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Background A self-expandable metal stent is often placed as a bridge to elective surgical treatment of left-sided malignant obstruction of the colon because it allows for primary anastomosis without the need for a temporary stoma, which has a positive impact on the patient’s quality of life. However, although a relatively safe procedure, colonic stenting can have complications that require emergency surgery. This case report describes a rare case of abdominal compartment syndrome that occurred as a complication during colonic stenting. Case presentation: The patient was a 72-year-old woman who presented complaining of several days of constipation and loss of appetite. Computed tomography of the abdomen revealed obstruction of the sigmoid colon by a tumor. There were no symptoms or computed tomography findings to suggest perforation. Therefore, an attempt was made to insert a self-expandable metal stent. Acute respiratory disturbance and a change in consciousness occurred during the stenting procedure, with marked abdominal distention. Abdominal compartment syndrome was diagnosed and treated by decompressive laparotomy. Conclusions To the best of our knowledge, this is the first reported case of abdominal compartment syndrome as a complication of colonic stenting. The possibility of abdominal compartment syndrome should be considered if acute respiratory disturbance or altered consciousness occurs during placement of a colonic stent.

Background In transitioning from the 7th edition of the tumor‐node‐metastasis classification (TNM‐7) to the 8th edition (TNM‐8), colorectal cancer with peritoneal metastasis was newly categorized as M1c. In the 9th edition of the Japanese Classification of colorectal, appendiceal, and anal carcinoma (JPC‐9), M1c is further subdivided into M1c1 (without other organ involvement) and M1c2 (with other organ involvement). This study aimed to compare the model fit and discriminatory ability of the M category of these three classification systems, as no study to date has made this comparison. Methods The study population consisted of stage IV colorectal cancer patients who were referred to the National Cancer Center Hospital from 2000 to 2017. The Akaike information criterion (AIC), Harrell's concordance index (C‐index), and time‐dependent receiver operating characteristic (ROC) curves were used to compare the three classification systems. Subgroup analyses, stratified by initial treatment year, were also performed. Results According to TNM‐8, 670 (55%) patients had M1a, 273 (22%) had M1b, and 279 (23%) had M1c (87 M1c1 and 192 M1c2 using JPC‐9) tumors. Among the three classification systems, JPC‐9 had the lowest AIC value (JPC‐9: 10546.3; TNM‐7: 10555.9; TNM‐8: 10585.5), highest C‐index (JPC‐9: 0.608; TNM‐7: 0.598; TNM‐8: 0.599), and superior time‐dependent ROC curves throughout the observation period. Subgroup analyses were consistent with these results. Conclusions While the revised M category definition did not improve model fit and discriminatory ability from TNM‐7 to TNM‐8, further subdivision of M1c in JPC‐9 improved these parameters. These results support further revisions to M1 subcategories in future editions of the TNM classification system., In transitioning from the TNM 7th edition to the TNM 8th edition, colorectal cancer with peritoneal metastasis was newly categorized as M1c, and in the Japanese Classification (9th edition), M1c is further subdivided into M1c1 (without other organ involvement) and M1c2 (with other organ involvement). To date, no study has compared the model fit and discriminatory ability of the M category of these three classification systems. In this study, with 1222 consecutive stage IV colorectal cancer patients, we clearly demonstrated that, by comparing AIC, Harrell's c‐index, and time‐dependent ROC curves between the three classification systems, while the revised M category definition did not improve model fit and discriminatory ability from TNM 7th edition to the TNM 8th edition, further subdivision of M1c in the Japanese Classification improved these parameters.

Previous studies investigating the impact of tumor location on colorectal cancer prognosis only compared two groups by location, e.g., ‘right-sided colon vs. left-sided colon,’ ‘colon vs. rectum,’ and ‘right-sided (right-sided colon) vs. left-sided (left-sided colon and rectum).’ This nationwide multicenter retrospective study aimed to clarify the prognostic impact of tumor location in patients with stage III colorectal cancer by classifying tumors into three groups: right-sided colon, left-sided colon, and rectum. Subjects were 9194 patients with stage III colorectal cancer who underwent curative surgery from 1997 to 2012. Relapse-free survival (RFS) after primary surgery and overall survival (OS) after recurrence were examined. Rectal cancer (n = 2922) was associated with worse RFS compared to right-sided colon cancer (n = 2362) (hazard ratio (HR) 0.65; 95% CI 0.59–0.72; p

The feasibility of laparoscopic surgery for elderly patients remains unclear, as these patients usually present with comorbidities. Recently, the controlling nutritional status (CONUT) score has drawn attention as an evaluation score of patients' general status as well as a predictor of survival. We retrospectively analyzed overall survival in 424 patients aged ≥75 years with colon cancer, who underwent curative surgery (laparoscopic (

