The Hint1 protein, a member of the histidine triad (HIT) family, is highly conserved in diverse species and ubiquitously expressed in mammalian tissues. Previous studies in mice provided evidence that Hint1 may be haplosufficient with respect to its function as a tumor suppressor. In the present study, we investigated the aberrant methylation of Hint1 and explored possible relationships between aberrant methylation and clinicopathological features in hepatocellular carcinoma (HCC). Hypermethylation of Hint1 was evaluated by the methylation specific PCR (MSP) method in 40 patients with HCC (tumor and paired adjacent non-tumor tissues) from Taiwan, 22 cases of normal liver tissue (14 from Taiwan and 8 from the U.S.). HINT1 expression in tissues was detected by immunohistochemistry. The frequencies of hypermethylation of Hint1 in tumor, paired adjacent non-tumor and normal liver tissue were 55.0%, 37.5% and 9.1%, respectively. A statistically significant inverse association was found between Hint1 methylation status and expression of the HINT1 protein in tumor tissues (p<0.003). The relationship between Hint1 methylation status and clinical features and other, previously measured biomarkers was also analyzed. p16 hypermethylation was statistically significantly associated with Hint1 methylation status (p=0.035). There were no correlations between Hint1 methylation and HBV or HCV infection status or AFB1- and PAH-DNA adduct levels. These results suggest that promoter hypermethylation of Hint1 may play a role in hepatocarcinogenesis.

For many years, the understanding of gastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the gastrointestinal tract, has been very limited. However, it is now possible to provide a more precise definition through the use of pathology classification and molecular techniques. Coupled with the advancement of clinical practice, especially the development of targeted therapy, there is now a much better insight into its treatment. At present, organizations such as the National Comprehensive Cancer Network in the USA and the European Society for Medical Oncology in Europe have established a consensus and drawn up guidelines for the diagnosis, treatment, and follow-up of GISTs.

With experts coming from various districts in Taiwan and combining the most recent clinical data and experiences, the Taiwan Surgical Society of Gastroenterology drafted the first national GIST treatment guidelines after a consensus meeting in 2007. Following subsequent advances in GIST diagnosis and treatment, further revisions and modifications have been made to the original guidelines. We present here the updated consensus and recommendations of the Taiwan Surgical Society of Gastroenterology for the diagnosis and treatment of GIST. We hope these guidelines can help enhance the quality of diagnosis, treatment, and care of patients with GIST in Taiwan.

The grades of neurosensory adverse events (NSAEs) induced by FOLFOX4 treatment were compared between Asian and Western colorectal cancer patients and correlated with cumulative oxaliplatin doses. A total of 3359 patients treated with FOLFOX4 were analyzed: 1515 from two Asian studies (Japanese Post Marketing Surveillance [J-PMS] and MASCOT) and 1844 from four Western studies (EFC2962, N9741, EFC4584, and MOSAIC). The onset of NSAEs was analyzed in terms of treatment duration and cumulative dose of oxaliplatin. The incidence of grade ≥3 NSAEs ranged from 2.0% to 4.4% in Asian studies and 9.3% to 19% in Western studies. The cumulative doses of oxaliplatin that induced grade ≥3 NSAEs in 10% of patients were higher in Asian studies (1526 mg/m2 or not reached) than in Western studies (805–832 mg/m2). No significant correlations were noted between occurrence of grade ≥3 NSAEs and demographic/baseline characteristics. The frequency of escalation from grade 0 to 1 in J-PMS was statistically significantly lower than that in EFC4584, and that from grade 0 to 1 and from grade 1 to 2 in MASCOT lower than that in MOSAIC. The cumulative oxaliplatin doses administered during grade escalation in J-PMS were similar to those in EFC2962 or EFC4584. All grade-3 NSAEs in MASCOT and 96% of those in MOSAIC improved to grade 2 or less within 12 months of follow-up. The Asian populations accrued to these studies appear to be less susceptible to the neurotoxicity of oxaliplatin than the mainly Caucasian populations in the Western studies.

