Lymphocyte-C-reactive Protein Ratio as Promising New Marker for Predicting Surgical and Oncological Outcomes in Colorectal Cancer.

BACKGROUND: Systemic inflammation via host-tumor interactions is currently recognized as a hallmark of cancer. The aim of this study was to evaluate the prognostic value of various combinations of inflammatory factors using preoperative blood, and to assess the clinical significance of our newly developed inflammatory score in colorectal cancer (CRC) patients. METHOD: In total 477 CRC patients from the discovery and validation cohorts were enrolled in this study. We assessed the predictive impact for recurrence using a combination of nine inflammatory markers in the discovery set, and focused on lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for peri-operative risk in both cohorts. RESULTS: A combination of lymphocytic count along with C-reactive protein levels demonstrated the highest correlation with recurrence compared with other parameters in CRC patients. Lower levels of preoperative LCR significantly correlated with undifferentiated histology, advanced T stage, presence of lymph node metastasis, distant metastasis, and advanced stage classification. Decreased preoperative LCR (using an optimal cut-off threshold of 6000) was an independent prognostic factor for both disease-free survival and overall survival, and emerged as an independent risk factor for postoperative complications and surgical-site infections in CRC patients. Finally, we assessed the clinical feasibility of LCR in an independent validation cohort, and confirmed that decreased preoperative LCR was an independent prognostic factor for both disease-free survival and overall survival, and was an independent predictor for postoperative complications and surgical-site infections in CRC patients. CONCLUSION: Preoperative LCR is a useful marker for perioperative and postoperative management of CRC patients.

Rate of Reoperation Decreased Significantly After Year 2002 in Patients With Crohn's Disease.

BACKGROUND & AIMS: Patients with Crohn's disease (CD) can require multiple intestinal surgeries. We examined time trends and risk factors for reoperation in patients with CD who underwent intestinal surgery, focusing on the effects of postoperative medical treatments. METHODS: We performed a retrospective analysis of 1871 patients with CD who underwent initial intestinal resection at 10 tertiary care institutions in Japan, with an initial surgical date after May 1982. We collected data on the background characteristics of all patients, including Montreal Classification, smoking status, and medical therapy after surgery (tumor necrosis factor antagonists [anti-TNF] agents or immunomodulators). The primary outcome was requirement for first reoperation. Rate of reoperation was estimated using the Kaplan-Meier method, and risk factors for reoperation were identified using the Cox regression model. RESULTS: The overall cumulative 5- and 10-year reoperation rates were 23.4% and 48.0%, respectively. Multivariable analysis showed that patients who underwent the initial surgery after May 2002 had a significantly lower rate of reoperation than patients who underwent surgery before April 2002 (hazard ratio [HR], 0.72; 95% CI, 0.61-0.86). Preoperative smoking (HR, 1.40; 95% CI, 1.18-1.68), perianal disease (HR, 1.50; 95% CI, 1.27-1.77), and ileocolic type of CD (HR, 1.42; 95% CI, 1.20-1.69) were significant risk factors for reoperation. Postoperative use of immunomodulators (HR, 0.60; 95% CI, 0.44-0.81) and anti-TNF therapy (HR, 0.71; 95% CI, 0.57-0.88) significantly reduced the risk. Anti-TNF was effective in the bionaive subgroup. CONCLUSIONS: The rate of reoperation in patients with CD significantly decreased after May 2002. Postoperative use of anti-TNF agents might reduce the reoperation rate for bionaive patients with CD.

Advanced Lung Cancer Inflammation Index Predicts Outcomes of Patients With Colorectal Cancer After Surgical Resection.