Background Preoperative and early postoperative serum carcinoembryonic antigen (CEA) levels are known prognostic factors in rectal cancer. Recently, a large‐scale study on colon cancer revealed that “preoperatively elevated and postoperatively normalized CEA levels” is not an indicator of poor prognosis. However, whether this hold true in rectal cancer patients is unknown. This study aimed to investigate the prognostic significance of preoperatively elevated and postoperatively normalized CEA levels in rectal cancer patients undergoing curative resection. Methods Subjects were consecutive stage I‐III rectal cancer patients who underwent curative resection without preoperative treatment at National Cancer Center Hospital between 2000 and 2015. Overall survival (OS) and the hazard function of recurrence or death were analyzed according to the CEA levels, as follows: normal preoperative CEA (normal group), preoperatively elevated but postoperatively normalized CEA (normalized group), and preoperatively and postoperatively elevated CEA (elevated group). Results The normalized group (n =235) had worse OS (HR 1.49, 95% CI 1.08‐2.04; P = .0142) compared to the normal group (n = 1208), and better OS compared to the elevated group (n = 47) (HR 0.53, 95% CI 0.31‐0.91; P = .0208). The elevated group had the highest and earliest peak in hazard function, followed by the normalized group and the normal group, with median times to recurrence of 8.8, 15.5, and 18.5 months, respectively (P = .0223). Conclusions Prognosis after resection of rectal cancer was worse in patients with preoperatively elevated and postoperatively normalized CEA compared to those with normal preoperative CEA. Patients with elevated preoperative CEA might require intensive follow‐up even if levels normalize after resection, especially in earlier periods, for early detection of recurrence., Recently, a large‐scale study on colon cancer revealed that “preoperatively elevated and postoperatively normalized CEA levels” is not an indicator of poor prognosis. In this study, we demonstrated that, in rectal cancer, “preoperatively elevated and postoperatively normalized CEA levels” is a definitive indicator of poor prognosis.

BACKGROUND Systemic inflammation contributes to the progression of malignancies. The preoperative lymphocyte-to-C-reactive protein ratio has recently been shown to predict survival of patients with colorectal cancer who undergo surgery, but its prognostic value remains unclear in patients with unresectable metastatic colorectal cancer. OBJECTIVE This study aimed to examine the prognostic values of inflammation-based prognostic scores in patients with metastatic colorectal cancer, focusing on the lymphocyte-to-C-reactive protein ratio. DESIGN This is a retrospective study from a prospectively collected database. SETTINGS This study was conducted at a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS The subjects were 756 consecutive patients with unresectable metastatic colorectal cancer who received systemic chemotherapy from 2000 to 2015. The prognostic value of the lymphocyte-to-C-reactive protein ratio was evaluated by univariable and multivariable analyses. Time-dependent receiver operating characteristics curve analysis was conducted to compare the prognostic impact of the lymphocyte-to-C-reactive protein ratio with the impact of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, or the modified Glasgow Prognostic Score. MAIN OUTCOME MEASURES The primary outcomes measured were the correlations of prognostic scores with overall survival. RESULTS Median survival times of patients with high, intermediate, and low lymphocyte-to-C-reactive protein ratios were 29.4, 19.3, and 13.1 months (p < 0.001). In all subgroups according to key prognostic factors (performance status, use of targeted agents, pretreatment CEA levels, tumor sidedness, M category, and primary tumor resection), patient prognosis could be clearly stratified into 3 groups by the lymphocyte-to-C-reactive protein ratio. Multivariable analysis revealed that decreased lymphocyte-to-C-reactive protein ratio was independently associated with reduced survival (low vs high: HR 1.96, p < 0.001; intermediate vs high: HR 1.44, p < 0.001). The time-dependent receiver operating characteristics curve analysis revealed that the lymphocyte-to-C-reactive protein ratio was the most sensitive predictor of survival among all inflammation-based prognostic scores on a continuous basis. LIMITATIONS This study was retrospective in nature. CONCLUSIONS The lymphocyte-to-C-reactive protein ratio is a useful prognostic biomarker for unresectable metastatic colorectal cancer and could contribute to accurate prognostication and therapeutic decision making. See Video Abstract at http://links.lww.com/DCR/B600. RELACIN ENTRE LINFOCITOS Y PROTENA C ES EL SCORE PRONOSTICO INFLAMATORIO MAS SENSIBLE EN PACIENTES CON CNCER COLORRECTAL METASTSICO IRRESECABLE ANTECEDENTES:La inflamacion sistemica contribuye en la progresion de neoplasias malignas. Recientemente se ha demostrado que la proporcion preoperatoria de linfocitos -proteina C reactiva predice la supervivencia de los pacientes con cancer colorrectal que se sometieron a cirugia, pero su valor pronostico sigue sin estar claro en pacientes con cancer colorrectal metastasico irresecable.OBJETIVO:Evaluar el valor pronostico de los scores inflamtorios centrandose en linfocito- proteina c reactiva en pacientes con cancer colorrectal metastasico.DISENO:Estudio retrospective evaluando una base de datos.AJUSTE:Este estudio se llevo a cabo en un centro oncologico terciario multidisciplinario de gran volumen en Japon.PACIENTES:Se incluyeron 756 pacientes consecutivos todos con cancer colorrectal metastasico irresecable que recibieron quimioterapia sistemica de 2000 a 2015. El valor pronostico de la proteina C reactiva se evaluo mediante analisis univariables y multivariables. Se realizo analisis de la curva de caracteristicas operativas del receptor dependiente del tiempo para comparar el impacto pronostico de la proteina linfocito-C-reactiva con el de la proporcion de neutrofilos a linfocitos, la proporcion de plaquetas a linfocitos, la proporcion de linfocitos a monocitos o la proporcion de puntuacion pronostica segun escala de Glasgow modificada.PRINCIPALES MEDIDAS DE RESULTADO:Correlacion de las puntuaciones pronosticas con la supervivencia global.RESULTADOS:La mediana de supervivencia de los pacientes con niveles altos, intermedios y bajos de proteina C reactiva de linfocitos fue de 29,4, 19,3 y 13,1 meses, respectivamente (p

