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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.

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.

Background The predictive factors for chronic pouchitis after ileal pouch–anal anastomosis (IPAA) in pediatric-onset ulcerative colitis (UC) remain unclear. This study evaluated the predictive factors for chronic pouchitis after IPAA in patients with pediatric UC. Methods The data from 52 patients with pediatric-onset UC who underwent IPAA in Mie University Hospital were retrospectively reviewed. The endoscopy surveillance was performed yearly or at the timing of the symptom. Chronic pouchitis was defined as antibiotic-dependent/-refractory and relapsing cases. Potential predictors of chronic pouchitis were analyzed. Results During the first 5 years after IPAA, pouchitis was identified in 32.7%. Of these patients, 12 (70.6%) developed chronic pouchitis. The predictor of chronic pouchitis was a preoperative history of immunomodulator use before IPAA (p = 0.04). Life table analysis revealed that patients with chronic pouchitis tended to develop pouchitis earlier after IPAA than did patients without chronic pouchitis (p = 0.012). Receiver operating characteristic curve analysis showed that the occurrence of pouchitis within 15 months after IPAA surgery predicted the development of chronic pouchitis (sensitivity, 92%; specificity, 80%). Conclusion In pediatric patients with UC, the predictive factors for chronic pouchitis are immunomodulator use and early occurrence of the first episode of pouchitis within 15 months after IPAA. Level of evidence III

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.

Although indigo naturalis (IN) is effective for patients with active ulcerative colitis (UC), IN was associated with adverse events (AEs), including pulmonary arterial hypertension (PAH). Our aim was to evaluate the occurrence of IN-associated AEs and to evaluate any IN dose–effect on AEs. A nationwide survey, using questionnaires, was conducted by conducted by the research group funded by the Ministry of Health, Labour and Welfare of Japan, between June 2017 and September 2018. A first questionnaire determined the occurrence of AEs associated with the therapeutic use of IN or herbal medicines containing IN in patients with UC. A second survey identified the clinical characteristics of patients who developed IN-associated critical AEs, namely, liver dysfunction, PAH, and intussusception. Across 337 participating institutions, 49,320 patients with UC were identified, with IN used in 877 (1.8%). AEs were reported in 91 patients (107 events), including liver dysfunction (n = 40), gastrointestinal symptoms (n = 21), headache (n = 13), and PAH (n = 11). No dose–effect relationship between IN and AEs was identified. Liver dysfunction tended to be mild and reversible. Ten cases of intussusception were reported, with 40% of these patients requiring surgical resection. IN-induced PAH was recovered in patients who discontinued to use IN. No IN-associated deaths were reported. IN-associated AEs were identified among patients with UC, with liver dysfunction often being reversible, while surgical resection was required in a high proportion of patients who developed intussusception. Both healthcare workers and patients should adequately recognize the potential for AEs with the use of IN.

Background Sarcopenia frequently occurs in metastatic cancer patients. Emerging evidence has revealed that various secretory products from metastatic tumours can influence host organs and promote sarcopenia in patients with malignancies. Furthermore, the biological functions of microRNAs in cell‐to‐cell communication by incorporating into neighbouring or distal cells, which have been gradually elucidated in various diseases, including sarcopenia, have been elucidated. Methods We evaluated psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) using pre‐operative computed tomography imaging in 183 colorectal cancer (CRC) patients. miR‐203 expression levels in CRC tissues and pre‐operative serum were evaluated using quantitative polymerase chain reaction. Functional analysis of miR‐203 overexpression was investigated in human skeletal muscle cells (SkMCs), and cells were analysed for proliferation and apoptosis. Expressions of several putative miR‐203 target genes (CASP3, CASP10, BIRC5, BMI1, BIRC2, and BIRC3) in SKMCs were validated. Results A total of 183 patients (108 men and 75 women) were included. The median age of enrolled patients at diagnosis was 68.0 years (range 35–89 years). High IMAC status significantly correlated with female gender (P = 0.004) and older age (P = 0.0003); however, no other clinicopathological factors correlated with IMAC status in CRC patients. In contrast, decreased PMI significantly correlated with female gender (P = 0.006) and all well‐established disease development factors, including advanced T stage (P = 0.035), presence of venous invasion (P = 0.034), lymphovascular invasion (P = 0.012), lymph node (P = 0.001), distant metastasis (P = 0.002), and advanced Union for International Cancer Control tumour–node–metastasis stage classification (P = 0.0004). Although both high IMAC status and low PMI status significantly correlated with poor overall survival (IMAC: P = 0.0002; PMI: P