BACKGROUND: The advanced lung cancer inflammation index is considered a useful prognostic biomarker of clinical outcomes in patients with malignancies. However, the prognostic value of the advanced lung cancer index in patients with colorectal cancer who underwent surgical resection remains unclear. OBJECTIVE: In this study, we evaluated the prognostic value of the advanced lung cancer index in patients with colorectal cancer. DESIGN: Prospectively obtained data of patients with colorectal cancer were retrospectively evaluated to clarify the clinical relevance of the advanced lung cancer index. SETTINGS: We conducted this study at a single expert center. PATIENTS: We enrolled 298 patients with colorectal cancer who underwent surgical resection in this retrospective study. MAIN OUTCOME MEASURES: The primary outcome was the clinical relevance of the advanced lung cancer index in patients with rectal cancer. RESULTS: Low status of advanced lung cancer index was significantly correlated with undifferentiated histology (p = 0.004), T stage progression (p < 0.001), R1/R2 resection for primary surgery (p = 0.004), and distant metastasis (p < 0.001). Multivariate analysis showed that low advanced lung cancer index status was an independent prognostic factor for both overall survival (HR = 3.21 (95% CI, 1.97-5.19); p < 0.001) and disease-free survival (HR = 2.13 (95% CI, 1.23-3.63); p = 0.008) in patients with colorectal cancer. Furthermore, the clinical burden of the advanced lung cancer index was consistent between sexes, and its prognostic value was verified in patients with clinically relevant stage III colorectal cancer. LIMITATIONS: The present study had several limitations, including retrospective observation and a small sample size of Japanese patients from a single institution. CONCLUSIONS: The advanced lung cancer index could be a useful prognostic indicator of clinical outcomes in patients who underwent surgical resection for colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B267. EL ÍNDICE AVANZADO DE INFLAMACIÓN DEL CÁNCER DE PULMÓN, PREDICE LOS RESULTADOS DE LOS PACIENTES CON CÁNCER COLORRECTAL DESPUÉS DE LA RESECCIÓN QUIRÚRGICA: El índice avanzado de inflamación del cáncer de pulmón, es considerado como un útil biomarcador pronóstico, en los resultados clínicos de pacientes con neoplasias malignas. Sin embargo, aún no está claro el valor pronóstico del índice avanzado de cáncer de pulmón, en pacientes con cáncer colorrectal sometidos a resección quirúrgica.Evaluar el valor pronóstico del índice avanzado del cáncer de pulmón, en pacientes con cáncer colorrectal.Los datos obtenidos prospectivamente de pacientes con cáncer colorrectal, fueron evaluados retrospectivamente, para aclarar la relevancia clínica del índice avanzado del cáncer de pulmónEstudio realizado en un solo centro experto.Estudio retrospectivo, incluyendo 298 pacientes con cáncer colorrectal, sometidos a resección quirúrgica.El resultado primario fue la relevancia clínica del índice avanzado de cáncer de pulmón, en pacientes con cáncer rectal.Un índice avanzado de cáncer de pulmón bajo, se correlacionó significativamente con la histología indiferenciada (p = 0.004), la progresión de la etapa T (p <0.001), la resección R1 / R2 para cirugía primaria (p = 0.004) y la metástasis a distancia (p <0.001). El análisis multivariante mostró que el índice avanzado de cáncer de pulmón bajo, era un factor pronóstico independiente, tanto para la supervivencia general (HR = 3.21 IC 95% 1.97-5.19 p <0.001) como para la supervivencia libre de enfermedad (HR = 2.13, IC 95% 1.23-3.63, p = 0,008), en pacientes con cáncer colorrectal. Además, la carga clínica del índice avanzado de cáncer de pulmón, fue consistente entre los sexos y su valor pronóstico se verificó clínicamente relevante, en pacientes con cáncer colorrectal en estadio III.El presente estudio tuvo varias limitaciones, incluyendo la observación retrospectiva y la pequeña muestra de pacientes japoneses, en una sola institución.El índice avanzado de cáncer de pulmón, podría ser un indicador pronóstico útil, en los resultados clínicos de pacientes sometidos a resección quirúrgica por cáncer colorrectal. Consulte Video Resumen http://links.lww.com/DCR/B267.

Risk factors and intraoral breast milk application for methicillin-resistant Staphylococcus aureus colonization in surgical neonates.

BACKGROUND: Our previous study identified methicillin-resistant Staphylococcus aureus (MRSA) colonization as an independent risk factor for neonatal surgical site infection. Here we introduce intraoral breast milk application (IBMA) during a fasting state to prevent MRSA colonization. We aimed to evaluate both the risk factors for MRSA colonization and the efficacy of IBMA in neonatal surgical patients. METHODS: A retrospective review was performed using admission data from 2007 to 2016. Neonatal patients who underwent surgery and were tested periodically for MRSA colonization were evaluated for an association between MRSA colonization and perinatal or perioperative factors. RESULTS: The overall incidence of MRSA colonization for the 159 patients enrolled in this study was 16.4%. Univariate analysis showed that MRSA colonization was significantly more frequent in the following patients: those with Down syndrome, those admitted on their day of birth, those in need of fasting immediately after birth, and those not receiving IBMA. Multivariate analysis showed that comorbid Down syndrome was an independent risk factor (hazard ratio: 4.6; 95% confidence interval: 1.2-19.5, P = 0.03) and implementation of IBMA was an independent preventive factor for MRSA colonization (hazard ratio: 0.4; 95% confidence interval: 0.1-0.9, P = 0.04). MRSA-positive patients admitted significantly earlier and stayed longer preoperatively than MRSA-negative patients. CONCLUSIONS: In neonates undergoing surgery, and patients with Down syndrome, early diagnosis after birth and a long waiting period before operation may be associated with MRSA colonization. Intraoral breast milk application may be beneficial for preventing MRSA colonization.

