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.

Preoperative heat shock protein 47 levels identify colorectal cancer patients with lymph node metastasis and poor prognosis.

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.

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.

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.

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

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

Lymphocyte-to-C-reactive protein ratio and score are clinically feasible nutrition-inflammation markers of outcome in patients with gastric cancer.

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.

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

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

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

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

The prognostic nutritional index for postoperative infectious complication in patients with ulcerative colitis undergoing proctectomy with ileal pouch-anal anastomosis following subtotal colectomy.

OBJECTIVES: Restorative proctocolectomy and ileal pouch-anal anastomosis is frequently performed in patients with ulcerative colitis and factors suspected of increasing the risk of postoperative infectious complications. Using a three-stage approach may result in improvement in overall outcomes, because this leads to improvement in nutritional status and reduction of immunosuppressive doses. However, the influence of preoperative nutritional status on postoperative infectious complications after this procedure has not been examined. The aim of this study was to clarify the potential associations between nutritional status and postoperative infectious complications in patients with ulcerative colitis undergoing proctectomy with ileal pouch-anal anastomosis. METHODS: The records of 110 patients who had undergone proctectomy with ileal pouch-anal anastomosis from January 2000 to March 2018 in Mie University and met the eligibility criteria were reviewed and possible associations between postoperative infectious complications and clinical factors were assessed. RESULTS: Of the remaining 110 patients, 18 (16.4%) had developed postoperative infectious complications. Multivariate analysis revealed that operative bleeding ≥270 g and prognostic nutritional index <47 were significant predictors of postoperative infectious complications (P = 0.033, 0.0076, respectively). Various variables associated with immunosuppressives before ileal pouch-anal anastomosis were not associated with postoperative infectious complications. CONCLUSIONS: Our findings suggest that immunosuppressives have no association with postoperative infectious complications, whereas a poor prognostic nutritional index may be a significant predictor of postoperative infectious complications in patients with ulcerative colitis undergoing proctectomy with ileal pouch-anal anastomosis.

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

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

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.

Laparoscopic esophagogastrostomy using a knifeless linear stapler after proximal gastrectomy.

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

Circulating miR-203 derived from metastatic tissues promotes myopenia in colorectal cancer patients.

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 < 0.0001; log-rank test) and disease-free survival (IMAC: P = 0.0003; PMI: P = 0.0002; log-rank test), multivariate Cox's regression analysis revealed that low PMI was an independent prognostic factor for both overall survival (hazard ratio: 4.69, 95% confidence interval (CI): 2.19-10, P = 0.0001) and disease-free survival (hazard ratio: 2.33, 95% CI: 1.14-4.77, P = 0.021) in CRC patients. Serum miR-203 expression negatively correlated with pre-operative PMI level (P = 0.0001, ρ = -0.25), and multivariate logistic regression analysis revealed that elevated serum miR-203 was an independent risk factor for myopenia (low PMI) in CRC patients (odds ratio: 5.16, 95% CI: 1.8-14.8, P = 0.002). Overexpression of miR-203 inhibited cell proliferation and induced apoptosis via down-regulation of BIRC5 (survivin) expression in human SkMC line. CONCLUSIONS: Assessment of serum miR-203 expression could be used for risk assessment of myopenia, and miR-203 might be a novel therapeutic target for inhibition of myopenia in CRC.

Adverse events in patients with ulcerative colitis treated with indigo naturalis: a Japanese nationwide survey.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Phase I study of preoperative chemoradiotherapy with sequential oxaliplatin and irinotecan with S-1 for locally advanced rectal cancer.

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/m2/day) on days 1-5, 8-12, 15-19, 22-27 and 29-33, and irinotecan (40 mg/m2/day) on days 1 and 8, followed by oxaliplatin on days 22 and 29. The dose of oxaliplatin was initially 40 mg/m2 (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/m2 (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/m2 (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.

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

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

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

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

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

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

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.

Laparoscopic diagnosis of retrograde peristalsis and intussusception in Roux-en-Y limb after laparoscopic gastrectomy: A case report.

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.