Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis.

INTRODUCTION: We have previously reported that overexpression of visinin-like protein 1 (VSNL1) is frequently observed in advanced colorectal adenocarcinomas and correlates with poorer prognosis. In this study, we determined the levels of VSNL1 expression in the earlier stages of colorectal tumors including adenomas and adenocarcinomas, and attempted to clarify the functional significance of VSNL1 overexpression in colorectal carcinogenesis. METHODS: Levels of VSNL expression in colorectal tumor tissues were analyzed using immunohistochemistry. The effects of VSNL1 downregulation and overexpression on cell proliferation, resistance to apoptosis, and invasiveness were determined using two VSNL1-overexpressing colorectal cancer cell lines, CW-2 and HCT-116 and VSNL1 inducibly expressing SNU-C5, respectively. Gene expression signatures in VSNL1-downregulated CW-2 and HCT-116 were identified using transcriptome and gene set enrichment analyses. RESULTS: VSNL1 expression was restricted to only a few crypt cells in the non-tumorous epithelium, whereas it became enhanced in adenomas and adenocarcinomas with the progression of tumorigenesis. Downregulation of VSNL1 in CW-2 and HCT-116 cells suppressed their proliferation through induction of apoptosis. Conversely, overexpression of VSNL1 in SNU-C5 cells enhanced resistance to anoikis. Transcriptome and gene set enrichment analyses revealed that downregulation of VSNL1 altered the expression level of the apoptosis-related gene set in CW-2 and HCT-116 cells. CONCLUSION: VSNL1 plays a role in both the development and progression of colorectal tumors by enhancing cell viability.

Current status and issues regarding surgical education in the region: a questionnaire survey in Oita prefecture in Japan.

BACKGROUND: The shortage and aging of surgeons in regional surgical care has been remarkable, and the importance of surgical education for young surgeons in the region is only increasing. However, there are very few reports about regional surgical education. This study aimed to clarify the current status and issues regarding surgical education in regional surgical care and to examine the ideal way to provide surgical education in the region. METHODS: Two questionnaire surveys were carried out. (1) "Survey on the awareness regarding the education of young surgeons" was conducted by mail in institutions where surgeons worked. (2) "Survey on the current status of surgical education for young surgeons" was conducted via the Internet with surgeons under 40 years old and mentors at the same facility. RESULTS: There were 175 respondents to survey (1), among whom 131 (75%) surgeons were interested in educating young surgeons, and 112 (64%) were actively participating in this educating. Regarding the best evaluation methods for mentors who are educating young surgeons, the most frequent answer was "I don't know (51%)". The number of respondents in survey (2) was 87, including 27 (31%) young surgeons and 60 (69%) mentors. Although there was no difference between young surgeons and mentors in the level of satisfaction with the current status of young surgeons, 37% of young surgeons in urban areas were dissatisfied with their current status, compared to 0% in the regional area (p < 0.05). CONCLUSIONS: Although surgeons did not have confidence in their own education, the level of satisfaction among young surgeons was high even in those providing regional surgical care. Development of an evaluation system for surgical education is necessary for young surgeons to receive more effective surgical education in the region.

Association of immune-related expression profile with sensitivity to chemotherapy in esophageal squamous cell carcinoma.

Neoadjuvant chemotherapy (NAC) followed by surgery is one of the standard therapeutic approaches in Japan for patients with locally advanced esophageal carcinoma. Recently, the JCOG1109 study revealed that NAC with docetaxel, cisplatin and 5-fluorouracil (5-FU) (DCF-NAC) is superior to NAC with cisplatin and 5-FU, and has now become the standard preoperative chemotherapy. Using a microarray system, we have previously investigated the expression profiles of endoscopic biopsy samples from patients with esophageal squamous cell carcinoma (ESCC) before DCF-NAC (preNAC) and identified 17 molecules as biomarkers predictive of a pathologically complete response to DCF-NAC. Here, we re-grouped our previous dataset based on the histopathological response grade with the addition of several microarray profiles and conducted a re-analysis using bioinformatic web tools including DAVID, GSEA, UALCAN, and CIBERSORTx. We identified 204 genes that were differentially expressed between the highly resistant and sensitive groups. Some of these differentially expressed genes (DEGs) were related to the immune response and showed higher expression in the sensitive group. UALCAN showed that high expression of 28 of the top 50 DEGs was associated with a favorable prognosis (p < 0.25), and that this reached a significant (p < 0.05) level for 18 of them, suggesting that patients with high expression of these genes might have benefited from chemotherapy and thus had a better outcome. In preNAC biopsy tissues from a DCF-sensitive case, we demonstrated the presence of cells expressing mRNA for CXCL9, one of the prognosis-related DEGs. Our results highlight the association of immune-related expression profile in preNAC ESCC with the DCF-NAC efficacy.