Modified neutrophil-platelet score as a promising marker for stratified surgical and oncological outcomes of patients with gastric cancer.

PURPOSE: Gastric cancer (GC) is a common malignancy, especially in East Asian countries. There is emerging evidence that circulating neutrophil and platelet levels correlate with cancer progression. We evaluated the short- and long-term outcomes of GC patients systemically, to compare the original neutrophil-platelet score (NPS) and our modified NPS (mNPS). METHODS: We analyzed the original pre-operative NPS and the mNPS of 621 GC patients. RESULTS: Racial differences between the United Kingdom and East Asian countries accounted for compelling deviation in classification using the original NPS, which could not reliably stratify the prognoses of Japanese GC patients. We developed the mNPS using appropriate cutoff levels for pre-operative neutrophils and platelets, and demonstrated that the pre-operative mNPS was significantly correlated with all of the well-established clinicopathological factors for disease development, including advanced T stage, venous and lymphatic vessel invasion, lymph node/peritoneal /distant metastasis, and tumor-node-metastasis stage. The pre-operative mNPS could stratify prognostication for both overall survival (OS) and disease-free survival (DFS): a high pre-operative mNPS was an independent prognostic factor for the OS and DFS of GC patients and also an independent predictor of post-operative surgical site infection after gastrectomy. CONCLUSION: Calculating the mNPS could help clinicians to stratify the surgical and oncological risks of patients with GC.

Clinical significance and biological role of L1 cell adhesion molecule in gastric cancer.

BACKGROUND: L1 cell adhesion molecule (L1CAM) is highly expressed in malignant tumours and might play a pivotal role in tumour progression. METHODS: We analysed by immunohistochemistry L1CAM protein expression in formalin-fixed, paraffin-embedded specimens from 309 GC patients. We performed propensity score matching (PSM) analysis to clarify the prognostic impact of L1CAM in GC patients. We evaluated L1CAM gene expression in fresh frozen specimens from another group of 131 GC patients to establish its clinical relevance. The effects of changes in L1CAM were investigated in vitro and in vivo. RESULTS: L1CAM was mainly expressed in tumour cells of GC tissues. Elevated L1CAM expression was an independent prognostic factor for overall and disease-free survival, and an independent risk factor for distant metastasis in GC patients. PSM analysis showed that high L1CAM expression was significantly associated with poor prognosis. L1CAM gene expression using fresh frozen specimens successfully validated all of these findings in an independent cohort. Inhibition of L1CAM suppressed cell proliferation, cycle progress, invasion, migration and anoikis resistance in GC cells. Furthermore, L1CAM inhibition suppressed the growth of peritoneal metastasis. CONCLUSION: L1CAM may serve as a feasible biomarker for identification of patients who have a high risk of recurrence of GC.

Surveillance Colonoscopy for Ulcerative Colitis-Associated Colorectal Cancer Offers Better Overall Survival in Real-World Surgically Resected Cases.

OBJECTIVES: To determine the effectiveness of surveillance colonoscopy (SC) and optimize its use by assessing real-world surgically resected cases of ulcerative colitis (UC)-associated colorectal cancer (CRC) and dysplasia. METHODS: Clinicopathological data of 406 (238 CRC and 168 dysplasia) patients who underwent surgical resection in 10 UC specialized institutions were retrospectively reviewed. The overall survival (OS) rates were compared between the SC and non-SC groups. The incidence of and risk factors for early-onset CRC (<8 years after UC onset) were identified. The distribution of CRC lesions was also assessed. RESULTS: Cancer stages were significantly more advanced in the non-SC group than in the SC group (P < 0.001). The patients in the SC group showed significantly better OS than those in the non-SC group (5-year OS: 89% vs 70%; log-rank test: P = 0.001). Seventeen percent of patients developed CRC within 8 years after UC onset. The age at UC onset was a risk factor and a good predictor of early-onset CRC (<8 years) (P < 0.01; AUC: 0.85). The most common sites of CRC were the rectum (51%) and sigmoid colon (20%). Multiple CRC was identified in 16% of patients. CONCLUSIONS: Surveillance colonoscopy was effective and improved the OS in patients with UC. We recommend that patients with late-onset UC (>40 years) undergo SCs earlier because of the high incidence of CRC within 8 years of UC onset. Moreover, the rectum and sigmoid colon should be more thoroughly examined.

