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JCOG-CCSG has been conducting several surgical trials and experienced several challenges. The first point is the appropriate timing of conducting the trial. Once a certain number of surgeons acquire the new technique and its utility is accepted, it suddenly becomes difficult to maintain ‘equipoise’ between the standard and new treatment, which may lead to poor patient accrual. Smooth preparation and commencement of the trial at an appropriate timing is necessary for its success. Second is the appropriate quality assurance of surgery. High-level quality assurance will strengthen the comparability of randomized control trials and minimize the heterogeneity among hospitals. On the other hand, it may impair the generalizability of the trial. Large observational studies help to bridge the gap of heterogeneity among hospitals. Third is the selection of an appropriate endpoint. Overall survival (OS) is the gold-standard primary endpoint; however, the number of events is much less due to more effective treatment. JCOG0212 and JCOG0404 were unable to demonstrate the non-inferiority of omission of lateral lymph node dissection and laparoscopic surgery partly due to a lack of power. Disease-free survival (DFS) is also a promising candidate for primary endpoint, but as in JCOG0603, special attention must be paid when DFS does not correlate with OS. Although careful discussion is required because the precision of the hazard ratio depends on the number of events, an alternative population-level summary of variables, including restricted mean survival time, can be considered as the primary endpoint. Future surgical trials should be planned considering these points.

Dysphonia has been reported with anti-angiogenic chemotherapy agents. Dysphonia in patients with cancer receiving chemotherapy tends to be overlooked in clinical practice since it is non-life-threatening. However, it reduces quality of life. Although inhibition of vascular endothelial growth factor receptor is the reported mechanism of dysphonia, it has not been elucidated. We report 6 cases of patients with dysphonia suspected to be due to panitumumab and nivolumab that have not been reported previously. Peripheral edema, a factor in dysphonia, can be seen with aflibercept, bevacizumab, panitumumab, and nivolumab. Therefore, chemotherapy drugs with peripheral edema may be related to dysphonia.

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 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.

Introduction Currently, laparoscopic surgery generally relies on 2 K high-definition image quality. The National Cancer Center Hospital, Olympus Corporation, and NHK Engineering System Inc. recently developed a new laparoscopic system with an 8 K ultra-high-definition (UHD) camera that provides images with a high-resolution, wide color range, high frame rate, and high dynamic range. This study aimed to investigate the effectiveness and safety of a new laparoscopic system which uses an 8 K UHD camera system (8K UHD system). Methods This phase II study enrolled 23 patients with colon or rectosigmoid cancer who were indicated for radical resection with laparoscopic colectomy using the 8 K UHD system. The primary endpoint was the proportion of patients with ≥30 mL of intraoperative blood loss. Results Of the 23 patients, 22 completed laparoscopic surgery with the 8 K UHD system. One patient was converted to the 2 K high-definition laparoscopic system due to technical difficulties with the 8 K UHD system during surgery. The median amount of intraoperative blood loss was 14 mL (range, 2-71 mL), and number of patients with intraoperative blood loss ≥30 mL was four (17.4%). None of the patients had >100 mL of intraoperative blood loss. No intraoperative complications were noted, and four (17.4%) patients developed postoperative complications. Pathological complete resection was achieved in all patients, and no conversion to open surgery was required. Conclusions Laparoscopic surgery using the 8 K UHD system appears to be both safe and effective. However, further refinements may be necessary to improve usability.

Backgrounds Clinical evidence of the preventive effectiveness of medium-class topical corticosteroids for capecitabine-induced hand foot syndrome (HFS) is limited. Although the pathogenesis and mechanism of HFS are unclear, inflammatory reactions are thought to be involved in HFS development. This study aimed to evaluate the preventive effect of medium-class topical corticosteroids (hydrocortisone butyrate 0.1% topical therapy) for capecitabine-induced HFS in patients with colorectal cancer receiving adjuvant chemotherapy with capecitabine plus oxaliplatin. Methods This is a single-center, single-arm, phase 2 study. Patients with colorectal cancer scheduled to receive adjuvant chemotherapy with capecitabine plus oxaliplatin are enrolled, and topical hydrocortisone butyrate 0.1% is applied prophylactically in addition to standard moisturizing therapy. The primary endpoint is the incidence of grade ≥ 2 HFS within three months. The secondary endpoints are the time to onset of HFS, rates of dose reduction, schedule delay, discontinuation caused by capecitabine-induced HFS, and other adverse events. All adverse events are evaluated by clinical pharmacists and attending physicians. Discussion This study is expected to contribute to the establishment of new supportive care for preventing HFS, not only for colorectal cancer patients receiving adjuvant chemotherapy, but also for various cancer patients receiving capecitabine-based chemotherapy. Trial registration: This trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCTs031220002. Registered 5 April 2022, https://jrct.niph.go.jp/search Protocol version V.1.0, 16 February 2022.

