Ka Wing Ma

The effect of wide resection margin in patients with intrahepatic cholangiocarcinoma: A single-center experience.

Introduction: Prognosis of intrahepatic cholangiocarcinoma (ICC) remained poor despite the multitude advancement of medical care. Resection margin status is one of the few modifiable factors that a surgeon could possibly manipulate to alter the disease outcome. However, the significance of margin status and margin width is still controversial. This study serves to further elucidate the role of them. Method: This is a retrospective cohort from the Queen Mary Hospital, The University of Hong Kong. Consecutive patients diagnosed to have ICC and with surgical resection performed in curative intent were retrieved, while patients with cholangiohepatocellular carcinoma, Klaskin tumor, tumor of extrahepatic bile duct, and uncertain tumor pathology were excluded. Results: From 1991 to 2013, there were 107 patients underwent hepatectomy for ICC. Gender predilection was not observed with 58 males and 49 females, median age of the patients was 61. The median tumor size was 6 cm and most of them (43%) were moderately differentiated adenocarcinoma. Clear resection margin were achieved in 95 patients (88.8%) and the median margin width was 0.5 cm. The hospital length of stay and operative mortality were 11 days and 3%, respectively. The disease-free survival and overall survival were 17.5 and 25.1 months, respectively. Multivariate analysis showed that margin width was an independent factor associated with disease-free survival (P = 0.015, 95% confidence interval [CI] 0.4–0.9). Subgroup analysis in patients with solitary tumor showed that margin width is an independent factor affecting overall survival (P = 0.048; odds ratio: 0.577; 95% CI: 0.334–0.996). Discriminant analysis showed that the overall survival increased from 36 to 185 months when margin width was >0.9 cm (P = 0.025) in patients with solitary tumor. Conclusion: Aggressive resection to achieve resection margin of at least 1 cm maximizes chance of cure in patients with early ICC.

Surgical management of neuroendocrine tumor-associated liver metastases: a review

Liver metastasis is common among patients who suffer from neuroendocrine tumors (NETs). Radical surgery is the standard treatment whenever possible but there is still controversies concerning the treatment strategies such as resection of the primary, role of debulking surgery, liver transplantation (LT) and neoadjuvant or adjuvant therapies. This article aims to review the current evidence available, together with some latest updates, focusing on the surgical management.

Importance of surgical margin in the outcomes of hepatocholangiocarcinoma

AIM To evaluate the significance of resection margin width in the management of hepatocholangiocarcinoma (HCC-CC). METHODS Data of consecutive patients who underwent hepatectomy for hepatic malignancies in the period from 1995 to 2014 were reviewed. Patients with pathologically confirmed HCC-CC were included for analysis. Demographic, biochemical, operative and pathological data were analyzed against survival outcomes. RESULTS Forty-two patients were included for analysis. The median age was 53.5 years. There were 29 males. Hepatitis B virus was identified in 73.8% of the patients. Most patients had preserved liver function. The median preoperative indocyanine green retention rate at 15 min was 10.2%. The median tumor size was 6.5 cm. Major hepatectomy was required in over 70% of the patients. Hepaticojejunostomy was performed in 6 patients. No hospital death occurred. The median hospital stay was 13 d. The median follow-up period was 32 mo. The 5-year disease-free survival and overall survival were 23.6% and 35.4% respectively. Multifocality was the only independent factor associated with disease-free survival [P < 0.001, odds ratio 4, 95% confidence interval (CI): 1.9-8.0]. In patients with multifocal tumor (n = 20), resection margin of ≥ 1 cm was associated with improved 1-year disease-free survival (40% vs 0%; log-rank, P = 0.012). CONCLUSION HCC-CC is a rare disease with poor prognosis. Resection margin of 1 cm or above was associated with improved survival outcome in patients with multifocal HCC-CC.

