Genomewide Expression Profiling Identifies a Novel miRNA-based Signature for the Detection of Peritoneal Metastasis in Patients With Gastric Cancer.

OBJECTIVE: This study aimed to conduct a genomewide transcriptomic profiling to develop a microRNA (miRNA)-based signature for the identification of peritoneal metastasis (PM) in patients with gastric cancer (GC). SUMMARY BACKGROUND DATA: Even though PM in patients with GC has long been recognized to associate with poor prognosis, currently there is lack of availability of molecular biomarkers for its robust diagnosis. METHODS: We performed a systematic biomarker discovery by analyzing miRNA expression profiles in primary tumors from GC patients with and without PM, and subsequently validated the expression of candidate miRNA biomarkers in 3 independent clinical cohorts of 354 patients with advanced GC. RESULTS: Five miRNAs (miR-30a-5p, -134-5p, -337-3p, -659-3p, and -3917) were identified during the initial discovery phase; three of which (miR-30a-5p, -659-3p, and -3917) were significantly overexpressed in the primary tumors from PM-positive patients in the testing cohort (P = 0.002, 0.04, and 0.007, respectively), and distinguished patients with versus without peritoneal metastasis with the value of area under the curve (AUC) of 0.82. Furthermore, high expression of these miRNAs also associated with poor prognosis (hazard ratio = 2.18, P = 0.04). The efficacy of the combination miRNA signature was subsequently validated in an independent validation cohort (AUC = 0.74). Finally, our miRNA signature when combined together with the macroscopic Borrmann's type score offered a much superior diagnostic in all 3 cohorts (AUC = 0.87, 0.76, and 0.79, respectively). CONCLUSIONS: We have established an miRNA-based signature that have a potential to identify peritoneal metastasis in GC patients.

High platelet × C-reactive protein level multiplier is a negative prognostic marker in rectal cancer treated by neoadjuvant chemoradiotherapy.

PURPOSE: The clinical significance of the platelet count × C-reactive protein level multiplier (P-CRP) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy followed by curative surgery has not been fully evaluated. METHODS: In this retrospective study, the correlation between the P-CRP and prognosis was evaluated in 135 patients with LARC. We also performed a subgroup analysis limited to patients with pathological TNM stage III [ypN(+)] LARC. RESULTS: The cut-off value of the P-CRP for prognosis was set at 4.11. The high and low P-CRP groups comprised 39 (28.89%) and 96 (71.11%) patients, respectively. Among the investigated clinicopathological factors, the serum carcinoembryonic antigen level and presence of recurrence were significantly associated with the P-CRP value. In the Kaplan-Meier analysis, both overall survival (OS) and disease-free survival (DFS) were shorter in the high P-CRP group (p < 0.0001 and p = 0.0002, respectively; log-rank test). Multivariate analysis using a Cox proportional hazards model showed that a high P-CRP was an independent prognostic factor for OS [hazard ratio (HR) 29.20; 95% confidence interval (CI), 3.42-294.44; p = 0.0024] and DFS (HR 5.89; 95%CI 1.31-22.69; p = 0.023) in patients with LARC. In addition, a high P-CRP predicted poor OS and DFS in patients with pathological TNM stage III [ypN(+)] LARC (p = 0.0001 and p = 0.0012, respectively; log-rank test). CONCLUSIONS: The P-CRP is a promising predictor of survival and recurrence in patients with LARC treated by neoadjuvant chemoradiotherapy followed by curative surgery.

Risk factors for arthropathy in patients with ulcerative colitis after total colectomy.