Soluble PD-L1 Expression in Circulation as a Predictive Marker for Recurrence and Prognosis in Gastric Cancer: Direct Comparison of the Clinical Burden Between Tissue and Serum PD-L1 Expression.

BACKGROUND: This study assessed programmed cell death ligand 1 (PD-L1) expression in primary tissues and soluble PD-L1 (sPD-L1) concentration in matched preoperative serum in gastric cancer (GC) patients to perform direct comparison between tissue and serum PD-L1 expression and to clarify the prognostic implication in GC. METHODS: The study enrolled 180 GC patients who underwent surgery for GC at the authors' institution. The study evaluated tissue PD-L1 expression using immunohistochemistry and quantified sPD-L1 concentration in preoperative serum using enzyme-linked immunosorbent assay in GC patients. RESULTS: The findings showed that PD-L1 was overexpressed in GC tissues compared with normal mucosa. Tissue PD-L1 expression was significantly higher in the GC patients with advanced T stage, presence of lympho-vascular invasion, lymph node metastasis, and peritoneal metastasis. Furthermore, elevated tissue PD-L1 expression was significantly associated with poor prognosis for overall survival (OS) and disease-free survival (DFS). Serum sPD-L1 was significantly higher in the GC patients than in the healthy volunteers. Although serum sPD-L1 was not correlated with any clinicopathologic factors, the patients with high serum sPD-L1 showed poorer OS and DFS than those with low sPD-L1. Multivariate analyses showed that both elevated tissue PD-L1 and serum sPD-L1 were independent prognostic factors for poor OS [tissue PD-L1: hazard ratio (HR), 4.28; 95% confidence interval (CI), 1.43-12.8; P = 0.0094 vs. serum sPD-L1: HR, 11.2; 95% CI, 3.44-36.7; P = 0.0001] and poor DFS (tissue PD-L1: HR, 6.96; 95% CI, 2.48-19.6; P = 0.0002 vs. serum sPD-L1: HR, 8.7; 95% CI, 3.16-23.9; P < 0.0001) for the GC patients. Furthermore, infiltrative CD8- and Foxp3-positive T cells were significantly increased in the GC patients with elevated tissue PD-L1 expression. CONCLUSION: Both serum sPD-L1 and tissue PD-L1 expression may serve as predictive biomarkers for recurrence and prognosis in GC patients.

Identification of Predictors of Recurrence in Patients with Lower Rectal Cancer Undergoing Neoadjuvant Chemotherapy: A Direct Comparison of Short-Course and Long-Course Chemoradiotherapy.

OBJECTIVE: This study aimed to investigate clinicopathological responses and oncological outcome in patients receiving short- or long-course chemoradiotherapy (CRT) and to assess the predictive factor for recurrence in each treatment. METHODS: A total of 118 rectal cancer patients receiving preoperative CRT were enrolled. Clinicopathological responses and oncological outcome in patients receiving short- or long-course CRT were investigated. RESULTS: Despite there being no significant differences in the prognosis of disease-free survival (DFS) based on TNM stage classification in patients receiving long-course CRT, patients with advanced stage demonstrated poor DFS after short-course CRT. The presence of lymph node metastasis was a predictor of poor DFS in short-course CRT, whereas poor pathological response was a predictor of recurrence in long-course CRT. CONCLUSIONS: Distinct predictors of recurrence depending on the CRT course might be needed to discriminate candidates from rectal cancer patients receiving preoperative CRT who might benefit from more intensive adjuvant therapy after surgery.

Rac GTPase-Activating Protein 1 (RACGAP1) as an Oncogenic Enhancer in Esophageal Carcinoma.