BACKGROUND Whether prolonged survival with current chemotherapy using molecular target agents has changed the rate of primary tumor-related complications in patients with unresectable stage IV colorectal cancer is unclear. OBJECTIVE This study aimed to investigate the rate of primary tumor-related complications among patients receiving targeted therapy as compared with patients receiving chemotherapy without molecular target agents. DESIGN This was a retrospective review of data from a prospectively maintained database. SETTINGS The study was conducted at a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS Subjects were 352 consecutive patients with unresectable stage IV colorectal cancer who received systemic chemotherapy without primary tumor resection from 2001 to 2015. Patients were categorized into nontargeted and targeted groups according to the use of molecular target agents. MAIN OUTCOME MEASURES Complication rates attributed to primary tumors were measured. RESULTS Of the 352 patients, 159 were categorized into the nontargeted group and 193 patients into the targeted group. Competing risk-adjusted univariate analysis revealed that the primary tumor-related complication rates in the nontargeted group were 6.9% (95% CI, 3.8%-11.9%) at 1 year and 8.2% (95% CI, 4.8%-13.8%) at 2 years, whereas the targeted group had complication rates of 11.5% (95% CI, 7.5%-16.6%) at 1 year and 16.7% (95% CI, 12.4%-23.3%) at 2 years. Multivariate analysis revealed that the targeted group was ≈2 times more likely to have primary tumor-related complications (subdistribution HR = 2.04 (95% CI, 1.12-4.01); p = 0.020). Median survival time was 12.0 months in the nontargeted group and 24.1 months in the targeted group (p < 0.001). LIMITATIONS This study was limited by the retrospective design. CONCLUSIONS Targeted therapy was associated with a significantly increased risk of primary tumor-related complications during chemotherapy. However, targeted therapy also improved overall survival, making it a tolerable therapy. See Video Abstract at http://links.lww.com/DCR/B536. COMPLICACIONES PRIMARIAS RELACIONADAS CON EL TUMOR ENTRE PACIENTES CON CNCER COLORRECTAL EN ESTADIO IV IRRESECABLE EN LA ERA DE LA TERAPIA DIRIGIDA UN ANLISIS DE REGRESIN DEL RIESGO COMPETITIVO ANTECEDENTES:No esta claro si la supervivencia prolongada con la quimioterapia actual utilizando agentes moleculares dirigidos ha cambiado la tasa de complicaciones relacionadas con el tumor primario en pacientes con cancer colorrectal en estadio IV irresecable.OBJETIVO:Este estudio tuvo como objetivo investigar la tasa de complicaciones relacionadas con el tumor primario entre los pacientes que reciben terapia dirigida, en comparacion con pacientes que reciben quimioterapia sin agentes moleculares dirigidos.DISENO:Revision retrospectiva de datos de una base de datos mantenida prospectivamente.ESCENARIO CLINICO:Centro oncologico de tercer nivel multidisciplinario de alto volumen en Japon.PACIENTES:352 pacientes consecutivos con cancer colorrectal en estadio IV irresecable que recibieron quimioterapia sistemica sin reseccion del tumor primario entre 2001 y 2015. Los pacientes se clasificaron en grupos dirigidos y no dirigidos segun el uso de agentes moleculares dirigidos.PRINCIPALES MEDIDAS DE VALORACION:Tasas de complicaciones debidas a tumores primarios.RESULTADOS:De los 352 pacientes, 159 se clasificaron en el grupo no dirigido y 193 pacientes en el grupo dirigido. El analisis univariado ajustado al riesgo competitivo revelo que las tasas de complicaciones primarias relacionadas con el tumor en el grupo no dirigido fueron del 6,9% (intervalo de confianza (IC) del 95%, 3,8 - 11,9%) al ano y del 8,2% (IC del 95%, 4,8%). - 13,8%) a los dos anos, mientras que el grupo dirigido tuvo tasas de complicaciones del 11,5% (IC del 95%, 7,5 - 16,6%) al ano y del 16,7% (IC del 95%, 12,4 - 23,3%) a los dos anos. El analisis multivariado revelo que el grupo dirigido tenia aproximadamente dos veces mas probabilidades de tener complicaciones relacionadas con el tumor primario (razon de riesgo de subdistribucion, 2,04; IC del 95%, 1,12 a 4,01; p = 0,020). La mediana del tiempo de supervivencia fue de 12,0 meses en el grupo no dirigido y de 24,1 meses en el grupo dirigido (p

