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Background: Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years. Summary: Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system. Key Messages: Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS.

Oxaliplatin (OHP) is a reagent for the standard treatment of advanced and recurrent colorectal cancer (CRC), although OHP resistance mechanisms are not fully elucidated. We found that HCT116-derived OHP-resistant clones (HCT/OHPs), but not DLD1-derived OHP-resistant clones also were resistant to the other drugs used for CRC treatment (5-fluorouracil, irinotecan, and trifluorothymidine), and HCT/OHP-derived tumors were resistant to OHP treatment. Among the candidate genes derived from microarray analysis using the samples of HCT/OHP cells and HCT/OHP-derived tumors, Forkhead box Q1 (FOXQ1) was further assessed to validate OHP resistance and its association with clinicopathological features. In our 173 cohort and 587 TCGA samples, FOXQ1 was upregulated in most CRC tumors compared to normal colonic mucosa and associated with tumor location of the right-sided colon and KRAS/BRAF mutation status. Possible association with prognosis in advanced CRC in our cohort and with microsatellite instability and advanced stage in TCGA samples were indicated. Modification of FOXQ1 via siRNA knockdown and expression vector could not confirm the involvement of FOXQ1 in OHP resistance. In conclusion, our results indicates that FOXQ1 is upregulated in CRC and FOX1 expression is associated with tumor location and KRAS/BRAF mutation status, but is not involved in the OHP resistance mechanism.

Complex interactions among endogenous and exogenous factors influence the incidence of colorectal cancer (CRC). Germline mutations in mismatch repair (MMR) genes causing Lynch syndrome (LS) are major endogenous factors. The exogenous factor, alcohol consumption, is potentially associated with CRC incidence among patients with LS. However, insufficient data are available to determine whether alcohol consumption influences the time of the first onset of CRC associated with sex, MMR gene mutations, and anatomical tumor site.Among 316 patients with LS identified in a Japanese LS cohort, we included 288 with data on age, sex, proband status, alcohol status, smoking status, tumor location, and MMR gene mutations. Multivariable analysis assessed the association of alcohol consumption with earlier onset of the first CRC.Ever drinkers were associated with higher risk of the first onset of CRC than never drinkers (HR 1.54, 95%CI 1.14-2.07, P = 0.004). The association of the first onset of CRC with alcohol consumption was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations (vs those with pathogenic MSH6, PMS2 and EPCAM mutations), and tumors in the proximal colon cancer (vs distal colon and rectal cancer).Alcohol consumption was associated with earlier onset of the first CRC in Japanese LS cohort. The association was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations, and tumors located in the proximal colon. Our findings illuminate the mechanism of LS-associated carcinogenesis and serve as a recommendation for discontinuing or ceasing alcohol consumption.

Objectives We evaluated the cost-effectiveness of a 12-month regimen of oral capecitabine versus a standard 6-month regimen as postoperative adjuvant chemotherapy for stage III colon cancer. Methods We utilized patient-level data from a multi-institutional randomized controlled trial (JFMC37-0801) that investigated prolonged oral fluoropyrimidine monotherapy. The analysis considered three health states: stable disease, post-metastasis, and death. A parametric statistical model with a cure model was used to estimate the survival curve. The analysis was conducted from the Japanese public healthcare payer’s perspective, considering only direct medical costs. A lifetime horizon was used, with a discount rate of 2% for both cost and health outcomes. Health outcomes were evaluated in terms of quality-adjusted life-years (QALYs). Results The estimated cure rates for colon cancer were 0.726 [95% confidence interval (CI) 0.676–0.776] and 0.694 (95% CI 0.655–0.733) with the 12- and 6-month regimens, respectively; and the estimated 5-year relapse-free survival rates were 74.4% and 69.8%, respectively. The estimated lifetime cost for 12 months of capecitabine was JPY 3.365 million (USD 31,159), compared with JPY 3.376 million (USD 31,262) for 6 months. The estimated QALY were 12.48 and 11.77 for the 12- and 6-month regimens, respectively. Thus, the 12-month capecitabine regimen was dominant. Using a willingness-to-pay threshold of JPY 5 million per QALY, we determined a 97.4% probability that the 12-month capecitabine regimen is more cost-effective than the 6-month regimen. Conclusions Twelve months of capecitabine is the favorable option for postoperative adjuvant chemotherapy for stage III colon cancer from the perspective of cost-effectiveness.

