Search

Background Self-expandable metal stent (SEMS) placement is commonly used as a bridge to surgery (BTS) for left-sided malignant colorectal obstruction (MCO). However, the optimal time interval between BTS stenting and surgery for left-sided MCO is unclear, and the results of previous studies are conflicting. This study aimed to determine the differences in clinical outcomes according to the time interval between BTS stenting and surgery in left-sided MCO. Methods Data from 594 patients who underwent SEMS placement for MCO between January 2009 and December 2018 were reviewed. Among them, 148 patients who underwent SEMS placement as BTS treatment and curative surgery were enrolled. The enrolled patients were divided into three groups according to the interval between BTS stenting and surgery: group 1 (interval ≤2 weeks), group 2 (interval 2–3 weeks), and group 3 (interval >3 weeks). Results Group 2 and 3 patients underwent significantly higher rates of laparoscopic surgery than those in group 1 (83.7, 81.0 vs. 53.2 %, respectively; P=0.003, P=0.003, respectively). Also, rates of stoma formation directly after resection were significantly higher in group 1 compared to groups 2 and 3 (21.3 vs 2.3, 6.9%, respectively; P=0.008, P=0.043, respectively). Bridging interval had no effect on SEMS-related complications, resection-related complications, 90-day mortality, permanent stoma formation, 3-year disease-free survival, and 3-year overall survival. Conclusions A bridging interval of > 2 weeks between BTS stenting and surgery for left-sided MCO is preferable for lower stoma formation rates and higher rates of laparoscopic approach operation, with no difference in short-term and long-term outcomes including complication, mortality, and survival.

Backgrounds Intestinal alkaline phosphatase (IAP) plays important role in gut homeostasis. We aimed to evaluate the expression of endogenous IAP and to assess the clinical course according to the expression of endogenous IAP in patients with Crohn’s disease (CD). Methods A total of 32 consecutive patients (14 males) with CD were included in the study. We measured the level of endogenous iAP in inflamed and noninflamed colonic mucosa. To verify the inflammation status, we measured the level of mRNA for IL-6, TNF-α, and TLR-4. We monitored the clinical courses of patients during follow-up after acquisition of biopsy specimens. Results Median age of patients was 22.5 years (range, 15–49). Median CD activity index (CDAI, range) was 93.7 (22.8~ 154.9). There were colonic involvements in all patients and perianal involvement in 43.8% patients. The mRNA levels of IL-6 (p = 0.005) and TLR-4 (p = 0.013) in inflamed mucosa were significantly higher than those in non-inflamed mucosa. However, there was no difference of expression of TNF-α mRNA (p = 0.345). During a 14-month follow-up (range, 9 months–54 months), there were 19 patients with clinical recurrences. There were 9 patients (9/19, 47.4%) with IAP expression ratio (inflamed to non-inflamed) ≤ 1.0 in patients with clinical recurrence while there was one patient (1/13, 7.7%) with IAP ratio ≤ 1.0 in patients without clinical recurrence (p = 0.024). Conclusion Lower expression of IAP in inflamed mucosa compared to non-inflamed mucosa may be associated with clinical recurrence in patients with CD.

Prospero homeobox 1 (PROX1) functions as a tumor suppressor gene or an oncogene in various cancer types. However, the distinct function of PROX1 in gastric cancer is unclear. We determined whether PROX1 affected the oncogenic behavior of gastric cancer cells and investigated its prognostic value in patients with gastric cancer. A small interfering RNA against PROX1 was used to silence PROX1 expression in gastric cancer cell lines AGS and SNU638. Expression of PROX1 in gastric cancer tissues was investigated by performing immunohistochemistry. Apoptosis, proliferation, angiogenesis, and lymphangiogenesis were determined by performing the TUNEL assay and immunohistochemical staining for Ki-67, CD34, and D2-40. PROX1 knockdown induced apoptosis by activating cleaved caspase-3, caspase-7, caspase-9, and poly(ADP-ribose) polymerase, and by decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. PROX1 knockdown also suppressed tumor cell proliferation. In addition, PROX1 knockdown decreased lymphatic endothelial cell invasion and tube formation and the expression of vascular endothelial growth factor (VEGF)-C and -D and cyclooxygenase (COX)-2. However, PROX1 knockdown only decreased umbilical vein endothelial cell invasion, not tube formation. The mean Ki-67 labeling index and lymphatic vessel density value of PROX1-positive tumors were significantly higher than those of PROX1-negative tumors. However, no significant difference was observed between PROX1 expression and apoptotic index or microvessel density. PROX1 expression was significantly associated with age, cell differentiation, lymph node metastasis, cancer stage, and poor survival. These results indicate that PROX1 mediates the progression of gastric cancer by inducing tumor cell proliferation and lymphangiogenesis.