BACKGROUND In Japan, total mesorectal excision plus lateral lymph node dissection without preoperative therapy is the standard treatment for advanced lower rectal cancer. Although long-term oncologic outcomes with preoperative therapy based on circumferential resection margin status in preoperative MRI has been reported, outcomes without preoperative therapy are unknown. OBJECTIVE This study evaluated long-term oncologic outcomes of radical surgery without preoperative therapy in advanced lower rectal cancer based on circumferential resection margin status in preoperative MRI, with the aim of defining appropriate patient populations for preoperative therapy. DESIGN This retrospective analysis compared long-term oncologic outcomes with preoperative MRI in patients with lower rectal cancer. SETTINGS Patients were identified through a database managed by our institute. PATIENTS In total, 338 patients with lower rectal cancer who underwent radical surgery between 2000 and 2014 at the National Cancer Center Hospital without preoperative therapy were included. MAIN OUTCOME MEASURES The main outcome was relapse-free survival. RESULTS The median follow-up period was 61.7 months (range, 3-153 months). Five-year relapse-free survival rates in MRI-predicted circumferential resection margin negative patients and positive patients were 76.0% and 55.6% (p < 0.001). Univariate and multivariate analyses revealed pN stage (HR, 2.35; 95% CI, 1.470-3.770; p < 0.001), lymphatic invasion (HR, 2.03; 95% CI, 1.302-3.176; p = 0.002), venous invasion (HR, 2.15; 95% CI, 1.184-3.9; p = 0.01), surgical procedure (HR, 1.72; 95% CI, 1.115-2.665; p = 0.01), and MRI-predicted circumferential resection margin (HR, 1.850; 95% CI, 1.206-2.838; p = 0.0051) to be independent risk factors for postoperative recurrence. LIMITATIONS This study was retrospective in design. CONCLUSIONS Magnetic resonance imaging-predicted circumferential resection margin was associated with relapse-free survival without preoperative therapy, indicating its potential for use in selecting optimal preoperative therapy. See Video Abstract at http://links.lww.com/DCR/B335. ESTADO DEL MARGEN DE RESECCION CIRCUNFERENCIAL COMO FACTOR PREDICTIVO DE RECURRENCIA EN LA RESONANCIA MAGNETICA PREOPERATORIA, PARA EL CANCER RECTAL BAJO AVANZADO SIN TERAPIA PREOPERATORIA: En Japon, la escision mesorrectal total con diseccion de ganglios linfaticos laterales y sin terapia preoperatoria, es el tratamiento estandar para el cancer rectal bajo avanzado. Aunque se han reportado resultados oncologicos a largo plazo con terapia preoperatoria, basada en el estado del margen de reseccion circunferencial en la resonancia magnetica preoperatoria, se desconocen los resultados sin terapia preoperatoria.Este estudio evaluo los resultados oncologicos a largo plazo de cirugia radical sin terapia preoperatoria, en cancer rectal bajo avanzado, basado en el estado del margen de reseccion circunferencial en la resonancia magnetica preoperatoria, con el objetivo de definir poblaciones de pacientes apropiadas para terapia preoperatoria.Este analisis retrospectivo comparo los resultados oncologicos a largo plazo con resonancia magnetica preoperatoria, en pacientes con cancer rectal bajo.Los pacientes fueron identificados a traves de una base de datos administrada por nuestro instituto.Se incluyeron un total de 338 pacientes con cancer rectal bajo, que se sometieron a cirugia radical entre 2000 y 2014 en el Hospital Nacional del Centro de Cancer, sin terapia preoperatoria.El resultado principal fue la supervivencia libre de recaidas.La mediana del periodo de seguimiento fue de 61,7 meses (rango, 3-153 meses). Las tasas de supervivencia sin recaidas a cinco anos, con margen de reseccion circunferencial predicho por resonancia magnetica, en pacientes negativos y pacientes positivos fueron 76.0% y 55.6% (p

Background Recent evidence suggests that both preoperative and postoperative inflammation-based prognostic markers are useful for predicting the survival of colorectal cancer (CRC) patients. However, associations between longitudinal changes in inflammation-based prognostic markers and prognosis are controversial. Methods The subjects of this study were 568 patients with stage III CRC between 2008 and 2014. Preoperative and postoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein/albumin ratio (CAR) and lymphocyte-to-C-reactive protein ratio (LCR) were calculated to assess the inflammatory state of subjects. Subjects were stratified into three groups for each marker: preoperatively low inflammatory state (normal group), preoperatively high but postoperatively low inflammatory state (normalised group) and persistently high inflammatory state (elevated group). Multivariable analyses for overall survival (OS) and recurrence-free survival (RFS) were performed to adjust for well-established clinicopathologic factors. Results For all assessed markers, the normalised group had a significantly better prognosis than the elevated group and a similar prognosis as the normal group for both OS and RFS. Conclusions Postoperative, but not preoperative, inflammation-based prognostic markers more accurately predict OS and RFS in patients with stage III CRC.

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

OBJECTIVE This study aimed to investigate transitions of recurrence hazard and peak recurrence time in patients with nonmetastatic CRC using the hazard function. SUMMARY OF BACKGROUND DATA A postoperative surveillance period of 5 years is consistent across major guidelines for patients with nonmetastatic CRC, but surveillance intervals differ. Estimates of instantaneous conditional recurrence rate can help set appropriate intervals. METHODS The study population consisted of 4330 patients with stage I to III CRC who underwent curative resection at the National Cancer Center Hospital between January 2000 and December 2013. Hazard rates of recurrence were calculated using the hazard function. RESULTS Recurrence rates in patients with stage I, II, and III CRC were 4% (50/1432), 11% (136/1231), and 25% (424/1667), respectively. The hazard curve for stage I was relatively flat and hazard rates were consistently low (

Diagnosis of secondary ovarian tumors originating from colorectal cancer has previously been based upon history of malignancy and radiological findings of bilateral masses with a “stained glass appearance.” The purpose of this study was to perform a detailed investigation of the radiological and macroscopic features of ovarian metastases originating from colorectal cancer, which remain to be fully characterized. Study participants were 48 consecutive patients with ovarian metastases from colorectal cancer who underwent resection of ovarian tumors at the National Cancer Center Hospital between August 1998 and January 2019. Ovarian tumors were classified into subgroups using computed tomography (CT), magnetic resonance imaging (MRI), and macroscopic appearance. CT/MRI findings and macroscopic appearance were classified into the following four types: type 1 (oval, homogeneous-solid) (n = 5); type 2 (heterogeneous-solid, small in size with multinodular surface) (n = 3); type 3 (solid-cystic, predominantly solid) (n = 18); and type 4 (cystic-solid, multilocular with solid components) (n = 22). Type 1 mimics Krukenberg tumors, type 2 mimics ovarian metastases from breast cancer, type 3 mimics primary ovarian endometrioid cancer, and type 4 mimics primary ovarian mucinous cancer, with a “stained glass appearance”. Twenty-eight (58%) patients had bilateral metastases. Eleven patients (23%) underwent hysterectomy and/or pelvic lymph node dissection in addition to ovarian resection. We introduced a novel classification system for ovarian metastases originating from colorectal cancer, which may be beneficial for assessing ovarian metastases from colorectal cancer and avoiding unnecessary surgery due to misdiagnosis of primary ovarian tumors.

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 (

Pancytopenia associated with vitamin B12 and folic acid deficiency has been reported in patients who have undergone total gastrectomy. Therefore, myelosuppression due to chemotherapy following total gastrectomy is considered to be more serious. We encountered three cases of severe thrombocytopenia in patients who received chemotherapy after total gastrectomy. The lowest platelet levels in these patients were 1.7 × 104/mm3, 2.3 × 104/mm3, and 0.9 × 104/mm3, respectively. None of the patients presented with vitamin B12 deficiency, and one patient presented with folic acid deficiency. The association between serum vitamin levels and chemotherapy-related adverse events is controversial. Since folic acid has a shorter half-life (6 hours) and cannot accumulate in the body, unlike vitamin B12 that is stored for a long time in the liver, folic acid deficiency is suspected to be associated with thrombocytopenia induced by post-total gastrectomy chemotherapy. However, serum folic acid levels fluctuate depending on the timing of evaluation and require a few days to evaluate. In conclusion, patients who undergo chemotherapy after total gastrectomy should be monitored for severe thrombocytopenia but serum vitamin B12 levels are not necessarily clinically important. By measuring serum folic acid levels at appropriate times, folic acid deficiency may prove to be a reference for predicting severe thrombocytopenia.

