Woo Song Ha

Totally laparoscopic distal gastrectomy after learning curve completion: comparison with laparoscopy-assisted distal gastrectomy.

Purpose The aims are to: (i) display the multidimensional learning curve of totally laparoscopic distal gastrectomy, and (ii) verify the feasibility of totally laparoscopic distal gastrectomy after learning curve completion by comparing it with laparoscopy-assisted distal gastrectomy. Materials and Methods From January 2005 to June 2012, 247 patients who underwent laparoscopy-assisted distal gastrectomy (n=136) and totally laparoscopic distal gastrectomy (n=111) for early gastric cancer were enrolled. Their clinicopathological characteristics and early surgical outcomes were analyzed. Analysis of the totally laparoscopic distal gastrectomy learning curve was conducted using the moving average method and the cumulative sum method on 180 patients who underwent totally laparoscopic distal gastrectomy. Results Our study indicated that experience with 40 and 20 totally laparoscopic distal gastrectomy cases, is required in order to achieve optimum proficiency by two surgeons. There were no remarkable differences in the clinicopathological characteristics between laparoscopy-assisted distal gastrectomy and totally laparoscopic distal gastrectomy groups. The two groups were comparable in terms of open conversion, combined resection, morbidities, reoperation rate, hospital stay and time to first flatus (P>0.05). However, totally laparoscopic distal gastrectomy had a significantly shorter mean operation time than laparoscopy-assisted distal gastrectomy (P<0.01). We also found that intra-abdominal abscess and overall complication rates were significantly higher before the learning curve than after the learning curve (P<0.05). Conclusions Experience with 20~40 cases of totally laparoscopic distal gastrectomy is required to complete the learning curve. The use of totally laparoscopic distal gastrectomy after learning curve completion is a feasible and timesaving method compared to laparoscopy-assisted distal gastrectomy.

Up-regulation of RhoGDI2 in Human Breast Cancer and Its Prognostic Implications

PURPOSE Recent research has identified many genes and proteins that play specific roles in the process of systemic metastasis in various types of cancer. Rho GDP dissociation inhibitor 2 (RhoGDI2) has been shown to inhibit metastasis in human bladder cancer, but its role in breast cancer is controversial. MATERIALS AND METHODS We examined the regulation and clinical significance of RhoGDI2 in Korean breast cancer patients by using proteomic approaches. RESULTS By using a proteomic approach, we observed an increased expression of RhoGDI2 in human breast cancer tissues when compared to that of the normal breast tissues, and we validated its up-regulation in an independent cohort of 8 breast cancer patients. The clinical implication of a RhoGDI2 expression was investigated in 57 breast cancer patients by performing immunohistochemistry. RhoGDI2 did not show a significant association with the tumor size, lymph node metastasis, the histologic grade or the hormone receptor status. However, the patients with RhoGDI2-expressing tumors had significantly shorter disease-free survival (p=0.043; hazard ratio, 3.87) and distant metastasis-free survival (p=0.039; hazard ratio, 5.15). CONCLUSION Our results demonstrated a potential role of RhoGDI2 as a poor prognostic marker as well as a potential therapeutic target. The pro-metastatic nature of RhoGDI2 shown in our study may indicate its organ-specific role in cancer metastasis.

CD44 Variant 9 Serves as a Poor Prognostic Marker in Early Gastric Cancer, But Not in Advanced Gastric Cancer

Purpose The present study is to investigate the significance of CD44 variant 9 (CD44v9) expression as a biomarker in primary gastric cancer. Materials and Methods With various gastric tissues, we performed immunohistochemical staining for CD44v9. Results The positive expression rates for CD44v9 in tumor, including adenoma, early gastric cancer (EGC), and advanced gastric cancer (AGC), were higher than those in non-tumor tissues (p=0.003). In addition, the higher expression for CD44v9 was observed as the tissue becomes malignant. In the analysis of 333 gastric cancer tissues, we found that positive expression rates for CD44v9 were higher in the intestinal type or well differentiated gastric cancer than in the diffuse type or poorly differentiated gastric cancer. Interestingly, the positive expression indicated poor prognosis in EGC (5-year survival rate [5-YSR] in stage I, 81.7% vs. 95.2%; p=0.013), but not in AGC (5-YSR in stage II, 66.9% vs. 62.2%; p=0.821; 5-YSR in stage III, 34.5% vs. 32.0%; p=0.929). Moreover, strong positive expression (3+) showed a trend suggesting worse prognosis only in EGC, and it appeared to be associated with lymph node metastasis. Conclusion This study suggests that CD44v9 may be a good biomarker for prognosis prediction and for chemoprevention or biomarker-driven therapies only for EGC.