Technical and oncological safety of laparoscopic gastrectomy for gastric cancer in elderly patients ≥ 80 years old.

BACKGROUND: As the incidence of gastric cancer increases in elderly patients worldwide, laparoscopic gastrectomy (LG) for elderly patients with gastric cancer is also increasing. However, whether LG is an optimal surgical modality for elderly patients with gastric cancer remains unclear. This study aimed to evaluate the technical and oncological safety of LG for elderly patients ≥ 80 years old with gastric cancer. METHODS: Patients who received curative gastrectomy for gastric cancer from 2003 to 2015 were enrolled in the study. They were divided into the LG in elderly patients aged over 80 years (LG-E) group, open gastrectomy (OG) in elderly patients (OG-E) group, and LG in non-elderly patients < 80 years (LG-NE) group. Patients' demographics and short- and long-term outcomes, such as postoperative complications and 5-year survival rate, were compared between the three groups, retrospectively. RESULTS: The LG-E, OG-E, and LG-NE groups comprised 45, 43, and 329 patients, respectively. In the comparison between the LG-E and OG-E groups, the incidence of distal gastrectomy (DG) and the proportions of patients with pathological tumor stage T1, pathological N0, and final stage I were significantly higher in the LG-E versus OG-E group (89 vs. 56%, 76% vs. 16%, 82% vs. 37%, and 84% vs. 35%, p < 0.01, respectively). Blood loss and the incidence of overall postoperative complications in the LG-E group were significantly lower than those in the OG-E group (40 vs. 240 g, p < 0.01, and 29% vs. 53%, p < 0.05, respectively). Although the 5-year overall survival (OS) rate was not significantly different between the two groups, the 5-year disease-specific survival (DSS) rate was significantly higher in the LG-E group versus OG-E group (93% vs. 78%, p < 0.05). Overall comorbidities were significantly higher in the LG-E group versus LG-NE group, but there were no significant differences in short-term outcomes between the two groups. Further, although the 5-year OS rate was significantly lower in the LG-E group versus LG-NE group (67% vs. 87%, p < 0.01), there was no significant difference between the two groups in 5-year DSS rate. CONCLUSION: LG is technically and oncologically safe for the treatment of gastric cancer in both elderly patients aged ≥ 80 years and the non-elderly and can be an optimal surgical modality for elderly patients with gastric cancer.

Clinical significance of sarcoid-like reaction in lymph nodes of gastric cancer patients.

BACKGROUND: Although granulomatous formation (sarcoid-like reaction [SR]) similar to sarcoidosis occasionally occurs in regional lymph nodes of malignant tumors, the pathological significance of SR is unknown. We aimed to elucidate the clinicopathological significance and prognostic relevance of SR in gastric cancer. METHODS: We evaluated 391 patients who underwent curative gastrectomy for gastric cancer between 2007 and 2016 at our hospital. The patients were divided into two groups according to presence of SR in lymph nodes, and clinicopathological factors and prognosis were compared between the two groups. RESULTS: SR was found in 67 (17.1%) of the 391 patients, and 332 (3.3%) of 10,149 lymph nodes examined. Regarding clinicopathological factors, SR-positive group showed significantly higher average age (p < 0.01) and numbers of differentiated tumors than SR-negative group (p < 0.05). Three-year overall survival rate in elderly patients aged ≥75 years was significantly more favorable in SR-positive group (n = 27, 85.2%) versus SR-negative group (n = 97, 63.4%) (p < 0.05). Immunohistochemical studies showed the predominant presence of CD68-positive macrophages for SR, with CD4/CD8-positive T cells and interleukin-10 also positive. CONCLUSION: The presence of SR in gastric cancer is frequent in elderly patients and might be a favorable indicator of prognosis. SR is suggested to reflect immune activation in the host.