MINI: In the present study, we systemically and comprehensively evaluated the prognostic significance of a combination of inflammatory factors using preoperative blood examination, and focused on the potential feasibility of our newly developed lymphocyte-CRP ratio (LCR) as a prognostic biomarker in CRC patients. We have firstly identified that a combination of lymphocytic counts along with CRP levels, which we defined as LCR, is a more reliable indicator of poor prognosis compared with other combinations of inflammatory markers, in CRC patients. Furthermore, preoperative LCR could also identify CRC patients who are at higher risk for postoperative infectious complications. 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.

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.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.Cancer stages were significantly more advanced in the non-SC group than in the SC group (P0.001). 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) (P0.01; 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.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.

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. 147 patients received SNNS for early-gastric cancer at our institution. Of these, 26 patients diagnosed with early-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

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 INDICE AVANZADO DE INFLAMACION DEL CANCER DE PULMON, PREDICE LOS RESULTADOS DE LOS PACIENTES CON CANCER COLORRECTAL DESPUES DE LA RESECCION QUIRURGICA: El indice avanzado de inflamacion del cancer de pulmon, es considerado como un util biomarcador pronostico, en los resultados clinicos de pacientes con neoplasias malignas. Sin embargo, aun no esta claro el valor pronostico del indice avanzado de cancer de pulmon, en pacientes con cancer colorrectal sometidos a reseccion quirurgica.Evaluar el valor pronostico del indice avanzado del cancer de pulmon, en pacientes con cancer colorrectal.Los datos obtenidos prospectivamente de pacientes con cancer colorrectal, fueron evaluados retrospectivamente, para aclarar la relevancia clinica del indice avanzado del cancer de pulmonEstudio realizado en un solo centro experto.Estudio retrospectivo, incluyendo 298 pacientes con cancer colorrectal, sometidos a reseccion quirurgica.El resultado primario fue la relevancia clinica del indice avanzado de cancer de pulmon, en pacientes con cancer rectal.Un indice avanzado de cancer de pulmon bajo, se correlaciono significativamente con la histologia indiferenciada (p = 0.004), la progresion de la etapa T (p

Accumulating evidence suggests that overexpression of heat shock protein 47 (HSP47) increases cancer progression, and that HSP47 level in the tumor-associated stroma may serve as a diagnostic marker in various cancers. The present study aimed to evaluate whether HSP47 gene expression in colorectal cancer (CRC) tissues could be used to identify lymph node (LN) metastasis status preoperatively in patients with CRC. To do so, HSP47 gene expression was determined and its association with the clinicopathological characteristics of patients with CRC was analyzed. A total of 139 surgical specimens from patients with CRC and 36 patients with benign colonic disease undergoing surgery at Mie University Hospital were analyzed. HSP47 gene expression was determined by reverse transcription quantitative PCR using Power SYBR Green PCR methods. Expression level of HSP47 was significantly higher in CRC tissues compared with normal tissue from patients with benign colonic disease. Furthermore, high HSP47 expression was significantly associated with tumor progression, including high T stage, lymph node metastasis and venous invasion, and high TNM stage. High HSP47 expression may therefore serve as a novel predictive biomarker for determining patients with CRC and LN metastasis. According to Kaplan-Meier analysis, patients with high HSP47 expression level had significantly poorer overall survival than those with low HSP47 expression level. Furthermore, multivariate analyses identified HSP47 expression as an independent predictive marker for LN metastasis and poor overall survival in patients with CRC. In summary, the present study demonstrated that HSP47 expression may be considered as a novel biomarker for predicting LN metastasis status and prognosis in patients with CRC.