Blocking CDK1/PDK1/β-Catenin signaling by CDK1 inhibitor RO3306 increased the efficacy of sorafenib treatment by targeting cancer stem cells in a preclinical model of hepatocellular carcinoma

Rationale: Hepatocellular carcinoma (HCC) is an aggressive malignant solid tumor wherein CDK1/PDK1/β-Catenin is activated, suggesting that inhibition of this pathway may have therapeutic potential. Methods: CDK1 overexpression and clinicopathological parameters were analyzed. HCC patient-derived xenograft (PDX) tumor models were treated with RO3306 (4 mg/kg) or sorafenib (30 mg/kg), alone or in combination. The relevant signaling of CDK1/PDK1/β-Catenin was measured by western blot. Silencing of CDK1 with shRNA and corresponding inhibitors was performed for mechanism and functional studies. Results: We found that CDK1 was frequently augmented in up to 46% (18/39) of HCC tissues, which was significantly associated with poor overall survival (p=0.008). CDK1 inhibitor RO3306 in combination with sorafenib treatment significantly decreased tumor growth in PDX tumor models. Furthermore, the combinatorial treatment could overcome sorafenib resistance in the HCC case #10 PDX model. Western blot results demonstrated the combined administration resulted in synergistic down-regulation of CDK1, PDK1 and β-Catenin as well as concurrent decreases of pluripotency proteins Oct4, Sox2 and Nanog. Decreased CDK1/PDK1/β-Catenin was associated with suppression of epithelial mesenchymal transition (EMT). In addition, a low dose of RO3306 and sorafenib combination could inhibit 97H CSC growth via decreasing the S phase and promoting cells to enter into a Sub-G1 phase. Mechanistic and functional studies silencing CDK1 with shRNA and RO3306 combined with sorafenib abolished oncogenic function via downregulating CDK1, with downstream PDK1 and β-Catenin inactivation. Conclusion: Anti-CDK1 treatment can boost sorafenib antitumor responses in PDX tumor models, providing a rational combined treatment to increase sorafenib efficacy in the clinic.

Defining optimal surgical treatment for recurrent hepatocellular carcinoma - a propensity score matched analysis

Salvage liver transplantation (sLT) and repeated resection (RR) are effective treatments for recurrent hepatocellular carcinoma (HCC), and comparisons of the oncological outcomes between these 2 modalities were scarce. Consecutive patients admitted for either sLT or RR for recurrent HCC were recruited. All patients in the present series received either prior hepatectomy, ablative therapy, or both before RR or sLT. Patient demographic, perioperative, and outcome data were analyzed. A survival analysis was performed after propensity score matching. There were 277 eligible patients recruited, and 67 and 210 of them underwent sLT and RR, respectively. Significant differences in preoperative hemoglobin, albumin, Model of End‐Stage Liver Disease (MELD) score, and tumor number were found between the sLT and RR groups. After 1:3 propensity score matching, there were 36 sLT and 108 RR patients for comparison. The median age, MELD, alpha fetoprotein, and tumor size and number of the matched population were 57 years, 7.5, 16 ng/mL, 2.5 cm, and 1, respectively. There was no difference in the hospital mortality and complication rate (Clavien IIIa or above) between the groups. The recurrence rate after RR was significantly higher than for the patients who received sLT (72.2% versus 27.8%; P < 0.001). Following RR, 3 patients received liver transplantation for further recurrence, and 54.6% of the patients developed nontransplantable recurrence. The 5‐year disease‐free survival (DFS) and overall survival (OS) were both superior in the sLT group (DFS, 71.6% versus 32.8%, P < 0.001; OS, 72.8% versus 48.3%, P = 0.007). In conclusion, sLT is superior to RR for treatment of recurrent HCC in terms of DFS and OS. The high rate of nontransplantable recurrence after reresection underscores the importance of timely sLT.