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

Japanese Society for Cancer of the Colon and Rectum guidelines recommend regular, more intensive surveillance of patients who have undergone curative resection of pathological stages I–III colorectal cancer compared with guidelines in Western countries. We conducted a questionnaire survey to clarify the status of surveillance for patients with stage I or II colorectal cancer in high-volume centers in Japan on behalf of the Colorectal Cancer Study Group of the Japan Clinical Oncology Group. Questionnaires were distributed in September 2019. The response rate was 98.3% (59/60 institutions). The survey results indicated that about half of colorectal cancer specialists in Japan perform surveillance for stages I and II colorectal cancer according to the Japanese Society for Cancer of the Colon and Rectum guidelines. For stages I and II disease, 45% and 55% of surgeons, respectively, perform surveillance less intensively than recommended. Our findings suggest the possibility of less intensive surveillance for patients with stage I or II colorectal cancer in Japan.

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

It is controversial whether chemotherapy with or without primary tumour resection is effective for the patients with incurable Stage IV colorectal cancer. A randomized controlled trial, initiated in Japan in 2012, is being conducted to evaluate the survival benefit and safety of primary tumour resection plus chemotherapy compared with chemotherapy alone in asymptomatic Stage IV colorectal cancer patients with unresectable metastatic disease. Patients are randomly assigned to either chemotherapy alone or primary tumour resection followed by chemotherapy. The primary endpoint is overall survival. Secondary endpoints are progression-free survival, incidence of adverse events, proportion of patients with R0 resection and proportion of palliative surgery for the chemotherapy-alone group. This trial was registered in June 2012 with the UMIN Clinical Trials Registry as UMIN000008147 [http://www.umin.ac.jp/ctr/index-j.htm]. In December 2017, the study protocol was amended for reducing sample size. A total of 280 patients will be enrolled over the course of 8.5 years., This study is a randomized controlled trial to evaluate the survival benefit of primary tumour resection in asymptomatic patients with incurable Stage IV colorectal cancer.

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.

In Japan, R0 resection has been recommended for colorectal cancer patients with peritoneal metastases confined to the adjacent peritoneum and those with a few metastases to the distant peritoneum. R0 resection for M1c disease has drawn attention in Western countries and is currently considered an acceptable therapeutic option in the US National Comprehensive Cancer Network guidelines. However, clinical factors that affect the choice of R0 resection are unknown. This multicenter, prospective, observational study was conducted by the Japanese Society for Cancer of the Colon and Rectum. Colorectal cancer patients with synchronous peritoneal metastases were enrolled at 28 institutions in Japan from October 2012 to December 2016. To determine factors affecting R0 resection and R1 resection with intended R0 resection, stepwise logistic regression analyses were performed on clinical factors including age, sex, performance status (PS), body mass index, peritoneal cancer index (PCI) score, presence of ascites, presence of distant metastases, and primary tumor site. R0/R1 resection was performed in 36 (31/5; 25%) of 146 patients. No distant metastases [odds ratio (OR) 52.9; 95% confidence interval (CI) 13.3–210.1; p

Adjuvant chemotherapy is the current standard treatment for stage III colorectal cancer after curative resection. However, the prognosis of stage III colorectal cancer is still poor even after curative resection and adjuvant chemotherapy. Several observational studies suggested that the anti-tumor effect of aspirin. Therefore, we planned a randomized double-blind placebo-controlled phase III trial, which commenced in Japan in March 2018, to confirm the superiority of aspirin over placebo added to adjuvant chemotherapy in terms of disease-free survival (DFS) for stage III colorectal cancer patients after curative resection. A total of 880 patients will be accrued from 20 Japanese institutions within 3 years. The primary endpoint is DFS and the secondary endpoints are overall survival, relapse-free survival, relative dose intensity, adverse events, and serious adverse events. This trial has been registered at Japan Registry of Clinical Trials as jRCTs031180009 (https://jrct.niph.go.jp/detail/589).

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.

Background The giant multilocular prostatic cystadenoma is a very rare benign tumor of the prostate gland. It is composed of predominantly cystic enlarged prostatic glands in a fibrous stroma and spreads extensively into the pelvis. Because of the large size at the time of diagnosis, it is not always possible to determine the exact point of origin for these multilocular cystic neoplasms. Thus, diagnosis before histological examination of a surgical specimen is often difficult. Here, we present a case involving one of the largest giant multilocular prostatic cystadenomas reported in the literature and discuss preoperative diagnoses and appropriate surgical approaches for this rare retroperitoneal tumor. Case presentation A 50-year-old man presented with a 2-year history of abdominal distension and lower urinary symptoms. Enhanced CT showed a large retroperitoneal mass with multiple septations in the pelvis and lower abdomen, measuring 30 cm in size, surrounding the rectum and displacing the bladder, prostate, and seminal vesicle to the right anterior side. MRI showed multiple cysts with a simple fluid appearance on T2-weighted images and enhanced solid components on gadolinium-enhanced fat-saturated T1-weighted images, suggesting the retroperitoneal mass as leiomyoma with cystic degeneration or perivascular epithelioid cell tumor. Biopsy of the mass showed a spindle cell tumor with focal smooth muscle differentiation. Differential diagnosis comprising leiomyoma, low-grade leiomyosarcoma, and perivascular epithelioid cell tumor was made. Complete resection of the tumor with low anterior resection of the rectum was performed. The tumor was solid with multilocular cavities containing blackish-brown fluid and measured 33 × 23 × 10 cm. Histologically, the tumor was composed of variously sized dilated glandular structures lined by prostatic epithelia surrounded by fibromuscular stroma. The prostatic nature of the lesions was confirmed by immunohistochemical staining of the epithelium for prostate-specific antigen. Thus, pathological diagnosis was a giant multilocular prostatic cystadenoma. Conclusions We present our experiences with one of the largest giant multilocular prostatic cystadenomas. When a retroperitoneal huge lesion with locular cavities fills the pelvis in a male patient, the possibility of giant multilocular prostatic cystadenoma should be considered before planning for retroperitoneal tumor treatment.

Preoperative T staging of colon cancer, in particular, for distinguishing T3 from T2 and T4, has been a challenge. The aim of this study was to evaluate newly developed criteria for preoperative T staging of colorectal cancer using computed tomography colonography (CTC) with multiplanar reconstruction (MPR), based on the spatial relationship of tumors and “bordering vessels,” that is, marginal vessels that are detectable by multi-detector row CT with MPR. A total of 172 patients with colon and upper rectal cancer who underwent preoperative CTC and surgery between August 2011 and September 2013 were included. Preoperative T staging using the new criteria was performed prospectively and compared with pathologic results. Sensitivity, specificity, and accuracy of T staging by CTC using the new criteria were 63%, 80%, and 77% for T2 (n = 30); 72%, 94%, and 81% for T3 (n = 95); and 79%, 99%, and 97% for T4a (n = 14), respectively. Positive predictive value for T3 was 93%, indicating that a T3 diagnosis by CTC is precise. In addition, negative predictive value for pathological T4a was 98%, indicating that a “not T4a” diagnosis by CTC is also precise. Our newly developed criteria are useful for preoperative T staging, particularly for distinguishing T3 from T2 and T4.

