Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2.

Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl4), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4-induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH.

Long-term outcomes of a phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumors of the stomach.

BACKGROUND: Neoadjuvant treatment is recommended for large GISTs due to their friability and risk of extensive operations; however, studies on the indications and long-term results of this approach are lacking. METHODS: Patients with large (≥ 10 cm) gastric GISTs were enrolled from multiple centers in Korea and Japan after a pathologic confirmation of c-KIT ( +) GISTs. Imatinib (400 mg/d) was given for 6-9 months preoperatively, and R0 resection was intended. Postoperative imatinib was given for at least 12 months and recommended for 3 years. RESULTS: A total of 56 patients were enrolled in this study, with 53 patients receiving imatinib treatment at least once and 48 patients undergoing R0 resection. The 5-year overall survival and progression-free survival rates were 94.3% and 61.6%, respectively. Even patients with stable disease by RECIST criteria responded well to preoperative imatinib treatment and could undergo R0 resection, with most being evaluated as partial response by CHOI criteria. The optimal reduction in tumor size was achieved with preoperative imatinib treatment for 24 weeks or more. No resumption of imatinib treatment was identified as an independent prognostic factor for recurrence after R0 resection. No additional size criteria for a higher risk of recurrence were identified in this cohort with a size of 10 cm or more. CONCLUSIONS: Neoadjuvant imatinib treatment is an effective treatment option for gastric GISTs 10 cm or larger. Postoperative imatinib treatment is recommended even after R0 resection to minimize recurrence.

Muscle fat contents rather than muscle mass determines nonalcoholic steatohepatitis and liver fibrosis in patients with severe obesity.

OBJECTIVE: This study aimed to investigate the association of muscle fat contents, nonalcoholic steatohepatitis (NASH), and liver fibrosis in patients with severe obesity. METHODS: Patients with severe obesity who underwent bariatric surgery were evaluated for NASH and liver fibrosis. Skeletal muscle was assessed by dual energy x-ray absorptiometry, and muscle fat contents (skeletal muscle fat index [SMFI]) were evaluated by computed tomography-based psoas muscle mass and density. RESULTS: A total of 104 patients with severe obesity were enrolled (57 with nonalcoholic fatty liver disease activity score <5 and 47 with NASH with nonalcoholic fatty liver disease activity score ≥5). SMFI was higher in patients with NASH than those without NASH (mean [SD], 39.0 [14.5] vs. 46.5 [14.2] for without NASH vs. with NASH; p = 0.009). SMFI was also correlated with hepatic steatosis grade, ballooning severity, and fibrosis stage. Multiple logistic regression analysis showed that SMFI was associated with higher risk of NASH and liver fibrosis (odds ratio = 2.37, 95% CI: 1.13-4.98, p = 0.022 for NASH; odds ratio = 2.93, 95% CI: 1.32-6.48, p = 0.008 for significant liver fibrosis). CONCLUSIONS: Muscle fat infiltration rather than muscle mass reflects the severities of hepatic steatosis and fibrosis in patients with severe obesity.

Early experience of laparoscopic resection and comparison with open surgery for gastric gastrointestinal stromal tumor: a multicenter retrospective study.

The advantages of laparoscopic resection over open surgery in the treatment of gastric gastrointestinal stromal tumor (GIST) are not conclusive. This study aimed to evaluate the postoperative and oncologic outcome of laparoscopic resection for gastric GIST, compared to open surgery. We retrospectively reviewed the prospectively collected database of 1019 patients with gastric GIST after surgical resection at 13 Korean and 2 Japanese institutions. The surgical and oncologic outcomes were compared between laparoscopic and open group, through 1:1 propensity score matching (PSM). The laparoscopic group (N = 318) had a lower rate of overall complications (3.5% vs. 7.9%, P = 0.024) and wound complications (0.6% vs. 3.1%, P = 0.037), shorter hospitalization days (6.68 ± 4.99 vs. 8.79 ± 6.50, P < 0.001) than the open group (N = 318). The superiority of the laparoscopic approach was also demonstrated in patients with tumors larger than 5 cm, and at unfavorable locations. The recurrence-free survival was not different between the two groups, regardless of tumor size, locational favorableness, and risk classifications. Cox regression analysis revealed that tumor size larger than 5 cm, higher mitotic count, R1 resection, and tumor rupture during surgery were independent risk factors for recurrence. Laparoscopic surgery provides lower rates of complications and shorter hospitalizations for patients with gastric GIST than open surgery.

