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.

Artificial intelligence for surgical safety during laparoscopic gastrectomy for gastric cancer: Indication of anatomical landmarks related to postoperative pancreatic fistula using deep learning.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a critical complication of laparoscopic gastrectomy (LG). However, there are no widely recognized anatomical landmarks to prevent POPF during LG. This study aimed to identify anatomical landmarks related to POPF occurrence during LG for gastric cancer and to develop an artificial intelligence (AI) navigation system for indicating these landmarks. METHODS: Dimpling lines (DLs)-depressions formed between the pancreas and surrounding organs-were defined as anatomical landmarks related to POPF. The DLs for the mesogastrium, intestine, and transverse mesocolon were named DMP, DIP, and DTP, respectively. We included 50 LG cases to develop the AI system (45/50 were used for training and 5/50 for adjusting the hyperparameters of the employed system). Regarding the validation of the AI system, DLs were assessed by an external evaluation committee using a Likert scale, and the pancreas was assessed using the Dice coefficient, with 10 prospectively registered cases. RESULTS: Six expert surgeons confirmed the efficacy of DLs as anatomical landmarks related to POPF in LG. An AI system was developed using a semantic segmentation model that indicated DLs in real-time when this system was synchronized during surgery. Additionally, the distribution of scores for DMP was significantly higher than that of the other DLs (p < 0.001), indicating the relatively high accuracy of this landmark. In addition, the Dice coefficient of the pancreas was 0.70. CONCLUSIONS: The DLs may be used as anatomical landmarks related to POPF occurrence. The developed AI navigation system can help visualize the DLs in real-time during LG.

Clinical significance of colonoscopy before laparoscopic bariatric/metabolic surgery in Japanese patients.

PURPOSE: Obesity is known to be associated with colorectal adenoma (CRA) and colorectal cancer (CRC); yet colonoscopy is not considered an essential preoperative evaluation before bariatric/metabolic surgery. The aim of this study was to clarify the clinical significance of preoperative colonoscopy for obese Japanese patients. METHODS: The subjects of this retrospective study were 114 patients who underwent screening colonoscopy before bariatric/metabolic surgery. Multivariate analyses were performed to evaluate the independent predictors of CRA/CRC among the characteristics identified as significant or nearly significant by univariate analyses. RESULTS: Colonoscopy revealed abnormal findings indicating the need for biopsy or polypectomy in 20 of the 114 patients (17.5%), and CRA was diagnosed in 13 patients (11.4%). Three patients (2.6%), who were all ≥ 56 years old, had a CRA ≥ 10 mm in diameter. The multivariate analysis showed that older age and male sex were significant predictors of CRA/CRC, which was identified in 46.2% of the male patients aged ≥ 46 years. CONCLUSION: Our findings suggest that older age and male sex may be risk factors for CRA/CRC in obese Japanese candidates for bariatric/metabolic surgery; thus, preoperative colonoscopy should be considered for these high-risk patients.

Success rate of acquiring informed consent and barriers to participation in a randomized controlled trial of laparoscopic versus open surgery for non-curative stage IV colon cancer in Japan (JCOG1107).

BACKGROUND: Successful achievement of randomized controlled trials (RCTs) is dependent on the acquisition of informed consent (IC) from patients. The aim of this study was to prospectively calculate the proportion of participation in a surgical RCT and to identify the reasons for failed acquisition of IC. METHODS: A 50-insitution RCT was conducted to evaluate oncological outcomes of open and laparoscopic surgery for stage IV colon cancer (JCOG1107: UMIN-CTR 000000105). The success rate of obtaining IC was evaluated in eight periods between January 2013 and January 2021. In addition, reasons for failed acquisition of IC were identified from questionnaires. RESULTS: In total, 391 patients were informed of their eligibility for the trial, and 168 (42%) were randomly assigned to either the laparoscopic surgery group (n = 84) or open surgery group (n = 84). The success rate of IC acquisition ranged from 33 to 58% in three periods. The most common reasons for failed IC acquisition were the patients' preference for one approach of surgery based on recommendations from referring doctors and family members, and anxiety/unhappiness about randomization. CONCLUSIONS: The success rate of acquiring IC from patients for an RCT of laparoscopic versus open surgery for stage IV colon cancer was lower than the expected rate planned in the protocol. To obtain the planned rate, investigators should make efforts to inform patients and their families about the medical contributions a surgical RCT can make and recognize that the period in equipoise may be limited.