A 60-year-old Japanese woman was diagnosed with celiac disease (CeD) and treated with a gluten-free diet. For five years, she had a good clinical course. However, she complained of inappetence and nausea. Colonoscopy revealed ulcerative tumors in the terminal ileum. A histological examination of biopsy specimens from the ulcerative tumor showed diffuse infiltration of large atypical lymphocytes. Immunohistologically, the atypical lymphoid cells were positive for cluster of differentiation (CD) 10 and CD20. Many Epstein-Barr virus-encoded small RNA (EBER)-positive atypical lymphocytes were detected by in situ hybridization. This represents the first reported case of Epstein-Barr virus-positive intestinal diffuse large B-cell lymphoma complicated with CeD.

Background For brain metastases from non-specific primary tumors, the most frequently used and validated clinical prognostic assessment tool is Karnofsky performance status (KPS). Given the lack of prognostic factors of brain metastases from colorectal cancer (CRC) other than KPS, this study aimed to identify new prognostic factors. Methods This retrospective cohort study was conducted at a tertiary care cancer center. Subjects were patients with brain metastases from CRC among all patients who received initial treatment for CRC at the National Cancer Center Hospital from 1997 to 2015 (n = 7147). Prognostic clinicopathological variables for overall survival (OS) were investigated. Results There were 68 consecutive patients with brain metastases from CRC, corresponding to 1.0% of all patients with CRC during the study period. Median survival time was 6.8 months. One-year and 3-year OS rates were 28.0 and 10.1%, respectively. Among the six covariates tested (age, KPS, presence of extracranial metastases, control of primary lesion, number of brain metastases, and history of chemotherapy), multivariate analysis revealed KPS (score ≥ 70), number of brain metastases (1–3), and no history of chemotherapy to be independent factors associated with better prognosis. Conclusions In addition to KPS, the number of brain lesions and history of chemotherapy were independent prognostic factors for OS in patients with brain metastases from CRC. An awareness of these factors may help gastrointestinal surgeons make appropriate choices in the treatment of these patients.

In the current era of targeted therapies, the benefits of resection of primary tumors in patients with unresectable stage IV colorectal cancer, specifically with regard to overall survival, are unknown. Our study population comprised 208 consecutive patients with unresectable stage IV colorectal cancer who received chemotherapy containing at least one molecular target agent, bevacizumab, cetuximab, and panitumumab, at the National Cancer Center Hospital from 2006 to 2013. To lessen the effects of confounding factors between two treatment groups (resection versus non-resection) such as performance status, presence of severe symptoms, M subcategories (M1a versus M1b, M1c) according to the TNM classification, primary tumor site, and CEA value, we conducted three different propensity score analyses (regression adjustment, stratification, and matching). Of the 208 patients, 108 (52%) underwent resection of the primary tumor, while 100 (48%) did not. Regression adjustment revealed that resection was not associated with longer overall survival (hazard ratio of 0.70 (95% CI [0.49–1.00]; p = 0.051)). Stratification analysis of five strata revealed inconsistent results (hazard ratios ranged from 0.50 to 1.58); specifically, resection was associated with longer overall survival in four strata, but with shorter survival in one stratum. The propensity score-matched cohort (64 matched pairs) yielded a hazard ratio of 0.76 (95% CI [0.51–1.15]; p = 0.197). All three analyses revealed that, in the current era of chemotherapy with target agents, primary tumor resection was only marginally influential and did not significantly improve overall survival over chemotherapy alone.

Background. Helicobacter pylori (H. pylori) infection is an important risk factor for developing gastric cancer. However, even after H. pylori eradication, early gastric cancer (EGC) can develop. We elucidated the characteristics of EGCs diagnosed after H. pylori eradication. Methods. Thirty-six EGCs in 32 patients diagnosed after H. pylori eradication were defined as the eradication group (H. pylori-EG). The clinicopathological and endoscopic features were compared with those of 156 EGCs in 140 patients in the H. pylori-positive group (H. pylori-PG). Twenty-nine EGC lesions in the H. pylori-EG were further divided into two subgroups: the first included six lesions of none to mild atrophic mucosa around the EGC, and the second included 23 lesions of moderate to severe atrophic mucosa around the EGC. We compared them between the two subgroups. Results. Endoscopic features of EGCs in the H. pylori-EG were characterized as small (P = 0.049) and of the depressed type (P = 0.022) compared with those in the H. pylori-PG. EGCs in the H. pylori-EG were detected on the upper region of the stomach more frequently than those in the H. pylori-PG (P = 0.002). As for submucosal ECGs in the H. pylori-EG, it was more likely to be seen in the none to mild atrophic mucosa subgroup compared to the moderate to severe atrophic gastric mucosa subgroup (P = 0.003). Conclusions. EGCs after H. pylori eradication were characterized as small and of the depressed type. Submucosal invasive EGCs developed more frequently in the none to mild atrophic mucosa after H. pylori eradication. Therefore, careful patient follow-up is important after H. pylori eradication.