Bariatric surgery versus medical therapy in Korean obese patients: prospective multicenter nonrandomized controlled trial (KOBESS trial).

PURPOSE: The aim of this study was to show that bariatric surgery (BS) is more effective than medical therapy (MT) in Asian obese patients. METHODS: In this prospective, multicenter, nonrandomized, controlled trial, obese patients with body mass index of ≥35 kg/m2 or 30.0-34.9 kg/m2 with obesity-related comorbidities were assigned to undergo BS, such as laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass, or MT. Patients who underwent BS were evaluated 4, 12, 24, and 48 weeks after surgery, whereas patients who received MT were monitored at a hospital every 6 weeks for 1 year. At each visit, weight, waist and hip circumference, and blood pressure were measured, and patients underwent physical examination and laboratory testing. Health-related quality of life (HQOL) was investigated using Euro QOL-5 Dimension, Impact of Weight on Quality of Life questionnaire-Lite and Obesity-related Problems scale. RESULTS: The study included 264 patients from 13 institutions; of these, 64 underwent BS and 200 received MT. Of the patients who underwent BS, 6.3% experienced early complications. Relative weight changes from baseline to 48 weeks were significantly greater in the BS than in the MT group (26.9% vs. 2.1%, P < 0.001), as were the rates of remission of diabetes (47.8% vs. 16.7%, P = 0.014), hypertension (60.0% vs. 26.1%, P < 0.001), and dyslipidemia (63.2% vs. 22.0%, P < 0.001). HQOL was better in the BS than in the MT group at 48 weeks. CONCLUSION: BS was safe and effective in Korean obese patients, with greater weight reduction, remission of comorbidities, and quality of life improvement than MT.

Short-term changes in the serum metabolome after laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass.

INTRODUCTION: Bariatric surgery is known to be the most effective treatment for weight loss in obese patients and for the rapid remission of obesity-related comorbidities. These short-term improvements result from not only limited digestion or absorption but also dynamic changes in metabolism throughout the whole body. However, short-term metabolism studies associated with bariatric surgery in Asian individuals have not been reported. OBJECTIVES: The aim of this study was to investigate the short-term metabolome changes in the serum promoted by laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) and to determine the underlying mechanisms that affect obesity-related comorbidities. METHODS: Serum samples were collected from Korean patients who underwent RYGB or SG before and 4 weeks after the surgery. Metabolomic and lipidomic profiling was performed using UPLC-Orbitrap-MS, and data were analyzed using statistical analysis. RESULTS: Metabolites mainly related to amino acids, lipids (fatty acids, glycerophospholipids, sphingolipids, glycerolipids) and bile acids changed after surgery, and these changes were associated with the lowering of risk factors for obesity-related diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and atherosclerosis. Interestingly, the number of significantly altered metabolites related to the lipid metabolism were greater in SG than in RYGB. Furthermore, the metabolites related to amino acid metabolism were significantly changed only after SG, whereas bile acid changed significantly only following RYGB. CONCLUSION: These differences could result from anatomical differences between the two surgeries and could be related to the gut microbiota. This study provides crucial information to expand the knowledge of the common but different molecular mechanisms involved in obesity and obesity-related comorbidities affected by each bariatric procedure.

Prediction of Long-Term Diabetes Remission After Metabolic Surgery in Obese East Asian Patients: a Comparison Between ABCD and IMS Scores.