Pure laparoscopic hepatectomy with augmented reality-assisted indocyanine green fluorescence versus open hepatectomy for hepatocellular carcinoma with liver cirrhosis: A propensity analysis at a single center: ICG-assisted laparoscopic hepatectomy

Laparoscopic hepatectomy is considered an acceptable treatment of choice in selected patients with primary hepatocellular carcinoma (HCC). Whether indocyanine green (ICG) immunofluorescence, a new technology, may improve surgery outcomes has yet to be tested. The aim of the present study was to investigate and compare the effect of ICG fluorescence imaging on the outcomes of pure laparoscopic hepatectomy and open hepatectomy for primary HCC with background cirrhosis.

The role of radiofrequency ablation to liver transection surface in patients with close tumor margin of HCC during hepatectomy—a case matched study

BACKGROUND To review the outcome of using radiofrequency ablation (RFA) for patients with close resection margin during hepatectomy. METHODS From Oct 2004 to Sept 2013, 862 patients received hepatectomy for hepatocellular carcinoma (HCC) in the Department of Surgery, Queen Mary Hospital in Hong Kong. Fourteen patients received additional RFA because of close resection margin (<1 cm) during the operation for HCC. The result of 28 patients with close liver resection margin was selected for comparison. The two groups of patients were matched in terms of tumor size, tumor number, stage of disease and magnitude of resection. RESULTS In the RFA group (n=14), the median age of the patients was 58.5 (range, 25-78 years). The median tumor size was 2.25 cm (range, 1.2-12 cm). In the resection alone group (n=28), the median age for the patients was 61 (range, 36-79 years). The median tumor size was 2.7 cm (range, 1-11 cm). There was no difference in terms of liver function assessment between the two groups. There was no RFA related complication recorded during the study period. There was no hospital mortality in both groups. The 1- and 3-year disease free survival was 38.3% and 25.5% respectively in the RFA group vs. 57.4% and 39.3% respectively in the liver resection alone group (P=0.563). The 1- and 3-year overall survival was 81.5% and 69.8% respectively in the RFA group vs .88.4% and 59.9% respectively in the liver resection alone group (P=0.83). CONCLUSIONS RFA to hepatectomy resection surface in patients with close margin is a safe treatment option but its effectiveness on prevention of local recurrence has yet to be confirmed.

A new formula for estimation of standard liver volume using computed tomography–measured body thickness

The objective of this article is to derive a more accurate and easy‐to‐use formula for finding estimated standard liver volume (ESLV) using novel computed tomography (CT) measurement parameters. New formulas for ESLV have been emerging that aim to improve the accuracy of estimation. However, many of these formulas contain body surface area measurements and logarithms in the equations that lead to a more complicated calculation. In addition, substantial errors in ESLV using these old formulas have been shown. An improved version of the formula for ESLV is needed. This is a retrospective cohort of consecutive living donor liver transplantations from 2005 to 2016. Donors were randomly assigned to either the formula derivation or validation groups. Total liver volume (TLV) measured by CT was used as the reference for a linear regression analysis against various patient factors. The derived formula was compared with the existing formulas. There were 722 patients (197 from the derivation group, 164 from the validation group, and 361 from the recipient group) involved in the study. The donors body weight (odds ratio [OR], 10.42; 95% confidence interval [CI], 7.25‐13.60; P < 0.01) and body thickness (OR, 2.00; 95% CI, 0.36‐3.65; P = 0.02) were found to be independent factors for the TLV calculation. A formula for TLV (cm3) was derived: 2 × thickness (mm) + 10 × weight (kg) + 190 with R2 0.48, which was the highest when compared with the 4 other most often cited formulas. This formula remained superior to other published formulas in the validation set analysis (R2, 5.37; interclass correlation coefficient, 0.74). Graft weight/ESLV values calculated by the new formula were shown to have the highest correlation with delayed graft function (C‐statistic, 0.79; 95% CI, 0.69‐0.90; P < 0.01). The new formula (2 × thickness + 10 × weight + 190) represents the first study proposing the use of CT‐measured body thickness which is novel, easy to use, and the most accurate for ESLV. Liver Transplantation 23 1113–1122 2017 AASLD.