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. 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. 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 (

// Yuji Toiyama 1 , Yoshinaga Okugawa 1 , Satoru Kondo 1 , Yoshiki Okita 1 , Toshimitsu Araki 1 , Kurando Kusunoki 2 , Motoi Uchino 2 , Hiroki Ikeuchi 2 , Seiichi Hirota 3 , Akira Mitsui 4 , Kenji Takehana 5 , Tsutomu Umezawa 5 and Masato Kusunoki 1 1 Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Graduate School of Medicine, Mie University, Mie, Japan 2 Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan 3 Department of Surgical Pathology, Hyogo College of Medicine, Hyogo, Japan 4 Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan 5 RD methylation; ulcerative colitis Abbreviations: AUC: area under the ROC curve; CRC: colorectal cancer; FFPE: formalin-fixed paraffin-embedded; ROC: received operating characteristic; UC: ulcerative colitis Received: June 19, 2018 Accepted: August 10, 2018 Published: September 04, 2018 ABSTRACT Background: There are no biomarkers to facilitate the identification of patients with ulcerative colitis (UC) who are at high risk for developing colorectal cancer (CRC). In our current study, we used rectal tissues from UC patients to identify aberrant DNA methylations and evaluated whether they could be used to identify UC patients with coexisting colorectal neoplasia. Results: Using a training set, we identified 484 differentially methylated regions (DMRs) with absolute delta beta-values > 0.1 in rectal mucosa by using the ChAMP algorithm. Next, pathway enrichment analysis was performed using 484 DMRs to select coordinately methylated DMRs, resulting in the selection of 187 aberrant DMRs in rectal tissues from UC-CRC. Then, the Elastic Net classification algorithm was performed to narrow down optimal aberrant DMRs, and we finally selected 11 DMRs as biomarkers for identification of UC-CRC patients. The 11 chosen DMRs could discriminate UC patients with or without CRC in a training set (area under the curve, 0.96) and the validation set (area under the curve, 0.81). Conclusions: In conclusion, we identified 11 DMRs that could identify UC patients with CRC complications. Prospective studies should further confirm the validity of these biomarkers. Methods: We performed genome-wide DNA methylation profiles in rectal mucosal tissues ( n = 48) from 24 UC-CRC and 24 UC patients in a training set. Next, we performed comprehensive DNA methylation analysis using rectal mucosal tissues ( n = 16) from 8 UC-CRC and 8 UC patients for validation.

Establishment of evidence-based best practices for preventing surgical site infection (SSI) in neonates is needed. SSI in neonates, especially those with a low birth weight, is potentially life-threatening. We aimed to identify risk factors associated with SSI in neonates. A retrospective review was performed using 2007–2016 admission data from our institution. Neonatal patients who were admitted to the neonatal intensive care unit and underwent surgery were evaluated for a relationship between development of SSI and perinatal or perioperative factors and methicillin-resistant Staphylococcus aureus (MRSA) colonization during hospitalization. One hundred and eighty-one patients were enrolled in this study. Overall SSI incidence was 8.8%. Univariate analysis showed that SSI was significantly more frequent in both patients with contaminated or dirty wound operations and patients with MRSA colonization during hospitalization. Both of these factors were identified as independent risk factors for SSI by multivariate analysis [hazard ratio (HR): 6.1, 95% confidence interval (CI) 2.0–19.9; HR: 3.3, 95% CI 1.1–10.4, respectively]. This study identified contaminated or dirty wound operations and MRSA colonization during hospitalization as risk factors for SSI in neonates. MRSA colonization may be a preventable factor, unlike previously reported risk factors.

In neonatal surgical patients requiring an enterostomy, there is no definitive recommendation regarding the ideal enterostomy location: at the edge of the primary incision or at a different incision. We retrospectively reviewed 2005–2017 administration data in our institution. All neonatal patients who underwent contaminated or dirty wound laparotomy and enterostomy construction were evaluated regarding the enterostomy location, occurrence of postoperative incisional surgical-site infection (SSI) at the primary incision, and stoma-related complications. Patients were divided into two groups based on stoma location: at the primary incision (the same incision group: SI group, n = 16) or at another incision (different incision group: DI group, n = 23). We performed 2 jejunostomies, 13 ileostomies, and 1 colostomy in the SI group, and 4 jejunostomies, 18 ileostomies, and 1 colostomy in the DI group. One of 16 patients (6.3%) in the SI group and 2/23 patients (8.7%) in the DI group experienced superficial incisional SSI, with comparable SSI incidence between groups (p = 0.78). Every SSI did not result in stoma-related complications. Although the enterostomy location did not influence the incidence of laparotomy wound infection in this study, prospective studies are mandatory to fully assess the safety of enterostomy construction at the edge of the primary incision.