Background: Helicobacter pylori (H. pylori) infection is an important risk factor for developing gastric cancer. However, even after H. pylori eradication, early gastric cancer (EGC) can develop. We elucidated the characteristics of EGCs diagnosed after H. pylori eradication. Methods: Thirty-six EGCs in 32 patients diagnosed after H. pylori eradication were defined as the eradication group (H. pylori-EG). The clinicopathological and endoscopic features were compared with those of 156 EGCs in 140 patients in the H. pylori-positive group (H. pylori-PG). Twenty-nine EGC lesions in the H. pylori-EG were further divided into two subgroups: the first included six lesions of none to mild atrophic mucosa around the EGC, and the second included 23 lesions of moderate to severe atrophic mucosa around the EGC. We compared them between the two subgroups. Results: Endoscopic features of EGCs in the H. pylori-EG were characterized as small (P = 0.049) and of the depressed type (P = 0.022) compared with those in the H. pylori-PG. EGCs in the H. pylori-EG were detected on the upper region of the stomach more frequently than those in the H. pylori-PG (P = 0.002). As for submucosal ECGs in the H. pylori-EG, it was more likely to be seen in the mild atrophic mucosa subgroup (4/6, 67%) compared to the moderate to severe atrophic gastric mucosa subgroup (1/23, 4%) (P = 0.003).Conclusions: EGCs after H. pylori eradication were characterized as small and of the depressed type. Submucosal invasive EGCs developed more frequently in the none to mild atrophic mucosa after H. pylori eradication. Therefore, careful patient follow-up is important after H. pylori eradication.

Intussusception in adults is, especially with ulcerative colitis (UC), rare and only described in a few cases. Most adult patients with intussusception develop abdominal pain or other symptoms of bowel obstruction. This case describes an 18-year-old male with UC who treated with 5-aminosalycilicacid and underwent annual screening colonoscopies. Two attempts revealed that it was impossible to achieve total surveillance through the colonoscopy because multiple polyps were preventing the colonoscope from traversing the entire colon. Therefore, CT scan was performed and colonic intussusception was discovered incidentally, and the patient underwent elective laparoscopic total colectomy. To the best of our knowledge, this is the first reported case of asymptomatic intussusception in the adult patient with UC. When total surveillance colonoscopy fails to yield results, a CT may be advisable to pick up such an asymptomatic intussusception.

Background Inguinal lymph node metastasis from rectum is uncommon but well-known occurrence, whereas that from colon adenocarcinoma is extremely rare. Inguinal lymph node metastasis from colon adenocarcinoma has only been reported in previous cases involving primary tumor invasion of the abdominal wall, or in those involving colon cancer metastasis to external iliac lymph nodes. We describe a case of inguinal lymph node metastasis from colon cancer without primary tumor invasion to the abdominal wall. Case presentation A 42-year-old female, who had undergone twice cesarean sections before, underwent open sigmoidectomy for sigmoid colon adenocarcinoma and received 12 cycles of FOLFOX regimen as adjuvant chemotherapy. Two years after sigmoidectomy, a follow-up CT scan revealed enlarged inguinal lymph nodes as well as growth of enhanced mass lesions on the abdominal wall at site of the cesarean section scar. Biopsy of both lesions revealed well-differentiated adenocarcinoma, and immunohistochemistry demonstrated positive expression of CDX2, substantiating its gastrointestinal origin. We therefore performed dissection of left inguinal lymph nodes and mass lesion of the abdominal wall. The patient died 51 months after lymph node dissection. Conclusions This is the first reported case of inguinal lymph node metastasis from colon cancer without invasion of the primary tumor to the abdominal wall or without involvement of the external iliac lymph nodes, suggesting that the pathway of inguinal metastasis originated from the abdominal wall metastasis. When inguinal lymph node metastasis from colon cancer is suspected, if an R0 resection was possible, inguinal lymph node dissection may be a potentially effective treatment. Electronic supplementary material The online version of this article (10.1186/s12885-019-5386-x) contains supplementary material, which is available to authorized users.