Ephexin4, a guanine nucleotide-exchange factor for RhoG, promotes engulfment of apoptotic cells and cancer cell migration in a RhoG-dependent manner, which is synergistically augmented by Elmo1, an Ephexin4-interacting protein. However, the underlying molecular mechanism remains elusive. Here, we report a mechanism by which Elmo1 cooperates with Ephexin4 to activate RhoG. We found that Ephexin4 activity was increased by elimination of its SH3 domain which intermolecularly interacts with the N20 region of Ephexin4. This interaction prevented RhoG from binding to Ephexin4 and thus inhibited RhoG activation. Moreover, we also found that Elmo1 associated with the SH3 domain as well as the N20 region and competed with the SH3 domain for binding to the N20 region, interrupting the interaction of the SH3 domain with the N20 region and thereby promoting RhoG binding to Ephexin4. In addition, the activity of Ephexin4 lacking the SH3 domain was comparable to that of Ephexin4 with Elmo1. Taken together, the data suggest that Elmo1 relieves the steric hindrance of Ephexin4 generated by the intermolecular interaction of the SH3 domain and makes Ephexin4 more accessible to RhoG.

Piperine, a kind of natural alkaloid found in peppers, has been reported to exhibit anti-oxidative and anti-tumor activities, both in vitro and in vivo. Interleukin-6 (IL-6) is an important cytokine that activates the signal transduction, promotes tumor cell metastasis, and induces malignancy, including in gastric cancer. However, the effects of piperine on IL-6 expression in gastric cancer cells have not yet been well defined. In this study, we investigated the effects of piperine on the IL-6 expression, and examined the underlying signaling pathways via RT-PCR, promoter studies and Western blotting in human gastric cancer TMK-1 cells. Our results showed that piperine inhibited interleukin-1β (IL-1β)-induced IL-6 expression in a dose-dependent manner. In addition, piperine also inhibited IL-6 promoter activity. Experiments with mitogen-activated protein kinase (MAPK) inhibitors and dominant negative mutant p38 MAPK indicated that p38 MAPK was essential for IL-6 expression in the TMK-1 cells. Additionally, signal transducer and activator of transcription 3 (STAT3) was also involved in the IL-1β-induced IL-6 expression in gastric cancer cells. Piperine inhibited IL-1β-induced p38 MAPK and STAT3 activation and, in turn, blocked the IL-1β-induced IL-6 expression. Furthermore, gastric cancer cells pretreated with IL-1β showed markedly enhanced invasiveness, which was partially abrogated by treatment with IL-6 siRNA, piperine, and inhibitors of p38 MAPK and STAT3. These results suggest that piperine may exert at least part of its anti-cancer effect by controlling IL-6 expression through the suppression of p38 MAPK and STAT3.

There are still concerns about the oncologic safety of stent insertion for colorectal cancer obstruction. This study investigated whether the use of stents as a bridge to surgery negatively affect the long-term outcome compared to curative surgery for left-sided colorectal cancer obstruction. Between January 2004 and December 2009, patients with left-sided colorectal cancer obstruction without distant metastasis were retrospectively reviewed. Forty-three patients underwent radical resection after preoperative stent insertion (stent group), whereas 48 underwent emergency surgery with curative intent (surgery group). The short- and long-term outcomes between the two groups were compared. The stent and surgery groups had similar demographics. There were no significant differences in primary anastomosis, laparoscopic-assisted surgery, operation time, time until first defecation and oral intake after surgery, postoperative hospital stay, and reoperation. The stent group had an average hospital stay 7 days longer than the surgery group. During the median follow-up period of 48.1 months, the 5-year disease-free survival rates were not significantly different between the stent and surgery groups (47.2 vs. 48.9 %, respectively; p = 0.499). Overall, the 5-year survival rate was also similar in the two groups (70.4 vs. 76.4 %, respectively; p = 0.941). For left-sided colorectal cancer obstruction, stent insertion followed by surgery showed short-term advantages and similar oncologic outcomes compared to surgery without preoperative intervention. Stent insertion as a bridge to surgery is a safe and feasible treatment option for patients with colorectal cancer obstruction.

