Sang Young Han

Prognostic factors for gallbladder cancer in the laparoscopy era.

Purpose Hepatobiliary surgery has changed dramatically in recent decades with the advent of laparoscopic techniques. The aim of this retrospective study was to compare survival rates according to stages, adjusting for important prognostic factors. Methods A retrospective study of a 17-year period from January 1994 to April 2011 was carried out. The cases studied were divided into two time period cohorts, those treated in the first 9-years (n = 109) and those treated in the last 7-years (n = 109). Results An operation with curative intent was performed on 218 patients. The 5-year survival rates according to the depth of invasion were 86% (T1), 56% (T2), 45% (T3), and 5% (T4). The number of cases of incidental gallbladder cancer found during 3,919 laparoscopic cholecystectomies was 96 (2.4%). Incidental gallbladder cancer revealed a better survival rate (P = 0.003). Iatrogenic bile spillage was found in 20 perforations of the gallbladder during laparoscopic cholecystectomies, 16 preoperative percutaneous transhepatic gallbladder drainages and 16 percutaneous transhepatic biliary drainages; only percutaneous transhepatic biliary drainage patients showed a significantly lower survival rate than patients without iatrogenic bile spillage (P < 0.034). Chemoradiation appeared to improve overall survival (P < 0.001). Multivariate analysis also revealed that time period, type of surgery, surgical margin, lymphovascular invasion, lymph node involvement, and chemoradiation therapy had significant effects. Conclusion This study found that the prognosis of gallbladder cancer is still determined by the stage at presentation due to the aggressive biology of this tumor. Early diagnosis, radical resection and appropriate adjuvant therapy can increase overall survival.

A Case of Sorafenib-induced DRESS Syndrome in Hepatocelluar Carcinoma

Sorafenib is currently the only targeted therapy available for advanced stage hepatocellular carcinoma (HCC). Cutaneous adverse events associated with sorafenib treatment include hand-foot skin reaction, but there has been no report of drug reaction (or rash) with eosinophilia and systemic symptoms (DRESS) syndrome. Here, we report a case of 72-year-old man with HCC and alcoholic liver cirrhosis who developed skin eruptions, fever, eosinophilia, and deteriorated hepatic and renal function under sorafenib treatment. He has since successfully recovered with conservative care.

Lessons learned from 100 initial cases of laparoscopic liver surgery

Purpose Laparoscopic liver resection (LLR) is now widely accepted and is being increasingly performed. The present study describes our experience with LLR at a single center over an eight-year period. Methods This retrospective study enrolled 100 patients between October 2002 and February 2010. Forty-six benign lesions and 54 malignant lesions were included. The LLR performed included 58 pure laparoscopy procedures, 18 hand-assisted laparoscopy procedures and 24 hybrid technique procedures. Results The mean age of the patients was 57 years; among these patients, 31 were over 65 years of age. The mean operation time was 220 minutes. The overall morbidity was 11% and the mortality was zero. Among the 20 patients with simple hepatic cysts, 50% unexpectedly recurred. Among the 41 patients with hepatocellular carcinoma, 21 patients (51%) underwent preoperative radiofrequency ablation therapy or transarterial chemoembolization. During parenchymal-transection, 11 received blood transfusion. The width of the resection margins was under 0.5 cm in 11 cases (27%); 0.5 to 1 cm in 22 cases (54%) and over 1 cm in eight cases (12%). There was no port site seeding, but argon beam coagulation-induced tumor dissemination was observed in two cases. The overall two-year survival rate was 75%. Conclusion This study suggests that the applications for LLR can be gradually expanded when assuring that the safety and curability of LLR are equivalent to that of open liver resection.

Intraoperative radiofrequency ablation for hepatocellular carcinoma in 112 patients with cirrhosis: a surgeon's view

Purpose This retrospective study was an investigation of overall survival (OS), disease-free survival (DFS) and prognostic factors affecting OS and DFS in cirrhotic patients who received intraoperative radiofrequency ablation (IORFA). Methods Between April 2009 and November 2013, 112 patients (94 men, 84%; 18 women, 16%) underwent IORFA for 185 cases of hepatocellular carcinomas (HCC). Repeat IORFA was done in 9 patients during the same period (total of 121 treatments). Results All patients were followed-up for at least 12 months (mean follow-up, 32 months). Surgical resection combined with IORFA was performed in 20 patients. The technical effectiveness at 1 week was 91.78% (111 of 121). Readmission was 9.1% (11 of 121) and the most common cause was ventral hernia. Procedure-related mortality was 2.7% (3 of 112) and continued fatal biliary leakage was 1.8% (2 of 112). Local recurrence developed in 10 patients (8.9%). Most recurrence was intrahepatic. Cumulative survival was assessed in 33 patients who received IORFA as primary treatment (naive patients) and 79 non-naive patients. The cumulative DFS and OS rate at l and 3 years was 54% and 24%, and 87% and 66%, respectively. Moderate ascites (P = 0.001), tumor located segment I (P = 0.001), portal vein thrombosis (P = 0.001) had poor survival were significant factors by multivariate analysis. Conclusion IORFA alone or in combination with surgical resection extends the spectrum of liver surgery. A fundamental understanding of RFA, additional comorbidities, and postablation complication are necessary to maximize the safety and efficacy of IORFA for treating HCC with cirrhosis.