The molecular mechanisms underlying the serrated pathway of colorectal tumourigenesis, particularly those related to traditional serrated adenomas (TSAs), are still poorly understood. In this study, we analysed genetic alterations in 188 colorectal polyps, including hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), TSAs, tubular adenomas, and tubulovillous adenomas by using targeted next-generation sequencing and reverse transcription-PCR. Our analyses showed that most TSAs (71%) contained genetic alterations in WNT pathway components. In particular, PTPRK-RSPO3 fusions (31%) and RNF43 mutations (24%) were frequently and almost exclusively observed in TSAs. Consistent with the WNT pathway activation, immunohistochemical analysis showed diffuse and focal nuclear accumulation of β-catenin in 53% and 30% of TSAs, respectively. APC mutations were observed in tubular and tubulovillous adenomas and in a subset of TSAs. BRAF mutations were exclusively and frequently encountered in serrated lesions. KRAS mutations were observed in all types of polyps, but were most commonly encountered in tubulovillous adenomas and TSAs. This study has demonstrated that TSAs frequently harbour genetic alterations that lead to WNT pathway activation, in addition to BRAF and KRAS mutations. In particular, PTPRK-RSPO3 fusions and RNF43 mutations were found to be characteristic genetic features of TSAs. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Background The 8th edition of the tumor-node-metastasis (TNM) classification classifies inguinal lymph nodes as regional lymph nodes for anal canal carcinoma but non-regional lymph nodes for rectal carcinoma. This difference might reflect the different prognosis of inguinal lymph node metastasis from anal canal carcinoma and rectal carcinoma. However, long-term outcomes of inguinal lymph node metastasis from rectal or anal canal adenocarcinoma are unclear, which we aimed to investigate in this study. Methods The study population included 31 consecutive patients with rectal or anal canal adenocarcinoma who underwent inguinal lymph node dissection with curative intent at the National Cancer Center Hospital from 1986 to 2017. Long-term outcomes were assessed and clinicopathologic variables analyzed for prognostic significance. Results Of the 31 patients, 12 patients had rectal adenocarcinoma and 19 patients had anal canal adenocarcinoma. Synchronous metastasis were observed in 14 patients and metachronous metastasis in 17 patients. After dissection of inguinal lymph node metastasis with curative intent, the 5-year overall survival rate was 55.2%, with 12 patients surviving for more than 5 years. Median survival time was 66.6 months. Multivariate analyses revealed that location of primary tumor (rectum versus anal canal) was not a prognostic factor, whereas lateral lymph node metastasis and histological findings were independent prognostic factors. Conclusion Given the good prognosis, inguinal lymph node metastasis in patients with rectal or anal canal adenocarcinoma appears to be regional rather than distant. If R0 resection can be achieved, inguinal lymph node dissection may be indicated for these patients.

When treated with molecular targeted agents, patients with unresectable colorectal cancer with right-sided tumors have poorer prognoses than those with left-sided tumors. While primary tumor sidedness may have prognostic value, the prognostic value of tumor sidedness in chemotherapy regimens without targeted therapy is unclear. Our study population comprised 678 consecutive patients with unresectable stage IV colorectal cancer who received systemic chemotherapy at the National Cancer Center Hospital in Japan from 1999 to 2015. Patients were stratified by treatment subgroup (with or without molecular targeted agents and with or without palliative primary tumor resection), and relationships between overall survival (OS) and primary tumor sidedness were evaluated. Multivariate analyses were also performed. Overall, 193 (28%) tumors were right-sided (cecum to transverse colon) and 485 (72%) were left-sided (splenic flexure to rectum). In the overall population, median survival time was 16.4 months for those with right-sided tumors and 23.4 months for those with left-sided tumors (p

Background The incidence of colorectal cancer in adolescent and young adult patients is increasing. However, survival and clinical features of young patients, especially those with stage IV disease, relative to adult patients remain unclear. Methods This retrospective single-institution cohort study was conducted at a tertiary care cancer center. Subjects were 861 consecutive patients who were diagnosed with stage IV colorectal cancer at the age of 15 to 74 years and who were referred to the division of surgery or gastrointestinal oncology at the National Cancer Center Hospital from 1999 to 2013. Overall survival (OS) was investigated and clinicopathological variables were analyzed for prognostic significance. Results Of these, 66 (8%) were adolescent and young adult patients and 795 (92%) were adult patients. Median survival time was 13.6 months in adolescent and young adult patients and 22.4 months in adult patients, and 5-year OS rates were 17.3% and 20.3%, respectively, indicating significant worse prognosis of adolescent and young adult patients (p = 0.042). However, age itself was not an independent factor associated with prognosis by multivariate analysis. When compared with adult patients, adolescent and young adult patients consisted of higher proportion of the patients who did not undergo resection of primary tumor, which was an independent factor associated with poor prognosis in multivariate analysis. In patients who did not undergo resection (n = 349), OS of adolescent and young adult patients were significantly worse (p = 0.033). Conclusions Prognoses were worse in adolescent and young adult patients with stage IV colorectal cancer compared to adult patients in Japan, due to a higher proportion of patients who did not undergo resection with more advanced and severe disease, but not due to age itself.