BACKGROUND In the TNM eighth edition, nutritional status and inflammatory scores are newly described as host-related prognostic factors for esophageal cancer, hepatocellular carcinoma, and pancreatic cancer. However, only age and race are listed as host-related prognostic factors for colorectal cancer. OBJECTIVE The purpose of this study was to evaluate the prognostic significance of nutritional and inflammatory scores for postoperative outcomes in patients with colorectal cancer. DESIGN This was a retrospective study using a database that prospectively collects data. SETTINGS The study was conducted at a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS Study participants were 1880 consecutive patients with stage II to III colorectal cancer who underwent curative resection at the National Cancer Center Hospital between 2004 and 2012. Two nutritional scores (prognostic nutritional index and controlling nutritional status score) and 4 inflammatory scores (modified Glasgow prognostic score, neutrophil:lymphocyte ratio, platelet:lymphocyte ratio, and C-reactive protein:albumin ratio) were calculated. MAIN OUTCOME MEASURES Correlations of nutritional scores and inflammatory scores with overall survival and postoperative complications were measured. RESULTS After adjusting for key clinical and pathologic factors by multivariable analysis, 2 nutritional scores (prognostic nutritional index and controlling nutritional status score) and 2 inflammatory scores (neutrophil:lymphocyte ratio and C-reactive protein:albumin ratio) were independent prognostic factors for overall survival. With respect to discriminative ability, time-dependent receiver operating characteristic curves and Harrell concordance index revealed that prognostic nutritional index and controlling nutritional status score were superior to the 4 inflammatory scores for predicting overall survival. Multivariable logistic regression analyses also revealed that prognostic nutritional index, controlling nutritional status score, and C-reactive protein:albumin ratio were independent predictors for postoperative complications. LIMITATIONS The retrospective design of the study was a limitation. CONCLUSIONS Preoperative nutritional scores are promising host-related prognostic factors for overall survival and postoperative complications in patients with stage II and III colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B587. EVALUACIN DE SCORE NUTRICIONALES PREOPERATORIOS COMO FACTORES PRONSTICOS PARA SOBREVIDA Y COMPLICACIONES POSTOPERATORIAS EN PACIENTES CON CANCER COLORECTAL ETAPA II Y III ANTECEDENTES:En las ultimas etapificaciones T-N-M, tanto el estado nutricional como inflamatorio han sido descritos como factores pronosticos en cancer de esofago, hepatico y pancreatico. Sin embargo en cancer colorectal solo la edad y la raza son enumerados como factores pronosticos.OBJETIVO:Evaluar la importancia pronostica de los scores nutricionales e inflamatorias para los resultados posoperatorios en pacientes con cancer colorrectal.DISENO:Estudio retrospectivo utilizando una base de datos.AJUSTE:Centro oncologico teciario en Japon.PACIENTES:Fueron incluidos en el estudio 1880 pacientes, consecutivos, con cancer colorectal etapa II y III sometidos a reseecion curativa en el National Cancer Center Hospital entre 2004 y 2012. Se aplicaron dos scores: nutricional (indice nutricional pronostico y puntuacion del estado nutricional) e inflamatorias (Glasgow modificada, proporcion de neutrofilos a linfocitos, de plaquetas a linfocitos y de proteina C reactiva a albumina).PRINCIPALES MEDIDAS DE RESULTADO:Evaluar scores nutricional e inflamatorio con sobrevida y complicaciones postoperatoria.RESULTADOS:Despues de ajustar los factores clinicos y patologicos clave mediante analisis multivariable, dos scores nutricionales (indice nutricional pronostico y puntuacion del estado nutricional de control) y dos inflamatorias (proporcion de neutrofilos a linfocitos y proporcion de proteina C reactiva a albumina) fueron pronosticos independientes factores para la sobrevida. Con respecto a la capacidad discriminativa, las curvas de caracteristicas operativas del receptor, dependientes del tiempo y el indice de concordancia de Harrell, revelaron que el indice nutricional pronostico y del estado nutricional de control eran superiores a las cuatro inflamatorias para predecir la sobrevida general. Los analisis de regresion logistica multivariable tambien revelaron que el indice nutricional pronostico, el estado nutricional de control y la relacion proteina C reactiva / albumina fueron predictores independientes de complicaciones postoperatorias.LIMITACIONES:Estudio de tipo retrospectivo.CONCLUSIONES:Los scores nutricionales preoperatorias son factores pronosticos prometedores relacionados con la sobrevida y las complicaciones postoperatorias en pacientes con cancer colorrectal en estadio II y III. Consulte Video Resumen en http://links.lww.com/DCR/B587.

Introduction Patients with high-risk T1 colorectal cancer (CRC) after endoscopic resection (ER) should undergo surgery in view of the risk of lymph node metastasis. Although additional surgery can potentially prevent recurrence, there is a paucity of data and longitudinal studies exploring this potential. Hence, this study aimed to evaluate the prolonged influence of ER before additional surgery on recurrence in T1 CRC. Methods Between January 2004 and October 2015, 162 patients who underwent secondary surgery (SS) after ER ([ER + SS] group) and 392 consecutive patients with T1 CRC who underwent primary surgery at our institution were retrospectively analyzed. Recurrence was analyzed in these 2 groups. High-risk CRC patients were histologically defined according to the Japanese Society for Cancer of the Colon and Rectum guidelines (2016) for the treatment of CRC. Data were analyzed based on clinical and histological features, including lymph node metastasis, and the number of lymph nodes evaluated. Results The recurrence rate was comparable between the ER + SS and primary surgery groups, with no significant difference (P = 0.625, log-rank test). There was no significant difference in the recurrence in patients receiving adjuvant chemotherapy in both groups (7.4% vs 10.4%, P = 0.27). The difference in the mean number of lymph nodes dissected between both groups was also not significant (24.3 vs 25.3, P = 0.43). Discussion There was no significant difference in recurrence rates between patients undergoing ER before surgery and those undergoing primary surgery for high-risk T1 CRC. Hence, ER may be acceptable for high-risk T1 CRC.