PURPOSE: Rac GTPase-activating protein 1 (RACGAP1) is associated with cell proliferation, and there is much evidence of its oncogenic role. This study investigated the clinical importance and functional role of RACGAP1 in esophageal carcinoma (EC). METHODS: A total of 81 EC patients were enrolled in the study. We assessed the immunohistochemical score of EC tissues and adjacent normal esophageal mucosae, and then performed multiple cell function tests by means of in vitro experiments to elucidate the functional role of RACGAP1 using RNA interference technology in EC cell lines. RESULTS: RACGAP1 was significantly overexpressed in EC tissues compared with the adjacent normal esophageal mucosae (p < 0.0001). Moreover, RACGAP1 overexpression was significantly correlated with poor overall survival (p = 0.032) and disease-free survival (p = 0.012) in EC patients. High RACGAP1 expression was also significantly correlated with the presence of lymphatic invasion (p = 0.012), vessel invasion (p = 0.003), and advanced TNM (tumor-node-metastasis) stage (p = 0.046) in EC patients. In vitro analysis demonstrated that RACGAP1 was involved in the proliferation, tumorigenicity, invasion, migration, and anoikis resistance in EC cells. CONCLUSIONS: RACGAP1 plays a pivotal role in EC development, suggesting that it could be used as an indicator of prognosis in EC patients.

Clinical Implications of Pretreatment: Lymphocyte-to-Monocyte Ratio in Patients With Rectal Cancer Receiving Preoperative Chemoradiotherapy.

BACKGROUND: Despite advances in local control of rectal cancer, recurrence in distant organs is still one of the main causes of mortality. Prognostic biomarkers would be valuable for the treatment of patients who have rectal cancer. OBJECTIVE: The aim of our study was to investigate the prognostic impact of lymphocyte-to-monocyte ratio in patients with rectal cancer receiving preoperative chemoradiotherapy, and to clarify the clinical significance of lymphocyte-to-monocyte ratio. DESIGN: Prospectively maintained data of patients with rectal cancer were retrospectively evaluated to clarify the clinical relevance of the lymphocyte-to-monocyte ratio. SETTING: This study was conducted at a single expert center. PATIENTS: A total of 119 consecutive patients with rectal cancer through chemoradiotherapy followed by total mesorectal excision at our institute were enrolled in this study. Eight patients were excluded because of a lack of laboratory data, and finally 111 patients were assessed in this study. MAIN OUTCOME MEASURES: The primary outcome measured was the clinical relevance of the lymphocyte-to-monocyte ratio in patients with rectal cancer receiving chemoradiotherapy. RESULTS: Patients with a low pretreatment lymphocyte-to-monocyte ratio showed poor prognosis significantly both in overall survival and disease-free survival of those with rectal cancer receiving chemoradiotherapy. Multivariate analyses showed that low pretreatment lymphocyte-to-monocyte ratio level, presence of pathological lymph node metastasis (ypN(+)), and high pretreatment serum C-reactive protein level were independent prognostic factors of overall survival and disease-free survival. In addition, time-to-event analysis divided into 2 groups by ypN status showed that low pretreatment lymphocyte-to-monocyte ratio was correlated with poor overall survival and disease-free survival not only in group ypN(-) but also in group ypN(+). LIMITATIONS: The present study had several limitations, including that it was a retrospective observational and single institutional study with Japanese patients. CONCLUSIONS: The combination of lymphocyte-to-monocyte ratio and ypN status can be a predictive marker of poor prognosis and recurrence among patients with rectal cancer undergoing preoperative chemoradiotherapy. See Video Abstract at http://links.lww.com/DCR/A780.

Predictors for Pouchitis After Ileal Pouch-Anal Anastomosis for Pediatric-Onset Ulcerative Colitis.

BACKGROUND: The predictive factors for the development of pouchitis after ileal pouch-anal anastomosis (IPAA) in pediatric-onset ulcerative colitis (UC) have not been well investigated. The present study aimed to determine the predictive factors for the development of pouchitis after IPAA in the pediatric UC population. METHODS: The data from 54 patients with pediatric-onset UC who underwent IPAA in Mie University Hospital between 2000 and 2017 were retrospectively reviewed. A modified pouchitis disease activity index of ≥5 was defined as pouchitis. Potential preoperative, intraoperative, and postoperative predictors for pouchitis including various demographic and clinical variables were analyzed using Cox regression analysis, Students' t-tests, Mann-Whitney U tests, and Kaplan-Meier curves. The optimal cutoff value for continuous variables was determined using the receiver operating characteristic curve analysis. RESULTS: Pouchitis was identified in 17 (31.5%) patients within 5 y of follow-up. In multivariable analysis, the independent predictors for pouchitis were preoperative cumulative steroid dose of >10,000 mg (P = 0.0056) and >65% neutrophils just before IPAA (P = 0.032). Multivariate analysis revealed that the independent predictors of pouchitis were a total steroid dose of >10,000 mg (P = 0.0002) and a neutrophil percentage of >65% (P = 0.0078). No patient for whom both of these independent predictors were negative developed pouchitis, whereas >40% of patients who had one or both predictors developed pouchitis. CONCLUSIONS: In pediatric patients with UC, the predictive factors for pouchitis development are a greater cumulative total dose of steroids and a greater percentage of neutrophils before IPAA.