The cause of jejunojejunal intussusception, a rare complication after Roux-en-Y gastric surgery, remains unclear. Here, we present a case of retrograde jejunojejunal intussusception that occurred after laparoscopic distal gastrectomy with Roux-en-Y reconstruction. A 51-year-old woman who had undergone laparoscopic distal gastrectomy and Roux-en-Y reconstruction for early gastric cancer 6 years previously was admitted to our hospital with abdominal pain. Abdominal CT revealed the "target sign," and she was diagnosed as having small bowel intussusception. Laparoscopic surgery resulted in a diagnosis of retrograde intussusception of the distal jejunum of the Roux-en-Y anastomosis with retrograde peristalsis in the same area. The Roux-en-Y anastomosis site and intussuscepted segment were resected laparoscopically. To the best of our knowledge, this is the first report of laparoscopic diagnosis of retrograde peristalsis in the distal jejunum of a Roux-en-Y anastomosis. Additionally, relevant published reports concerning this unusual condition are discussed.

Background: Sarcopenia is defined as the loss of skeletal muscle mass, accompanied by decreased muscle strength, and consists of myopenia and myosteatosis. Recent evidence has suggested the predictive value of sarcopenia for the risk of perioperative and oncological outcomes in various malignancies. The aim of this study was to clarify the clinical impact of myopenia and myosteatosis in colorectal cancer (CRC) patients. Methods: We analyzed the preoperative psoas muscle mass index and intramuscular adipose tissue content using preoperative computed tomography images from 308 CRC patients using statistical methods. Results: Despite no significant correlation between myosteatosis and prognosis, preoperative myopenia significantly correlated with clinicopathological factors for disease development, including advanced tumor depth (P = 0.009), presence of lymphatic vessel invasion (P = 0.006), distant metastasis (P = 0.0007), and advanced stage classification (P = 0.013). Presence of preoperative myopenia was an independent prognostic factor for both cancer‐specific survival (hazard ratio [HR]: 2.75, 95% confidence interval [CI]: 1.5–5.05, P = 0.001) and disease‐free survival (HR: 3.15, 95% CI: 1.8–5.51, P = 0.0001), and was an independent risk factor for postoperative infectious complications in CRC patients (odds ratio: 2.03, 95% CI:1.17–3.55, P = 0.013). Furthermore, these findings were successfully validated using propensity score matching analysis. Conclusions: Preoperative myopenia could be useful for perioperative management, and quantification of preoperative skeletal muscle mass could identify patients as a high risk for perioperative and oncological outcomes in CRC patients.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.

Background Malnutrition can adversely affect treatment responses and oncological outcomes in cancer patients. However, among patients with rectal cancer who undergo chemoradiotherapy (CRT), the significance of peri-treatment nutrition assessment as a predictor of treatment response and outcome remains unclear. Objective The aim of this study was to determine whether the Prognostic Nutrition Index (PNI) based on peri-treatment serum can be used as a predictor of treatment response and outcome in patients with rectal cancer who undergo CRT. Design, setting, and patients We analyzed 114 patients with rectal cancer who received preoperative CRT followed by total mesorectal excision at our institution. Results Post-CRT PNI was significantly lower than pre-CRT PNI in rectal cancer patients. Although post-CRT PNI did not significantly correlate with either overall survival or disease-free survival, low pre-CRT PNI was significantly associated with shorter overall survival and disease-free survival in this population and was also an independent risk factor for ineffectiveness of long-course preoperative CRT. Finally, low pre-CRT PNIs were a stronger indicator of poor prognosis and early recurrence in patients with pathological lymph node metastasis (who generally need to receive postoperative chemotherapy), than in those with no pathological lymph node metastasis. Conclusion Pretreatment PNI could be useful in evaluating and managing patients with rectal cancer who undergo CRT followed by curative resection.

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.

Aim To identify predictors of poor prognosis of patients with colon cancer (CC) who underwent surgery with curative intent, we investigated the association between the albumin to globulin ratio (AGR) with clinicopathological findings such as overall (OS) and disease-free (DFS) survival. Patients and methods We conducted a retrospective study of clinicopathological findings, including preoperative laboratory data, for 248 patients with stage I-III CC. Results Patients with low AGR had shorter DFS and OS compared to those with high AGR. Multivariate analyses identified low AGR as an independent variable independently associated with recurrence and poor prognosis of patients with CC who underwent surgery with curative intent regardless of lymphnode metastasis. Conclusion The preoperative AGR was an independent predictor of recurrence and poor prognosis of patients with CC who underwent surgery with curative intent. The AGR indicates that these patients may benefit from intensive adjuvant therapy.