This phase III trial evaluated whether the no touch was superior to the conventional in patients with cT3/T4 colon cancer.No touch involves ligating blood vessels that feed the primary tumor to limit cancer cell spreading. However, previous studies did not confirm the efficacy of the no touch.This open-label, randomized, phase III trial was conducted at 30 Japanese centers. The eligibility criteria were histologically proven colon cancer; clinical classification of T3-4, N0-2, andM0; and patients aged 20 to 80years. Patients were randomized (1:1) to undergo open surgery with conventional or the no touch. Patients with pathological stage III disease received adjuvant capecitabine chemotherapy. The primary endpoint was disease-free survival (DFS) according to the intention-to-treat principle.Between January 2011 and November 2015, 853 patients were randomized to the conventional group (427 patients) or the no touch group (426 patients). The 3-year DFS were 77.3% [95% confidence interval (CI) 73.1%-81.0%] and 76.2% (95% CI 71.9%-80.0%) in the conventional and no touch groups, respectively. The superiority of no touch was not confirmed: hazard ratio for DFS = 1.029 (95% CI 0.800- 1.324; 1-sided P = 0.59). Operative morbidity was observed in 31 of 427 conventional patients (7%) and 26 of 426 no touch patients (6%). All grade adverse events were similar between the conventional and no touch groups. No in-hospital mortality occurred in either group.The present study failed to confirm the superiority of the no touch.

Background Paraduodenal hernia is a rare internal hernia which accounts for only 1% of all intestinal hernias. There have been limited reported cases of paraduodenal hernia treated by laparoscopic surgery. We report a case of left paraduodenal hernia that was successfully treated by single-incision laparoscopic surgery (SILS). Case presentation A 17-year-old woman presented with left upper abdominal pain. An abdominal enhanced multi-detector computed tomography demonstrated encapsulated cluster of small bowel loops in the left upper quadrant which passed through the dorsal side of the inferior mesenteric vein, and showed that blood flow of the prolapsed small bowel was preserved. We preoperatively diagnosed left paraduodenal hernia without ischemia or necrosis. We performed elective SILS because she was a young actress training school student and cosmetic benefit was thought to be important. We pulled out the protruded small bowel and closed a defect with a running suture by SILS. The patient was discharged 3 days after the surgery with no complications. Conclusions We reported the case of left paraduodenal hernia successfully diagnosed and treated by SILS.

Colonoscopy surveillance reduces the incidence of colorectal cancer through the detection and endoscopic removal of adenomas. Current guidelines recommend that patients with Lynch syndrome should have colonoscopy surveillance every 1-2 years starting at the age of 20-25. However, insufficient data are available to evaluate the quality and safety of colonoscopy surveillance for patients with Lynch syndrome nationwide in Japan.Patients with Lynch syndrome (The colonoscopy completion rate was 98.8% and a history of previous colorectal cancer surgery was significantly associated with a higher completion rate. All complications were associated with endoscopic treatment and the rate of bleeding needing hemostasis and perforation needing surgical repair were both 0.16% after colonoscopy with polypectomy. The adenoma detection rate at the first colonoscopy was 25%. Although there was no difference in the completion and complication rates based on differences in the colonoscopy experience of the endoscopist, the detection rate of adenomas and intramucosal cancers was significantly higher with more experienced endoscopists. The proportion of patients developing cancer was significantly higher with a 24 months than a ≤24 months interval.High-volume experienced endoscopists and appropriate surveillance intervals may minimize the risk of developing colorectal cancers in patients with Lynch syndrome.

Background Colon cancer (CC) incidence in young adults (age 20-49 years), termed early-onset CC (EO-CC), is increasing. Methods Individual patient data on 35 713 subjects with stage III colon cancer from 25 randomized studies in the Adjuvant Colon Cancer ENdpoint database were pooled. The distributions of demographics, clinicopathological features, biomarker status, and outcome data were summarized by age group. Overall survival, disease-free survival, time to recurrence, and survival after recurrence were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for sex, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness, and molecular markers. All statistical tests were 2-sided. Results Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III EO-CC had similar sex, race, performance status, risk group, tumor sidedness, and T stage compared with patients with late-onset CC (age 50 years and older). EO-CC patients were less likely to be overweight (30.2% vs 36.2%) and more commonly had 12 or more lymph nodes resected (69.5% vs 58.7%). EO-CC tumors were more frequently mismatch repair deficient (16.4% vs 11.5%) and less likely to have BRAFV600E (5.6% vs 14.0%), suggesting a higher rate of Lynch syndrome in EO-CC. Patients with EO-CC had statistically significantly better overall survival (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.74 to 0.89; P Conclusion Tumor biology was found to be a more important prognostic factor than age of onset among stage III colon cancer patients in the Adjuvant Colon Cancer ENdpoint database.