AIM: To determine global DNA methylation in paired hepatocellular carcinoma (HCC) samples using several different assays and explore the correlations between hypomethylation and clinical parameters and biomarkers, including that of aflatoxin B1 exposure.

METHODS: Using the radio labeled methyl acceptance assay as a measure of global hypomethylation, as well as two repetitive elements, including satellite 2 (Sat2) by MethyLight and long interspersed nucleotide elements (LINE1), by pyrosequencing.

RESULTS: By all three assays, mean methylation levels in tumor tissues were significantly lower than that in adjacent tissues. Methyl acceptance assay log (mean ± SD) disintegrations/min/ng DNA are 70.0 ± 54.8 and 32.4 ± 15.6, respectively, P = 0.040; percent methylation of Sat2 42.2 ± 55.1 and 117.9 ± 88.8, respectively, P < 0.0001 and percent methylation LINE1 48.6 ± 14.8 and 71.7 ± 1.4, respectively, P < 0.0001. Aflatoxin B1-albumin (AFB1-Alb) adducts, a measure of exposure to this dietary carcinogen, were inversely correlated with LINE1 methylation (r = -0.36, P = 0.034).

CONCLUSION: Consistent hypomethylation in tumor compared to adjacent tissue was found by the three different methods. AFB1 exposure is associated with DNA global hypomethylation, suggesting that chemical carcinogens may influence epigenetic changes in humans.

A 27-year-old man, previously healthy, had an enlarging liver mass incidentally noted at a health check-up 6 months earlier. There were no known risk factors for hepatocellular carcinoma. The hepatic tumour seen on magnetic resonance imaging had characteristics of high T2 and low T1 signals, early hyper-enhancement and mild delayed enhancement, which was atypical for focal nodular hyperplasia (FNH). An atypical hepatectomy was performed smoothly and the pathologic confirmation of FNH was finally made. He was discharged without complications.

Male gender is a risk factor for the development of hepatocellular carcinoma (HCC) but the mechanisms are not fully understood. The RNA binding motif gene on the Y chromosome (RBMY), encoding a male germ cell-specific RNA splicing regulator during spermatogenesis, is aberrantly activated in human male liver cancers. This study investigated the in vitro oncogenic effect and the possible mechanism of RBMY in human hepatoma cell line HepG2 and its in vivo effect with regards to the livers of human and transgenic mice. RBMY expression in HepG2 cells was knocked down by RNA interference and the cancer cell phenotype was characterized by soft-agar colony formation and sensitivity to hydrogen-peroxide-induced apoptosis. The results revealed that RBMY knockdown reduced the transformation and anti-apoptotic efficiency of HepG2 cells. The expression of RBMY, androgen receptor (AR) and its inhibitory variant AR45, AR-targeted genes insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) was analyzed by quantitative RT-PCR. Up-regulation of AR45 variant and reduction of IGF-1 and IGFBP-3 expression was only detected in RBMY knockdown cells. Moreover, RBMY positive human male HCC expressed lower level of AR45 as compared to RBMY negative HCC tissues. The oncogenic properties of RBMY were further assessed in a transgenic mouse model. Liver-specific RBMY transgenic mice developed hepatic pre-cancerous lesions, adenoma, and HCC. RBMY also accelerated chemical carcinogen-induced hepatocarcinogenesis in transgenic mice. Collectively, these findings suggest that Y chromosome-specific RBMY is likely involved in the regulation of androgen receptor activity and contributes to male predominance of HCC.

Background

To investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC).

Methods

The Aurora B and Aurora A mRNA level was measured in 160 HCCs and the paired nontumorous liver tissues by reverse transcription-polymerase chain reaction. Mutations of the p53 and β-catenin genes were analyzed in 134 and 150 tumors, respectively, by direct sequencing of exon 2 to exon 11 of p53 and exon 3 of β-catenin. Anticancer effects of AZD1152-HQPA, an Aurora B kinase selective inhibitor, were examined in Huh-7 and Hep3B cell lines.