OBJECTIVE: Patients with ulcerative colitis (UC) often develop arthropathy. The purpose of this study was to determine the frequency of and risk factors for arthropathy in patients with UC who underwent total colectomy which is the final radical treatment lead to remission. METHODS: Patients who underwent total colectomy from January 2007 to April 2016 were analyzed for the development of arthropathy. The type of arthropathy and risk factors for developing arthropathy were analyzed by clinical and endoscopic severity classification, extraintestinal manifestations (EIMs) and medical treatment. RESULTS: Total of 219 patients who underwent total colectomy with sufficient medical records were analyzed. Forty-eight cases (21.9%) had EIMs, and 40 cases (18.2%) developed arthropathy (57.0% polyarthropathy; 42.5% peripheral arthropathy). Multivariate analysis showed that severity of Matts classification grade 3 or 4 versus grade 1 or 2 (hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.22-4.36, p < .05) and EIMs other than arthropathy (HR 3.29, 95% CI 1.43-7.58, p < .05) were risk factors for the development of arthropathy. CONCLUSION: This study showed that approximately one fifth of patients with UC who underwent total colectomy developed arthropathy. The risk factors for the development of arthropathy were preoperative endoscopic disease activity and EIMs.

Preoperative computed tomography predicts the risk of recurrent laryngeal nerve paralysis in patients with esophageal cancer undergoing thoracoscopic esophagectomy in the prone position.

BACKGROUND: Recurrent laryngeal nerve paralysis (RLNP) after thoracoscopic esophagectomy for esophageal cancer (EC) is known to be a major complication leading to poor quality of life. RLNP is mainly associated with surgical procedures performed near the RLN. Therefore, with focus on the region of the RLN, we used preoperative computed tomography to investigate the risk factors of RLNP in patients with EC undergoing thoracoscopic esophagectomy. METHODS: We retrospectively examined 77 EC patients who underwent thoracoscopic esophagectomy in the prone position at our department between January 2010 and December 2018. Bilateral cross-sectional areas (mm2) of the fatty tissue around the RLN at the level of the lower pole of the thyroid gland were measured on preoperative axial computed tomography (CT) images. Univariate and multivariate logistic regression analysis was used to evaluate the association between the incidence of RLNP and patient clinical factors, including the cross-sectional areas. RESULTS: RLNP occurred in 24 of 77 patients (31.2%). The incidence of RLNP was significantly more frequent on the left side than on the right. (26% vs. 5.2%, respectively). Univariate analysis identified the following left RLNP risk factors: intrathoracic operative time (> 235 min), and area around the RLN (> 174.3 mm2). Multivariate analysis found that the area around the RLN was an independent risk factor of left RLNP. CONCLUSION: An increased area around the RLN measured on an axial CT view at the level of the lower pole of the thyroid gland was a risk factor of RLNP in EC patients undergoing thoracoscopic esophagectomy in the prone position.

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.

Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients.

BACKGROUND: Programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) play a pivotal role in cancer immunotherapy. Each of these molecules has a membrane-bound receptor form (mPD-L1/mCTLA-4) and a soluble form (sPD-L1/sCTLA-4). However, these prognostic impacts in colorectal cancer (CRC) remain unclear. METHODS: We immunohistochemically scored tumoral mPD-L1/mCTLA-4 expression and quantified preoperative circulating sPD-L1/sCTLA-4 levels using matched serum specimens from 131 patients with pStage I-III CRC. We also examined the association between these statuses and tumor infiltrating lymphocytes (TILs) in these patients. RESULTS: Elevated levels of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 were significantly correlated with poor overall survival (OS) and disease-free survival (DFS). Co-high expression of tumoral mPD-L1 and mCTLA-4 or co-elevated levels of serum sPD-L1 and sCTLA-4 were strongly correlated with poor OS and DFS. Multivariate analysis revealed that both statuses were negative independent prognostic factors for OS [hazard ratio (HR) 3.86, 95% confidence interval (95% CI) 1.71-8.51, p = 0.001; HR 5.72, 95% CI 1.87-14.54, p = 0.004, respectively] and DFS (HR 2.53, 95% CI 1.23-4.95, p = 0.01; HR 6.88, 95% CI 2.42-17.13, p = 0.0008, respectively). Although low expression of tumoral mCTLA-4 was significantly correlated with increased CD8(+) TILs, there was no correlation in any other combination. CONCLUSIONS: We verified the prognostic impacts of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 in pStage I-III CRC patients. Dual evaluation of immune checkpoint molecules in primary tissues or preoperative serum could identify a patient population with poor prognosis in these patients.

Crohn's-Like Lymphoid Reaction is Associated with Oncological Prognosis and Nutritional Status in Patients with Pathological Stage II/III Gastric Cancer.