Intraperitoneal Phototherapy Suppresses Inflammatory Reactions in a Surgical Model of Peritonitis.

BACKGROUND: Standard treatment for diffuse peritonitis due to colorectal perforation may be insufficient to suppress inflammatory reaction in sepsis. Thus, developing new treatments is important. This study aimed to examine whether intraperitoneal irradiation by artificial sunlight suppresses inflammatory reaction in a lipopolysaccharide (LPS)-induced peritonitis model after surgical treatments. MATERIALS AND METHODS: Mice were divided into naive, nontreatment (NT), and phototherapy (PT) groups. In the latter two groups, LPS was intraperitoneally administered to induce peritonitis and removed by intraperitoneal lavage after laparotomy. The PT group was irradiated with artificial sunlight intraperitoneally. We evaluated the local and systemic inflammatory reactions. Murine macrophages were irradiated with artificial sunlight after stimulation by LPS, and cell viability and expression of tumor necrotizing factor-α (TNF-α) were evaluated. RESULTS: As a local inflammatory reaction, the whole cell count, the expression of interleukin-6 and TNF-α in the intra-abdominal fluid, and the peritoneal thickness were significantly lower in the PT group than in the NT group. As a systematic inflammatory reaction, the expression of serum TNF-α, granulocyte macrophage colony-stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1α, and MIP-1ß were significantly lower in the PT group than in the NT group. Irradiation by artificial sunlight suppressed the expression of TNF-α in murine macrophages without affecting cell viability. CONCLUSIONS: Intraperitoneal irradiation by artificial sunlight could suppress local and systemic inflammatory reactions in the LPS-induced peritonitis murine model. These effects may be associated with macrophage immune responses.

Short- and long-term outcomes of laparoscopic surgery for colorectal cancer in the elderly aged over 80 years old versus non-elderly: a retrospective cohort study.

BACKGROUND: Recently, colorectal cancer has increased in elderly patients worldwide, with laparoscopic colorectal surgery increasing in elderly patients with colorectal cancer. However, whether laparoscopic colorectal surgery is an optimal procedure for colorectal cancer in the elderly remains unclear. This study aimed to verify safety and curability of laparoscopic colorectal surgery in elderly patients ≥80 years old. METHODS: Patients undergoing curative colorectal surgery from 2006 to 2014 were enrolled and classified into the laparoscopic surgery in elderly patients aged ≥80 years (LAC-E) group, open surgery in elderly patients (OC-E) group, and laparoscopic surgery in non-elderly patients (LAC-NE) group. Short- and long-term outcomes were compared between these groups. RESULTS: The LAC-E, OC-E, and LAC-NE groups comprised 85, 25, and 358 patients, respectively. Intraoperative blood loss and incidence of postoperative complications were significantly lower in the LAC-E versus OC-E group (97 vs. 440 mL, p < .01 and 14% vs. 32%, p < .05, respectively). Long-term outcomes were not different between these two groups. Operation time was significantly shorter in the LAC-E versus LAC-NE group (249 vs. 288 min, p < .01). Intraoperative blood loss and postoperative complications were similar between the groups. Although the 5-year overall survival rate in the LAC-E group was lower than that in the LAC-NE group (64% vs. 80%, p < .01), there was no difference in 5-year disease-specific survival between the groups. CONCLUSION: Laparoscopic colorectal surgery is technically and oncologically safe for colorectal cancer in the elderly as well as the non-elderly and can be an optimal procedure for colorectal cancer in the elderly.

Anti-proliferation effect of blue light-emitting diodes against antibiotic-resistant Helicobacter pylori.

BACKGROUND AND AIM: Infection by Helicobacter pylori is implicated in a wide range of upper gastrointestinal diseases. Owing to the rapid emergence of antibiotic-resistant strains of H. pylori, the development of novel treatment modalities for antibiotic-resistant H. pylori infection is a key priority. Blue light-emitting diodes (LED) may represent a unique option owing to their antimicrobial effect. In this study, we aimed to evaluate the anti-proliferative effect of blue LED against antibiotic-resistant H. pylori. METHODS: Ten antibiotic-resistant strains and one sensitive H. pylori strain were used in this study. After irradiation by blue LED along time course, the viability of H. pylori was evaluated by enumerating colony forming units. Morphological changes in H. pylori were observed using a scanning electron microscope. Reductase activity was measured as an indicator of bacterial cellular activity. Total reactive oxygen species was monitored using fluorescence intensity and fluorescence microscope imaging. RESULTS: After irradiation by blue LED, the numbers of H. pylori in all the strains were significantly reduced compared with control group. The H. pylori exhibited a short rod-shaped morphology after irradiation; no such change was observed in H. pylori not exposed to blue LED. Re-irradiation of surviving strain after the initial irradiation also exhibited the same anti-proliferation effect. After blue LED irradiation, bacterial cellular activity was lower, and total reactive oxygen species production was significantly higher in blue LED group, compared with that in control. CONCLUSIONS: Blue LED could be a new treatment to eradicate infection with antibiotic-resistant H. pylori.

