Estimation of the physiologic ability and surgical stress scoring system as a useful predictor of postoperative recurrence in patients with stage II colorectal cancer: a multicenter study.

PURPOSE: We determined the usefulness of the estimation of physiologic ability and surgical stress (E-PASS), initially reported as a predictive factor for postoperative morbidity and mortality, as a prognostic indicator in stage II colorectal cancer (CRC). METHODS: Overall, 739 patients who underwent proctocolectomy for CRC at Tottori University Hospital and affiliated hospitals and histologically diagnosed with stage II CRC were included in the current study. RESULTS: A receiver operating characteristic (ROC) analysis of the five-year recurrence-free survival indicated that the comprehensive risk score (CRS) of E-PASS predicted postoperative recurrence. A multivariate analysis revealed that the presence of preoperative perforation, T4, v ≥ 2, and CRSHigh (≥ 0.2267) were independent predictors of postoperative recurrence. Patients were assigned a score using these factors, as follows: the presence of perforation = 1, the absence of preoperative perforation = 0, T4 = 1, T3 = 0, v2/3 = 1, v0/1 = 0, CRSHigh = 1, and CRSLow = 0 (total score: 0-4). Accordingly, the respective 5-year relapse-free survival rates were 91.0%, 83.6%, 70.3%, and 52.0% among those with scores of 0, 1, 2, and both 3 and 4 (P < 0.001). CONCLUSIONS: The CRS predicts postoperative recurrence in patients with stage II CRC.

GPX4 Regulates Tumor Cell Proliferation via Suppressing Ferroptosis and Exhibits Prognostic Significance in Gastric Cancer.

BACKGROUND/AIM: Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. Glutathione peroxidase 4 (GPX4) is a glutathione-dependent antioxidant enzyme known to regulate ferroptosis, which is a non-apoptotic form of cell death accompanied by iron-dependent accumulation of reactive oxygen species (ROS). This study evaluated the expression and function of GPX4 in GC. MATERIALS AND METHODS: The expression of GPX4 was examined in five human GC cell lines (KATO-III, MKN-1, MKN-28, MKN-45, and MKN-74) using real-time quantitative PCR and western blotting. The role of GPX4 in GC was examined using small interference RNA and cell proliferation and ROS assays. Finally, we analyzed GPX4 expression in tumor tissues from 106 patients who underwent GC surgery using immunohistochemistry and evaluated the relationship between GPX4 levels and clinical outcomes of GC. RESULTS: GPX4 was expressed in all GC cell lines at various levels. GPX4 silencing and inhibition significantly reduced cell proliferation and increased ROS generation. Furthermore, the mRNA levels of prostaglandin-endoperoxide synthase 2, a known biomarker of ferroptosis, were increased after GPX4 silencing. GPX4 expression was found to be an independent prognostic factor for overall and disease-specific survival in GC patients. CONCLUSION: GPX4 can regulate cancer cell death via ferroptosis in GC cell lines and represents a significant risk factor for survival in patients with GC.

Risk factors for recurrence in elderly patients with stage II colorectal cancer: a multicenter retrospective study.

BACKGROUND: Adjuvant chemotherapy for stage II colorectal cancer (CRC) is considered appropriate for patients with risk factors for recurrence, rather than for all patients uniformly. However, the risk factors for recurrence remain controversial, and there is limited information, especially for elderly patients. The Geriatric Nutritional Risk Index (GNRI) is widely used as a simple nutritional screening tool in the elderly and is associated with cancer prognosis and recurrence. This study aimed to investigate the risk factors for recurrence in the elderly with stage II CRC, focusing on the GNRI. METHODS: We enrolled 348 elderly patients (≥ 75 years) with stage II CRC who underwent curative resection at the Department of Surgery, Tottori University and our 10 affiliated institutions. The patients were divided into GNRIhigh (≥ 93.465) and GNRIlow (< 93.465) groups. RESULTS: The GNRIlow group showed a significantly worse overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) (P < 0.001, P < 0.001, and P < 0.001, respectively). In a multivariate analysis, GNRIlow (hazard ratio [HR]: 2.244, P < 0.001), pathologic T4 stage (HR: 1.658, P = 0.014), and moderate to severe lymphatic or venous invasion (HR: 1.460, P = 0.033) were independent factors affecting RFS. By using these three factors to score the risk of recurrence from 0 to 3 points, the prognosis was significantly stratified in terms of OS, CSS, and RFS (P < 0.001, P < 0.001, and P < 0.001, respectively). The recurrence rate for each score was as follows: 0 points, 9.8%; 1 point, 22.0%; 2 points, 37.3%; and 3 points, 61.9%. CONCLUSIONS: GNRIlow, pathologic T4 stage, and moderate to severe lymphatic or venous invasion are high-risk factors for recurrence in the elderly with stage II CRC. The scoring system using these three factors appropriately predicted their recurrence and outcome.