Familial adenomatous polyposis (FAP), an autosomal dominant disorder characterized by multiple colonic polyps, is caused by a germline pathogenic variant of the APC gene. However, this variant is not detected in up to 30% of patients with the adenomatous polyposis phenotype. We performed next-generation sequencing (NGS) to identify the causative genes in FAP patients with 10 or more polyps. For patients in whom the APC germline variant was not able to be identified, we screened for APC mosaicism using high-coverage NGS of APC with DNA from leucocytes and/or frozen tissue. The pathogenic APC germline variant was found in 93.3%, 71.6%, and 17.1% of patients with profuse-type polyposis, sparse-type polyposis, and oligo-polyposis, respectively. The APC germline variant detection rate in patients with FAP-related diseases was 69.7% for fundic gland polyposis, 79.7% for duodenal adenoma, 94.7% for desmoid tumor, and 71.4% for thyroid cancer, with increasing numbers of extracolonic lesions associated with an increasing APC germline variant detection rate. A mosaic test detected nine patients with APC mosaicism. A comparison of APC-associated polyposis with APC mosaicism showed that patients with APC mosaicism had a low frequency of duodenal adenoma and a family history of colonic polyposis. We determined the detection rate of the APC germline variant by phenotype and identified APC mosaicism. Genetic testing of FAP patients is important because it can help with surgical decision-making, monitoring, and genetic counseling. Furthermore, genetic testing by NGS proved to be an effective method of detecting APC germline variants.

Lynch syndrome is a hereditary disease characterized by an increased risk of colorectal and other cancers. Germline variants in the mismatch repair (MMR) genes are responsible for this disease. Previously, we screened the MMR genes in colorectal cancer patients who fulfilled modified Amsterdam II criteria, and multiplex ligation-dependent probe amplification (MPLA) identified 11 structural variants (SVs) of MLH1 and MSH2 in 17 patients. In this study, we have tested the efficacy of long read-sequencing coupled with target enrichment for the determination of SVs and their breakpoints. DNA was captured by array probes designed to hybridize with target regions including four MMR genes and then sequenced using MinION, a nanopore sequencing platform. Approximately, 1000-fold coverage was obtained in the target regions compared with other regions. Application of this system to four test cases among the 17 patients correctly mapped the breakpoints. In addition, we newly found a deletion across an 84 kb region of MSH2 in a case without the pathogenic single nucleotide variants. These data suggest that long read-sequencing combined with hybridization-based enrichment is an efficient method to identify both SVs and their breakpoints. This strategy might replace MLPA for the screening of SVs in hereditary diseases.