Although patients with metastatic colorectal cancer (CRC) are often unable to undergo treatment after resection of primary tumors, identifying such patients before surgery is not easy. In this study, we evaluated the association among clinicopathological findings, survival outcomes, and ability to undergo multimodal therapy after primary tumor resection in patients with Stage IV CRC. We collected clinicopathological findings and preoperative laboratory data, including carcinoembryonic antigen (CEA) and systemic inflammatory response markers for 92 patients who were treated for Stage IV CRC between 2005 and 2014. We used multivariate analysis on factors that affect prognosis and ability to undergo postoperative treatment. Postoperative multimodal therapy improved overall survival (OS) significantly. Among serum markers, elevated CEA, neutrophil-to-lymphocyte ratio, and modified Glasgow prognosis score (mGPS) were significant indicators of shorter OS. In multivariate analysis, low performance status (P = 0.003), undifferentiated histology type (P = 0.019), and elevated mGPS (P = 0.042) were independent predictors of worse prognosis; and older age (P = 0.016), right-sided colon cancer (P = 0.043), and elevated mGPS (P = 0.031) were independent risk factors for difficulty of introducing postoperative multimodal therapy. Preoperative mGPS is a useful objective indicator for CRC patients with multiple metastases who are able to undergo primary site resection followed by postoperative multimodal therapy.

Surgical site infection (SSI) is a potentially morbid and costly complication of surgery. The purpose of this study was to determine preoperative and operative predictors of SSIs after gastric resection with lymphadenectomy in patients with gastric cancer (GC). Data on clinicopathologic factors, including operative and preoperative laboratory factors, for 384 patients with GC who had undergone curative surgery were analyzed in this retrospective study to assess their associations with SSIs. Superficial/deep incisional SSIs (iSSIs) and organ/space SSIs (o/sSSIs) occurred in 18 (4.6%), and 27 (7.0%), respectively. The o/sSSIs were significantly associated with surgery-related factors such as duration of operation, blood loss, and extent of tumor. Additionally, high levels of preoperative indicators of systemic inflammation, including neutrophil counts, neutrophil/lymphocyte ratio, and C-reactive protein concentrations, were significantly associated with o/sSSIs. Multivariate analyses demonstrated that preoperative neutrophil counts and duration of surgery were independent predictors for o/sSSIs, whereas only preoperative serum albumin concentration was predicted for iSSIs. In patients with GC undergoing curative surgery, preoperative neutrophil count and operation time are potentially valuable predictors of o/sSSIs, whereas only preoperative serum albumin predicts iSSIs.

We report a patient who experienced colonic necrosis after laparoscopic high anterior resection for sigmoid colon cancer, and review the literature to evaluate the clinical features of colonic necrosis following surgery for sigmoid colon and rectal cancer. A 76-year-old man with sigmoid colon cancer underwent laparoscopic high anterior resection. The operation included high ligation of the inferior mesenteric artery and end-to-end anastomosis using circular staples. Pathology findings revealed a pT4N2M0 lesion. Beginning on postoperative day (POD) 1, the patient experienced a high, spiking fever, and gradually developed leukocytosis and high inflammatory condition. The patient complained of abdominal distention, but had no signs of peritonitis. Abdominal computed tomography on POD4 showed wall thickness of the proximal colon from the anastomosis site and ascites with free air. An anastomotic leakage was suspected. Emergency laparotomy revealed a disrupted anastomosis without feces in the abdomen and a gangrenous 15 cm segment of the colon proximal to the anastomosis. The affected area of the colon was excised and Hartmann's procedure was performed. His postoperative period was uneventful. Our review of the literature demonstrates that elderly male patients with cardiovascular and pulmonary complications undergoing laparoscopic sigmoid and rectal cancer surgery with high ligation have high risk of postoperative colonic necrosis. We experienced colonic necrosis following laparoscopic high anterior resection for sigmoid colon cancer and required immediate resection. Elderly male patients with cardiovascular and pulmonary complications undergoing laparoscopic sigmoid and rectal cancer surgery with high ligation should be carefully monitored for postoperative colonic necrosis.