We describe the clinical and radiographic characteristics of fungus balls in the bilateral paranasal sinuses. The medical records of 8 of 245 patients with fungus balls of the bilateral paranasal sinuses between 2000 and 2010 were retrospectively reviewed. The incidence of bilateral paranasal sinus fungus balls was 3.3%. Fungus balls were located in the maxillary sinuses bilaterally in 4 cases (50%), followed by the maxillary sinus and contralateral sphenoid sinus in 3 cases (37.5%), and the sphenoid sinuses bilaterally in 1 case (12.5%). There were no predisposing anatomic variations for the occurrence of bilateral paranasal fungus balls. Although the presenting symptoms and signs were non-specific, CT findings were helpful in the diagnosis of bilateral fungus balls. Endonasal removal by an endoscopic approach was performed in all patients. No peri-operative complications or recurrences were noted. Fungus balls in the bilateral paranasal sinuses are most frequently found in the maxillary sinuses bilaterally. Because symptoms of bilateral paranasal fungus balls and findings on nasal endoscopic examination are frequently non-specific, a high index of suspicion is needed and imaging studies, such as CT, are essential to establish the correct pre-operative diagnosis.

Knowledge of the intraoperative location of lesions is a prerequisite for deciding the proper extent of gastric resection or the choice of anastomosis technique during totally laparoscopic distal gastrectomy (TLDG) for early gastric cancer (EGC). In this study we introduce a novel tumor localization method for TLDG: endoscopic blood tattooing.Twenty-three consecutive patients scheduled for TLDG for EGC were enrolled in this prospective study. The day before surgery, 2-3 ml of autologous blood was injected into the gastric muscle layer at 3-4 cm proximal to the lesion during endoscopy.The study subjects consisted of 15 males and 8 females with a mean age of 61 ± 10.4 years. During surgery, the endoscopic blood tattooed sites were successfully identified in all 23 patients. No complications associated with the procedure occurred, and no patient had microscopic residual tumor cells at the proximal resection margin, with a mean proximal margin length of 3.3 ± 2.7 cm. Eighteen patients underwent TLDG with Billroth II anastomosis, four patients with Roux-en-Y gastrojejunostomy, and one patient with laparoscopic total gastrectomy. At final pathologic examinations, 20 patients were of stage IA and 3 were of stage IB according to the UICC TNM classification (6th ed.).Endoscopic blood tattooing provides a simple and useful means of localizing lesions during TLDG for EGC. Although the superiority of this technique over other localization methods needs to be evaluated further, the authors recommend endoscopic blood tattooing as an alternative to other intraoperative localization methods for laparoscopic surgery for EGC.

Altered Recepteur d'Origine nantais (RON) expression transduces signals inducting invasive growth phenotype that includes cell proliferation, migration, matrix invasion, and protection of apoptosis in human cancer cells. The aims of the current study were to evaluate whether RON affects tumor cell behavior and cellular signaling pathways including activator protein-1 (AP-1) and Akt/forkhead box O (FoxO) in human colorectal cancer cells.To study the biological role of RON on tumor cell behavior and cellular signaling pathways in human colorectal cancer, we used small interfering RNA (siRNA) to knockdown RON gene expression in human colorectal cancer cell line, DKO-1.Knockdown of RON diminished migration, invasion, and proliferation of human colorectal cancer cells. Knockdown of RON decreased AP-1 transcriptional activity and expression of AP-1 target genes. Knockdown of RON activated cleaved caspase-3, -7, -9, and PARP, and down-regulated the expression of Mcl-1, survivin and XIAP, leading to induction of apoptosis. Knockdown of RON induced cell cycle arrest in the G2/M phase of cancer cells by an increase of p27 and a decrease of cyclin D3. Knockdown of RON inhibited the phosphorylation of Akt/FoxO signaling proteins such as Ser473 and Thr308 of Akt and FoxO1/3a.These results indicate that knockdown of RON inhibits AP-1 activity and induces apoptosis and cell cycle arrest through the modulation of Akt/FoxO signaling in human colorectal cancer cells.