PURPOSE: Recently, more than 10 models have been developed to predict remission of type 2 diabetes mellitus (T2DM) after metabolic surgery. The ABCD score was compared to the individualized metabolic surgery (IMS) score in terms of prediction of T2DM remission, but which of the two scoring systems is better remains controversial. METHODS: Patient data from 463 obese East Asian patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or SG with duodenojejunal bypass (SG-DJB) as a primary operation and were followed for at least 3 years were retrospectively collected from 24 institutions. The correlation between the ABCD and IMS scoring systems and the discrimination power of the models was evaluated. The cut-off point for the IMS stage of T2DM severity was also revised to adjust the scoring system to obese East Asian patients. RESULTS: The two scoring systems were significantly well correlated. The IMS scoring system showed significant differences in T2DM remission rates between the procedures in the moderate stage, but the ABCD score showed no significant differences in each category. The discrimination power of the IMS score was comparable to that of the ABCD score at both 3 and 5 years. The revised IMS scoring system showed that SG-DJB had significantly higher T2DM remission rates in the moderate stage at 5 years than RYGB or SG. CONCLUSION: IMS score may be comparable to ABCD score to predict T2DM remission in obese East Asian patients. The revised IMS scoring system may also select candidates for SG or SG-DJB.

Actual compliance to adjuvant chemotherapy in gastric cancer.

PURPOSE: This study aims to investigate the actual compliance with chemotherapy and analyze several factors affecting the compliance in patients with gastric cancer. METHODS: From February 2012 to December 2014, we collected data of patients with gastric cancer who received adjuvant chemotherapy (TS-1 monotherapy or XELOX: capecitabine/oxaliplatin) in Korea. RESULTS: We collected data of 1,089 patients from 31 institutions. The completion rate and dose reduction rate by age (≥60 years vs. <60 years) were 57.5% vs. 76.8% (P < 0.001) and 17.9% vs. 21.3% (P = 0.354); by body mass index (BMI) (≥23 kg/m2 vs. <23 kg/m2) were 70.2% vs. 63.2% (P = 0.019) and 19.2% vs. 19.9% (P = 0.987), respectively. The compliance by American Society of Anesthesiologists physical status (ASA PS) classification was as follows: completion rate was 74.4%, 62.8%, and 60% (P = 0.001) and the dose reduction rate was 18.4%, 20.7%, and 17.8% (P = 0.946) in ASA PS classification I, II, and III, respectively. The completion rate of TS-1 and XELOX was 65.9% vs. 70.3% (P = 0.206) and the dose reduction rate was 15.7% vs. 33.6% (P < 0.001). Furthermore, the completion rate of chemotherapy by surgical oncologists and medical oncologists was 69.5% vs. 63.2% (P = 0.028) and the dose reduction rate was 17.4% vs. 22.3% (P = 0.035), respectively. CONCLUSION: The compliance was lower in patients who were older than 60 years, had BMI <23 kg/m2, and had higher ASA PS classification. Furthermore, the patients showed higher compliance when they received chemotherapy from surgical oncologists rather than from medical oncologists.

Korean OBEsity Surgical Treatment Study (KOBESS): protocol of a prospective multicentre cohort study on obese patients undergoing laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass.

INTRODUCTION: Bariatric surgery effectively induces long-term weight loss in Western populations. However, its effectiveness in Asians remains to be confirmed objectively. The Korean Society for Metabolic and Bariatric Surgery proposes the first prospective cohort study on Koreans undergoing bariatric surgery. METHODS AND ANALYSIS: The Korean OBEsity Surgical treatment Study (KOBESS) is a prospective, multicentre, single-arm, observational, cohort study on morbidly obese patients who undergo primary sleeve gastrectomy or Roux-en-Y gastric bypass in Korea. In total, 100 consecutive obese Asian patients who will undergo bariatric surgery will be recruited in 2016-2017; follow-up will be for 1 year. Primary outcomes are change in body weight and waist circumference at 1 year. All patients will undergo anthropometry, laboratory tests, bioelectrical impedance analysis, gastrofibroscopy, polysomnography and fat-measuring CT before and after surgery. Patients with diabetes will also undergo perioperative oral glucose tolerance and endocrinological hormone tests. Hypertensive patients will also undergo perioperative echocardiography and carotid Doppler ultrasonography. Female patients suspected of having polycystic ovarian syndrome will also undergo perioperative hormone tests and abdominal ultrasonography. Visceral and subcutaneous fat will be harvested during surgery. Blood, stool and urine samples will be taken at various perioperative time points. Although the cohort is small and the follow-up duration is relatively short, this study will determine whether bariatric surgery induces satisfactory weight loss in obese Koreans. Significantly, the tissue samples will also facilitate many studies examining the effects of bariatric surgery and their mechanisms. ETHICS AND DISSEMINATION: Ethics approval was obtained from the institutional review board of each participating hospital. All findings arising from this cohort study will be published in open-access peer-reviewed journals and will be presented at national and international meetings. All KOBESS investigators will be able to propose research studies and potential publications based on KOBESS data and tissue samples. TRIAL REGISTRATION NUMBER: NCT03100292; Pre-results.