Results

Aurora B was overexpressed in 98 (61%) of 160 HCCs and in all 7 HCC cell lines examined. The overexpression of Aurora B was associated with Aurora A overexpression (P = 0.0003) and p53 mutation (P = 0.002) and was inversely associated with β-catenin mutation (P = 0.002). Aurora B overexpression correlated with worse clinicopathologic characteristics. Multivariate analysis confirmed that Aurora B overexpression was an independent poor prognostic factor, despite its interaction with Aurora A overexpression and mutations of p53 and β-catenin. In Huh-7 and Hep3B cells, AZD1152-HQPA induced proliferation blockade, histone H3 (Ser10) dephosphorylation, cell cycle disturbance, and apoptosis.

Conclusion

Aurora B overexpression is an independent molecular marker predicting tumor invasiveness and poor prognosis of HCC. Aurora B kinase selective inhibitors are potential therapeutic agents for HCC treatment.

Conventional laparoscopic Roux-en-Y gastric bypass (LRYGB) is a gold standard for bariatric surgery, but the procedure requires five to seven incisions for placement of multiple trocars and thus may produce less-than-ideal cosmetic results. We have developed a new approach, single-incision transumbilical LRYGB (SITU-LRYGB) to treat morbid obesity. We compared the surgical results and patient satisfaction in a study of five-port LRYGB and SITU-LRYGB. Fifty morbidly obese patients (14 males, 36 females) underwent either Roux-en-Y gastric bypass with five-port LRYGB or the SITU-LRYGB approach. During the operation, we used a novel intraoperative liver traction method with a “liver suspension tape” that we specifically designed for SITU-LRYGB. Compared to five-port surgery with SITU-LRYGB, there were no intraoperative complications, wound healing was excellent, and there was no abdominal scarring. SITU surgical time was longer than that with five-port LRYGB (99.8 vs. 67.6 min, P < 0.001). Patients treated with the five-port method were more obese than those in the SITU group (127.9 vs. 112.4 kg, P = 0.016). After the bariatric surgery, no difference in comorbidity was found in both groups. Patient satisfaction was greater with SITU than with the five-port method (4.48 vs. 3.96, P = 0.006). Roux-en-Y gastric bypass can be successfully achieved via a single umbilical incision, a method that provides a short operative time and good recovery and eliminates abdominal scarring.

Introduction

Hepatorenal syndrome (HRS) is one of the serious complications in patients with advanced cirrhosis and ascites. In tertiary centers, most patients were classified as having type 1 HRS for their rapid progressive diseases. However, no significant predictors have been assessed previously for patients with type 1 HRS. In addition to the initial model of end-stage liver disease (MELD) scores and biochemistry parameters, we want to further investigate the prognostic importance of changes in MELD scores and biochemistry parameters over time for patients with type 1 HRS.

Materials and methods

Data from type 1 HRS patients were incorporated, including their demographic, clinical progression, all recording biochemical parameters, therapeutic methods, and outcomes.

Results

A total of 103 patients were included in our study. According to the definition of the International Ascites Club, 67 patients (or 65%) had type 1 HRS whereas 36 (or 35%) had type 2 HRS. According to the multivariate COX proportional hazards regression model, either initial biochemistry parameters or MELD scores were not significantly associated with prognosis. By time-dependent proportional hazards model, each point elevated in creatinine (CRE) and total bilirubin (TBI) levels during the admission increased mortality risk by 29 and 4%, respectively. Increasing albumin level during the admission showed its protective value. Changes in MELD score simple during the admission, which were calculated by CRE and TBI [3.8 × log (bilirubin (mg/dl)] + 9.6 × log [Creatinine (mg/dl) + 6.43], were significant predictor for patients with type 1 HRS.