BACKGROUND Anal lesions in cases of Crohn's disease can give rise to adenocarcinoma of the anal canal; however, the oncologic outcomes in these patients have not yet been thoroughly investigated. OBJECTIVE This study aimed to clarify the influence of Crohn's disease on the oncologic outcomes in patients with adenocarcinoma of the anal canal. DESIGN This was a retrospective observational study from a prospectively collected database. SETTINGS The study was conducted at a single institution. PATIENTS This study included 102 patients with adenocarcinoma of the anal canal, including 34 (33.3%) with Crohn's disease-associated lesions and 68 (66.7%) with non-Crohn's disease-associated lesions. MAIN OUTCOME MEASURES Prognostic factors were detected using a Cox regression analysis, and the oncologic outcomes were calculated using the Kaplan-Meier method. RESULTS Crohn's disease-associated patients were significantly younger (45 vs 62 y; p < 0.001), had a high incidence of external/anal gland-type disease (61.8% vs 5.9%, p < 0.001) and had large tumors (7.1 ± 3.0 vs 4.7 ± 2.3 cm; p = 0.03) in comparison with non-Crohn's disease-associated patients. A Cox regression analysis showed that an advanced clinical T stage (T3 or T4; tumor size ≥5 cm) was an independent risk factor for 5-year local recurrence-free survival (HR = 3.49; p = 0.04), disease-free survival (HR = 2.82; p = 0.008), and overall survival (HR = 2.92; p = 0.006), and Crohn's disease association was an independent prognostic factor for local recurrence-free survival (HR = 2.29; p = 0.04) and overall survival (HR = 2.86; p = 0.04). The oncologic outcomes of patients who had the 2 abovementioned negative factors (cT3,4 Crohn's disease-associated patients) were significantly poorer than those of T3,4 non-Crohn's disease-associated patients (5-year local recurrence-free survival: 32.5% vs 70.4%, p = 0.001; disease-free survival: 15.9% vs 40.7%, p = 0.04; overall survival: 25.8% vs 71.0%, p = 0.007). LIMITATIONS This was a single-arm, retrospective study. CONCLUSIONS Significantly poorer oncologic outcomes were confirmed in Crohn's disease-associated patients with large tumors. Thus, it is important to perform careful surveillance of anal lesions in patients with Crohn's disease while taking these facts into consideration. See Video Abstract at http://links.lww.com/DCR/B449. RESULTADOS ONCOLGICOS ADVERSOS DEL ADENOCARCINOMA DEL CANAL ANAL EN PACIENTES CON ENFERMEDAD DE CROHN ANTECEDENTES:Las lesiones anales en casos de enfermedad de Crohn pueden dar lugar a un adenocarcinoma del canal anal; sin embargo, los resultados oncologicos en estos pacientes aun no se han investigado a fondo.OBJETIVOS:Este estudio tuvo como objetivo aclarar la influencia de la enfermedad de Crohn en los resultados oncologicos en pacientes con adenocarcinoma del canal anal.DISENO:Estudio observacional retrospectivo de una base de datos recopilada prospectivamente.ENTORNO CLINICO:El estudio se realizo en una sola institucion.PACIENTES:Este estudio incluyo 102 pacientes con adenocarcinoma del canal anal, incluidos 34 (33,3%) con lesiones asociadas a la enfermedad de Crohn y 68 (66,7%) con lesiones no asociadas a la enfermedad de Crohn.PRINCIPALES MEDIDAS DE VOLARACION:Los factores pronosticos se detectaron mediante un analisis de regresion de Cox y los resultados oncologicos se calcularon utilizando el metodo de Kaplan-Meier.RESULTADOS:Los pacientes asociados a la enfermedad de Crohn eran significativamente mas jovenes (45 versus a 62 anos, p

BackgroundHartmann’s procedure (HP) has been performed for colorectal perforation to avoid the risk of anastomotic leakage. Few reports have compared the safety between primary anastomosis without diverting stoma (PAWODS) and HP for colorectal perforation, and whether PAWODS or HP should be performed has remained controversial. We aimed to investigate the feasibility and safety of performing PAWODS in comparison to HP for colorectal perforation.Methods We retrospectively collected the data of 97 consecutive patients with colorectal perforation who underwent surgery from April 2010 to December 2020. PAWODS and HP were performed in 51 and 46 patients, respectively. Univariate and multivariate analyses were performed to compare the clinical characteristics and postoperative outcomes of patients treated with PAWODS with those treated with HP . ResultsIn the multivariate analysis, low serum albumin (hazard ratio [HR]=3.49 [95%CI=1.247-9.757] P=0.017) and left-sided colon and rectum perforation (HR=16.8 [95%CI=1.792-157.599] P=0.014) were significantly associated with the decision to perform HP. There was significant difference in the mortality of the two groups (PAWODS vs. HP: 0% vs. 8.7%; P=0.047). The severe morbidity rate (Clavien-Dindo III-V) was significantly higher in the HP group (PAWODS vs. HP: 10% vs. 30%; P=0.020). In the PAWODS group, anastomotic leakage occurred in 5 of 51 patients (9.8%), 4 (8.7%) of whom required re-operation.ConclusionsIn appropriately selected patients, PAWODS could be safely performed with an acceptable rate of anastomotic leakage. The serum albumin level and site of perforation may be simple and useful factors for guiding decision-making on the surgical procedure.