BACKGROUND: Peritumoral lymphoid aggregates, termed Crohn's-like lymphoid reaction (CLR), are markers of an antitumor immune response, which is an important predictor of patient outcome. In this study, we investigated the prognostic utility of CLR and its relationship with nutritional status in patients with gastric cancer (GC). METHODS: The study included 170 patients who underwent curative surgery for pathological stage (pStage) II/III GC. The maximum diameters of peritumoral and normal mucosal CLR aggregates were measured, and the median peritumoral diameter (0.57 mm) was used to stratify patients into two groups (large-CLR and small-CLR). The relationships between CLR size and preoperative nutritional status (body mass index, body composition status, Onodera's prognostic nutritional index), tumor-infiltrating CD8+ T-lymphocyte count, and survival were evaluated. RESULTS: Peritumoral CLR aggregates were significantly larger than aggregates in the normal mucosa. Clinicopathological variables were not significantly different between the two patient groups; however, the large-CLR group had better cancer-specific survival (p = 0.018) and recurrence-free survival (p = 0.03) than the small-CLR group. Multivariate analysis revealed that CLR size was an independent prognostic factor for cancer-specific survival [hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.3-3.56, p = 0.002] and recurrence-free survival (HR 1.96, 95% CI 1.22-3.19, p = 0.005). Nutritional status markers were significantly poorer for the small-CLR group than the large-CLR group. CD8+ T-cell tumor infiltration was positively correlated with CLR size but not with patient survival. CONCLUSIONS: CLR size correlated with patient nutritional status and prognosis and may be helpful in identifying high-risk populations of pStage II/III GC patients.

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.

The relationship between preoperative T helper cytokines in the ileal mucosa and the pathogenesis of pouchitis.

BACKGROUND: Although the etiology of pouchitis remains unknown, inflammatory cytokines are significantly associated with the pathogenesis of pouchitis. The cytokine responses that characterize inflammatory bowel diseases (IBD) are key pathogenic components of the disease. Although cytokine profiles in the colonic mucosa have been investigated in experimental colitis models or IBD patients, cytokine profiles in the ileal mucosa at colectomy have been rarely assessed. AIM: To assess the relationship between pouchitis and T helper (Th) cytokines in the ileal mucosa collected at the time of colectomy and pouch construction. METHODS: This retrospective study involved 68 consecutive patients from January 2004 to May 2011 who underwent ileal pouch-anal anastomosis for ulcerative colitis. Samples were obtained from the terminal ileum of resected specimens at time of total colectomy or subtotal colectomy. mRNA expression levels of Th cytokines (IFN-γ, IL-23A, IL-5, IL-13 and IL-17A) were determined. RESULTS: Forty of 68 patients (58.8%) developed pouchitis. There was no association between IL-23A expression levels and incidence of pouchitis (p = 0.301). Patients with elevated IFN-γ had a significantly higher incidence of pouchitis compared with low IFN-γ patients (p = 0.043). Univariate analysis demonstrated a total dose of prednisolone > 7000 mg administered before colectomy (p = 0.04) and high IFN-γ expression (p = 0.02) were significant risk factors for pouchitis onset. In multivariate analysis, elevated IFN-γ messenger(m)RNA levels were significantly associated with pouchitis onset (p = 0.03). CONCLUSION: IFN-γ expression in the normal ileal mucosa at the time of colectomy may be an important factor in the pathophysiology of pouchitis.

Safety of double-balloon enteroscopy in postoperative pediatric patients.