The National Comprehensive Cancer Network guidelines recommend R0 resection and targeted therapy, a combination of cytotoxic and molecular targeted agents, such as bevacizumab, cetuximab, and panitumumab, for colorectal cancer with synchronous peritoneal metastasis (M1c). While these therapeutic strategies are drawing attention, their efficacy has not been fully examined. The study population comprised 248 consecutive M1c patients who were treated at the National Cancer Center Hospital from 1997 to 2013. Multivariate analyses were performed to evaluate relationships between overall survival and R0 resection and targeted therapy using Cox proportional hazards regression models. The 3-year overall survival (3 yOS) was 19.5%, and median survival time (MST) was 16.2 months in 248 M1c patients. R0 resection was performed in 34 patients (14%), yielding a 3-year overall survival (OS) of 48.3% and median survival time (MST) of 29.9 months. Targeted therapy was performed in 54 patients (22%) at least once during the course of treatment, yielding a 3-yr OS of 38.2% and MST of 23.9 months. After adjusting for other key clinical factors, such as the number of organs involved with metastases, performance status, primary tumor site, and extent of peritoneal metastasis, both R0 resection and targeted therapy were independent factors associated with longer OS. Targeted therapy was associated with a significantly longer OS compared with multiple cytotoxic agent therapy [hazard ratio 0.65; 95% confidence interval (0.44–0.94); p = 0.02]. If achievable, R0 resection is a desirable therapeutic strategy for patients with M1c colorectal cancer. Moreover, targeted therapy might be the optimal chemotherapy in this patient population.

A novel conducting polymer, Poly(3-methoxythiophene-2,5-diyl-co-3,4-ethylenedioxythiophene-2,5-diyl]/tosylate (P1/tos), was synthesized by oxidative in situ polymerization using Fe(tos) 3 as an oxidant. Compared with poly(3,4-ethylenedioxythiophene) (PEDOT), P1 has a deeper HOMO level and a wider energy gap as observed by ultraviolet–visible spectroscopy and photoelectron yield spectroscopy. P1/tos showed electrical conductivity of 10 S/cm and a carrier mobility of about 0.6 cm 2 /(V s), which was extracted by using ion-gel thin film transistors. The calculated carrier concentration was on the order of 10 20 cm −3 , which is lower than that of PEDOT/tos. The Seebeck coefficient of P1/tos was higher than that of PEDOT/tos.

The molecular mechanisms underlying the serrated pathway of colorectal tumourigenesis, particularly those related to traditional serrated adenomas (TSAs), are still poorly understood. In this study, we analysed genetic alterations in 188 colorectal polyps, including hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), TSAs, tubular adenomas, and tubulovillous adenomas by using targeted next-generation sequencing and reverse transcription-PCR. Our analyses showed that most TSAs (71%) contained genetic alterations in WNT pathway components. In particular, PTPRK-RSPO3 fusions (31%) and RNF43 mutations (24%) were frequently and almost exclusively observed in TSAs. Consistent with the WNT pathway activation, immunohistochemical analysis showed diffuse and focal nuclear accumulation of β-catenin in 53% and 30% of TSAs, respectively. APC mutations were observed in tubular and tubulovillous adenomas and in a subset of TSAs. BRAF mutations were exclusively and frequently encountered in serrated lesions. KRAS mutations were observed in all types of polyps, but were most commonly encountered in tubulovillous adenomas and TSAs. This study has demonstrated that TSAs frequently harbour genetic alterations that lead to WNT pathway activation, in addition to BRAF and KRAS mutations. In particular, PTPRK-RSPO3 fusions and RNF43 mutations were found to be characteristic genetic features of TSAs. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John WileySons, Ltd.

The [Tp′Rh(PR3)] fragments, where Tp′ = tris(3,5-dimethylpyrazolyl)borate, R3 = Me3 (a) or PhMe2 (b), were shown to be applicable for the activation of the C−H and C−CN bonds of acetonitrile. The photoirradiation of Tp′Rh(PR3)H2 (1a,b) in acetonitrile at room temperature afforded the complexes Tp′Rh(PR3)(CH2CN)H (3a,b), by the selective oxidative addition of the primary C−H bond of acetonitrile to the [Tp′Rh(PR3)] fragment generated by the dehydrogenation of 1. The thermal reactions of Tp′Rh(PMe3)(Ph)H (2a) or Tp′Rh(κ2-C6H4-2-PMe2)H (2b) in acetonitrile at 80 °C also resulted in the formation of 3a and 3b, respectively, by the oxidative addition of the C−H bond to the [Tp′Rh(PR3)] fragment, generated by the reductive elimination of benzene (from 2a) or intramolecular reductive elimination of the PPhMe2 ligand (from 2b). Heating the isolated C−H bond activated complexes 3a,b in acetonitrile at higher temperature (100 °C) for longer times (≈5 days) resulted in the formation of the corresponding C−CN bond ac...