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.

Early response in phosphorylation of ribosomal protein S6 is associated with sensitivity to trametinib in colorectal cancer cells.

Mutations in RAS or BRAF are associated with poor prognosis and resistance to epidermal growth factor receptor (EGFR)-targeted therapy in colorectal cancer (CRC). Despite their common ability to activate downstream genes such as MEK and ERK, the therapeutic benefit of MEK inhibitors for patients with RAS/BRAF mutant CRC is limited, highlighting the need for biomarkers to predict the efficacy of MEK inhibition. Previously, we reported that a change in phosphorylation of ribosomal protein S6 (pS6) after MEK inhibition was significantly associated with sensitivity to MEK inhibition in gastric cancer cells. Here, we investigated the value of the response in pS6 for predicting the efficacy of trametinib, a MEK inhibitor, in patients with RAS/BRAF mutant CRC using patient-derived CRC organoids. We found that a subset of CRC cell lines and organoids were sensitive to trametinib. The change in phosphorylated ERK, a downstream molecule of the RAS/RAF/MEK pathway, was not significantly associated with trametinib sensitivity. On the other hand, only those with sensitivity showed a reduction of pS6 levels in response to trametinib. The change in pS6 after trametinib treatment was detectable by Western blotting, immunohistochemistry or immunocytochemistry. We also demonstrated an impact of MEK inhibition on pS6 in vivo using a xenograft model. Our data suggest that, in combination with patient-derived organoids, immunostaining-based detection of pS6 could be useful for prediction of trametinib sensitivity.

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.

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.

[NATURAL ORIFICE TRANSLUMENAL ENDOSCOPIC SURGERY].

The clinical application of natural orifice translumenal endoscopic surgery (NOTES) began in 2007, and several thousand patients worldwide have undergone the technique. In this review, we summarize and highlight the current status and future directions of NOTES. The most common procedures are cholecystectomy and appendectomy, mainly performed as hybrid NOTES through the transvaginal route. In addition, direct-target NOTES such as per oral endoscopic myotomy (POEM) or transanal total mesorectal excision has spread rapidly, because it allows access to the operative field without injuring healthy visceral organs. In Japan, a clinical registration system was established, and clinical applications are carried out safely. NOTES performed in Japan is characterized by procedures requiring extensive techniques of endoscopic treatment such as endoscopic full-thickness resection, POEM, and the submucosal tunnel method. It will be necessary to develop instruments and determine social needs to achieve pure NOTES. It will also be necessary to determine the significance of reducing surgical wounds on the body surface. Although much work is still needed to refine the techniques for NOTES, it appears to be developing as a new minimally invasive form of surgical and endoscopic treatment.

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.

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.

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.

Investigation of the impact of COVID-19 on postoperative outcomes using a nationwide Japanese database of patients undergoing laparoscopic distal gastrectomy and low anterior resection for gastric cancer and rectal cancer.

Background: The COVID-19 outbreak made conventional medical care impossible, forcing changes in both healthcare providers and patients. In Japan, COVID-19 infection began spreading in earnest in 2020 and exploded in 2021. There was concern that the medical impact of COVID-19 in 2021 would differ from that in 2020. We aimed to clarify the impact of COVID-19 on mortality and anastomotic leakage in laparoscopic surgery for gastric cancer and rectal cancer in Japan using the National Clinical Database (NCD). Methods: We collected data from patients who underwent laparoscopic distal gastrectomy (LDG) and laparoscopic low anterior resection (LLAR) from January 2018 to December 2021 from the NCD, a web-based surgical registration system in Japan. The number of surgical cases, monthly incidence of mortality and morbidity (anastomotic leakage), standardized mortality ratio (SMR), and standardized morbidity-leakage ratio (SMLR [ratio of observed patients to expected patients calculated using the risk calculator established in the NCD]) were evaluated. Results: The numbers of LDG and LLAR cases continued to decline in the first year of the pandemic in 2020 and were as low in 2021 as in 2020. Although the numbers of robot-assisted LDG and LLAR cases increased, the growth rate was lower than the rate of increase prior to the pandemic. Mortality and anastomotic leakage, two of the most important complications, as assessed by SMR and SMLR, did not worsen during the pandemic in comparison to the pre-pandemic period. Conclusions: Laparoscopic surgeries were performed safely in Japan and were not affected by the COVID-19 pandemic.