Background This study aimed to evaluate the prognostic impact of nutritional and inflammatory measures (controlling nutritional status (CONUT) score, prognostic nutritional index (PNI), and modified Glasgow prognostic score (mGPS)) on overall survival (OS) in patients with stage IV colorectal cancer (CRC). Methods Subjects were 996 patients with stage IV CRC who were referred to the National Cancer Center Hospital between 2001 and 2015. We retrospectively investigated correlations between OS and CONUT score, PNI, and mGPS. Multivariate analyses were performed using Cox proportional hazards regression models. Results After adjusting for known factors (age, gender, BMI, ECOG performance status, location of primary tumor, CEA levels, histological type, M category, and prior surgical treatment), all three measures were found to be independent prognostic factors for OS in patients with stage (CONUT score, p p p n = 614; 61%) and intermediate CONUT score (2/3) (n = 276; 28%) (hazard ratio (HR) = 1.20, 95% confidence interval (CI): 1.02–1.42, p = 0.032), and intermediate CONUT score and high CONUT score (≥4) (n = 106; 11%) (HR = 1.30, 95% CI: 1.01–1.67, p = 0.045). Significant differences in OS were found between mGPS = 0 (n = 633; 64%) and mGPS = 1 (n = 234; 23%) (HR = 1.84, 95% CI: 1.54–2.19, p n = 129; 13%) (HR = 1.12, 95% CI: 0.88–1.41, p = 0.349). Patients with low PNI (n = 443; 44%) showed a significantly lower OS rate than those with high PNI (≥48.0) (n = 553; 56%) (HR = 1.39, 95% CI: 1.19–1.62, p Conclusions CONUT score, PNI, and mGPS were found to be independent prognostic factors for OS in patients with stage IV CRC, suggesting that nutritional and inflammatory status is a useful host-related prognostic indicator in stage IV CRC.

Immunotherapy, especially immune checkpoint inhibitors, has revolutionized the standard-of-care of multiple types of tumors. For colorectal cancer, the clinical development of immune checkpoint inhibitors is mainly separated according to the status of microsatellite instability or mismatch repair in a tumor. High-level microsatellite instability/deficient mismatch repair metastatic colorectal cancer generally has a tumor microenvironment with infiltration of T cells, associated with a favorable response to immune checkpoint inhibitors. Immune checkpoint inhibitors, including pembrolizumab (anti-PD-1 inhibitor) and nivolumab (anti-PD-1 inhibitor) with or without ipilimumab (anti-CTLA-4 inhibitor), have been integrated into the standard-of-care for high-level microsatellite instability/deficient mismatch repair metastatic colorectal cancer. Conversely, limited T-cell infiltration in the tumor microenvironment of microsatellite stable/proficient mismatch repair metastatic colorectal cancer, which constitutes the majority of metastatic colorectal cancer, is assumed to be a major resistant mechanism to immune checkpoint inhibitors. Currently, clinical trials to improve the clinical activity of immune checkpoint inhibitors by immunomodulation are ongoing for metastatic colorectal cancer. Furthermore, immune checkpoint inhibitors are under development in neoadjuvant and/or adjuvant setting. Here, we review the existing clinical data with ongoing trials and discuss the future perspectives with a focus on the immunotherapy of colorectal cancer.

Previous studies of stage III colon cancer using the hazard function demonstrated that the risk of recurrence in patients with adjuvant chemotherapy never exceeded that of patients without adjuvant chemotherapy. However, it is unclear whether the same can be said for rectal cancer patients and whether adjuvant chemotherapy reduces recurrence. This study aimed to compare the recurrence hazard of stage III rectal cancer with that of colon cancer by adjuvant chemotherapy status using the hazard function, a method that allows for the assessment of instantaneous risk of recurrence over time. This retrospective nationwide study consisted of 10,356 patients with stage III colorectal cancer who underwent curative resection between January 1997 and December 2012 in Japan. Recurrence hazards of rectal and colon cancers were compared between patients treated with adjuvant chemotherapy and those who were not. Analyses in which recurrence was divided into local and distant recurrence were also performed. The hazard rate of recurrence in rectal cancer patients with adjuvant chemotherapy was consistently lower throughout the follow-up period, and the peak time of recurrence later, compared to patients without adjuvant chemotherapy (peaked at 15.7 vs. 7.1 months). Adjuvant chemotherapy also strongly suppressed distant recurrence but not local recurrence in rectal cancer patients. Similar results were observed in colon cancer patients. Our results using nationwide real-world data in Japan suggest that, similar to what is observed in colon cancer patients, adjuvant chemotherapy delays the peak of recurrence and suppresses distant recurrence in stage III rectal cancer patients.

Spontaneous regression of cancer is a rare phenomenon, with 33 colorectal cancer cases reported between 1900 and 2020.1-4 Spontaneous regression is defined as the partial or complete disappearance of a tumor without treatment.1,3 Several factors may be involved in this process, including biopsy, mechanical stress, humoral factors, and infection.1,5 However, no concrete evidence for the mechanistic insights has been indicated.

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.

Intersphincteric resection has been performed for very low rectal cancer in place of abdominoperineal resection to avoid permanent colostomy.This study aimed to evaluate long-term oncologic outcomes of intersphincteric resection compared with abdominoperineal resection.In this retrospective study, propensity score matching and stratification analyses were performed to reduce the effects of confounding factors between groups, including age, sex, BMI, CEA value, tumor height, tumor depth, lymph node enlargement, and circumferential resection margin measured by MRI.A database maintained at our institute was used to identify patients during the period between 2000 and 2014.A total of 285 patients who underwent curative intersphincteric resection (n = 112) or abdominoperineal resection (n = 173) for stage I to III low rectal cancer without preoperative chemoradiotherapy were enrolled in this study.The main outcome was recurrence-free survival.Patients in the abdominoperineal resection group were more likely to have a preoperative diagnosis of advanced cancer before case matching. After case matching, clinical outcomes were similar between intersphincteric resection and abdominoperineal resection groups. Five-year relapse-free survival rates were 69.9% for the intersphincteric resection group and 67.9% for abdominoperineal resection group (p = 0.64), and were similar in the propensity score-matched cohorts (89 matched pairs). Three-year cumulative local recurrence rates were 7.3% for intersphincteric resection and 3.9% for abdominoperineal resection (p = 0.13). In the propensity score-matched model, the hazard ratio for recurrence after intersphincteric resection in comparison with abdominoperineal resection was 0.90. Stratification analysis revealed similar recurrence rates (HR, 0.75-1.68) for intersphincteric resection in comparison with abdominoperineal resection.Eight covariates were incorporated into the model, but other covariates were not included.Our findings suggest similar oncologic outcomes for intersphincteric resection and abdominoperineal resection without preoperative chemoradiotherapy in patients with low rectal cancer adjusted for background variables. See Video Abstract at http://links.lww.com/DCR/A661.