Overcrowded silanedichalcogenols Tbt(Mes)Si(EH)(E′H), such as silanedithiol (E = E′ = S), hydroxysilanethiol (E = O, E′ = S) and hydroxysilaneselenol (E = O, E′ = Se), bearing an efficient combination of steric protection groups, Tbt and Mes (Tbt = 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl, Mes = 2,4,6-trimethylphenyl), were synthesized and isolated as air- and moisture-stable crystals, and their structures were fully characterized by spectroscopic and elemental analyses together with X-ray crystallographic analyses. The results of IR spectroscopy and the X-ray structural analyses suggested that these compounds exist as monomers without any intra- and intermolecular interactions such as hydrogen bonds even in the solid state and in solution. Novel four-membered-ring compounds, such as Tbt(Mes)Si(μ-S) 2 PnBbt and [Tbt(Mes)Si(μ-E)(μ-E′)ML n ] [E, E′ = O, S, Se; Pn = Sb, Bi; Bbt = 2,6 - bis[bis(trimethylsilyl)methyl] - 4 - [tris(trimethylsilyl)methyl]phenyl; ML n = Pd(PPh 3 ) 2 , Pt(PPh 3 ) 2 , Ru(η 6 -benzene)] were synthesized by utilizing the silanedichalcogenols as key building blocks. The molecular structures of these newly isolated compounds were determined by NMR spectroscopic data together with X-ray crystallographic analyses.

In this paper, we report the synthesis and the structural characterization of stable examples of silanedithiol [Tbt(Mes)Si(SH)2 (1)], hydroxysilanethiol [Tbt(Mes)Si(OH)(SH) (3)], and hydroxysilaneselenol [Tbt(Mes)Si(OH)(SeH) (7)], which are kinetically stabilized by an effective combination of steric protection groups, Tbt (2,4,6-tris[bis(trimethylsilyl)methyl]phenyl) and Mes (2,4,6-trimethylphenyl). Silanedichalcogenols 1, 3, and 7 are suggested to exist as a monomer without any intermolecular contact such as hydrogen bonds both in the solid state and in solution as judged by X-ray structural analysis and IR spectroscopy. Treatment of 1 with 2 equiv. of butyllithium resulted in the quantitative formation of the corresponding dilithium silanedithiolate, Tbt(Mes)Si(SLi)2 (8), the generation of which was confirmed by a trapping experiment using MeI. Furthermore, the addition of cis-[MCl2(PPh3)2] (M = Pd, Pt) to a THF solution of 8 afforded the corresponding silanedithiolato complexes, [Tbt(Mes)Si(μ-S)2M(PPh3)2] (9a: M = Pd; 9b: M = Pt), respectively. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Novel silacyclic compounds containing a titanium and some chalcogen atoms, [Tbt(Mes)Si(μ-Ch)2TiCp2] and [Tbt(Mes)Si(μ-Ch)(μ-Ch2)TiCp2] (Ch = S and Se; Tbt = 2,4,6-tris[bis(trimethylsilyl)methyl]phe...

Platinum siloxides bridged by a sulfur or selenium atom, [Tbt(Mes)Si(μ-O)(μ-E)Pt(PPh3)2] (1a: E = S, 1b: E = Se), were synthesized by utilizing hydroxysilanechalcogenols, Tbt(Mes)Si(OH)(EH) (2a: E ...

Se -Arylmethyl selenoformates were synthesized by the reaction of aluminum arylmethaneselenolates with formates. Se -Benzyl selenoformate is an unstable compound, but steric protection by some bulky substituents enabled the stable isolation of the selenoformates. To the best of our knowledge, this is the first example of the synthesis of Se -alkyl selenoformates.

A series of complexes of the type Tp'Rh(PR(3))(Ar(F))H, where PR(3) = PMe(3) (3) and PMe(2)Ph (9), Ar(F) = C(6)F(5) (a), 2,3,4,5-C(6)F(4)H (b), 2,3,5,6-C(6)F(4)H (c), 2,4,6-C(6)F(3)H(2) (d), 2,3-C(6)F(2)H(3) (e), 2,5-C(6)F(2)H(3) (g), and 2-C(6)FH(4) (h) and Tp' = tris(3,5-dimethylpyrazolyl)borate, has been synthesized as stable crystalline compounds by the reactions of the [Tp'Rh(PR(3))] fragment with the corresponding fluorinated aromatic hydrocarbons, and their structures were characterized by NMR spectroscopy and elemental analysis together with X-ray crystallography. The kinetics of the reductive eliminations of fluoroarenes from complexes 3a-h in benzene-d(6) solutions at 140 °C were investigated, but were complicated by the formation of the rhodium(I) bisphosphine complex, Tp'Rh(PMe(3))(2) (4). On the other hand, thermal reactions of (9) in THF-d(8) solutions at 120 °C resulted in the formation of an intramolecular C-H bond activated complex of the phenyl group on the phosphorus atom, Tp'Rh(κ(2)-C(6)H(4)-2-PMe(2))H (7), which prevents the formation of the corresponding bisphosphine complex. The experimentally determined rates of the reductive eliminations of fluoroarenes from the complexes 9a-h and their kinetic selectivities for formation in competition with the metallacycle have been used to determine relative Rh-CAr(F) bond energies. The Rh-CAr(F) bond energy is found to be dependent on the number of ortho fluorines. A plot of Rh-CAr(F) vs. C-H bond strengths resulted in a line with a slope R(M-C/C-H) of 2.15 that closely matches the DFT calculated value (slope = 2.05).