Characteristics of advanced gastric cancer with negative or only perigastric lymph node metastasis in elderly patients.

OBJECTIVES: After gastrectomy with extended lymph node (LN) dissection, the damage of celiac plexus seems to cause of disorder of eating habits. To clarify the indication of gastrectomy with limited LN dissection for elderly patients, the pathological characteristics of advanced gastric cancer in elderly patients were examined in this study. METHODS: Forty-seven patients aged ≥80 years with advanced gastric cancer (deeper than pT2) who underwent curative gastrectomy from 1998 to 2015 were enrolled. Patients were classified into two groups by extent of LN metastasis: Group A, with N0 or only perigastric LN metastasis (n = 33); Group B, LN metastasis beyond the perigastric area (n = 14). Pathological factors were then evaluated. RESULTS: No significant differences were observed in age, sex, body mass index, American Society of Anesthesiologists physical status classification, serum level of carcinoembryonic antigen, surgical procedure, extent of LN dissection, and number of dissected LNs. Pathological findings showed no significant differences in tumor location, macroscopic type, histologic type, and lymphovascular invasion. However, significant differences were observed in tumor maximum diameter at the cut-off level of 40 mm (Group A: ≤40 mm, n = 10 and >40 mm, n = 23; Group B: ≤40 mm, n = 0 and >40 mm, n = 14; P = 0.02). CONCLUSION: In the elderly patients, LN metastasis in advanced gastric cancer of ≤40 mm in diameter was limited to be within the perigastric area. Gastrectomy with only perigastric LN dissection may be adopted in these patients.

Gastric lanthanosis (lanthanum deposition) in dialysis patients treated with lanthanum carbonate.

Lanthanum carbonate (LaC) is used to prevent hyperphosphatemia in dialysis patients. It is commonly believed that there is little LaC absorption from the intestines. However, La deposition in the gastric mucosa, which we coined "gastric lanthanosis", was recently reported. We describe here the clinicopathological features of and a possible mechanism for gastric lanthanosis. This study included 23 patients with definite gastric lanthanosis. We extracted characteristic clinicopathological features of gastric lanthanosis by computed tomography (CT) imaging and endoscopic, histologic, electron-microscopic, and element analysis examinations. The Helicobacter pylori infection rate in the lanthanosis group was much lower than that among the general population. The clinicopathological features characteristic of gastric lanthanosis were mucosal high-density linear appearance by CT, reflective bright-white spots (BWS) by gastroscopy, eosinophilic histiocytes occasionally phagocytizing foreign materials by histology, and numerous electron-dense particles in the histiocytes. The particles had burr-like skeletons resembling La crystals. Gastric lanthanosis is an under-reported, but not a rare lesion. It is characterized by endoscopic BWS and histologic eosinophilic histiocytes in dialysis patients treated with LaC. The proposed mechanism for gastric lanthanosis is that LaC is dissolved by gastric juice, crystallized within the mucosa and is phagocytized by histiocytes.

Laparoscopic sentinel node navigation surgery for early gastric cancer: a prospective multicenter trial.