Introduction: The clinical benefit of extended lymphadenectomy for synchronous extraregional lymph node metastasis, such as para-aortic lymph node (PALN) metastasis in colorectal cancer, remains highly controversial. Aim: To evaluate the clinical benefit of PALN dissection in colorectal cancer patients with synchronous PALN metastasis with or without multiorgan metastases. Methods: Thirty-six patients with pathologically positive PALN metastasis below the renal veins who underwent concurrent PALN dissection and primary colorectal cancer resection from January 1984 through September 2011 at the National Cancer Center Hospital in Tokyo, Japan, were included in this retrospective cohort study. We examined 5-year recurrence-free survival (RFS) rates in patient groups depending on the number of nodes involved (≤2 and ≥3 nodes) and on the presence or absence of other organ involvement (M1a and M1b,c categories in TNM staging). Results: The 5-year RFS rate was significantly different depending on the number of metastatic PALNs (42.1 and 0.6% for PALN ≤2 and ≥3, respectively, p = 0.01). The 5-year RFS rate was significantly better in patients in the M1a category than in patients in the M1b and M1c categories (27.6 and 0.0%, respectively, p < 0.01). Twenty-nine patients (80.6%) experienced recurrence after PALN dissection. Postoperative complications were seen in 14 (38.9%) patients. Conclusion: PALN dissection below the renal veins for patients with isolated PALN metastasis with 2 or fewer involved PALNs may be effective in improving prognosis in colorectal cancer.

Background Growing evidence suggests the importance of stroma in determining cancer biology and recent studies have identified that genes closely associated with poor prognosis subtypes of colorectal cancer are expressed by the stroma rather than epithelial cancer cells. We aimed to clarify the prognostic value of the novel histologic classification of desmoplastic reaction in stage III colorectal cancer. Methods A pathologic review was conducted for 466 stage III colorectal cancer patients in a single Japanese institution (1999–2006). Desmoplastic reaction was classified as mature, intermediate, or immature according to existence of hyalinized collagen bundles and myxoid stroma, both appear exclusively at the desmoplastic front. An additional 432 patients treated at four independent institutions (2007–2008) were examined as a second cohort to validate the results. Results According to desmoplastic reaction, 164, 133, and 169 patients were classified as mature, intermediate, and immature, respectively. Five-year relapse-free survival rates were highest in the mature group (86.0%), followed by the intermediate (73.7%) and immature (50.9%) groups. An adverse prognostic impact of desmoplastic reaction was invariably observed in stage IIIB, which contained 71% of stage III cases. Harrell's concordance index for relapse-free survival was greater in desmoplastic reaction (0.66) than any conventional tumor-associated prognostic factors including tumor node metastasis substage (0.62) and tumor grade (0.53). Similar results were observed in the second cohort, wherein desmoplastic reaction categorization was the most influential prognostic factor. Conclusion Histologic desmoplastic reaction categorization could be a key to solve the issue of prognostic heterogeneity in stage III colorectal cancer, thereby enhancing the value of tumor node metastasis stage.

Background: Clinical evidence of thiamine-related neuropsychiatric symptoms, including the initial stage, is limited because serum thiamine levels tend to be evaluated only for patients who develop severe neuropsychiatric symptoms suspected to be related to severe thiamine deficiency. This study aimed to evaluate the relationship between thiamine decline and neuropsychiatric symptoms, including initial symptoms, and the effect of chemotherapy on serum thiamine levels in gastrointestinal and hematological cancer patients receiving chemotherapy. Method: We retrospectively identified 87 patients who were diagnosed with gastrointestinal and hematological cancers at our hospital. We evaluated the risk factors associated with neuropsychiatric symptoms, including initial symptoms (neuropsychiatric symptoms), the relationship between the presence of neuropsychiatric symptoms and serum thiamine levels, and changes in serum thiamine levels after chemotherapy. Results: Logistic regression analysis identified thiamine decline as a significant factor associated with neuropsychiatric symptoms (p

Background Preoperative T staging of lower rectal cancer is an important criterion for selecting intersphincteric resection (ISR) or abdominoperineal resection (APR) as well as selecting neoadjuvant therapy. The aim of this study was to evaluate the accuracy of preoperative T staging using CT colonography (CTC) with multiplanar reconstruction (MPR), in which with the newest workstation the images can be analyzed with a slice thickness of 0.5 mm. Methods Between 2011 and 2013, 45 consecutive patients with very low rectal adenocarcinoma underwent CTC with MPR. The accuracy of preoperative T staging using CTC with MPR was evaluated. The accuracy of preoperative T staging using MRI in the same patient population (34 of 45 patients) was also examined. Results Overall accuracy of T staging was 89% (41/45) for CTC with MPR and 71% (24/34) for MRI. CTC with MPR was particularly sensitive for pT2 tumors (82%; 14/17), whereas MRI tended to overstage pT2 tumors and its sensitivity for pT2 was 53% (8/15). Conclusions CTC with MPR, with an arbitrary selection, could be aligned to the tumor axis and better demonstrated tumor margins consecutively including the deepest section of the tumor. The accuracy of T2 and T3 staging using CTC with MPR seemed to surpass that of MRI, suggesting a potential role of CTC with MPR in preoperative T staging for very low rectal cancer.

The National Comprehensive Cancer Network (NCCN) guidelines for colon cancer recently added the following footnote regarding the therapeutic strategy for peritoneal metastases: “If R0 resection can be achieved, surgical resection of isolated peritoneal disease may be considered at experienced centers.” This study investigated the efficacy of R0 resection of peritoneal metastasis from colorectal cancer without cytoreductive surgery or hyperthermic intraperitoneal chemotherapy (HIPEC). This retrospective cohort study was conducted at a single-institution tertiary care cancer center. Among 496 consecutive M1c colorectal cancer patients, R0 resection was achieved for 94 patients (19%). The subjects were 78 consecutive patients with colorectal cancer and simultaneous peritoneal metastasis but no other distant metastases who underwent R0 resection at the National Cancer Center Hospital from 1971 to 2016 (16% of all M1c patients). Overall survival (OS) was investigated, and clinicopathologic variables were analyzed for prognostic significance. No perioperative mortality was noted. The 3-year OS rate was 45%, and the 5-year OS rate was 28.7%. The median survival time was 33.4 months. Notably, 17 patients survived for more than 5 years, and 9 of these patients did not receive any chemotherapy. Multivariate analysis showed cancer location in the colon and harvesting of 12 or more lymph nodes to be independent factors associated with a better prognosis. From the perspective of long-term outcomes and no perioperative mortality, R0 resection of peritoneal metastasis from colorectal cancer, without complete peritonectomy or HIPEC, appeared to be an acceptable therapeutic option for some patients with peritoneal metastasis.