Postoperative oral nutritional supplementation after major gastrointestinal surgery: a randomized controlled clinical trial.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the efficacy of post-operative oral nutrition supplementation after major gastrointestinal surgery. METHODS AND STUDY DESIGN: A prospective randomized controlled trial was conducted to evaluate 174 subjects who were discharged within 2 weeks after major gastrointestinal surgery. The subjects in the study group were prescribed 400 ml/day of Encover® from the day of discharge for 8 weeks, but no supplementation was allowed in the control group. The primary endpoint was the weight loss rate at 8 weeks after discharge compared with the pre-operative weight, and the secondary endpoints included changes in body weight, body mass index, Patient-Generated Subjective Global Assessment score/grade, hematological/ biochemical parameters, and adverse events evaluated at 2, 4, and 8 weeks after discharge. RESULTS: The weight loss rate at 8 weeks after discharge did not differ between two groups (4.23±5.49% vs 4.80±4.84%, p=0.481). The total lymphocyte count, the level of total cholesterol, total protein, and albumin were significantly higher in the study group after discharge. Diarrhea was the most frequent adverse event, and the incidence of adverse events with a severity score of >=3 did not differ between groups (2.3% vs 1.2%). CONCLUSIONS: The utility of routine oral nutritional support after major gastrointestinal surgery was not proven in terms of weight loss at 8 weeks after discharge. However, it can be beneficial for early recovery of biochemical parameters.

Epidemiologic Study of Human Epidermal Growth Factor Receptor 2 Expression in Advanced/Metastatic Gastric Cancer: an Assessment of Human Epidermal Growth Factor Receptor 2 Status in Tumor Tissue Samples of Gastric and Gastro-Esophageal Junction Cancer.

PURPOSE: The Trastuzumab for gastric cancer (GC) trial identified human epidermal growth factor receptor 2 (HER2) as a predictor of successful treatment with trastuzumab (HER2 receptor targeting agent) among patients with advanced/metastatic GC. To date, the prevalence of HER2 overexpression in the Korean population is unknown. The present study aimed to assess the incidence of HER2 positivity among GC and gastroesophageal (GE) junction cancer samples and the relationship between HER2 overexpression and clinicopathological characteristics in Korean patients. MATERIALS AND METHODS: Tumor samples collected from 1,695 patients with histologically proven GC or GE junction enrolled at 14 different hospitals in Korea were examined. After gathering clinicopathological data of all patients, HER2 status was assessed by immunohistochemistry (IHC) at each hospital, and IHC 2+ cases were subjected to silver-enhanced in situ hybridization at 3 central laboratories. RESULTS: A total of 182 specimens tested positive for HER2, whereas 1,505 tested negative. Therefore, the overall HER2-positive rate in this study was 10.8% (95% confidence interval=9.3%-12.3%). The HER2-positive rate was higher among intestinal-type cases (17.6%) than among other types, and was higher among patients older than 70 years and 50 years of age, compared to other age groups. CONCLUSIONS: Our evaluation of the HER2 positivity rate (10.8%) among Korean patients with GC and GE junction indicated the necessity of epidemiological data when conducting studies related to HER2 expression in GC and GE junction.

Comparison of serum trefoil factor 3 with the pepsinogen test for the screening of diffuse-type gastric cancer.