BACKGROUND: Prospective multicenter trials have shown the feasibility of sentinel node (SN) navigation surgery using a dual tracer of dye and radioisotope for early gastric cancer. However, comparable trials using the indocyanine green (ICG) and the infrared ray laparoscopic system (IRLS) have not been reported. On the basis of our cohort studies, we assumed that the ICG imaging with the IRLS is as effective as the dual tracer in detecting SNs. Therefore, we conducted a prospective multicenter trial to assess the effectiveness and generalizability of the infrared ICG technique in patients with early gastric cancer. PATIENTS AND METHODS: Patients with previously untreated cT1 gastric adenocarcinomas less than 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using ICG combined with IRLS technique. Following biopsy of the identified SNs, D2 or modified D2 laparoscopic gastrectomy was performed according to the current Japanese Gastric Cancer Association guidelines. RESULTS: Among the 47 patients who gave written informed consent, 44 were eligible from the surgical findings, for whom SN biopsy was performed. The detection rate of the lymphatic basin by the ICG with IRLS was 100% (44/44). The accuracy was also 100% (7/7) for detecting metastatic lymph node, which was verified on the permanent pathologic examination. Following the median follow-up of 114 months (range, 60 to 120 months), no recurrence (0/40) was observed. Although the number of patients was unequally distributed among the hospitals participating in the trial, the detection rates of SNs in low-volume hospitals were comparable to those in high-volume hospitals. Consequently, there was no learning curve in this trial. CONCLUSION: The infrared ICG imaging accurately detected the lymphatic basin and SNs with occult metastasis in SN-navigated gastrectomy for gastric cancer. This method was feasible even for low-volume surgeons and hospitals.

Laparoscopic proximal gastrectomy for early gastric cancer.

The incidence of proximal early gastric cancer (EGC) is increasing, and while laparoscopic proximal gastrectomy (LPG) has been performed as a surgical option, it is not yet the standard treatment, because there is no established common reconstruction method following proximal gastrectomy (PG). We reviewed the English-language literature to clarify the current status and problems associated with LPG in treating proximal EGC. This procedure is considered indicated for EGC located in the upper third of the stomach with clinical T1N0, but not when it can be treated endoscopically. No operative mortality or conversion to open surgery was reported in our review, suggesting that this procedure is technically feasible. The most frequent postoperative complication involved problems with anastomoses, possibly caused by the technical complexity of the reconstruction. Although various reconstruction methods following open PG (OPG) and LPG have been reported, there is no standard reconstruction method. Well-designed multicenter, randomized, controlled, prospective trials to evaluate the various reconstruction methods are necessary.

A Multi-institutional, Prospective, Phase II Feasibility Study of Laparoscopy-Assisted Distal Gastrectomy with D2 Lymph Node Dissection for Locally Advanced Gastric Cancer (JLSSG0901).

BACKGROUND: The efficacy and safety outcomes of laparoscopy-assisted distal gastrectomy (LADG) with D2 lymph node dissection for locally advanced gastric cancer remain unclear. Therefore, we conducted a randomized, controlled phase II trial to confirm the feasibility of LADG in terms of technical safety, and short-term surgical outcomes were investigated. METHODS: Eligibility criteria included pre-operatively diagnosed advanced gastric cancer that could be treated by distal gastrectomy with D2 lymph node dissection; MP, SS, and SE without involvement of other organs; and N0-2 and M0. Patients aged 20-80 years were pre-operatively randomized. RESULTS: In total, 180 patients were registered and randomized to the open (89 patients) and laparoscopic arms (91 patients). Among 91 patients in the laparoscopic arm, 86 underwent laparoscopic gastrectomy according to the study protocol. Regarding the primary endpoint of the phase II trial, the proportion of patients with either anastomotic leakage or pancreatic fistula was 4.7 % (4/86). The grade 3 or higher morbidity rate, including systemic and local complications, was 5.8 %. Conversion to open surgery was required for 1 patient (1.2 %), without any intra-operative complication. The post-operative mortality rate was 0, and no patient required readmission for surgical complications within 6 months after initial discharge. CONCLUSIONS: The technical safety of LADG with D2 lymph node dissection for locally advanced gastric cancer was demonstrated. A phase III trial to confirm the non-inferiority of this procedure to open gastrectomy in terms of long-term outcomes is ongoing. Registered Number: UMIN 000003420 ( www.umin.ac.jp/ctr/).

Decreased expression of Bauhinia purpurea lectin is a predictor of gastric cancer recurrence.

