Kyong-Hwa Jun

The role of small intestinal bacterial overgrowth in postgastrectomy patients.

Backgroundu2002 Small intestinal bacterial overgrowth (SIBO) is expected in postgastrectomy patients; however, its role has not been clarified. This study was to estimate the prevalence of SIBO and investigate the clinical role of SIBO in postgastrectomy patients.

Susceptibility of gastric cancer according to leptin and leptin receptor gene polymorphisms in Korea

Purpose Leptin plays an important role in the control of body weight and also has a growth-factor-like function in epithelial cells. Abnormal expression of leptin and leptin receptor may be associated with cancer development and progression. We evaluated the relationship among leptin and leptin receptors polymorphisms, body mass index (BMI), serum leptin concentrations, and clinicopathologic features with gastric cancer and determined whether they could be the risk factor of gastric cancer. Methods We measured the serum leptin concentrations of 48 Korean patients with gastric cancer and 48 age- and sex-matched controls. By polymerase chain reaction-restriction fragment length polymorphism, we investigated one leptin gene promoter G-2548A genotype and four leptin receptor gene polymorphisms at codons 223, 109, 343, and 656. Results There was no significant difference between the mean leptin concentrations of the patient and control groups, while BMI was significantly lower in gastric cancer cases (22.9 ± 3.6 vs. 24.5 ± 2.8 kg/m2, P = 0.021). There was significant association between the LEPR Lys109Arg genotype and gastric cancer risk, heterozygotes for GA genotype had been proved to increased the risk of gastric cancer, and its corresponding odds ratio was 2.926 (95% confidence interval, 1.248 to 6.861). Conclusion Our results suggested that LEPR gene Lys109Arg polymorphism is associated with gastric cancer in Korean patients.

Impact of intra-abdominal fat on surgical outcome and overall survival of patients with gastric cancer.

BACKGROUNDnThe aim of this study was to evaluate the impact of obesity on surgical outcome and prognosis in patients with gastric cancer.nnnMETHODSnA total of 304 patients who underwent curative gastrectomy for gastric adenocarcinoma between January 2005 and March 2008were enrolled. Body mass index (BMI) was calculated before the operation and visceral fat area (VFA) was measured by abdominal computed tomography (CT). The patients were divided according to BMI class and VFA quartile. The influence of BMI and VFA on surgical outcome and survival was evaluated.nnnRESULTSnThe median BMI was 23.3 kg/m(2) and the median VFA was 103 cm(2). There was a significant positive correlation between BMI and VFA. According to BMI class and VFA quartile, there were no significant differences in patients characteristics or surgical outcome, with the exception of a significantly longer operation time and fewer retrieved lymph nodes in patients with a high BMI and VFA. The unadjusted overall and disease free survival were not significantly different between BMI classes or VFA quartiles.nnnCONCLUSIONSnObesity, as represented by BMI and VFA, may not be a poor prognostic factor in patients with gastric cancer.

Expression of claudin-7 and loss of claudin-18 correlate with poor prognosis in gastric cancer

BACKGROUNDnThe purpose of this study was to evaluate the expression of claudin-3, claudin-7, and claudin-18 in gastric cancer and to determine the significance of these proteins for patient outcome.nnnMATERIALS AND METHODSnA total of 134 samples were obtained from surgically resected specimens from patients who were diagnosed with gastric carcinoma at a single institution. Paraffin tissue sections from tissue microarray blocks were examined with immunohistochemistry for the expression of claudin-3, claudin-7, and claudin-18.nnnRESULTSnIn normal gastric tissues, positive immunoreactivity was detected for claudin-18 but not for claudin-3 or claudin-7. Claudin-3 and claudin-7 were expressed in 25.4% and 29.9% of the gastric cancer tissues, respectively. However, 51.5% of gastric cancer tissues exhibited reduced expression of claudin-18. Claudin-7 expression was significantly lower in cases with diffuse histologic type and positive lymphatic invasion. There was a significant inverse correlation between claudin-18 expression and perineural invasion. In the survival analysis, the overall survival time was shorter in patients with claudin-7 expression than in those without claudin-7 expression. However, the overall survival was longer in patients with claudin-18 expression than in those without claudin-18 expression.nnnCONCLUSIONSnOur data suggest that the up-regulation of claudin-3 and claudin-7 and the down-regulation of claudin-18 may play a role in the carcinogenesis of gastric cancer. Furthermore, the expression of claudin-7 and the loss of claudin-18 may be independent indicators of a poor prognosis in patients with gastric cancer.