Emerging data show that serum trefoil factor 3 (TFF3) alone and combined with the serum pepsinogen (PG) test can increase the diagnostic yield of gastric cancer. We aimed to evaluate the diagnostic value of serum TFF3 for the screening of gastric cancer in Korean patients, especially for the screening of the diffuse type of gastric cancer, and compared TFF3 to the serum PG test. We enrolled 25 healthy controls and 79 subjects with gastric cancer who underwent endoscopic resection or surgery from June 2006 to June 2015. Data about age, sex, histological type according to the Lauren classification, stage of gastric cancer, and status of H. pylori were collected. Serum levels of PG I and PG II were measured by the latex-enhanced turbidimetric immunoassay, and serum TFF3 levels were measured by enzyme-linked immunosorbent assay. The optimal cutoff value of serum TFF3 was ≥8.9 ng/mL to diagnose gastric cancer, with 73.4 % sensitivity and 92.0 % specificity, which were higher than those of the serum PG I/II ratio, with 69.6 % sensitivity and 68.0 % specificity. The optimal sensitivity and specificity of serum TFF3 for the diagnosis of diffuse-type gastric cancer were 68.0 and 92.0 %, respectively, which were lower than those for the diagnosis of intestinal-type gastric cancer (75.6 and 100 %, respectively). Serum TFF3 is a more stable and useful marker than the serum PG test for the screening of gastric cancer in Korean patients. Serum TFF3 showed good diagnostic power in detecting both intestinal- and diffuse-type gastric cancer although it showed decreased power in diffuse type.

Long-Term Surgical Outcome of 1057 Gastric GISTs According to 7th UICC/AJCC TNM System: Multicenter Observational Study From Korea and Japan.

The aim of this study was to evaluate the treatment and prognosis of gastric gastrointestinal stromal tumors (GISTs) according to the 7th UICC/AJCC tumor-node-metastasis (TNM) system and the modified National Institutes of Health (NIH) risk classification. The study cohort consisted of 1057 patients with gastric GIST who underwent surgery between January 2000 and December 2007 from 13 institutions in Korea and 2 in Japan. Clinicopathologic characteristics, surgical outcomes, recurrence, and 5-year recurrence-free survival were evaluated.The mean age of the patients was 58.6 years. Thirty patients (2.8%) had distant metastasis preoperatively. Median tumor size was 4.0 cm. Complete resection (R0 resection) was achieved in 1018 patients (96.3%). Eighty-six patients (8.1%) had postoperative complications, and 2 patients (0.2%) died within 30 days after surgery. According to the 7th UICC/AJCC TNM system, 5-year recurrence-free survival rates were 95% to 99% in stage I, 94.1% in stage II, 74.1% in stage IIIA, 48.6% in stage IIIB, and 50.0% in stage IV patients. On survival analysis of high-risk patients according to the TNM system, the 5-year recurrence-free survival rates were 91.6% in stage II, 74.1% in stage IIIA, and 48.6% in stage IIIB patients. Independent factors of recurrence following surgery for gastric GIST were gender, tumor size, mitotic count, and radicality on multivariate analysis.The treatment outcome and prognosis of gastric GIST in Korea and Japan seem more favorable compared to those in Western countries. Compared to the modified NIH risk classification, the 7th UICC/AJCC TNM system is more reflective of the 5-year recurrence-free survival of patients with gastric GIST.

Roux-en-Y gastric bypass stimulates hypothalamic miR-122 and inhibits cardiac and hepatic miR-122 expressions.

BACKGROUND: MicroRNAs (miRNAs) are endogenous noncoding small ribonucleic acids that have emerged as one of the central players of gene expression regulation. This study was designed to determine and identify miRNAs that are associated with Roux-en-Y gastric bypass (RYGB). METHODS: Male Sprague-Dawley rats were divided into two groups: sham and RYGB. Changes in food intake and body weight were measured. miRNA microarray analyses on the brain hypothalamus and heart were performed. The expressions of miR-122 were analyzed, and the activities of adenosine monophosphate-activated protein kinase (AMPK) were determined in the hypothalamus, heart, and liver. Antisense oligonucleotide miR-122 was transfected into hepatocellular carcinoma cells to validate in vivo results. RESULTS: Body weights decreased in the RYGB group compared with those in sham group. Food intake was different between sham and RYGB groups. Of 350 miRNAs that were investigated, we observed that miR-122, being predominantly found in the liver, markedly increased (>35-fold) in the hypothalamus and decreased (>4-fold) in the heart. Quantitative polymerase chain reaction analysis revealed that expression of miR-122 was induced in hypothalamus but attenuated in the heart and liver of the RYGB group. Activities of AMPK were decreased in the hypothalamus but increased in the heart and liver. Knockdown of miR-122 in hepatocellular carcinoma cells stimulated phosphorylation levels AMPK. CONCLUSIONS: The results in this study suggest that RYGB regulates the expressions of miR-122 in the hypothalamus, heart, and liver, which in turn may modulate the activities of AMPK, the master regulator of metabolism.