Introduction We conducted a multi-center pilot Phase II study to examine the safety of robotic rectal cancer surgery performed using the da Vinci Surgical System during the introduction period of robotic rectal surgery at two institutes based on surgical outcomes. Methods This study was conducted with a prospective, multi-center, single-arm, open-label design to assess the safety and feasibility of robotic surgery for rectal cancer (da Vinci Surgical System). The primary endpoint was the rate of adverse events during and after robotic surgery. The secondary endpoint was the completion rate of robotic surgery. Results Between April 2014 and July 2016, 50 patients were enrolled in this study. Of these, 10 (20%) had rectosigmoid cancer, 17 (34%) had upper rectal cancer, and 23 (46%) had lower rectal cancer; six underwent high anterior resection, 32 underwent low anterior resection, 11 underwent intersphincteric resection, and one underwent abdominoperineal resection. Pathological stages were Stage 0 in 1 patient, Stage I in 28 patients, Stage II in 7 patients and Stage III in 14 patients. Pathologically complete resection was achieved in all patients. There was no intraoperative organ damage or postoperative mortality. Eight (16%) patients developed complications of all grades, of which 2 (4%) were Grade 3 or higher, including anastomotic leakage (2%) and conversion to open surgery (2%). Conclusion The present study demonstrates the feasibility and safety of robotic rectal cancer surgery, as reflected by low morbidity and low conversion rates, during the introduction period.

BACKGROUND The influence of postoperative infectious complications, such as anastomotic leakage, on survival has been reported for various cancers, including colorectal cancer. However, it remains unclear whether intra-abdominal/pelvic inflammation after radical surgery for locally recurrent rectal cancer is relevant to its prognosis. OBJECTIVE The purpose of this study was to evaluate factors associated with survival after radical surgery for locally recurrent rectal cancer. DESIGN The prospectively collected data of patients were retrospectively evaluated. SETTINGS This study was conducted at a single-institution tertiary care cancer center. PATIENTS Between 1983 and 2012, patients who underwent radical surgery for locally recurrent rectal cancer with curative intent at the National Cancer Center Hospital were reviewed. MAIN OUTCOME MEASURES Factors associated with overall and relapse-free survival were evaluated. RESULTS During the study period, a total of 180 patients were eligible for analyses. Median blood loss and operation time for locally recurrent rectal cancer were 2022 mL and 634 minutes. Five-year overall and 3-year relapse-free survival rates were 38.6% and 26.7%. Age (p = 0.002), initial tumor stage (p = 0.03), pain associated with locally recurrent rectal cancer (p = 0.03), CEA level (p = 0.004), resection margin (p < 0.001), intra-abdominal/pelvic inflammation (p < 0.001), and surgery period (p = 0.045) were independent prognostic factors associated with overall survival, whereas CEA level (p = 0.01), resection margin (p = 0.002), and intra-abdominal/pelvic inflammation (p = 0.001) were associated with relapse-free survival. Intra-abdominal/pelvic inflammation was observed in 45 patients (25.0%). A large amount of perioperative blood loss was the only factor associated with the occurrence of intra-abdominal/pelvic inflammation (p = 0.007). LIMITATIONS This study was limited by its retrospective nature and heterogeneous population. CONCLUSIONS Intra-abdominal/pelvic inflammation after radical surgery for locally recurrent rectal cancer is associated with poor prognosis. See Video Abstract at http://journals.lww.com/dcrjournal/Pages/videogallery.aspx.

Background Controversy remains around whether the addition of lateral lymph node dissection to total mesorectal excision offers benefits in terms of survival or local control to patients with low rectal cancer. This study aimed to examine the impact of lateral lymph node dissection in the treatment of low rectal cancer on prognosis and local control and to identify patients who might benefit from lateral lymph node dissection at 2 high-volume centers in Japan that employ different policies with regard to adopting lateral lymph node dissection. Methods We reviewed outcomes from a total of 1,191 consecutive patients with low rectal cancer (rectal cancer distal to the peritoneal reflection) who underwent total mesorectal excision plus lateral lymph node dissection at 2 high-volume centers (the National Cancer Center and Aichi Cancer Center) in Japan. To assess the therapeutic outcomes of the respective node dissections, we applied an index calculated by multiplying the incidence by the 5-year overall survival of patients with metastasis in the respective lateral node stations. Multivariate analyses were performed to determine independent risk factors for local recurrence and prognostic factors. Results Outcomes according to the presence or absence of lateral nodal metastases showed long-term survival with lateral dissection, even in patients with lateral nodal metastases (5-year overall survival: 53.1% at the National Cancer Center vs 45.2% at Aichi Cancer Center), while stage I to III patients with no lateral nodal metastases had very good prognoses at both centers (5-year overall survival: 81.7% at the National Cancer Center vs 81.0% at Aichi Cancer Center). According to the index of estimated benefit from lateral lymph node dissection, dissection of the distal internal iliac nodes and obturator nodes yielded the greatest therapeutic benefit in patients at both centers. Compared to patients with bilateral lateral lymph node dissection, the relative risk for local recurrence was 2.0 for those with unilateral lateral lymph node dissection. Conclusion Lateral lymph node dissection outcomes observed at the 2 high-volume centers in Japan demonstrate high reproducibility with good results in terms of prognosis. Differences in policies concerning the adoption of lateral lymph node dissection affected local recurrence rate.

The aim of this study was to compare the oncologic results of abdominoperanal intersphincteric resection (ISR) and abdominoperineal resection (APR). Between 2003 and 2014, 277 consecutive patients with stage I–III low rectal cancer located within 5 cm from the anal verge underwent curative ISR and APR. A retrospective comparison of these two procedures was performed. Overall, 128 patients underwent ISR and 149 underwent APR. The ISR group had earlier clinical stages and shorter distal margins (p

Colorectal cancer is a major public health concern in Japan. While early-stage colorectal adenocarcinoma treatment entails radical resection of the primary tumor, the importance of perioperative treatment is growing as physicians seek to further improve treatment outcomes. For anal squamous cell carcinoma, definitive chemoradiotherapy is superior to radical surgery in terms of improved patient quality of life. The Colorectal Cancer Study Group of the Japanese Clinical Oncology Group was established in 2001 and has worked to provide answers to common clinical questions and improve treatment outcomes for colorectal and anal cancers through 15 large-scale prospective clinical trials. Here, we discuss the current state of perioperative treatment for early-stage colon, rectal and anal cancers in Japan and approaches taken by the Colorectal Cancer Study Group/the Japanese Clinical Oncology Group to improve treatment outcomes for these cancers.