Discrete Hypoechoic Ring in Hepatic Cavernous Hemangioma Resembling a Malignant Tumor: Correlation with Histologic Features

Differential diagnoses of hepatic nodules include hepatocellular carcinoma, focal nodular hyperplasia, hepatic adenoma, regenerative nodule, focal fatty changes, and hemangioma. However, differentiation of these nodules can often be difficult. Hemangiomas are frequently encountered during ultrasonogram incidentally and can be diagnosed easily because they have an almost distinctive sonographic appearance: a homogeneous hyperechogenicity and discrete posterior acoustic enhancement. They also sometimes have atypical findings, for example an internal echogenicity including hypoechogenicity, heterogeneous echogenicity, hyperechoic rim, central hypoechogenicity due to various changes (e.g., internal hemorrhage, necrosis, thrombosis, myxomatous change, and fibrosis), and (rarely) calcification. We report herein the case of an atypical hemangioma presenting with a hypoechoic peripheral ring, mimicking a hepatic malignancy. To our knowledge, there have been no other reports demonstrating a cavernous hemangioma with a discrete hypoechoic ring and without a pseudocapsule.

Thymosin Alpha-1 in Combination with Pegylated Interferon and Ribavirin in Chronic Hepatitis C Patients Who have Failed to Prior Pegylated Interferon and Ribavirin Treatment

Combination therapy with inteferon-alpha and ribavirin is an approved therapy for patients with chronic hepatitis C. However, even with the use of pegylated interferon, response rates are still poor in many difficult-to-treat groups, especially with genotype 1 and high viral loads. Retreatment of these patients remains challenging. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups. Thymosin alpha 1 is a polypeptide with immunomodulatory properties that has been suggested to increase response rates in patients with chronic hepatitis C. Herein, we describe two cases of retreatment patients with chronic hepatitis C who have failed prior pegylated interferon and ribavirin therapy. They received triple combination therapies of thymosin alpha 1, pegylated interferon and ribavirin and achieved sustained virological responses. These cases support that thymosin-alpha 1 may increase the efficacy of pegylated interferon plus ribavirin in the treatment of non-responders to previous combination therapy.

A case of focal nodular hyperplasia with growth progression during pregnancy.

Focal nodular hyperplasia (FNH) is the second most common benign solid tumor of the liver and is usually found in young females. In FNH, spontaneous bleeding or rupture rarely occurs and malignant transformation is unlikely. The etiology of FNH is unclear, but because of female predominance and young age at onset, it seems that female hormone has an important role for the development of FNH. Although the development and the complications of hepatocellular adenomas have been related to the use of oral contraceptives and pregnancy, the influence of oral contraceptives and pregnancy on the growth and complications of FNH is controversial. Most FNH are stable in size and rarely complicated during pregnancy. We describe here a case of FNH with growth progression during pregnancy in a 27-year-old female. Her course of pregnancy and delivery was uneventful. Two months after delivery, the size of FNH was decreased.

Gene expression in human gastric adenocarcinoma using cDNA array

Background: cDNA microarray provided a powerful alternative with an unprecedented view scope in monitoring gene expression levels and led to discoveries of regulatory pathways involved in complicated biological processes. Objective: To explore the different gene expression pattern in early and advanced gastric cancer (EGC and AGC) in this study, we have applied eDNA microarray slides containing 4608 human eDNA fragments. Materials and Methods: By using a eDNA microarray, we studied the expression profiling in 10 paired gastric adenocarcinoma samples (2 EGCs, 8 AGCs) and the adjacent noncancerous gastric tissues form the same patients. The alterations in gene expression levels were confirmed by Northern blot and reverse-transcription PCR in all of 4 randomly selected genes. Then, a weighted-voting classification algorithm was applied, and was tested by leave-one-out crossvalidation. The final model which minimized cross-validation errors was chosen. Results: Genes that were differently expressed in cancer and noncancerous tissues were identified. 44 (of which 25 were known) and 92 (of which 50 were known) genes or eDNA were upand down-regulated, respectively, in >80% of the gastric adenocarcinoma samples. In cancer tissues, genes related to signal transduction, metabolism and gene/protein expression were mostly up-regulated, whereas genes related to immunology, cell structure/motility and transcription were mostly down-regulated The semi-quantitative RT-PCR results, for the four genes we tested, were consistent with the array findings. A supervised learning classification process is repeated until all 10 samples are predicted in turn Predictors containing between 16 and 20 genes all yielded statistically significant predictions, with the highest accuracy obtained using 9 genes.(BE880748, NM 015379, AF011374, NM 017458, AL078581, A1524095, NM 018479, U00672, NM 004705) The accuracy of prediction using these 9 genes was 100 % suggesting strong correlation of gene expression pattern in distinction of AGC and EGC. However, there is no correlation between two groups when EGC was randomly selected in AGC. Moreover, the expression pattern strongly indicates that homogeneous gene expression pattern in EGC but not in AGC. Conclusion: Although the sample size is small, these results provide not only a new molecular basis for understanding biological properties of gastric adenocarcinoma, but also useful resources for future development of therapeutic targets and diagnostic markers for gastric adenocarcinoma.