Long-term outcomes after laparoscopy-assisted gastrectomy for advanced gastric cancer: a large-scale multicenter retrospective study.

BACKGROUND: Recently, the number of laparoscopic procedures for gastric cancer has increased rapidly. Laparoscopic surgery is reported to have many advantages over open gastrectomy with oncologic safety in early gastric cancer. However, there were few reports on long-term outcomes of laparoscopy-assisted gastrectomy (LAG) for advanced gastric cancer (AGC). The aim of this study was to investigate long-term survival outcomes after LAG for AGC. METHODS: The data of 1,485 patients who underwent LAG between April 1998 and December 2005 by ten surgeons at ten hospitals were collected retrospectively. Among them, 239 patients who were diagnosed with AGC on final pathologic examination were enrolled in the present study to investigate long-term clinical outcomes. RESULTS: The ratio of male to female patients was 151:88 and the mean age was 57.1 years. One hundred ninety-three subtotal gastrectomies, 41 total gastrectomies, and 5 proximal gastrectomies were performed. D1 + α, D1 + ß, and D2 lymph node dissections were performed for 14, 62, and 163 cases, respectively. The median follow-up period was 55.4 months. The overall 5-year survival rate of the 239 AGC patients was 78.8% and the disease-specific 5-year survival rate was 85.6%. The 5-year survival rates of the TNM staging system's (7th ed.) stages were 90.5% (stage Ib, n = 86), 86.4% (stage IIa, n = 53), 78.3% (stage IIb, n = 44), 52.8% (stage IIIa, n = 24), 52.9% (stage IIIb, n = 24), and 37.5% (stage IIIc, n = 8) (p < 0.001). CONCLUSION: The long-term survival outcome rates of LAG for AGC in the present study were comparable to those previously reported for open gastrectomy. Based on the present results, a well-designed phase III trial comparing LAG and open gastrectomy for AGC will be needed to affirm the validity of LAG for AGC.

Mitochondrial microsatellite instability in gastric cancer and gastric epithelial dysplasia as a precancerous lesion.

BACKGROUND: Genetic instability in gastric cancer represents a key molecular step that occurs early in the carcinogenesis process. To clarify the role of genetic instability in the progression from gastric dysplasia to gastric cancer, mitochondrial microsatellite instability (mtMSI) was studied in gastric cancer and gastric dysplasia. METHODS: DNA was isolated from paired normal and tumoral tissues in 24 patients with gastric dysplasia (low grade) and 49 patients with gastric cancer. mtMSI was analyzed using eight microsatellite markers. mtMSI in gastric dysplasia was studied prospectively to elucidate the relation between mtMSI and gastric carcinogenesis. RESULTS: mtMSI was found in 5 (10.2%) of 49 gastric cancer patients. The mtMSI phenotype was not associated with age, gender, and Helicobacter pylori infection. However, all of the mtMSI was found in intestinal-type gastric cancer (20.8%, p=0.02). In gastric dysplasia, mtMSI was detected in 3 (12.5%) of 24 patients with gastric dysplasia. mtMSI-positive gastric dysplasia showed a poor prognosis statistically compared to mtMSI negative through progression to high-grade dysplasia or gastric cancer. CONCLUSIONS: These data suggest that mtMSI may be an early and important event in the progression of gastric carcinogenesis, especially in intestinal-type gastric cancer.

Morbidity and mortality of laparoscopic gastrectomy versus open gastrectomy for gastric cancer: an interim report--a phase III multicenter, prospective, randomized Trial (KLASS Trial).