Gallbladder Cancer with Biliary Intraepithelial Neoplasia Complicated by Pancreaticobiliary Maljunction: A Case Report.

We report herein a case of gallbladder cancer with biliary intraepithelial neoplasia (BilIN) complicated by pancreaticobiliary maljunction (PBM). A 60-year-old woman was referred to our hospital for thickening of the gallbladder wall diagnosed via ultrasonography at the referring clinic. The Radiographic images showed thickening of the gallbladder wall and a high confluence of pancreaticobiliary ducts outside the duodenal wall without dilatation of the bile duct. The amylase level in the bile duct was highly elevated. The patient was initially diagnosed with PBM without biliary dilatation, and laparoscopic cholecystectomy was performed. Histopathology of the resected specimen revealed gallbladder cancer localized in the mucosa propria with widespread BilIN. Immunohistochemical analyses showed positive results for S100P,IMP3 and p16ink4a in tumor cells, but a positive result for only IMP3 in adenocarcinoma. Expression of p53 was negative. Oncogenic KRAS mutations were not detected in tumor cells. The patient was diagnosed with gallbladder cancer with BilIN complicated by PBM. This case report may be useful in clarifying the carcinogenic process and genetic mutations for gallbladder cancer associated with PBM.

Prognostic Significance of the Number of Teeth in Patients with Colorectal Cancer.

OBJECTIVES: Fusobacterium nucleatum, which is the predominant subgingival microbial species found in chronic periodontitis, has been recently proposed as a risk factor for both the initiation and progression of colorectal cancer. We evaluated whether the number of teeth, which represents oral health, is a marker for the prognosis of patients with colorectal cancer. METHODS: This retrospective single-center study recruited 179 patients who underwent primary colorectal cancer resection with curative intent between 2015 and 2017. The baseline characteristics and survival were analyzed according to the number of teeth observed in dental panoramic radiographs taken before surgical resection as a part of the perioperative surveillance for oral function and hygiene. RESULTS: The median number of teeth was 20 (interquartile range: 6-25), including 28 patients with no teeth. Patients with 20 or more teeth had better overall survival (p = 0.002) and colorectal cancer-specific survival (p = 0.032) than those with less than 20 teeth. Multivariate analyses confirmed that the number of teeth was a significant prognostic factor for overall survival (p = 0.045) but not for colorectal cancer-specific survival (p = 0.258). We also took a propensity score-weighting approach using inverse probability weighting, and the p-values of the number of teeth were 0.032 for overall survival and 0.180 for colorectal cancer-specific survival. CONCLUSIONS: A low number of teeth, which can be easily and noninvasively assessed, has been a poor prognostic factor for overall survival in colorectal cancer patients who underwent surgery with curative intent.

Initial Experience in Rectal Cancer Surgery for the Next Generation of Robotic Surgeons Trained in a Dual Console System.

BACKGROUND: Robotic surgery for rectal cancer is used worldwide, with an increasing incidence of robotic surgeons. Therefore, the most appropriate educational system for next-generation robotic surgeons should be urgently established. METHODS: We analyzed 39 patients who underwent robotic rectal surgery performed by a next-generation surgeon with limited experienced in laparoscopic rectal cancer surgery. The dual console system was used in the initial 15 cases, and we assessed short-term outcomes and the learning curve on operative time using the cumulative sum method. RESULTS: The patients were divided into two groups: 15 cases in the early phase, and 24 cases in the late phase. The operative time and surgeon console time were significantly shorter in the late phase than the early phase (P < 0.001). Postoperative complications were more frequently observed in the early phase (P = 0.049); however, the estimated blood loss and length of hospital stay were not significantly different. In the initial 15 cases that using the dual console, the average operative time changing to the expert surgeon was 82 minutes in the first 5 cases, 19 minutes on average in the next 5 cases, and no change occurred in the last 5 cases. The learning curve peaked after 14 cases, plateaued from case number 15 to 23, and decreased in a linear fashion until the final case. CONCLUSION: Education of a next generation surgeon using a dual console system for robotic rectal cancer surgery was performed safely.

AMIGO2 as a novel indicator of liver metastasis in patients with colorectal cancer.