PURPOSE: Molecular markers as indicators for gastric cancer recurrence are urgently required. The aim of this study was to identify lectins that can be used to predict gastric cancer recurrence after gastrectomy. METHODS: We created lectin expression profiles by microarray analysis for 60 patients, who underwent surgery for gastric cancer at the Oita University Hospital between January, 2005 and December, 2007. Lectin expression and clinicopathological factors in patients who suffered gastric cancer recurrence and those who did not were compared by univariate and multivariate analyses. RESULTS: Thirteen lectins showed a significant increase in binding to cancer tissues, whereas 11 lectins showed a significant decrease in binding to cancer tissues, when compared with binding to normal epithelia. Multivariate analysis revealed that lymph node metastasis and low Bauhinia purpurea lectin (BPL)-binding signals were independent predictive factors for recurrence. All patients with low BPL expression had significantly worse relapse-free survival than those with high BPL expression. CONCLUSIONS: Our results using a novel lectin microarray system provide the first solid evidence that BPL expression is a predictor of gastric cancer recurrence.

Phototherapy with artificial light suppresses dextran sulfate sodium-induced colitis in a mouse model.

BACKGROUND AND AIM: Medical treatment for inflammatory bowel disease (IBD) requires chronic administration and causes side effects. Recently, anti-inflammatory effects of phototherapy were reported in animal models. The present study evaluated whether phototherapy improves dextran sulfate sodium (DSS)-induced colitis in a mouse model of IBD. METHODS: Mice were divided into four equal groups: Control, DSS, DSS + light low (LL), and DSS + light high (LH) groups. Normal fluorescent light intensity in the Control and DSS groups was 200 lux. Artificial light intensities were as follows: DSS + LL group, 1000 lux; DSS + LH group, 2500 lux. After administering phototherapy for 7 days, we evaluated disease activity index (DAI), histological score, colon length/weight, serum 1,25-dihydroxyvitamin D(3) level, and serum and colonic cytokines in the mice. RESULTS: DAI and histological scores were significantly lower in the DSS + LL group than in the DSS group (both, P < 0.05). Colon length and weight were significantly higher in the DSS + LL group than in the DSS group (both, P < 0.05). Serum interleukin (IL)-6, TNF-α, and IL-17 in the DSS + LL group were significantly lower, and serum and colonic IL-10 were significantly higher in the DSS + LL group than in the DSS group (all, P < 0.05). Serum 1,25-dihydroxyvitamin D(3) levels in the DSS + LH group were significantly increased compared with those in the DSS + LL and DSS groups. CONCLUSION: Artificial light phototherapy suppressed DSS-induced colitis in mice by suppression of pro-inflammatory cytokines and promotion of anti-inflammatory cytokines.

A comparison of laparoscopic and open surgery following pre-operative chemoradiation therapy for locally advanced lower rectal cancer.

OBJECTIVE: Although pre-operative chemoradiation therapy for advanced lower rectal cancer is a controversial treatment modality, it is increasingly used in combination with surgery. Few studies have considered the combination of chemoradiation therapy followed by laparoscopic surgery for locally advanced lower rectal cancer; therefore, this study aimed to assess the usefulness of this therapeutic combination. METHODS: We retrospectively reviewed the medical records of patients with locally advanced lower rectal cancer treated by pre-operative chemoradiation therapy and surgery from February 2002 to November 2012 at Oita University. We divided patients into an open surgery group and a laparoscopic surgery group and evaluated various parameters by univariate and multivariate analyses. RESULTS: In total, 33 patients were enrolled (open surgery group, n = 14; laparoscopic surgery group, n = 19). Univariate analysis revealed that compared with the open surgery group, operative time was significantly longer, whereas intra--operative blood loss and intra-operative blood transfusion requirements were significantly less in the laparoscopic surgery group. There were no significant differences in post-operative complication and recurrence rates between the two groups. According to multivariate analysis, operative time and intra-operative blood loss were significant predictors of outcome in the laparoscopic surgery group. CONCLUSIONS: This study suggests that laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is a safe procedure. Further prospective investigation of the long-term oncological outcomes of laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is required to confirm the advantages of laparoscopic surgery over open surgery.

CO(2) pneumoperitoneum increases secretory IgA levels in the gut compared with laparotomy in an experimental animal model.