Risk factors and measures of pulmonary complications after thoracoscopic esophagectomy for esophageal cancer.

PURPOSE: Postoperative pulmonary complications (PCs) after thoracoscopic esophagectomy for esophageal cancer (EC) still occur too frequently. We conducted this study to identify the risk factors for PCs developing in EC patients who undergo thoracoscopic esophagectomy. METHODS: The subjects of this retrospective study were 89 patients with EC who underwent thoracoscopic esophagectomy in our department between January 2010 and December 2015. Univariate and multivariate logistic regression analyses were used to evaluate the association between the incidence of PC and clinical factors. In January 2016, we introduced a new prophylactic intervention for reducing the incidence of delirium and assessed its significance for PCs. RESULTS: PCs developed in 19 patients (21.3%). Univariate analysis revealed the following risk factors: age (> 69 years), ratio of the forced expiratory volume in 1 s to forced vital capacity (< 70%), chronic obstructive pulmonary disease (COPD), and postoperative delirium. Multivariate analysis found that COPD and postoperative delirium were independent risk factors for PCs. Our new intervention for delirium significantly reduced its occurrence (p = 0.00004) and also the frequency of PCs (p = 0.04148). CONCLUSIONS: Postoperative delirium and COPD were risk factors for PCs in patients who underwent thoracoscopic esophagectomy. Our intervention study showed clearly that reducing the occurrence of postoperative delirium could decrease the incidence of PCs.

Possibility of limited gastrectomy for early gastric cancer located in the upper third of the stomach, based on the distribution of sentinel node basins.

PURPOSE: Several recent studies have evaluated the feasibility of the sentinel node (SN) concept for gastric cancer. The aim of our study was to investigate limited gastrectomy with SN basin dissection in SN navigation surgery (SNNS) for patients with early-gastric cancer located in the upper-third of the stomach. METHODS: 147 patients received SNNS for early-gastric cancer at our institution. Of these, 26 patients diagnosed with early-gastric cancer < 4 cm in size and located in the upper-third of the stomach were retrospectively analyzed for the distribution of SN and SN basins. RESULTS: In three of the 26 patients, lymph node metastasis was limited to the left gastric artery (LGA) basin. The breakdown of the basins were as follows: A single LGA basin, 19 cases; a non-single LGA basin, seven cases. A non-single LGA basin was significantly associated with the clinicopathological factors, such as tumor spread to the middle-third of the stomach, tumor location at the center of the greater curvature, and undifferentiated adenocarcinoma, compared to the single LGA basin group. CONCLUSIONS: Our data revealed that the distribution of the SN basins in early-gastric cancer measuring less than 4 cm in size and located in the upper-third of the stomach was significantly correlated with tumor spread, tumor location, and the pathological findings.

Laparoscopic esophagogastrostomy using a knifeless linear stapler after proximal gastrectomy.

Proximal gastrectomy should improve the late postoperative function in patients with gastric cancer located in the upper third of the stomach or esophagogastric junction. However, a standard method of esophagogastrostomy has not been established for improving the postoperative function. To prevent reflux and stenosis following proximal gastrectomy, we introduced a novel esophagogastrostomy method using a knifeless linear stapler. The stapler was inserted into holes created in both the esophagus and remnant stomach and fired proximally. A 1.5-cm incision was made from the edge of the entry hole between the staples. The entry hole was then closed with continuous sutures, and fundoplication was performed by wrapping the remnant stomach. We performed this technique in 12 consecutive patients without observing any anastomosis-related complications. The proportion of weight lost 1 year after surgery was 8.8%. Our surgical procedure might be feasible for treating gastric cancer located in the upper third of the stomach or esophagogastric junction.