Conclusion

In patients with type 1 HRS, changes in TBI, CRE, and albumin level during the admission were associated with prognosis. Changes in MELD score simple is superior to initial and changes in MELD scores to predict prognosis in patients with type 1 HRS.

Background

Recently, single-incision laparoscopic surgery (SILS) has been used for bariatric procedures, and this surgery is considered a type of minimally invasive surgery. When SILS is performed via the transumbilical route, the resultant abdominal wound is hidden and the cosmetic outcome is better. However, because of the small angle of manipulation and difficulty in liver traction, this technique is not used to perform complex bariatric surgery. In this prospective study, we used our novel technique, which involves the use of a liver-suspension tape and umbilicoplasty of an omega-shaped incision (omega umbilicoplasty), to perform laparoscopic bariatric surgery via the single-incision transumbilical (SITU) approach. We then assessed the safety and effectiveness of our surgical technique.

Methods

We started performing and developing this technique from December 2008. Until July 2009, 40 consecutive patients underwent 40 bariatric procedures: two adjustable gastric band placements, six sleeve gastrectomies, and 32 Roux-en-Y gastric bypass operations, including five cases where concomitant cholecystectomy was performed.

Results

The mean operation time was 93.4 min and the mean duration of postoperative hospitalization was 1.15 days. No perioperative or postoperative complications or deaths occurred. Most patients were very satisfied with the cosmetic outcomes.

Conclusion

Our technique can be safely and effectively used for SITU laparoscopic bariatric surgery. This technique will soon be used for advanced abdominal surgeries besides bariatric ones.

Background

Our study aimed to assess the nationwide trends in the incidence of severe gallstone disease in Taiwan among adults aged ≥20.

Methods

A retrospective longitudinal study was conducted using Taiwan National Health Insurance Research Database collected during 1997–2005. Patients with incident severe gallstone disease (acute cholecystitis, biliary pancreatitis, acute cholangitis) and gallstone-related procedures (elective and non-elective cholecystectomy, endoscopic retrograde cholangiopancreatography [ERCP]) that led to hospital admission were identified using ICD-9-CM diagnostic and procedure codes. Annual incidence rates of gallstone-related complications and procedures were calculated and their 95% confidence intervals (CI) were estimated assuming a Poisson distribution.

Results

The hospital admission rate for severe gallstone disease increased with advancing age and the age-standardized rate (95% CI) per 1000 population was 0.60 (0.59–0.60) for men and 0.59 (0.59–0.60) for women. Men had a higher rate of acute cholecystitis, probably due to the substantially lower rate of elective cholecystectomy among men than women. For those aged 20–39, hospital admissions for all gallstone-related complications and procedures increased significantly. For those aged ≥60, incidences of biliary pancreatitis, acute cholangitis, and hospital admission for gallstone receiving ERCP increased significantly without substantial change in the incidence of acute cholecystitis and despite a decreased rate of elective cholecystectomy.

Conclusion

This population-based study found a substantial increase in the rate of admission for severe gallstone disease among those aged 20–39. Concurrently, the incidences of biliary pancreatitis and acute cholangitis have risen among those aged ≥60.

Introduction

Gastrojejunocolic (GJC) fistulae represent a significant post-surgical cause of morbidity and mortality. GJC fistulae represent rare post-surgical complications, and most are associated with gastric surgery. In the past, this complication has been under-recognized because a fistula may form years after surgery.

Case presentation

We describe two cases of gastrojejunocolic fistula in men aged 67 and 60 who both initially presented with watery diarrhea and weight loss. Upper GI studies with small bowel follow-through or barium contrast enema studies allowed a conclusive diagnosis to be made. Both patients underwent one-stage en bloc resection, and their postoperative course was uneventful.

Conclusion

With surgery, this condition is entirely correctable. Pre-operative nutritional status should be evaluated in patients undergoing corrective surgery, and total parenteral nutrition plays a major role in the provision of bowel rest to allow recovery in malnourished patients.