An accessory bile duct is found in up to 4% of necropsies and is usually a single thin-walled channel that drains a segment of the right lobe of the liver into the common bile duct or, rarely, into the gallbladder. However, accessory bile ducts draining into the gastrointestinal tract are extremely rare. We report a patient with an accessory bile duct draining into the stomach and review the literature pertaining to this condition.

We report a patient with massive gastrointestinal bleeding from jejunal varices, confirmed by emergency laparotomy. A 54-year-old woman was admitted to Chonnam National University Hospital with a 5-day history of melena with hematochezia. Fifteen years previously, she had undergone cholecystectomy for gallstone. Seven years previously, she had undergone an operation because of possible common bile duct stone. The details of this operation were not known. Upper gastrointestinal endoscopy revealed no varices in the esophagus, stomach, and proximal duodenum. Colonoscopy demonstrated black-colored blood clots throughout the colon. A technetium-99m-labeled red blood cell (RBC) scan showed active proximal small bowel bleeding. Abdominal aortic angiography revealed mesenteric varices in the upper abdomen, but no active bleeding source was recognized. Because of the patient's continued massive gastrointestinal bleeding despite medical therapy, emergency laparotomy was performed. We found evidence of micronodular cirrhosis of the liver and an apparent Roux-en-Y anastomosis. There were numerous collateral variceal vessels in the jejunal limb with the liver and abdominal wall. Segmental resection of the involved jejunum and end-to-end anastomosis were perdilated formed. Histologic examination revealed submucosal veins with mucosal erosion.

Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). Sixty-five patients who underwent surgery for gastric cancer in 1992 at Chonnam National University Hospital were selected for this study. The primary selection criteria were the availability of formalin-fixed and paraffin-embedded blocks and sufficient clinical follow-up for tumor-specific survival analysis. In this study, we examined the expression of TIMP-1 and TIMP-2 in human gastric cancer tissue by in situ hybridization and immunohistochemistry, and the correlation between their expression and clinicopathological parameters. TIMP-1 and TIMP-2 expressions were detected predominantly in the peritumor stromal cells rather than tumor cells themselves. Immunohistochemical stainings were concordant with the result obtained by in situ hybridization. The intensity of TIMP-1 immunohistochemical stromal staining correlated with tumor stage (P = 0.009) and patient survival (P = 0.025). However, the intensity of TIMP-2 immunohistochemical stromal staining did not correlate with tumor stage (P = 0.339) and patient survival (P = 0.474). The correlation between the increased TIMP-1 expression and cancer stage noted in this study reflects a role of TIMP-1 in predicting the aggressive behavior of gastric cancer. TIMP-2 expression did not correlate with clinicopathological parameters. However, expression of TIMP-1 and the possible additional value of TIMP-2 should be further explored in determining the prognosis of gastric cancer.

Background The aim of this study was to evaluate the time trend of seropositivity of Helicobacter pylori (H. pylori) over the period of 13 years in an asymptomatic Korean population, and investigate associated risk factors. Methods This cross-sectional nationwide multicentre study surveyed anti-H. pylori IgG antibodies in 19,272 health check-up subjects (aged [greater than and equal to]16 years) in 2011. Risk factors for H. pylori infection were investigated using logistic regression. Seropositivity in asymptomatic subjects without H. pylori eradication was compared between the years 1998 and 2005. Birth cohort effects were also evaluated. Results After exclusion of subjects with a history of H. pylori eradication therapy (n = 3,712, 19.3%) and gastric symptoms (n = 4,764, 24.7%), the seroprevalence of H. pylori infection was 54.4% in 10,796 subjects. This was significantly lower than the seroprevalence of 59.6% in 2005 and that of 66.9% in 1998, and this decrease of seropositivity of H. pylori became widespread across all ages and in most areas of the country. This decreasing trend could be explained by cohort analysis. All younger birth cohorts had a lower seroprevalence of H. pylori than older birth cohorts at the same age. Decreased seroprevalence within the same birth cohorts also accounted for this phenomenon. Clinical risk factors of H. pylori infection were higher cholesterol level ([greater than and equal to] 240 mg/dl) (OR = 1.33; 95% CI = 1.14-1.54), male gender, older age, low income, and residence in a rural area. Conclusions A decreasing trend of H. pylori seroprevalence due to a birth cohort effect requires further studies on its related human host factors as well as socio-economic and hygienic factors. In addition, the relationship between H. pylori infection and high cholesterol level needs more investigation regarding underlying pathogenesis.