BACKGROUND: Secretory immunoglobulin A (s-IgA) plays an important role in both gut and systemic immunity. This study aimed to investigate the production of s-IgA resulting from a CO2 pneumoperitoneum compared with a laparotomy. METHODS: Using enzyme-linked immunosorbent assays, s-IgA in stool, malondialdehyde (MDA), and Toll-like receptor 4 (TLR4) in the ileal tissue were evaluated as markers for gut and systemic immune responses in an animal model. The rats were randomly divided into (i) anesthesia-only as the control group; (ii) laparotomy-only as the open group; and (iii) CO2 pneumoperitoneum-only as the pneumoperitoneum group. To evaluate the gut immune system in a time-dependent manner, each group was further divided into short- and long-time subgroups. RESULTS: s-IgA levels did not increase in the open group but significantly increased in the pneumoperitoneum group compared with the control group (p < 0.05). In addition, s-IgA levels in the long-time subgroup significantly increased compared with the short-time subgroup of the pneumoperitoneum group (p < 0.05). TLR4 levels steeply and gradually increased in the open and pneumoperitoneum groups, respectively. MDA levels in the pneumoperitoneum group increased during the early phase and were significantly higher than those in the open group at 24 h (p < 0.05). CONCLUSIONS: This study demonstrated that s-IgA levels in stool increased in the pneumoperitoneum group compared with the open group, suggesting that CO2 pneumoperitoneum may cause transitory damage to the intestinal mucosa.

Evaluation of 0.6% sodium alginate as a submucosal injection material in endoscopic submucosal dissection for early gastric cancer.

BACKGROUND AND AIM: We have focused on sodium alginate (SA) solution as a potential submucosal injection material for endoscopic submucosal dissection (ESD). A previous SA solution had high viscosity and problems such as difficult handling. After its properties were adjusted, SA solution was examined in vitro and its clinical safety was evaluated. METHODS: With 0.4% sodium hyaluronate (SH) solution as a control, catheter injectability and mucosa-elevating capacity of 0.3-0.8% SA solutions were evaluated. Next, 0.6% SA solution was used for ESD in 10 patients with early gastric cancer in a prospective clinical study. RESULTS: Compared with 0.4% SH solution, 0.6% SA solution exhibited no significant difference in catheter injectability but significant superiority in mucosa-elevating capacity. In the clinical study, no adverse events were observed in any patient. CONCLUSION: The safety of 0.6% SA solution as a submucosal injection material was confirmed and it is suggested that its efficacy should be investigated in a larger number of cases.

Poor prognosis of advanced gastric cancer with metastatic suprapancreatic lymph nodes.

BACKGROUND: Whether gastrectomy with D2 lymphadenectomy improves survival of patients with advanced gastric cancer (AGC) remains controversial. Few studies have described the pathological features of AGC with metastatic suprapancreatic lymph nodes (LN), which are the target of D2 lymphadenectomy. This study therefore aims to clarify the prognosis and clinical pathological features including the number and location of metastatic LN in AGC with metastatic suprapancreatic LN. METHODS: 406 patients with AGC, who underwent gastrectomy with D2 lymphadenectomy from 1982 to 2007 at Oita University, were reviewed retrospectively with regard to presence or absence of metastatic suprapancreatic LN. The pathological factors associated with AGC with metastatic suprapancreatic LN were examined by univariate and multivariate analysis. RESULTS: Of 362 patients with AGC, 78 had suprapancreatic LN metastasis (21.5 %), differing significantly in terms of presence of vascular invasion and having a larger number of metastatic perigastric LN in comparison with only metastatic perigastric LN on univariate analysis. According to multivariate analysis, they were associated with presence of vascular invasion and a large number of total metastatic LN (more than two; N2≤). The overall 5-year survival rate of the AGC with perigastric LN metastasis (station 1-7) group was 37.9 % and of the AGC with suprapancreatic LN metastasis group was 12.8 %. There were significant differences in each group (P < 0.05). CONCLUSIONS: Patients with AGC with metastatic suprapancreatic LN had a large number of total metastatic LN and poor prognosis, suggesting that it may be a systemic disease.

Minimally invasive approaches for gastric cancer-Japanese experiences.

Since development of laparoscopy-assisted distal gastrectomy with lymph node dissection in 1991 in Japan, laparoscopic gastrectomy (LAG) is improving and evolving. Recently, advanced LAG techniques including D2 lymph node dissection or anastomosis after total gastrectomy have been developed. Retrospective and prospective multicenter studies have been conducted for early and non-early gastric cancers to establish high-quality evidence. This review summarizes the current trends of minimally invasive approaches for gastric cancer based on current Japanese experiences.