Background Assessment of preoperative general condition to predict postoperative outcomes is important, particularly in older patients who typically suffer from various comorbidities and exhibit impaired functional status. In addition to various indices such as Charlson Comorbidity Index (CCI), National Institute on Aging and National Cancer Institute Comorbidity Index (NIA/NCI), Adult Comorbidity Evaluation-27 (ACE-27), and American Society of Anesthesiologists Physical Status classification (ASA-PS), controlling nutritional status (CONUT) score is recently gaining attention as a tool to evaluate the general condition of patients from a nutritional perspective. However, the utility of these indices in older patients with colorectal cancer has not been compared. Methods The study population comprised 830 patients with Stage I - IV colorectal cancer aged 75 years or older who underwent surgery at the National Cancer Center Hospital from January 2000 to December 2014. Associations of each index with overall survival (OS) (long-term outcome) and postoperative complications (short-term outcome) were examined. Results For the three indices with the highest Akaike information criterion values (i.e., CONUT score, CCI and ACE-27), but not the remaining indices (NIA/NCI and ASA-PS), OS significantly worsened as general condition scores decreased, after adjusting for known prognostic factors. In contrast, for postoperative complications, only CONUT score was identified as a predictive factor (≥4 versus 0–3; odds ratio: 1.90; 95% CI: 1.13–3.13; P = 0.016). Conclusion For older patients with colorectal cancer, only CONUT score was a predictive factor of both long-term and short-term outcomes after surgery, suggesting that CONUT score is a useful preoperative risk assessment index.

Standard treatment for low advanced rectal cancer is total mesorectal excision(TME)plus bilateral pelvic lymph node dissection in Japan. It has been expanded sphincter-preserving rectal surgery due to improvement of surgical procedures for rectal cancer. However, autonomic nerves are close to rectum, it is important to establish a treatment strategy that is considering the patients of quality of life(QOL)after rectal cancer surgery. Here, we investigated the frequency and how to deal with dysuria, sexual dysfunction, defecation dysfunction and stoma related complications after rectal cancer surgery. It is considered that it is more important to increase the number of patients with rectal cancer, especially of elderly patients, to evaluate the preoperative function of each patient and select individual treatment based on the progress of the cancer.

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 benefits that palliative resection of the primary tumor offers patients with unresectable stage 4 colorectal cancer, specifically with regard to overall survival, are controversial, and the issue is complicated by marked differences in patient backgrounds and characteristics. The study enrolled 770 consecutive patients with unresectable stage 4 colorectal cancer referred to the divisions of surgery or gastrointestinal oncology at the National Cancer Center Hospital from 1997 to 2013. Of these patients, 429 (56 %) underwent palliative resection of the primary tumor, whereas 341 (44 %) did not. To lessen the effects of confounding factors between the groups, including age, year, severe symptoms, number of organs involved by metastases, primary tumor site, and carcinoembryonic antigen (CEA) value, propensity score analyses were used for regression adjustment, stratification, and matching, with overall survival as the primary end point. The regression adjustment including the propensity score as a linear predictor in the model showed that palliative resection was associated with a significantly improved overall survival (hazard ratio [HR] 0.60; 95 % confidence interval [CI] 0.50–0.71; p

Mesenteric traction syndrome (MTS) develops in the early phase of laparotomy, which is triggered by pulling of the mesentery. We attempted to analyze the circulatory dynamics of MTS by using the FloTrac sensor.Prospective randomized control study, the MTS trial, was conducted with or without prophylactic administration of flurbiprofen axetil in order to control MTS development in 57 elective open colorectal surgeries. None of the Flurbipurofen group patients (n = 23) develop MTS and were allocated to the non-MTS group. Among the non-flurbiprofen group, 28 patients (82%) developed MTS and were categorized into the MTS group. For these patients, in addition to blood pressure, stroke volume variation (SVV) and systemic vascular resistance index (SVRI) were measured by FloTrac sensor.The lowest blood pressure was noted within 30 minutes from the beginning of the intra-abdominal examination; in the non-MTS group, the mean blood pressure decreased by 16.7%, and in the MTS group, it decreased by 34.2% (P.01). SVV of the 28 MTS patients was as follows:9% in 10 patients (35.7%),9% and13% in 8 patients (28.6%), and13% in 10 patients (35.7%). SVRI rose in the non-MTS group by 5.1%, whereas it fell in the MTS group by 15.1% (P.01), indicating the close relationship between MTS and SVRI.The SVV results indicate that fluid loading is not that optimal treatment against hypotension of MTS and that it is also important to consider the use of a vasoconstrictor. FloTrac is therefore useful for making an appropriate decision on the treatment strategy for MTS.

Approximately one-third of patients survive for 5 years following curative resection of hepatic metastases from colorectal cancer, and the proportion of hepatectomy-related death is as low as 1-2 %. These observations strongly support the view that hepatectomy seems to be the most effective therapy for treating hepatic metastases from colorectal cancer, due to the potential for long-term survival that is not possible with other treatment modalities. However, a hepatectomy alone does not always provide a complete cure. Adjuvant chemo- therapy may reduce the risk of recurrence and improve long-term survival, but administering systemic agents to the patients with resectable hepatic metastases in the clinical practice is not universal. Until recently, there has been little support for requiring peri-operative chemotherapy in patients with resectable hepatic metastases from colorectal cancer. We, there- fore, conducted a phase II/II randomized controlled trial (JCOG0603) to evaluate modified FOLFOX(mFOLFOX) as adjuvant chemotherapy for patients with curatively resected liver metastases from colorectal cancer. We eagerly await the results of this trial.

Two procedures widely performed to treat locally advanced colorectal cancer adherent to the urinary bladder are total cystectomy (as part of pelvic exenteration) and partial cystectomy; however, little is known about outcomes following partial cystectomy. A retrospective database of patients with colorectal cancer involving the urinary bladder who underwent R0 or R1 resection at our institution from 2001 to 2015 was constructed. The histological extent of bladder invasion and long-term outcomes were examined. Of the 89 consecutive patients, 49 underwent partial cystectomy and all had negative margins of the bladder. Tumor invasion to the urinary bladder was confirmed histologically in 19 of 49 patients (coincidence rate of diagnosis, 39%): invasion only to the bladder serosa (n = 3), invasion to the bladder muscle (n = 4), and invasion beyond the bladder muscle without (n = 1) and with (n = 11) exposure to the bladder lumen. The 5-year recurrence-free and overall survival rates were 63.2% and 70.2% in the partial cystectomy group, and 66.2% and 72.7% in the total cystectomy group (p = 0.567 and 0.648), respectively. Except for the remnant bladder, recurrence sites were very similar to sites observed in patients who underwent total cystectomy. Intravesical recurrence occurred in four patients 3–13 months after the initial surgery, all of whom showed bladder lumen exposure to the tumor. With regard to long-term outcomes and low diagnostic concordance rates of clinical and pathological bladder invasion, partial cystectomy seems a generally acceptable treatment option. However, when the bladder lumen is exposed to a colorectal tumor, surgeons should be cognizant of possible intravesical recurrence and act accordingly.