OBJECTIVE: The aim of this study was to evaluate the safety of this trial with respect to morbidity and mortality. SUMMARY BACKGROUND DATA: Laparoscopic-assisted distal gastrectomy (LADG) is rapidly gaining popularity. However, there is limited evidence regarding its oncologic safety. We therefore conducted a phase III multicenter, prospective, randomized study comparing LADG with open gastrectomy (ODG). METHODS: Patient eligibility criteria were pathologically-proven adenocarcinoma, 20 to 80 years of age, preoperative stage I, no history of other cancer, chemotherapy, or radiotherapy. The primary end point was to determine whether there is a difference in overall survival between 2 groups. The morbidity and mortality were compared to evaluate the safety of this trial. The time was decided on the hypothesis that the morbidity of this trial was not significantly different from that of previous reports on open gastric cancer surgeries (17%-20%). This study is registered at ClinicalTrials.gov and carries the following ID number: NCT00452751. RESULTS: A total of 342 patients were randomized (LADG, 179 patients; ODG, 161 patients) between January 1, 2006 and July 19, 2007. There were no significant differences between the 2 groups in age, gender, and comorbidities. The postoperative complication rates of the LADG and ODG groups were 10.5% (17/179) and 14.7% (24/163), respectively (P = 0.137). Reoperations were required in 3 cases each group. The postoperative mortality was 1.1% (2/179) and 0% (0/163) in the LADG and ODG groups (P = 0.497), respectively. CONCLUSION: There was no significance difference in the morbidity and mortality between the 2 groups. Therefore, we conclude that this trial is safe and is thus ongoing.

Laparoscopy-assisted total gastrectomy for gastric cancer: a multicenter retrospective analysis.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) has been applied to the treatment of gastric cancer, and there are now several publications regarding its safety and feasibility. In contrast, there have been few reports on laparoscopy-assisted total gastrectomy (LATG), because this procedure is performed less frequently and is technically more difficult to perform than LADG. The purpose of the present study was to evaluate short-term outcomes in a multicenter study of LATG, as well as its safety and feasibility. METHODS: A retrospective multicenter study was carried out in Korea involving 1,485 patients who underwent laparoscopy-assisted gastrectomy for gastric cancer at 10 institutions between April 1998 and December 2005. Of these patients, 131 underwent LATG. We evaluated and analyzed the short-term outcomes and the clinicopathologic characteristics of the 131 patients. RESULTS: The mean (+/- SD) operation time was 270 +/- 79 min; 1 patient required conversion to an open procedure. The mean number of retrieved lymph nodes was 34.7. The mean duration of hospital stay was 11.3 days, and first intake of soft diet was at 5.8 days. The rate of postoperative morbidity was 19% (25/131 patients); there was no mortality. The most common postoperative morbidity was wound complications at the mini-laparotomy site, and there were 3 cases of anastomotic leakage. Six patients (5%) had recurrence of cancer, and 9 patients (7%) died during the follow-up period. CONCLUSION: Our results suggest that LATG is a safe and feasible procedure for gastric cancer patients. A prospective, multicenter, randomized trial of LATG is needed to confirm the efficacy of this procedure.

The impact of a high body mass index on laparoscopy assisted gastrectomy for gastric cancer.

BACKGROUND: Obesity is known to be associated with postoperative morbidity in gastric cancer surgery, but its impact on laparoscopy assisted gastrectomy (LAG) for gastric cancer has rarely been evaluated. METHODS: The clinical data for 1,485 LAG procedures for gastric cancer in 10 institutions were reviewed. The patients were divided into high body mass index (BMI) (BMI > or = 25 kg/m(2); n = 432) and low BMI (BMI <25 kg/m(2); n = 1,053) groups, and their clinical outcomes were compared. RESULTS: The mean age and proportion of comorbid patients were higher in the high BMI group than in the low BMI group. Postoperative morbidity and mortality did not differ between the high BMI (15.7% and 0.9%) and low BMI (14% and 0.5%) groups (p = 0.37 and p = 0.29). Only the operation time and the number of retrieved lymph nodes were significantly different between the high BMI (242.5 min and 30.4) and low BMI (223.7 min and 32.6) groups (p < 0.001 and p = 0.005), especially for male patients undergoing surgery by surgeons who have performed 40 or fewer LAGs. CONCLUSIONS: High BMI itself may not increase operative morbidity after LAG for gastric cancer. However, when a surgeon is relatively inexperienced with LAG, a careful approach is required for male patients with a high BMI.