Our previous study showed that adhesion molecule with immunoglobulin like domain 2 (AMIGO2) is a pivotal driver gene of liver metastasis via regulating tumor cell adhesion to liver endothelial cells in mouse models. The aim of the present study was to clarify the role of AMIGO2 in liver metastasis in patients the colorectal cancer (CRC). Two human CRC cell lines, Caco-2 (AMIGO2-low) and HCT116 (AMIGO2-high), were used in this study. AMIGO2-overexpressing Caco-2 and AMIGO2-knockdown HCT116 cells were generated by transfection with an AMIGO2 expression vector or AMIGO2 small interfering RNA, respectively. Cell proliferation, invasion and adhesion to human liver endothelial cells were examined in in vitro studies. Immunohistochemical analysis was also performed to evaluate the association between AMIGO2 expression and liver metastasis in patients with CRC. In vitro studies revealed that cell proliferation, invasion and adhesion to liver endothelial cells were accelerated by upregulation of AMIGO2 expression, but suppressed by downregulation of AMIGO2 expression in human CRC cells. Immunohistochemical analysis using clinical CRC specimens revealed that AMIGO2 expression was associated with the frequency of liver metastasis (P<0.01), but not that of pulmonary metastasis (P=0.611) and peritoneal dissemination (P=0.909). In addition, AMIGO2 expression levels in tumor cells were significantly higher in liver metastatic foci than primary lesions (P=0.012). In conclusion, the present results indicated that AMIGO2 expression may contribute to the formation of liver metastasis in CRC.

Disinfection with single or double usage of new antiseptic olanexidine gluconate in general surgery: a randomized study.

PURPOSE: Olanexidine gluconate is a newly developed solution for skin disinfection that was recently approved in Japan. We aimed to compare single and double application of the solution in preventing surgical site infection (SSI) in patients undergoing general surgery. METHODS: This randomized study was conducted at the Tottori University Hospital. Patients scheduled to undergo gastrointestinal or hernia surgery were randomly assigned to one of two groups using either one or two Olanedine applicators for skin disinfection. The primary endpoint was the difference in SSI incidence between the two groups. The secondary endpoint was all adverse events related to olanexidine gluconate. RESULTS: A total of 393 patients qualified for the study protocol: 193 received a single application, and 200 received a double application of Olanedine. SSI occurred in 10 patients (2.5%) overall; nine were superficial incisional SSIs, and one patient had a deep incisional SSI. Of the 10 patients who developed SSI, six (3.1%) were in the group receiving a single application, and four (2.0%) were in the group receiving a double application; there was no statistically significant difference between the two groups (P = 0.537). Allergic reactions or skin disorders related to olanexidine gluconate were not observed. CONCLUSION: There was no difference in the SSI incidence between the use of one or two Olanedine applicators for skin preparation in elective general surgery. Therefore, a single application of Olanedine is sufficient and is recommended for general surgery as a standard disinfection precaution. TRIAL REGISTRATION NUMBER: UMIN000027319; 5/12/2017.

Prognostic Significance of TYRO3 Receptor Tyrosine Kinase Expression in Gastric Cancer.

BACKGROUND: Despite improved treatment for gastric cancer (GC), the prognosis of advanced disease remains poor. Further investigation of the oncogenic sequence for GC is needed. MATERIALS AND METHODS: The expression of TYRO3 protein tyrosine kinase in five GC cell lines was confirmed using western blotting. TYRO3 knockdown in GC cells, and bromodeoxyuridine and Transwell assays were used to examine the functions of TYRO3 in tumor proliferation and invasion. Finally, TYRO3 expression in 138 patients who underwent curative gastric resection for advanced GC (Union for International Cancer Control stage II/III) was tested by immunohistochemistry, and the association between prognosis and TYRO3 expression was analyzed. RESULTS: TYRO3 was detected at various levels in all the tested GC cell lines. Deleting TYRO3 significantly suppressed proliferation and invasion. Immunohistochemistry revealed TYRO3 expression was an independent prognostic factor for overall survival in patients with GC. CONCLUSION: TYRO3 appears to mediate tumor progression and predict prognosis of patients with GC.

[A Case of Solitary Metastasis to the Small Intestine with Lymph Node Metastasis after Surgery in Rectal Cancer].