Acute gastric volvulus treated with laparoscopic reduction and percutaneous endoscopic gastrostomy

Acute gastric volvulus requires emergency surgery, and a laparoscopic approach for both acute and chronic gastric volvulus was reported recently to give good results. The case of a 50-year-old patient with acute primary gastric volvulus who was treated by laparoscopic reduction and percutaneous endoscopic gastrostomy is described here. This approach seems to be feasible and safe for not only chronic gastric volvulus, but also acute gastric volvulus.

Effectiveness of endoscopic clipping and computed tomography gastroscopy for the preoperative localization of gastric cancer

Purpose Before laparoscopic gastrectomy for gastric cancer can be planned, it is very important to know the precise location of the tumor. The aim of this study was to evaluate 3 methods of predicting the exact location of the tumor: preoperative gastrofibroscopy (GFS), preoperative computed tomography gastroscopy (CT), and intraoperative gastroscopy-guided laparoscopy (Lap). Methods In this study, 15 patients were prospectively identified, and endoscopic clips were preoperatively placed on the proximal 1 cm of the tumor, at the angle on the greater curvature and opposite the angle on the greater curvature. The distances between the pylorus and the proximal tumor clip (PT), the angle clip (PA), the greater curvature clip (PG), and the gastroesophageal junction were measured by preoperative GFS, preoperative CT, intraoperative Lap, and visual inspection (Vis). Results PT, PA, and PG values measured by preoperative GFS differed significantly from the Vis values (P < 0.01). However, preoperative CT measurements of PT, PA, and PG did not differ from the Vis values (P = 0.78, P = 0.48, and P = 0.53, respectively). Intraoperative Lap and Vis PT values differed by only 1.1 cm on an average (P = 0.10), but PA and PG values varied by 1.9 and 3.4 cm, respectively (P = 0.01 for both). Conclusion Endoscopic clipping combined with preoperative CT gastroscopy is more useful than preoperative GFS for preoperatively predicting the location of early gastric cancers and will be helpful for planning laparoscopic gastrectomy.

Pancreatic Diabetes after Distal Pancreatectomy: Incidence Rate and Risk Factors.

Purpose Pancreatectomy can impair production of endocrine and exocrine hormones. In this study, we evaluated: 1) the incidence rate of diabetes in patients undergoing distal pancreatectomy; 2) the correlation between the occurrence of pancreatic diabetes and the extent of the resected pancreas; and 3) factors associated with the development of pancreatic diabetes. Methods We retrospectively reviewed the cases of 26 patients who could be compared in abdominal computed tomography before and after distal pancreatectomy for benign or malignant lesions between January, 1999 to June, 2010. Results The incidence of pancreatic diabetes was 19.2%. Obese patients (BMI>25.0 kg/m2) had a higher incidence (p=0.029) of pancreatic diabetes after distal pancreatectomy than non-obese patients. The diabetes group had larger volumes of resected pancreas, but the difference was not statistically significant (p=0.105). Conclusion Several factors may be associated with the development of pancreatic diabetes after distal pancreatectomy. It is necessary to closely follow-up development of pancreatic diabetes regardless of the extent of resection.

A Phase II Trial of Haptaplatin/5-FU and Leucovorin for Advanced Stomach Cancer

PURPOSE Heptaplatin (SKI-2053 R) is a new platinum analogue, with a better toxicity profile than cisplatin, and has antitumor activity even in cisplatin resistant cell lines. 5-fluoruracil (5-FU) has shown synergy with platinum compounds. This phase II trial was designed to determine the efficacy and toxicities of heptaplatin/ 5-FU (5-fluorouracil) for treating stomach cancer. MATERIALS AND METHODS Thirty-two patients with advanced, measurable gastric adenocarcinomas were enrolled in this trial. The treatment consisted of heptaplatin, 400 mg/m(2)/day (1 hour IV infusion), on day 1 and 5-FU, 800 mg/m(2)/day (12 hours IV infusion), on days 1 to 5. The cycles were repeated every 3 weeks. RESULTS Of the 26 evaluable patients, 9 had partial responses and 1a complete response (overall response rate, 38%; 95% confidence interval, 19 approximately 57%). The median response duration was 23 weeks (range: 4 approximately 60 weeks). The median time to progression was 26 weeks (range: 3 approximately 68 weeks). The grades III-IV toxicities were mostly hematological toxicities: leucopenia was observed in 11 patients (35%) and thrombocytopenia 4 (13%). No definite neuropathy was observed. Grade I-II nephropathy was also noted: grade I high BUN/creatinine levels occurred in 5 patients (16%), grade II proteinuria 2 (6%), grade I proteinuria 5 (16%). Neutropenic fever developed in 5 patients (16%) and 1 died of pneumonia in a neutropenic state. CONCLUSION This study suggests that the regimen of Heptaplatin/5-FU should be effective and have a favorable toxicity profile for the patients suffering with advanced stomach cancer.