Background

To test the feasibility of laparoscopic approach in performing the simultaneous pelvic autonomic nerve preservation during standard anterior resection of sigmoid colon cancer.

Methods

Patients meeting appropriate eligibility criteria were recruited for the present study. The surgical procedures are shown in the video. The genitourinary function was evaluated on the basis of validated questionnaires including International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF), and Female Sexual Function Index (FSFI).

Results

A total of 112 patients (tumor, node, metastasis system stage I, n = 8; stage II, n = 54; stage III, n = 50; male, n = 58; female, n = 54; age [mean ± standard deviation], 55.8 ± 6.4 years) with good baseline genitourinary function were operated on with the intent of total preservation of pelvic autonomic nerves and curative resection of sigmoid colon cancer. The patients were prospectively followed (median time of follow-up, 18 months; range, 6–30 months). In patients with a successful nerve-preserving surgery (96.4%, n = 108), 104 patients completed the evaluation of urinary function. The median duration for indwelling urine Foley catheter was 3.0 days (range, 1.0–7.0 days). The voiding function after removal of the urine Foley catheter was good (IPSS, 0–7) in 98 (94.2%) patients, fair (IPSS, 8–14) in 5 (4.8%), and poor (IPSS, 15–35) in 1 (1.0%). Before and after nerve-preserving surgery, there were no significant changes of IPSS scores (3.20 ± 1.72 vs. 3.68 ± 2.82, P = .075, paired t-test) in the present patient series. Forty-four male patients completed the postoperative evaluation of sexual function, and ejaculation was ranked as good in 40 (90.9%), fair (decrease in ejaculatory amounts) in 3 (6.8%), and poor (retrograde ejaculation, failure of ejaculation) in 1 (2.3%), whereas the potency was good (IIEF, 60–75) in 41 (93.2%), fair (IIEF, 44–59) in 2 (4.5%), and poor (IIEF, 5–43) in 1 (2.3%). Moreover, before and after a successful nerve-preserving operation, there were no significant changes of IIEF scores (72.4 ± 4.6 vs. 70.3 ± 8.4, P = .082, paired t-test). For female patients (n = 42), the postoperative sexual function was ranked as good (FSFI score, 76–95) in 36 (85.7%), fair (FSFI, 58–75) in 4 (9.5%), and poor (FSFI, 4–57) in 2 (4.8%). Furthermore, there were no significant changes of FSFI scores (89.0 ± 9.2 vs. 85.4 ± 16.4, P = .122, paired t-test) before and after successful nerve-preserving surgery.

Conclusions

Under laparoscopy, we can clearly identify and preserve the pelvic autonomic nerves to retain genitourinary function in most patients undergoing oncologic resection of sigmoid colon cancer.

Electronic supplementary material

The online version of this article (doi:10.1245/s10434-008-9861-x) contains supplementary material, which is available to authorized users.

Preoperative diagnosis of hepatic angiomyolipoma is difficult, and the treatment for it remains controversial. The aim of this study is to review our experience in the treatment of hepatic angiomyolipoma and to propose a treatment strategy for this disease. We retrospectively collected the clinical, imaging, and pathological features of patients with hepatic angiomyolipoma. Immunohistochemical studies with antibodies for HMB-45, actin, S-100, cytokeratin, vimentin, and c-kit were performed. Treatment experience and long-term follow-up results are summarized. During a period of 9 years, 10 patients with hepatic angiomyolipoma were treated at our hospital. There was marked female predominance (nine patients). Nine patients received surgical resection without complications. One patient received nonoperative management with biopsy and follow-up. One patient died 11 months after surgery because of recurrent disease. We propose all symptomatic patients should receive surgical resection for hepatic angiomyolipoma. Conservative management with close follow-up is suggested in patients with asymptomatic tumors and meet the following criteria: (1) tumor size smaller than 5 cm, (2) angiomyolipoma proved through fine needle aspiration biopsy, (3) patients with good compliance, and (4) not a hepatitis virus carrier.