This pilot study aimed to develop a new technique, complete laparoscopic total mesorectal excision (TME) with an intersphincteric resection (ISR) and coloplasty pouch anal anastomosis to avoid any further abdominal incision other than laparoscopic port sites, and to assess the impact on short-quality of life and oncological outcomes of this technique. After laparoscopic TME, large bowel was dissected at the level of the promontory. Then, laparoscopic construction of the coloplasty pouch was performed. Simultaneously, a rectal specimen with ISR was excised using the transanal approach. Coloplasty pouch was gently pulled from pelvic thorough anal and a hand-sewn coloplasty pouch anal anastomosis was created. We had performed 8 surgeries using the new technique. Though one patient developed pelvic infections, but intestinal continuity could be maintained and no local and distant recurrence was recognized in other patients. We foresee this novel approach to have significant clinical potential for lower rectal cancer patients with ISR.

Objectives: Anti-tumor necrosis factor (TNF) antibodies have shown efficacy in the prevention of recurrence of Crohn's disease after intestinal resection. However, some patients develop surgical recurrence despite this therapy. We aimed to evaluate the risk factors for recurrence of Crohn's disease requiring surgery while receiving post-operative anti-TNF therapy. Methods: We performed a retrospective evaluation of 164 patients who had received post-operative anti-TNF maintenance therapy between 2002 and 2016. We classified Crohn's disease-related re-operation as surgical recurrence and analyzed its risk factors using the Cox proportional hazard model. Results: Of the 164 participants, 128 had received infliximab and 36 had received adalimumab maintenance therapy. We obtained follow-up data over a mean of 60.2 months. The proportion of patients with surgical recurrence at 5 years was 14.9%. The only independent risk factor for surgical recurrence, which we identified was post-operative smoking habit (odds ratio, 5.03; 95% CI, 1.14-12.8; P=0.033). Conclusions: Post-operative smoking may be a significant risk factor for post-operative surgical recurrence of Crohn's disease while receiving anti-TNF maintenance therapy.

To assess the relationship of C-reactive protein/albumin ratio (CAR) to outcomes and surgical site infection (SSI) in gastric cancer (GC) treated with curative intent, we retrospectively assessed 384 patients with GC for CAR, SSIs, disease-free survival (DFS), overall survival (OS) and other factors. We found SSIs in 42 patients (10.9%). Pathological T-stage, TNM classification, body mass index, duration of surgery, blood loss and preoperative CAR were significantly associated with SSIs; in multivariate analyses, CAR [hazard ratio (HR)=2.98, p=0.003] and duration of surgery (HR=2.34, p=0.029) independently predicted SSI. Age, sex, T-and N-stages, tumor size and serum carcinoembryonic antigen (CEA) were associated with high CAR, and high CAR, CEA and CA19-9 combined was associated with shorter OS (p=0.0001) and DFS (p=0.0001). Multivariate analyses also linked high CAR to early recurrence (HR=2.21, p=0.011) and poor prognosis (HR=1.82, p=0.038). We show, for the first time to our knowledge, that a high CAR predicts SSI, early recurrence and poor prognosis in patients with GC treated with curative intent.

We defined small bowel obstruction occurring around the limbs of the ileostomy as stoma-related obstruction (SRO) and investigated the clinical characteristics and predictive factors of SRO. From January 2002 to March 2016, 309 consecutive patients who underwent ileal pouch–anal anastomosis (IPAA) for ulcerative colitis were enrolled. Two-stage IPAA with diverting ileostomy was analyzed. We assessed the possible associations between SRO and clinical factors. A total of 205 patients met the inclusion criteria. Fifty-three (25.8%) patients with SRO before ileostomy closure were identified for review. All patients with SRO were at least transiently resolved by intubation though orifice of ileostomy (98.1%) or nasally (3.7%). In 18 (33.9%) patients, the ileostomy was taken down ahead of schedule and the small bowel obstruction improved in all cases. Multivariate analysis revealed that age at surgery