The patient was a 63-year-old man. He underwent laparoscopic anterior resection of a rectal cancer when he was 60 years. The tumor was diagnosed as T3N0M0, Stage Ⅱ, and he was followed up without adjuvant chemotherapy. Two years and 9 months after surgery, anemia and increased levels of tumor markers were observed. CT scan revealed a mass in the mesentery. We suspected rectal cancer recurrence and performed partial resection of the jejunum with regional lymph node dissection. As the tumor appearance and histological findings were similar to those of the previous rectal cancer, the tumor was diagnosed as hematogenous metastasis of rectal cancer with lymph nodes metastasis. The hematogenous metastasis of rectal cancer to the small intestine is rare; however, it may cause metastasis to regional lymph nodes. Therefore, lymph node dissection may be necessaryin surgical interventions for metastatic tumors of the small intestine.

Small bowel stenosis after blunt abdominal trauma: a case report.

BACKGROUND: Small bowel stenosis after blunt abdominal trauma is relatively rare, and progression from trauma to bowel stenosis might sometimes be delayed. Herein, we report the case of a patient who was diagnosed with small bowel stenosis relatively early and received laparoscopic surgery. CASE PRESENTATION: An 18-year-old Japanese male was in a traffic accident and was urgently transported to our hospital. On arrival, he was admitted with right kidney and right adrenal injury and abdominal aortic aneurysm. On hospital day 13, he vomited during conservative treatment without surgery, and computed tomography revealed small bowel stenosis and dilatation of the oral-side small bowel. No improvement with the ileus tube occurred, and he received laparoscopic surgery on hospital day 21. Briefly, the abdominal cavity was observed with a laparoscope. The mesentery was congested, scarring around the stenotic small bowel regions was present, and three stenotic regions were observed 40-50 cm from the Treitz ligament. The patient received partial resection and anastomosis of the small bowel. The postoperative course was stable, and he was discharged on postoperative day eight. CONCLUSIONS: Most cases of bowel stenosis after abdominal trauma are irreversible and usually require surgical treatment. Therefore, small bowel stenosis should be considered in patients with abdominal symptoms after blunt abdominal trauma.

Combination of C-reactive Protein and Monocyte Count Is a Useful Prognostic Indicator for Patients With Colorectal Cancer.

BACKGROUND/AIM: Several studies have demonstrated the usefulness of C-reactive protein (CRP) or cellular components obtained from complete blood count as prognostic indicators in colorectal cancer (CRC) patients. The aim of this study was to investigate the prognostic significance of the combination of CRP and blood cellular components in CRC patients. PATIENTS AND METHODS: A total of 463 patients who underwent curative surgery for CRC were enrolled in this study. RESULTS: ROC analysis revealed that the values of area under the curve of neutrophil, lymphocyte, platelet, and monocyte counts (MC) for overall survival (OS) were 0.594, 0.513, 0.553, and 0.625, respectively. Using cut-off values derived from ROC analysis, patients were divided into the following groups, CRPHigh, CRPLow, MCHigh, and MCLow The 5-year OS rates of CRPHigh and MCHigh, CRPHigh and MCLow, CRPLow and MCHigh, and CRPLow and MCLow patients were 60.2%, 75.7%, 82.1%, and 88.3%, respectively (p<0.0001). Multivariate analysis revealed that the combination of serum CRP levels and MC was an independent prognostic indicator. With regard to the cause of death, the combination of CRP and MC was significantly associated with both cancer-related and unrelated death. CONCLUSION: The combination of CRP and MC is useful in predicting the prognosis in CRC patients.

Neuroendocrine Tumor Arising From Meckel's Diverticulum Unexpectedly Diagnosed After Diverticulectomy and in Which Multiple Lymph Node Metastases Were Found After Reoperation: A Case Report.

A 47-year-old man with progressive anemia possibly due to digestive tract bleeding was referred to our hospital. Contrast-enhanced computed tomography of the abdomen showed a 2-cm tumor lesion arising near the small intestine. Enteroscopy revealed a 3-cm submucosal tumor at the ileum. A gastrointestinal stromal tumor of the small intestine was suspected, and the patient underwent surgery. During the operation, a diverticulum approximately 60 cm orad to the terminal ileum and a tumor at the top of the diverticulum were observed. Considering the location, Meckel's diverticulum was suspected. No lymphadenopathy was present in the mesentery. Laparoscopy-assisted resection of the diverticulum without lymph node dissection was performed. The histological diagnosis of the tumor was a well-differentiated neuroendocrine tumor. Given the possibility of lymph node metastasis, we performed a second operation to remove the small intestine and lymph nodes. Histologically, 7 of the 18 dissected lymph nodes were metastatic. The postoperative course was uneventful, and the patient survived without tumor recurrence for another 2 years 8 months. Neuroendocrine tumors of Meckel's diverticulum are aggressive. Therefore, small intestinal resection along with lymph node dissection might be necessary as part of the surgical strategy.