Introduction In high sacrectomy, it is difficult to secure the lateral surgical margin and prevent severe postoperative complications. In this report, we present our unique surgical procedure using transanal total mesorectal excision for locally recurrent rectal cancer. Technique A 49-year-old woman was diagnosed with locally rerecurrent rectal cancer, which was located at the height of the S3 vertebra by preoperative imaging, and posterior pelvic exenteration concomitant with high sacrectomy below the S2 vertebra was planned. A multiaccess transperineal platform was placed to secure the lateral surgical margin using transperineal minimally invasive surgery during the perineal and sacral side procedure. Transperineal minimally invasive surgery has several clinical benefits over the conventional approach. For the perineal approach, a 2-team laparoscopic approach was performed. This surgical intervention with laparoscopic perineal assistance contributed to the completion of the dissection of the planned lateral surgical margin, such as the distal piriformis muscles and the sacrotuberous and sacrospinous ligaments, which are the most difficult areas to access in the lithotomy position. Regarding the sacral approach, it facilitated the dissection of the dorsal space of the sacrum; therefore, only a 7-cm transverse skin incision was required during sacrectomy. Small skin incisions and minimal dissection may reduce surgical site infections. Results The operative time was 933 minutes, with 80 mL of blood loss. There were no major complications, and pathologically confirmed curative resection was achieved. Conclusions Our new technique utilizing transanal total mesorectum excision is feasible to secure the lateral surgical margin with minimal skin incision and dissection and may prevent severe postoperative complications.

Supplemental Digital Content is available in the text., Grade 3 (G3, poorly differentiated) is an important treatment-decision factor in stage II colon cancer, but no unified diagnostic criteria are established. According to previous studies, an intratumoural poorly differentiated area with no glandular formation (POR) that fills the microscopic field of a ×40 objective lens was an essential factor that defined G3. We aimed to prospectively validate this in a randomized controlled study of adjuvant chemotherapy (SACURA trial). We enrolled 991 patients with stage II colon cancer. POR was graded according to the ×40 objective lens rule and the intensity of poorly differentiated clusters (GradePOR), and its prognostic power was compared with that of the conventional tumor grade on the basis of predominant histology rule (Gradeconv). According to GradePOR, 313, 526, and 152 tumors were classified as G1POR, G2POR, and G3POR, respectively, and the 5-year relapse-free survival (RFS) rates were 91.1%, 82.9%, and 74.7%, respectively (P

Tumour-Node-Metastasis (TNM) staging of colorectal cancer (CRC) needs further classification for better treatment because of disease heterogeneity. Although molecular classifications which are expensive and laborious are under study, cost and labour efficient subtyping is desirable. We assessed the combinations of preoperative tumour marker (TM) elevation and tumour lymphovascular invasion (LVI) as a solution. We used the pooled data of 7151 colon cancer (CC) patients and 4620 rectal cancer (RC) patients who received curative surgery between 2004 and 2008 in Japan. The best-matched subtyping for predicting relapse-free survival (RFS) was statistically selected using the c-index and Akaike’s information criterion. This subtyping (TM-LVI), which consisted of three categories by TM elevation status and severity of LVI status, was an independent prognostic factor for RFS of CC (stage IIa, IIIb, and IIIc) and RC (stage I, IIa, IIb, IIIa, and IIIb) and also for disease specific survival of CC (stage IIa, IIb, IIIb, and IIIc) and RC (all stage except for IIc). Although TM-LVI classified CRC patients into low and high recurrence risk groups, the application of adjuvant therapy was not accordance with the TM-LVI status. TM-LVI may be a cost and labour efficient subtyping of colorectal cancer for better treatment strategy.

Chemotherapy in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy is under debate. REACT study aimed to investigate the efficacy of reintroducing modified FOLFOX6 (mFOLFOX6) or CAPOX with or without bevacizumab in recurrent colorectal cancer patients after oxaliplatin adjuvant chemotherapy. Patients that participated in this trial had a medical history of adjuvant chemotherapy, including oxaliplatin with a cumulative dose greater than 400 mg/m2, and recurrence that was diagnosed more six months post adjuvant chemotherapy. Primary endpoints were response rate (RR) and disease control rate (DCR), while key secondary endpoints were time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety. A total of 31 patients were enrolled between October 2012 and October 2016. Of the 29 eligible patients, 7 received mFOLFOX6 and 22 received CAPOX. The RR was 62.1% (95% confidence interval 42.3–79.3) and the DCR was 82.8% (95% confidence interval 64.2–94.2). The RR for oxaliplatin-free interval was 100.0% in months 6–12 and 56.0% after 12 months. Median TTF, PFS, and OS were 6.3, 10.8, and 28.7 months, respectively. Grade 3 or worse peripheral sensory neuropathy developed in 6.5%. Allergic reactions occurred in 12.9% of the patients, with one (3.2%) grade 3 episode. There were no other severe treatment-related adverse events. Reintroduction of oxaliplatin was feasible and achieved high RR or DCR in patients after more than 6 months post oxaliplatin adjuvant chemotherapy.