Surgical outcomes and survival after gastrectomy in octogenarians with gastric cancer

BACKGROUNDnThe aim of this study was to evaluate the surgical outcomes and survival after gastrectomy in octogenarians and identify the optimal treatment for these patients.nnnMETHODSnThe medical records of 1262 patients with gastric cancer who underwent gastrectomy from January 2003 to December 2012 were reviewed retrospectively. Patients were divided into two age groups: octogenarians (≥ 80 y, n = 75) and nonoctogenarians (<80 y, n = 1187). The patients clinicopathologic data, surgical outcomes, and survival were evaluated.nnnRESULTSnOctogenarians exhibited a higher proportion of female patients, poorer performance scale scores, higher comorbidities, and more advanced tumor-node-metastasis (TNM) stages than did nonoctogenarians. There was no difference in the surgical curability between the two groups, although octogenarians were more likely to have higher postoperative morbidity and mortality than those of nonoctogenarians. In an analysis of risk factors affecting survival after gastrectomy for octogenarians, only advanced TNM stage was an independent prognostic factor. Overall survival was significantly lower in octogenarians than in nonoctogenarians, whereas disease-specific survival was comparable between the two groups. There was no difference in the disease-specific survival for each stage of cancer after adjustment for tumor stage.nnnCONCLUSIONSnOctogenarians had higher postoperative morbidity and mortality rates but comparable cancer-specific survival compared with nonoctogenarians. Only an advanced TNM stage influenced the prognosis of octogenarians. Early detection and thorough postoperative care would improve the overall survival for octogenarians with gastric cancer.

HMGA1/HMGA2 protein expression and prognostic implications in gastric cancer

BACKGROUNDnThe high mobility group A1 (HMGA1) and high mobility group A2 (HMGA2) proteins are architectural transcription factors that have been implicated in the pathogenesis and progression of multiple malignant tumors, including gastric cancer. The aim of this study was to explore the roles of HMGA1 and HMGA2 in gastric carcinogenesis.nnnMETHODSnThe expression of HMGA1 and HMGA2 was examined in 110 gastric adenocarcinomas, 29 gastric adenomas, and 30 normal controls. The results were correlated with the clinicopathological parameters of the tumors and patient outcome.nnnRESULTSnThe levels of HMGA1 and HMGA2 proteins were significantly increased in gastric cancer samples compared with adenoma and normal gastric tissues. High HMGA1 nuclear immunoreactivity was not correlated with clinicopathological features; however, high levels of HMGA2 protein were significantly associated with T stage, N stage, lymphatic invasion, perineural invasion, and TNM stage. Moreover, HMGA2 expression was significantly associated with shorter recurrence free survival. Multivariate analysis showed that HMGA2 expression was an independent prognostic factor for tumor recurrence.nnnCONCLUSIONSnOur results suggest that HMGA1 and HMGA2 are implicated in gastric carcinogenesis and may play a role in tumor progression towards a more malignant phenotype. The HMGA2 protein may be a useful prognostic marker for predicting tumor recurrence.

Risk factors associated with conversion of laparoscopic simple closure in perforated duodenal ulcer

BACKGROUNDnPrecise patient selection criteria are necessary to guide the surgeon in selecting laparoscopic repair for patients with perforated peptic ulcers. The aims of this study are to report surgical outcomes after surgery for perforated duodenal ulcers and identify risk factors for predicting failure of laparoscopic simple closure for perforated duodenal ulcer.nnnMETHODSnIn total, 77 patients who underwent laparoscopic simple closure for perforated duodenal ulcers from January 2007 to September 2013 were retrospectively analyzed. Patients were divided into totally laparoscopic and conversion groups. The characteristics of patients, intraoperative findings, postoperative complications, conversion rates and suture leakage rates of each group were investigated.nnnRESULTSnLaparoscopic repair was completed in 69 (89.6%) of 77 patients, while 8 (10.4%) underwent conversion to open repair. Patients in the conversion group had longer perforation time, larger perforation size, more suture leakage, longer hospital stay, and higher 30-day mortality rate than those in the totally laparoscopic group. The size of perforation was the only risk factor for conversion in multivariable analysis. Patients with an ulcer perforation size of ≥9 mm or with perforation duration of ≥12.5 h had a significantly increased risk for conversion and suture leakage.nnnCONCLUSIONSnUlcer size of ≥9 mm is a significant risk factor for predicting conversion in laparoscopic simple closure. Suture leakage is associated with ulcer size (9 mm) and duration of perforation (12.5 h).