Changes in the rate of and trends in colectomy for ulcerative colitis during the era of biologics and calcineurin inhibitors based on a Japanese nationwide cohort study.

PURPOSE: We evaluated the recent incidence of surgery and the changing surgery trends for ulcerative colitis (UC) in Japan due to the increasing use of anti-tumor necrosis factor (TNF) agents. METHODS: A questionnaire survey was performed to assess the number of surgeries, surgical indications, surgical timing, and immunosuppressive treatments before surgery between 2007 and 2017. RESULTS: A total of 3801 surgical cases were reported over 11 years. The prevalence of UC surgery decreased over the period studied. The rate of prednisolone (PSL) use did not change. The prevalence of both calcineurin inhibitors (CNIs) and anti-TNF agents increased during the period studied (p < 0.01). The prevalence of urgent/emergent surgery did not change. The most distinctive change in surgical indications was the increase in cancer/dysplasia (CAC), the prevalence of which increased from 20.2% in 2007 to 34.8%. CONCLUSION: The prevalence of UC surgery seems to be decreasing according to the increasing rate of anti-TNF agent and CNI administration. However, the indication of CAC significantly increased. Further research should evaluate whether or not long-term remission maintained with several agents can lead to increasing CAC.

A Panel of Methylated MicroRNA Biomarkers for Identifying High-Risk Patients With Ulcerative Colitis-Associated Colorectal Cancer.

BACKGROUND & AIMS: Methylation of specific microRNAs (miRNAs) often occurs in an age-dependent manner, as a field defect in some instances, and may be an early event in colitis-associated carcinogenesis. We aimed to determine whether specific mRNA signature patterns (MIR1, MIR9, MIR124, MIR137, MIR34B/C) could be used to identify patients with ulcerative colitis (UC) who are at increased risk for colorectal neoplasia. METHODS: We obtained 387 colorectal tissue specimens collected from 238 patients with UC (152 without neoplasia, 17 with dysplasia, and 69 with UC-associated colorectal cancer [UC-CRC]), from 2 independent cohorts in Japan between 2005 and 2015. We quantified methylation of miRNAs by bisulfite pyrosequencing analysis. We analyzed clinical data to determine whether miRNA methylation patterns were associated with age, location, or segment of the colorectum (cecum, transverse colon, and rectum). Differences in tissue miRNA methylation and expression levels were compared among samples and associated with cancer risk using the Wilcoxon, Mann-Whitney, and Kruskal-Wallis tests as appropriate. We performed a validation study of samples from 90 patients without UC and 61 patients with UC-associated dysplasia or cancer to confirm the association between specific methylation patterns of miRNAs in non-tumor rectal mucosa from patients with UC at risk of UC-CRC. RESULTS: Among patients with UC without neoplasia, rectal tissues had significantly higher levels of methylation levels of MIR1, MIR9, MIR124, and MIR137 than in proximal mucosa; levels of methylation were associated with age and duration of UC in rectal mucosa. Methylation of all miRNAs was significantly higher in samples from patients with dysplasia or CRC compared with samples from patients without neoplasia. Receiver operating characteristic analysis revealed that methylation levels of miRNAs in rectal mucosa accurately differentiated patients with CRC from those without. Methylation of MIR137 in rectal mucosa was an independent risk factor for UC-CRC. Methylation patterns of a set of miRNAs (panel) could discriminate discriminate UC patients with or without dysplasia or CRC in the evaluation cohort (area under the curve, 0.81) and the validation cohort (area under the curve, 0.78). CONCLUSIONS: In evaluation and validation cohorts, we found specific miRNAs to be methylated in rectal mucosal samples from patients with UC with dysplasia or CRC compared with patients without neoplasms. This pattern also associated with patient age and might be used to identify patients with UC at greatest risk for developing UC-CRC. Our findings provide evidence for a field defect in rectal mucosa from patients with UC-CRC.

Enhanced AZIN1 RNA editing and overexpression of its regulatory enzyme ADAR1 are important prognostic biomarkers in gastric cancer.

