the cirrhotic PDX was associated with reduction in CD34, VEGFR2 and CLEC4G immunofluorescence area and intensity (all P ≤ .03). CONCLUSIONS: A clinically relevant cirrhotic PDX model preserves tumor angiogenesis and allows prediction of response to multikinase inhibitors for personalized therapy.

Laparoscopic cholecystectomy for acute cholecystitis: an analysis of early versus delayed cholecystectomy and predictive factors for conversion.

BACKGROUND: There is an increasing preference for early laparoscopic cholecystectomy (ELC) as compared to delayed LC (DLC) in the management of acute cholecystitis (AC). Conversion to open cholecystectomy (LOC) remains an important outcome. We aim to compare ELC and DLC outcomes and identify LOC predictors. METHODS: Retrospective analysis of 466 patients who underwent LC for AC from June 2010 to June 2015 was performed. Patients were divided into ELC and DLC groups, defined as LC performed within 7 days and between 4 to 24 weeks of symptom onset, respectively. Peri-operative outcomes and predictors for LOC were analyzed. RESULTS: Conversion rates were comparable [ELC, 8.6% vs. DLC, 8.0%] (P=0.867). While median operative time was longer in ELC (101.5 min [83.0-130.1]) than DLC (88.0 min [62.3-118.8]) (P<0.001), intraoperative (ELC, 1.9% vs. DLC, 3.0%; P=0.541) and postoperative morbidity (ELC, 13.5% vs. DLC, 12.5%; P=0.688) was comparable. Median total length of stay (LOS) was shorter in ELC (4 days [3-6]) than DLC (5 days [4-9]) (P<0.001). Univariate analysis showed increased age (LC, 57 [45-66] vs. LOC, 60 [56-72]; P=0.016), presence of comorbidities (LC, 69.0% vs. LOC, 87.8%; P=0.009), previous abdominal surgery (LC, 6.1% vs. LOC, 17.1%; P=0.014), fever (P=0.001), Murphy's sign (P=0.005) and lower albumin (LC, 42.0 [39.0-45.0] vs. LOC, 40.0 [36.0-43.0]; P=0.003) to be predictors for LOC. CONCLUSIONS: ELC provides shorter LOS and eliminates the risk of gallstone-related morbidity while awaiting surgery. It should be advocated for patients with AC. The presence of comorbidities, increased age, previous abdominal surgery and low albumin are predictors for conversion.

Delayed Presentation of Acute Cholecystitis: Comparative Outcomes of Same-Admission Versus Delayed Laparoscopic Cholecystectomy.

INTRODUCTION: Studies have shown that same-admission laparoscopic cholecystectomy (SALC) is superior to delayed laparoscopic cholecystectomy (DLC) for acute cholecystitis (AC). However, no studies have compared both modalities in patients with delayed presentation. The aim of the study was to compare outcomes between SALC and DLC in AC patients with more than 7-day symptom duration. METHODS: A retrospective analysis of 83 AC patients who underwent LC after presenting with >7 days of symptoms from June 2010 to June 2015 was performed. Patients were divided into L-SALC and L-DLC, defined as LC performed within the same admission and between 4 and 24 weeks after discharge, respectively. Peri-operative outcomes were evaluated. RESULTS: In L-SALC patients, the intra-operative severity was higher (p < 0.001) and median operative time was longer (L-SALC, 107 min (46-220) vs L-DLC, 95 mins (25-186)) (p = 0.048). Conversion rates were also higher in L-SALC than that in L-DLC (L-SALC, 21.4% vs L-DLC, 4.9%) (p = 0.048). While post-operative morbidity was similar, L-SALC was associated with a longer post-operative length of stay as compared to L-DLC (L-SALC, 2 (1-17) vs L-DLC, 1 (1-6)) (p < 0.001). CONCLUSION: DLC provides lower conversion rates and shorter length of stay in AC patients presenting beyond 7 days of symptoms. This group of patients should be offered DLC.

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 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.

Contrast CT in localization of acute lower gastrointestinal bleeding.

Localization of the source of acute lower gastrointestinal bleeding is of paramount importance in its management as it allows for planned segmental resection rather than a "blind" abdominal total colectomy. Various methods of localization with radionuclide scan, mesenteric angiography and colonoscopy have been utilized, but none has been shown to be superior to others. The recent use of contrast-enhanced multislice computed tomography (MSCT) has generated much interest as it is rapid, noninvasive and readily accessible, and allows for excellent reformation on different planes. These are clear advantages in an emergency setting for accurate localization prior to surgery. We report a case where the use of MSCT resulted in prompt and accurate localization in a patient who presented acutely with massive lower gastrointestinal bleed. We believe that contrast-enhanced MSCT has the potential of accurately localizing the source of bleeding in an emergency setting, and should be part of the algorithm in the management of acute lower gastrointestinal bleeding.