Characterization of residual cancer by comparison of a pair of organoids established from a patient with esophageal squamous cell carcinoma before and after neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) followed by surgery is a standard approach for management of locally advanced esophageal squamous cell carcinoma (ESCC). Patients who do not respond well to NAC have a poor prognosis. Despite extensive research, the mechanisms of chemoresistance in ESCC remain largely unknown. Here, we established paired tumor organoids-designated as PreNAC-O and PostNAC-O-from one ESCC patient before and after NAC, respectively. Although the two organoids did not exhibit significant differences in proliferation, morphology or drug sensitivity in vitro, the tumorigenicity of PostNAC-O in vivo was significantly higher than that of PreNAC-O. Xenografts from PreNAC-O tended to exhibit keratinization, while those from PostNAC-O displayed conspicuous necrotic areas. The tumorigenicity of PostNAC-O xenografts during the chemotherapy was comparable to that of PreNAC-O without treatment. Furthermore, the gene expression profiles of the xenografts suggested that expression of genes involved in the EMT and/or hypoxia response might be related to the tumorigenicity of PostNAC-O. Our data suggested that the tumorigenicity of residual cancer had been enhanced, outweighing the effects of chemotherapy, rather than being attributable to intrinsic chemoresistance. Further studies are required to clarify the extent to which residual cancers share a common mechanism similar to that revealed here.

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.

[Natural orifice translumenal endoscopic surgery: historical and future perspectives].

Natural orifice translumenal endoscopic surgery (NOTES) has gained much attention worldwide since the first report of transgastric peritoneoscopy in a porcine model in 2004. In this review, we summarize and highlight the current status and future directions of NOTES. Thousands of human NOTES procedures have been performed. The most common procedures are cholecystectomy and appendectomy, mainly performed through transvaginal access in a hybrid fashion with laparoscopic assistance, and the general complication rate is acceptable. Although much work is still needed to refine the techniques for NOTES, the development of NOTES has the potential to create a paradigm shift in minimally invasive surgery.

A case of sigmoid colon perforation due to segmental absence of intestinal musculature (SAIM) accompanied by vascular Ehlers-Danlos syndrome: a case report.

BACKGROUND: Segmental absence of intestinal musculature (SAIM) is a partial defect of the intrinsic muscular layer of the intestinal tract. In this report, we describe a case of perforation of the sigmoid colon due to SAIM accompanied by vascular Ehlers-Danlos syndrome (vEDS), which was successfully treated by surgical therapy. CASE PRESENTATION: A male in his 30 s was being followed up for vEDS diagnosed by genetic testing. He had undergone two major vascular surgeries, abdominal aortic artery revascularization and thoracic endovascular aortic repair for a residual dissection and enlarging abdominal aortic aneurysm. On postoperative day 11, the patient developed perforation of the sigmoid colon for which intraperitoneal lavage and drainage, Hartmann surgery, and transverse colostomy were performed. Histological findings showed no disturbance of blood flow or diverticulum but did show a defect in the intrinsic muscular layer around the perforation site, leading to the pathological diagnosis of SAIM and associated perforation of the sigmoid colon. Postoperatively, the patient had no complications and was discharged on postoperative day 18. The patient is being followed as an outpatient and has experienced no relapse. CONCLUSIONS: Both SAIM and vEDS, which may be related diseases, are associated with the presence of tissue fragility and have a high potential to cause intestinal perforation Caution should be exercised during surveillance in patients with constipation and examinations that cause increased intestinal pressure.