Tetraarsenic hexoxide demonstrates anticancer activity at least in part through suppression of NF-κB activity in SW620 human colon cancer cells

Tetraarsenic hexoxide (As4O6) has been used in Korean traditional medicine for the treatment of cancer since the late 1980s, and arsenic trioxide (As2O3) is currently used as a chemotherapeutic agent. Previous studies suggest that the As4O6-induced cell death pathway is different from that of As2O3 and its mechanism of anticancer activity remains unclear. Nuclear factor (NF)-κB is a well-known transcription factor involved in cell proliferation, invasion and metastasis. Hence, in the present study, we investigated the effects of As4O6 on NF-κB activity and NF-κB-regulated gene expression in vitro and in vivo. The cytotoxicity assay revealed that As4O6 inhibited the growth of SW620 cells in a dose-dependent manner, and the half maximal inhibitory concentration (IC50) was ~1 µM after a 48 h treatment. As4O6 suppressed NF-κB activation and suppressed inhibitory κBα (IκBα) phosphorylation stimulated by tumor necrosis factor (TNF). As4O6 also suppressed downstream NF-κB-regulated proteins involved in cancer anti-apoptosis, proliferation, invasion and metastasis. In addition, As4O6 marginally suppressed tumor growth and the anti-NF-κB activity was confirmed using an in vivo xenograft mouse model in which animals were injected with SW620 cells. The present study provides evidence that As4O6 has anticancer properties through suppression of NF-κB activity and NF-κB-mediated cellular responses.

Arsenic hexoxide enhances TNF-α-induced anticancer effects by inhibiting NF-κB activity at a safe dose in MCF-7 human breast cancer cells.

Arsenic hexoxide (As4O6) has been used in Korean folk remedy for the treatment of cancer since the late 1980s. Evidence suggests that the anticancer effects of As4O6 are different from those of As2O3. Tumor necrosis factor-α (TNF-α) is generally increased in advanced cancer and is closely related to cancer progression, although it has cancer-killing effects. The reason is that TNF-α activates nuclear factor-κB (NF-κB) that is involved in cell proliferation, invasion, drug resistance and metastasis. In the present study, we investigated the effects of As4O6 on NF-κB activity, NF-κB-mediated cellular responses, and NF-κB-regulated gene expressions involved in metastasis at the concentrations of As4O6 where no cytotoxicity was observed. As4O6 suppressed NF-κB activation in both TNF-α-treated and control cells, and also suppressed IκB phosphorylation in a time-dependent manner, suggesting the suppression of NF-κB results, in part, from the inhibition of IκB degradation. We also confirmed the anti-NF-κB activity of As4O6 with synergism with TNF-α by augmenting caspase-8 activation. As4O6 also suppressed NF-κB activation induced by TNF-α, and some of the downstream NF-κB-regulated proteins involved in cancer proliferation, anti-apoptosis and metastasis. In conclusion, the present study demonstrated that As4O6 has anticancer properties by inhibiting NF-κB activation and NF-κB-regulated proteins at least in part through the inhibition of IκB phosphorylation, especially in the conditions of advanced cancer where TNF-α is highly secreted.

Clinical Significance of the Levels of Serum Cholesterol in Patients with Gastric Cancer.

PURPOSE The relationship between serum cholesterol levels and mortality is complex. Serum cholesterol levels correlate positively with coronary artery disease, but some studies have suggested a negative relationship in cancer patients. Because the serum cholesterol levels are one of the most frequently assayed laboratory values, trends in the levels of cholesterol were investigated, in patients with gastric cancer and assumed a possible role in cancer screening. MATERIALS AND METHODS The serum cholesterol levels were retrospectively analyzed in a group of 220 patients, diagnosed with gastric cancer, and in 177 healthy subjects. Anthropometric (body mass index: BMI) and biochemical indices of their nutritional status were also determined in the study subjects. Statistical analyses were performed by analyses of variance and covariance, and a discriminant analysis. RESULTS The levels of serum cholesterol, albumin, Hb and the BMI were significantly lower in the gastric cancer-patients group than in the healthy-subjects group. The serum cholesterol and Hb levels were shown to be independent of each other, when adjusted for the effects of the BMI. In the patients with gastric cancer the levels of cholesterol and Hb showed decreasing tendencies as did the tumor extension, as defined by the TNM system. CONCLUSION The serum cholesterol and Hb levels were significantly lower in patients with gastric cancer than in the healthy subjects, which seemed to be linked to the progression of gastric cancer. Therefore, further study is required for the serum cholesterol and Hb levels to be used as markers in cancer screening and its progression, in patients with gastric cancer.