Risks and impacts of thromboembolism in patients with pancreatic cancer.

INTRODUCTION: Patients with pancreatic cancer have a high risk of thromboembolism (TE), which may increase mortality. Most relevant studies have been conducted in Western populations. We investigated risk factors for TE in a predominantly Chinese population of patients with pancreatic cancer, along with effects of TE on overall survival. METHODS: This retrospective cohort study included patients diagnosed with exocrine pancreatic cancer in Prince of Wales Hospital in Hong Kong between 2010 and 2015. Data regarding patient demographics, World Health Organization performance status, stage, treatment, TE-related information, and time of death (if applicable) were retrieved from electronic medical records. Univariate and multivariable logistic regression analyses were performed to identify risk factors for TE. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: In total, 365 patients were included in the study. The overall incidence of TE (14.8%) was lower than in Western populations. In univariate logistic regression analysis, stage IV disease and non-head pancreatic cancer were significantly associated with TE (both P=0.01). Multivariable logistic regression analysis showed that stage IV disease was a significant risk factor (odds ratio=1.08, 95% confidence interval [CI]=1.00-1.17; P=0.046). Median overall survival did not significantly differ between patients with and without TE (4.88 months vs 7.80 months, hazard ratio=1.08, 95% CI=0.80-1.49; P=0.58) and between patients with TE who received anticoagulation treatment or not (5.63 months vs 4.77 months, hazard ratio=0.72, 95% CI=0.40-1.29; P=0.27). CONCLUSION: The incidence of TE was low in our Chinese cohort. Stage IV disease increased the risk of TE. Overall survival was not affected by TE or its treatment.

Acute kidney injury following hepatectomy and its impact on long-term survival for patients with hepatocellular carcinoma.

BACKGROUND: Acute kidney injury (AKI) is increasingly being recognized after hepatectomy. This study aimed to identify factors predicting its occurrence and its impact on long-term outcome among patients with hepatocellular carcinoma (HCC). METHODS: This was a retrospective analysis of the incidence of AKI, factors predicting its occurrence, and its impact on patients undergoing hepatectomy between September 2007 and December 2018. A subgroup analysis included patients with histologically proven HCC. RESULTS: The incidence of AKI was 9.2 per cent in 930 patients. AKI was associated with increased mortality, morbidity, posthepatectomy liver failure (PHLF), and a longer hospital stay. On multivariable analysis, study period December 2013 to December 2018, diabetes mellitus, mean intraoperative BP below 72.1 mmHg, operative blood loss exceeding 377ml, high Model for End-Stage Liver Disease (MELD) score, and PHLF were predictive factors for AKI. Among 560 patients with HCC, hypertension, BP below 76.9 mmHg, blood loss greater than 378ml, MELD score, and PHLF were predictive factors. The 1-, 3-, and 5-year overall survival rates were 74.1, 59.2, and 51.6 per cent respectively for patients with AKI, and 91.8, 77.9, and 67.3 per cent for those without AKI. Corresponding 1-, 3-, and 5-year disease-free survival rates were 56.9, 42.3, and 35.4 per cent respectively in the AKI group, and 71.7, 54.5, and 46.2 per cent in the no-AKI group. AKI was an independent predictor of survival in multivariable analysis. CONCLUSION: AKI is associated with longer hospital stay, and higher morbidity and mortality rates. It is also associated with shorter long-term survival among patients with HCC. To avoid AKI, control of blood loss and maintaining a reasonable BP (72-77 mmHg) during hepatectomy is important.

Randomized clinical trial of hepatic resection versus radiofrequency ablation for early-stage hepatocellular carcinoma.

BACKGROUND: Hepatic resection and radiofrequency ablation (RFA) are treatment options for early-stage hepatocellular carcinoma (HCC). Whether tumour recurrence and long-term survival favour either treatment has not been established. This randomized trial aimed to test the hypothesis that RFA is superior to hepatic resection in terms of lower tumour recurrence rate and better long-term survival. METHODS: Patients with early-stage HCC (solitary tumour no larger than 5 cm; or no more than 3 tumours, each 3 cm or smaller) were randomized into hepatic resection and RFA groups. Demographic and clinical characteristics, and short- and long-term outcome measures were compared between groups. Primary and secondary outcome measures were overall tumour recurrence and survival respectively. RESULTS: Clinicopathological data were similar in the two groups, which each contained 109 patients. The RFA group had a shorter treatment duration, less blood loss and shorter hospital stay than the resection group. Mortality and morbidity rates were similar in the two groups. The overall tumour recurrence rate was similar in the resection and RFA groups (71·3 versus 81·7 per cent respectively). The 1-, 3-, 5- and 10-year overall survival rates were 94·5, 80·6, 66·5 and 47·6 per cent respectively in the resection group, compared with 95·4, 82·3, 66·4 and 41·8 per cent in the RFA group (P = 0·531). Corresponding disease-free survival rates were 74·1, 50·9, 41·5 and 31·9 per cent in the resection group, and 70·6, 46·6, 33·6 and 18·6 per cent in the RFA group (P = 0·072). CONCLUSION: RFA for early-stage HCC is not superior to hepatic resection, in terms of tumour recurrence, overall survival and disease-free survival. Registration number: HKUCTR-10 (http://www.hkuctr.com).