BACKGROUND: Adenosine-to-inosine (A-to-I) RNA editing is catalyzed by adenosine deaminases acting on RNA (ADAR) enzymes. Recent evidence suggests that RNA editing of antizyme inhibitor 1 (AZIN1) RNA is emerging as a key epigenetic alteration underlying cancer pathogenesis. METHODS: We evaluated AZIN1 RNA editing levels, and the expression of its regulator, ADAR1, in 280 gastric tissues from 140 patients, using a RNA editing site-specific quantitative polymerase chain reaction assays. We also analyzed the clinical significance of these results as disease biomarkers in gastric cancer (GC) patients. RESULTS: Both AZIN1 RNA editing levels and ADAR1 expression were significantly elevated in GC tissues compared with matched normal mucosa (P < 0.0001, 0.0008, respectively); and AZIN1 RNA editing was positively correlated with ADAR1 expression. Elevated expression of ADAR1 significantly correlated with poor overall survival (P = 0.034), while hyper-edited AZIN1 emerged as an independent prognostic factor for OS and disease-free survival in GC patients [odds ratio (OR):1.98, 95% CI 1.17-3.35, P = 0.011, OR: 4.55, 95% CI 2.12-9.78, P = 0.0001, respectively]. Increased AZIN1 RNA editing and ADAR1 over-expression were significantly correlated with key clinicopathological factors, such as advanced T stage, presence of lymph node metastasis, distant metastasis, and higher TNM stages in GC patients. Logistic regression analysis revealed that hyper-editing status of AZIN1 RNA was an independent risk factor for lymph node metastasis in GC patients [hazard ratio (HR):3.03, 95% CI 1.19-7.71, P = 0.02]. CONCLUSIONS: AZIN1 RNA editing levels may be an important prognostic biomarker in GC patients, and may serve as a key clinical decision-making tool for determining preoperative treatment strategies in GC patients.

Clinical Impact of Preoperative Albumin-Globulin Ratio in Patients with Rectal Cancer Treated with Preoperative Chemoradiotherapy.

OBJECTIVE: The serum albumin-globulin ratio (AGR) is associated with malignancy outcomes. However, among patients with rectal cancer (RC) who undergo neoadjuvant chemoradiotherapy (nCRT), the clinical and prognostic significance of the pretreatment AGR is unclear. METHODS: We investigated whether the pre-nCRT AGR can help predict oncological outcomes in patients with RC receiving nCRT. We analyzed 114 patients with RC who received nCRT followed by total mesorectal excision at our institution. RESULTS: A lower AGR in pre-nCRT serum was significantly correlated with shorter overall survival and disease-free survival in patients with nCRT-treated RC. In multivariate analysis, a high carcinoembryonic antigen (CEA) level and a low AGR in pre-nCRT serum were independent predictors of a poor prognosis in these patients. Furthermore, combining the AGR with CEA provided a more accurate indicator of poor prognosis and early recurrence in these patients. In particular, a low pre-nCRT AGR was a stronger indicator of a poor prognosis and early recurrence in patients without than with pathological lymph node metastasis. Combining the pre-nCRT AGR with CEA could more precisely stratify patients' oncological outcome risks. CONCLUSION: Assessment of the pretreatment AGR with or without CEA can guide postoperative treatment in patients with RC who undergo nCRT.

Colonic Histological Criteria Predict Development of Pouchitis after Ileal Pouch: Anal Anastomosis for Patients with Ulcerative Colitis.

BACKGROUND/AIMS: Pouchitis is one of the main complications after ileal pouch-anal anastomosis in patients with ulcerative colitis. The aim of this study was to determine whether the use of colonic histological criteria can predict the development of pouchitis. METHODOLOGY: We retrospectively reviewed 147 patients' clinical data and performed a histological evaluation of the resected total colon using Tanaka's criteria, which comprise the following 6 factors: ulceration (H1), crypt abscesses (H2), degree of mononuclear cell infiltration (MNCI) (H3), segmental distribution of MNCI (H4), eosinophil infiltration (H5), and extent of disease of resected colon (H6). RESULTS: The development of pouchitis and chronic pouchitis within 3 years after restoration of gastrointestinal continuity was recognized in 52 (35.4%) and 26 (17.7%) of the 147 patients, respectively. Using various combinations of each score, the H3 + H4 - H5 scores of patients with pouchitis or chronic pouchitis were significantly higher than those of patients without. A H3 + H4 - H5 score of >0.4 was a statistically significant risk factor for the development of both pouchitis and chronic pouchitis. CONCLUSIONS: The combination of the degree of MNCI, segmental distribution of MNCI, and eosinophil infiltration from histological criteria has utility in predicting the future development of pouchitis, especially chronic pouchitis.