Whether tumour side affects the anatomical extent and distribution of lymph node metastasis in colon cancer is unknown. The impact of tumour side on the anatomical pattern of lymphatic spread in colon cancer was assessed.Patients with stage III colon cancer from a Japanese multi-institutional database who underwent extensive (D3) lymphadenectomy, which is similar in concept to complete mesocolic excision with central venous ligation, were divided into groups with right- and left-sided tumours. Based on location, mesenteric lymph nodes were categorized as paracolic (L1), intermediate (L2) or central (L3). The Kaplan-Meier method was used to evaluate disease-free survival (DFS) and overall survival (OS), and multivariable Cox models were used to evaluate the association between anatomical lymph node level, metastatic pattern and outcome.A total of 4034 patients with stage III colon cancer (right 1618, left 2416) were included. Unadjusted OS was worse in patients with right colon cancer (hazard ratio 1·23, 95 per cent c.i. 1·08 to 1·40; P = 0·002), but DFS was similar. Right-sided tumours more frequently invaded L3 nodes than left-sided lesions (8·5 versus 3·7 per cent; P 0·001). The proportion of patients with a skipped pattern of lymphatic spread was higher in right than in left colon cancer (13·7 versus 9·0 per cent; P 0·001). In multivariable analysis, invasion of L3 nodes was associated with worse OS in left but not in right colon cancer. The presence of skipped metastasis was associated with worse DFS in left, but not right, colon cancer.There are significant differences in the pattern of lymph node invasion between right- and left-sided stage III colon cancer, and in their prognostic significance, suggesting that tumour side may dictate the operative approach.Se desconoce si la lateralidad del tumor influye en la extensión anatómica y en la distribución de las metástasis en los ganglios linfáticos (lymph node metastasis, LN) en el cáncer de colon. Se evaluó el impacto de la lateralidad del tumor en el patrón anatómico de diseminación linfática en el cáncer de colon. MÉTODOS: Los pacientes con cáncer de colon en estadio III recogidos en una base de datos japonesa multicéntrica, que se sometieron a una linfadenectomía ampliada (D3), conceptualmente similar a la escisión completa del mesocolon con ligadura venosa central, se dividieron en cáncer de colon del lado derecho y cáncer de colon del lado izquierdo. Según la ubicación, las LN mesentéricas se clasificaron como paracólicas (L1), intermedias (L2) o centrales (L3). Se utilizó el método de Kaplan-Meier para evaluar la supervivencia libre de enfermedad (disease-free survival, DFS) y la supervivencia global (overall-survival, OS), y se utilizaron modelos de Cox multivariados para evaluar la asociación entre el nivel L y el patrón metastásico con el resultado.Se incluyeron 4.034 pacientes con cáncer de colon en estadio III (cáncer de colon derecho: n = 1.618, cáncer de colon izquierdo: n = 2.416). La OS no ajustada fue peor en el cáncer de colon derecho (cociente de riesgos instantáneos, hazard ratio, HR 1,23, i.c. del 95%: 1,08-1,4; P = 0,002), pero la DFS fue similar. La afectación de los ganglios L3 fue más frecuente en pacientes con cáncer de colon derecho que izquierdo (8,5% versus 3,7%, P 0,001). En el cáncer de colon derecho, la proporción de pacientes con patrón de diseminación linfática discontinuo, con salto entre niveles, fue mayor en comparación con el cáncer de colon izquierdo (13,7% versus 9%; P 0,001). En el análisis multivariante, la invasión de los ganglios L3 se asoció con una peor OS en el cáncer de colon izquierdo, pero no en el cáncer de colon derecho. La presencia de metástasis discontinuas se asoció con una peor DFS en el cáncer de colon izquierdo, pero no en el cáncer de colon derecho. CONCLUSIÓN: Existen diferencias significativas en el patrón de invasión de los LN entre el cáncer de colon derecho e izquierdo en estadio III, así como en su importancia pronóstica, lo que sugiere que la lateralidad del tumor puede determinar el abordaje quirúrgico.