Background Ulcertive colitis (UC) is associated with a variety of extraintestinal manifestations (EIMs) that may have negative effects on performance status and quality of life. EIMs frequently affect musculoskeltal systems (peripheral and axial arthropathies), skin, hepatobiliary tract and eyes1,2. Previous studies showed that peripheral and axial arthropathies were seen 4-23% patients with UC and they tend to have peripheral rather than axial arthropathies3. UC is generally thought to become in remission when patients undergo total colectomy. However, in clinical practice, patients often suffered from arthropathy which is thought as EIMs even after total colectomy. The distribution and risk factors for the occurrence of peripheral and axial arthropathies among UC patients after total colectomy have not been investigated yet. Objectives In this study, we aimed to clarify frequency and distribution of arthropathy and to investigate risk factors for developing arthropathy among UC patients after colectomy. Methods In this retrospective, single center, observational study, we investigated the backgrounds and risk factors for arthropathy using patients underwent total colectomy from January 2007 to February 2016 in Mie University. As backgrounds, age, sex, presence and distribution of arthropathy, other EIMs, and duration after colectomy, clinical activity (mild/moderate/severe), Matts classification (grade 1+2 vs 3+4), presence of massive hemorrhage and toxic megacolon, previous therapies for UC were collected from electronic medical records. Arthropathy was defined as joint pain or swelling without definite cause which was improved by using glucocorticoid. Background factors were described as median (IQR) for continuous variables or as percentage (%) for categorical variables and difference was analyzed by Wilcoxon for continuous variables and by chi-square for categorical variables. Factors with p-value Results We enrolled 219 patients (female; 40.2% and median age at operation; 38.0 [27.0, 53.0] years). Among them, 40 (18.3%) patients had arthropathy, peripheral type in 23 (57.5%), axial type in 3 (7.5%), mixed type in 14 (35.0%). Duration from operation to onset of arthropathy was 0.7 [0.4, 1.2] years. The risk factors for developing arthropathy by univariate analyses were Matts classicification (grade 3+4 vs 1+2) (p Conclusion About one fifth patients with UC who underwent colectomy developed arthropathy presenting predominantly peripheral type. Long follow up period, High disease activity by endoscopic classification, and ileal pouchitis were risk factors of developing arthropathy in UC patients after total colectomy. The frequency and risk factors for developing arthropathy even after colectomy was demonstrated in this study for the first time. References [1] Paraskevi VV, et al. Ann Gastroenterol. 2011; 24: 173-80. [2] Orchard TR, et al. Gut. 1998; 42: 387–91. [3] Das KM, et al. Dig Dis Sci1999;44:1–13. Disclosure of Interests Kentaro Noda: None declared, Yuki Mizutani: None declared, Naohiro Sugitani: None declared, Yasuo Suzuki: None declared, Toshimitsu Araki: None declared, Masato Kusunoki Grant/research support from: Chugai Pharmaceutical Co., Shionogi Pharmaceutical Co., Taiho Pharmaceutical Co., and Mitsubishi Tanabe Pharma Co., Ayako Nakajima Grant/research support from: Asahi Kasei pharma co., Chugai Pharmaceutical, Daiichi Sankyo Co., Pfizer, Kissei Pharmaceutical Co., and Mitsubishi Tanabe Pharma Corporation.

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. A questionnaire survey was performed to assess the number of surgeries, surgical indications, surgical timing, and immunosuppressive treatments before surgery between 2007 and 2017. 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

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.

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). We analyzed the original pre-operative NPS and the mNPS of 621 GC patients. 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. Calculating the mNPS could help clinicians to stratify the surgical and oncological risks of patients with GC.

Summary Backgrounds Systemic inflammation arising from complex host–tumour interactions is considered the seventh hallmark of cancer. The aim of this study was to assess the clinical feasibility of our newly developed ‘lymphocyte-to-C-reactive protein (CRP) ratio’ (LCR) and ‘lymphocyte CRP score’ (LCS) for predicting short- and long-term outcomes in patients with gastric cancer (GC). Methods In this observational study, we retrospectively analysed pre-operative LCRs and LCSs from 551 GC patients to elucidate these prognostic value for overall survival (OS) and disease free survival (DFS) and to clarify these predictive value for peri-operative risk of surgical site infection (SSI) in GC patients. Results Reduced pre-operative LCRs significantly correlated with all of the well-established clinicopathological factors for disease development, including advanced T stage, venous and lymphatic vessel invasion, lymph node/hepatic/peritoneal metastasis, distant metastasis, and advanced tumour-node-metastasis stage. In the short-term outcome, low pre-operative LCR was an independent predictive factor for post-operative SSI. In the long-term outcome, low pre-operative LCR was an independent prognostic factor for OS and DFS, and prognostic impact of pre-operative LCR were verified in patients with metastatic and non-metastatic gastric cancer. Furthermore, our developed scoring system using lymphocyte and CRP (Lymphocyte–CRP Score; LCS) could also demonstrate all of clinical significance in GC patients, and both of LCR and LCS were significantly correlated with various representative nutrition markers, including BMI, PNI, and albumin, in GC patients. Conclusions Pre-operative LCR and LCS are clinically feasible nutrition-inflammation markers in GC patients. Assessment of lymphocytes and CRP could aid physicians in determining surgical risk and oncological risk, thus facilitating appropriate peri-operative and post-operative management of patients with GC.