Outcome after partial hepatectomy for hepatocellular cancer within the Milan criteria.

BACKGROUND: There is a trend to offer liver transplantation to patients with hepatocellular carcinoma (HCC) with tumour status within the Milan criteria but with preserved liver function. This study aimed to evaluate the outcome of such patients following partial hepatectomy as primary treatment. METHODS: A retrospective analysis was performed on all adult patients with HCC and tumour status within the Milan criteria undergoing partial hepatectomy at a single centre from 1995 to 2008. Their outcomes were compared with those of similar patients having right-lobe living donor liver transplantation (LDLT) as primary treatment. RESULTS: A total of 408 patients with HCC were enrolled. Some 384 patients with a solitary tumour 5 cm or less in diameter had a better 5-year survival rate than 24 patients with oligonodular tumours (2-3 nodules, each 3 cm or less in size) (70·7 versus 46 per cent; P = 0·025). Multivariable analysis identified younger age (65 years or less), lack of postoperative complications, negative resection margin, absent microvascular invasion and non-cirrhotic liver as predictors of favourable overall survival. The 5-year survival rate of 287 younger patients with chronic liver disease and R0 hepatectomy was 72·8 per cent, comparable to that of 81 per cent in 50 similar patients treated by LDLT (P = 0·093). CONCLUSION: Partial hepatectomy for patients with HCC and tumour status within the Milan criteria achieved a satisfactory 5-year survival rate, particularly in younger patients with solitary tumours and R0 hepatectomy. Patients with oligonodular tumours have a worse survival and might benefit from liver transplantation.

Delayed portal vein thrombosis after experimental radiofrequency ablation near the main portal vein.

BACKGROUND: Portal venous blood flow may protect adjacent tumour cells from thermal destruction with radiofrequency ablation (RFA). This study aimed to investigate the local effect of RFA on the main portal vein branch, and the completeness of cellular ablation in its vicinity, with or without a Pringle manoeuvre using a porcine model. METHODS: This was an in vivo study on 23 domestic pigs. RFA using a cooled-tip electrode was performed 5 mm from the left main portal vein branch under ultrasonographic guidance for 12 min with (n = 10) or without (n = 10) a Pringle manoeuvre. Ten pigs were killed 4 h after the procedure to study the early effects of RFA and ten others were killed 1 week later to determine any delayed effect. As a control, sham operations with a Pringle manoeuvre for 12 min were performed on three pigs. The flow velocity changes of portal vein and hepatic artery were measured using Doppler ultrasonography, and the completeness of cellular ablation around the portal vein was assessed qualitatively by histochemical staining and quantitatively by measuring intracellular levels of adenosine 5'-triphosphate (ATP). RESULTS: In the absence of the Pringle manoeuvre, there was no significant change in mean(s.d.) portal vein flow velocity before RFA (20.0(3.5) cm/s) and at 4 h (18.5(2.5) cm/s) (P = 0.210) and 1 week (19.5(2.2) cm/s) (P = 0.500) after the procedure. Gross and histological examination of the portal vein branches showed no damage without the Pringle manoeuvre. In all pigs that underwent RFA with a Pringle manoeuvre, the portal vein was occluded 1 week after the operation; histological examination of the affected portal vein showed severe thermal injury and associated venous thrombosis. The local effect of RFA on the hepatic artery was similar. With intact portal blood flow during RFA, complete ablation of liver tissue around the pedicle was demonstrated by histochemical staining and measurement of the intracellular ATP concentration. CONCLUSION: RFA was safe when applied close to the main portal vein branch without a Pringle manoeuvre, with complete cellular destruction. Use of the Pringle manoeuvre resulted in delayed portal vein and hepatic artery thrombosis and injury to the hepatic artery and bile duct.

Impact of radiofrequency ablation on the management of patients with hepatocellular carcinoma in a specialized centre.

BACKGROUND: Radiofrequency ablation (RFA) has been used increasingly in the treatment of hepatocellular carcinoma (HCC). The aim of this study was to investigate changes in the treatment pattern of primary HCC following the implementation of RFA in a specialized surgical centre. METHODS: This was a retrospective analysis of all 894 patients admitted for treatment of primary HCC over 36 months. RESULTS: There was no difference in the age, sex ratio, liver function according to Child-Pugh grade, serum alpha-fetoprotein concentration, hepatitis B surface antigen status and tumour size among patients before and after the introduction of RFA therapy. Fifty-one patients (10.6 per cent) with primary HCC received RFA treatment after its implementation. There was a 6.8 per cent reduction in the number of patients who had supportive treatment (P = 0.041) and a 3.2 per cent reduction in surgical treatment. The hospital mortality rates for RFA and surgery were 2.0 and 4.9 per cent respectively. The overall survival rates at 6, 12 and 18 months for patients treated with RFA were 92.2, 73.4 and 61.2 per cent respectively. The corresponding survival rates for the 213 patients who had surgery were 88.0, 77.0 and 71.5 per cent. These values were no different from those in patients who had RFA (P = 0.718). Patients treated with RFA or surgery survived longer than those who had other treatments. CONCLUSION: RFA had a significant impact on the management of primary HCC, increasing the number of patients suitable for liver-directed therapy and leading to survival benefit. RFA may become the treatment of choice for patients with irresectable HCC.