Fluorouracil and leucovorin combined with oxaliplatin or irinotecan plus bevacizumab (Bmab) or cetuximab (Cmab) are now widely accepted treatment options as first-line or second-line chemotherapy for metastatic colorectal cancer (mCRC). Sequential chemotherapy with oral 5-FU backbone for mCRC without using central venous ports is beneficial for both patients and physicians. We designed the SOBIC trial to validate the effectiveness of the first- and second-line oral combination chemotherapy for mCRC. From May 2010 through March 2013, 52 patients were enrolled from 47 institutions in the Hyogo Colorectal Cancer Surgery Group. First-line chemotherapy was S-1 + oxaliplatin (SOX) plus Bmab, and second-line chemotherapy after first-line failure was irinotecan + S-1 (IRIS) + Cmab, IRIS + Bmab, or IRIS based on the KRAS status. The 50 finally included patients received first-line chemotherapy. Second-line therapy was administered to 20 patients (40%): 12 patients received IRIS + Cmab and 8 patients received IRIS + Bmab. The median follow-up period was 48.6 months (range 35–67 months). The median second progression-free survival was 24.2 months (95% confidence interval [CI] 17.7–35.2). The response rate after first- and second-line chemotherapy was 46.7% and 15%, respectively. The median overall survival was 35.2 months (95% CI: 27.8 to not reached). The main grade 3–4 adverse events were sensory neuropathy (18%) and fatigue (10%). There were no treatment-related deaths. Sequential S-1-based combination regimens including oxaliplatin, irinotecan, Bmab, and Cmab were beneficial for patients with mCRC.

Waste management has been one of the major problems in Indonesia. Besides the inadequate waste management system, it is also due to the lack of awareness about waste disposal that leads to littering. Littering does not only occur in low educated community, but also occurs in educational institutes. This research aims to investigate the association of the presence of gakko soji in school curriculum to the development of anti-littering attitude. The study is conducted by measuring the environmental efficacy as one of the psychological determinants of littering attitude. The result shows that the average score of environmental efficacy is higher among Indonesian students than Japanese students, but both average scores are still in the same category. Another finding is that the score variation is lower with the students who have experienced gakko soji. The result indicates the presence of probability that gakko soji provides uniform environmental education to students.

Introduction: DNA microarrays, such as the consensus molecular subtype (CMS) classification using >600 genes, are used to predict cancer patient prognosis. We recently constructed a simple 55-gene classifier (55GC) system to risk stratify colon cancer (CC). Objective: Here, we validate the 55GC specifically for stage II CC and compare it with CMS categories. Methods: Tissue sections from 232 stage II CC patients who underwent curative surgery without adjuvant chemotherapy between 2009 and 2012 were subjected to DNA microarray analysis. Results: Based on the 55GC, patients were classified into microsatellite instability-like (27%), chromosomal instability-like (41%), and stromal (32%) subtypes with 5-year relapse-free survival (RFS) rates of 88.5, 83.3, and 71.2%, respectively (stromal vs. others: p = 0.0049). Multivariate analysis by Cox’s proportional hazard model revealed that the stromal subtype, pT4, and the number of lymph nodes examined (p = 0.0113). Conclusions: We conclude that the 55GC is a useful and reproducible grading system for stage II CC recurrence risk stratification.

Background/aim The difficulty of early diagnosis of colitis associated colorectal cancer (CACRC) due to colonic mucosal changes in long-standing ulcerative colitis (UC) patients is often experienced in daily clinical practice. Noninvasive objective monitoring for cancer development is advantageous for optimizing treatment strategies in UC patients. We aimed to examine the epigenetic alterations occurring in CACRC, focusing on DNA hypermethylation of CpG islands. Materials and methods The level of DNA methylation in CpG cites was compared between CACRC and the counterpart non-tumorous mucosa using Infinium HumanMethylation 450K BeadChip. Results Our subjects included 3 males and 3 females (median age, 49.5 years). The 450K CpG site DNA methylation microarray revealed that the difference in β value (level of hypermethylation) was the highest for corcicotropin releasing hormone receptor 2 (CRHR2) between CACRC and counterpart non-tumorous mucosa. Conclusion Detection of hypermethylation of CRHR2 may be promising for cancer screening in UC patients.