Short-term surgical outcomes of laparoscopy-assisted versus totally laparoscopic Billroth-II gastrectomy for gastric cancer: a matched-cohort study

BackgroundTo evaluate feasibility and benefits of intracorporeal anastomosis, we compared short-term surgical outcomes between laparoscopy-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) with Billroth-II (B-II) anastomosis for gastric cancer.MethodsSixty patients underwent attempted B-II TLDG from 2011 through 2013. Patients who underwent B-II LADG prior to 2011 were matched to TLDG cases for demographics, comorbidities, tumor characteristics, and TNM stage. Perioperative and short-term surgical outcomes were compared between the two groups.ResultsClinicopathological characteristics of both groups were comparable. The B-II TLDG group had a shorter hospital stay (9.4 vs. 12.0xa0days, Pu2009=u20090.038) and average incision size was smaller (3.5 vs. 5.4xa0cm, Pu2009=u20090.030) than in the B-II LADG group. Anastomotic leakage was not recorded in either group, and there were no differences in the rates of perioperative complications and in inflammatory parameters between the two groups.ConclusionsThis study suggests that B-II TLDG is feasible, compared to B-II LADG, and that it has several advantages over LADG, including a smaller incision, a shorter hospital stay, and more convenience during surgery. However, prospective randomized controlled studies are still needed to confirm that B-II TLDG can be used as a standard procedure for LDG.

Clinicopathological significance of N-cadherin and VEGF in advanced gastric cancer brain metastasis and the effects of metformin in preclinical models.

Gastric cancer is the second most common cause of cancer-related death worldwide. Although brain metastasis is a rare complication of gastric cancer, no standard therapy for gastric cancer brain metastasis has been established. We attempted to identify biological markers that predict brain metastasis, and investigated how to modulate such markers. A case-control study of patients newly diagnosed with gastric cancer who had developed brain metastasis during follow-up, was conducted. These patients were compared with patients who had advanced gastric cancer but no evidence of brain metastasis. Immunohistochemistry was used to analyze the expression of E-cadherin, N-cadherin, MSS1, claudin-3, claudin-4, Glut1, clusterin, ITGB4, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and p53. The expression of VEGF tended to be higher in the case group (33.3 vs. 0%, p=0.055). Median survival was significantly correlated with vascular invasion (12 vs. 33 months, p=0.008) and N-cadherin expression (36 vs. 12 months, p=0.027). We also investigated the effects of metformin in tumor-bearing mouse models. VEGF expression was decreased and E-cadherin increased in the metformin‑treated group when compared with the control group. The expression of the mesenchymal marker MMP9 was decreased in the metformin-treated group. Brain metastasis of advanced gastric cancer was associated with the expression of VEGF. Metformin treatment may be useful for modulating the metastatic capacity by reducing VEGF expression and blocking epithelial-to-mesenchymal transition.

The rationality of N3 classification in the 7th edition of the International Union Against Cancer TNM staging system for gastric adenocarcinomas: A case-control study

BACKGROUNDnThe 7th edition of the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) tumor-node-metastasis (TNM) classification system for gastric cancer is more detailed than the 6th edition with respect to tumor depth and lymph node metastasis. The purpose of this study was to evaluate the rationality of the 7th UICC/AJCC TNM classification system, focusing on N3 gastric cancers.nnnMETHODSnA total of 338 patients with N3 gastric cancer who underwent curative resection with ≥ 16 retrieved lymph nodes at two institutions between January 1997 and December 2007 were included in this study. Patients were divided into the N3a (n = 210) and N3b (n = 128) groups. Clinicopathologic characteristics and survival rates were compared between groups.nnnRESULTSnNo difference in clinicopathologic characteristics, including age (p = 0.989), sex (p = 0.382), tumor location (p = 0.124), surgery type (p = 0.909), depth of invasion (p = 0.313), histologic type (p = 0.111), and Lauren classification (p = 0.491), was observed between patients with N3a and N3b gastric cancer. However, overall survival (OS) rates of patients with N3a gastric cancer were greater than that of patients with N3b gastric cancer (5-year OS, 46% vs. 28%; 10-year OS, 33% vs. 19%; both p < 0.001). Five-year survival rates differed significantly between patients with T3N3a and T3N3b (p = 0.006) sub-stages and between those with T4aN3a and T4aN3b (p = 0.004) sub-stages.nnnCONCLUSIONSnThe results of this study support N3 sub-classification for gastric cancers, which warrant differential consideration according to TNM stage.