BACKGROUND: The aim of the present study was to investigate the efficacy and safety of double-balloon enteroscopy (DBE) in postoperative pediatric patients. METHODS: This was a retrospective analysis of pediatric patients 18 years and younger referred to Mie University Hospital. Twenty procedures in 11 children occurred postoperatively; 29 children (42 procedures) had not undergone surgery. RESULTS: Among postoperative patients, five DBE procedures were performed via the oral route, 12 via the anal route, and three via a stomal route. Among nonoperative patients, 14 DBE procedures were performed via the oral route and 28 via the anal route. Four postoperative patients and two nonoperative patients had difficult pleating via the transanal route because of adhesions or thickening of the intestinal wall resulting from inflammation (P = 0.02). Excluding patients with stenosis, the mean length of endoscopic insertion for transanal procedures was significantly shorter among postoperative patients than among nonoperative patients (73.6 cm vs 160.5 cm, P < 0.01). There were no major complications in either group. CONCLUSIONS: Insertion difficulty was encountered in postoperative pediatric patients. However, our findings indicate that DBE is a safe procedure in postoperative pediatric patients.

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.

Clinical significance of an increased red blood cell distribution width in patients with rectal cancer undergoing chemoradiotherapy followed by surgery.

PURPOSE: The clinical significance of the red blood cell distribution width (RDW) in patients with rectal cancer undergoing preoperative chemoradiotherapy (CRT) followed by surgery has not been fully evaluated. METHODS: In this retrospective study, we investigated the association between the RDW and the prognosis in 120 patients with locally advanced rectal cancer (LARC). We also performed a subgroup analysis limited to patients with pathological TNM stage I-II (ypN[-]) LARC. RESULTS: The RDW standard deviation was used to evaluate the RDW. We set 47.1% as the cut-off value of the RDW for the assessment of the prognosis. The RDW exhibited a significant negative relationship with the serum hemoglobin and albumin levels. An elevated RDW was an independent prognostic factor for the overall survival (OS) and disease-free survival (DFS) in patients with LARC. In addition, an elevated RDW predicted a poor OS and DFS in patients with pathological TNM stage I-II (ypN[-]) LARC. CONCLUSIONS: The RDW is a promising predictor of a poor survival and recurrence in patients with LARC treated by CRT.

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.

Neutrophil priming as a risk factor for surgical site infection in patients with colon cancer treated by laparoscopic surgery.

BACKGROUND: The purpose of this study is to identify perioperative marker predicting postoperative surgical site infection (SSI) including with anastomotic leakage (AL) in curative colon cancer patients, laparoscopically. METHODS: In total, 135 colon cancer patients (stage I-III) undergoing curative laparoscopic surgery between January 2004 and December 2013 were enrolled in this study. We collected data on clinicopathological factors, laboratory data on pre and postoperative day 3 (POD3) and tumor markers levels to assess the relation to surgical site infection (SSI) including with anastomotic leakage (AL). RESULTS: SSI and AL occurred in 16 cases (5.6%) and 4 cases (3%), respectively. SSI and AL were not association with clinicopathological factors. Within laboratory data and tumor markers preoperatively, high neutrophil counts were significantly associated with SSI (P < 0.05) and AL (P < 0.01), respectively. Area under curves (AUC) of SSI and AL were 0.656 and 0.854, respectively. In addition, high neutrophil counts on POD3 also were significantly associated with SSI (P < 0.01) and AL (P < 0.01), respectively. Area under curves (AUC) of SSI and AL were 0.747 and 0.832, respectively. CONCLUSION: Neutrophil count on pre and POD3 are potentially valuable indicators of SSI including with AL in colon cancer patients undergoing curative surgery laparoscopically.

Japan Gastroenterological Endoscopy Society guidelines for colorectal endoscopic submucosal dissection/endoscopic mucosal resection.

Suitable lesions for endoscopic treatment include not only early colorectal carcinomas but also several types of precarcinomatous adenomas. It is important to establish practical guidelines wherein preoperative diagnosis of colorectal neoplasia and selection of endoscopic treatment procedures are appropriately outlined and to ensure that actual endoscopic treatment is useful and safe in general hospitals when carried out in accordance with guidelines. In cooperation with the Japanese Society for Cancer of the Colon and Rectum, the Japanese Society of Coloproctology, and the Japanese Society of Gastroenterology, the Japan Gastroenterological Endoscopy Society compiled colorectal endoscopic submucosal dissection/endoscopic mucosal resection guidelines by using evidence-based methods in 2014. The first edition of these guidelines was published 5 years ago. Accordingly, we have published the second edition of these guidelines based on recent new knowledge and evidence.

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.

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.