Background: Chronic inflammation promotes aging and carcinogenesis in colorectal mucosa, particularly in ulcerative colitis (UC); providing a rationale for the development of these molecular alterations as useful biomarkers for diagnosis and risk prediction of UC-associated colorectal cancer (UC-CRC) and sporadic colorectal cancer (S-CRC). Methods: We performed array-based methylation analyses using tissues from 76 patients with S-CRC (vs. normal mucosa) and UC-CRC (vs. UC). In the evaluation phase, 945 colorectal specimens from 352 patients with S-CRC, 31 with UC-CRC, and 57 with UC, were analyzed for methylation levels of identified genes by quantitative pyrosequencing. In the validation phase, 199 non-cancerous rectal mucosa specimens from 20 patients with S-CRC, 61 with UC-CRC, 90 with UC, and 28 healthy volunteers were examined. Findings: Comprehensive analysis identified OPLAH as a hypermethylated CpG site in S-CRC and UC-CRC patients. In the evaluation phase, OPLAH methylation (met-OPLAH) differentiated S-CRC tissue from normal mucosa (area under the receiver operating characteristic curve (AUC):0.95, sensitivity:0.89, specificity:0.95), and met-OPLAH levels in normal mucosa were positively correlated with age. However, met-OPLAH was specifically hypermethylated in UC-CRC tissues and differentiated UC-CRC from UC mucosa (AUC:0.95, sensitivity:0.88, specificity:0.94). Levels of met-OPLAH were significantly higher in rectal tissues vs. proximal mucosa, and were associated with age and disease duration in rectal mucosa. In non-cancerous rectal mucosa, met-OPLAH could discriminate UC patients with or without UC-CRC (AUC:0.84, sensitivity:0.83, specificity:0.72). We further developed ∆met-OPLAH, which could distinguish S-CRC from UC-CRC (P=0.0002, AUC:0.81, sensitivity:0.92, specificity:0.65). Interpretation: Assessment of met-OPLAH can be used for screening of UC-CRC using non-cancerous rectal mucosa, diagnosis using cancerous tissues, and decision-making of surgical approaches using both tissue types in patients with UC and cancer. Funding: Grants in Aid for Scientific Research (17K10628, 18K08591) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. Declaration of Interest: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors have no conflict of interests to disclose. Ethical Approval Statement: Specimen collection and experiments were approved by the Institutional Review Boards of all participating institutions. All participants provided a written informed consent for participation in research.

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.

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.

The present study designed a novel preoperative chemoradiotherapy (CRT) with sequential oxaliplatin and irinotecan with S-1 for locally advanced rectal cancer (LARC). This phase I study evaluated the maximum tolerated dose and recommended dose (RD) of oxaliplatin following irinotecan with S-1. Patients with clinical stage T3 or 4 or involvement of the regional nodes and no evidence of distant metastases were treated with fixed doses of S-1 (80 mg/m(2)/day) on days 1–5, 8–12, 15–19, 22–27 and 29–33, and irinotecan (40 mg/m(2)/day) on days 1 and 8, followed by oxaliplatin on days 22 and 29. The dose of oxaliplatin was initially 40 mg/m(2) (level 1) with a predefined dose escalation schedule. The radiation dose was 1.8 Gy/fraction to a total dose of 45 Gy. A total of 9 patients were enrolled in the present study and 7 patients completely received CRT with this study protocol. The maximum tolerated dose for oxaliplatin was 50 mg/m(2) (level 2). Three of four patients experienced dose-limiting toxicity (grade 3 diarrhea) in oxaliplatin phase of level 2 dose. The RD of oxaliplatin was 40 mg/m(2) (level 1 dose). In addition, 2 patients had pathological CR (28.5%). Novel preoperative CRT with sequential oxaliplatin and irinotecan with S-1 for LARC resulted in acceptable toxicity and promising efficacy. However, the RD of oxaliplatin was lower than in previous CRT studies that combined oxaliplatin with S-1. To administer higher oxaliplatin, we have planned a phase I trial of preoperative CRT with sequential oxaliplatin followed by irinotecan with S-1 for LARC.