Prognostic impact of primary tumour location after curative resection in Stage I-III colorectal cancer: a single-centre retrospective study.

OBJECTIVE: The relationship of tumour site with post-recurrence course and outcome after primary surgery in resectable colorectal cancer is unclear. This study investigated the prognostic impact of primary tumour location following radical resection without preoperative treatment in Stage I-III colorectal cancer. METHODS: We analyzed 3770 patients with Stage I-III colorectal cancer who underwent curative resection at our hospital during 2000-15. We defined the right-sided colon as the cecum, ascending colon and transverse colon, and the left-sided colon as the descending colon, sigmoid and rectosigmoid junction. Patients were divided into three groups according to tumour site: right-sided colon, left-sided colon and rectum. Endpoints were overall survival, recurrence-free survival by stage and survival after recurrence, respectively. RESULTS: The 5-year overall survival rates of patients with stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 98.2, 97.3 and 97.2%, respectively (P = 0.488). The 5-year overall survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 96.2, 88.7 and 83.0, respectively (P = 0.070). The 5-year overall survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 88.7, 83.0 and 80.2, respectively (P = 0.001). The 5-year recurrence-free survival rates of patients with Stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 95.1, 94.5 and 90.6% (P = 0.027). The 5-year recurrence-free survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 85.2, 90.2 and 76.1%, respectively (P < 0.001). The 5-year recurrence-free survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 75.3, 75.3 and 59.8%, respectively (P < 0.001). Right-sided colon cancer was significantly associated with better recurrence-free survival compared with left-sided colon cancer (HR 1.29, 95% CI 1.03-1.63; P = 0.025) and rectal cancer (HR 1.89, 95% CI 1.51-2.38; P < 0.001) after adjusting for clinical factors. Amongst patients with recurrence, right-sided colon cancer was significantly associated with poorer survival after recurrence compared with left-sided colon cancer (HR 0.68, 95% CI 0.48-0.97; P = 0.036), and showed a tendency towards poorer survival after recurrence compared with rectal cancer (HR 0.79, 95% CI 0.57-1.10; P = 0.164). CONCLUSIONS: In Stage I-III colorectal cancer without preoperative treatment, our results suggest that the three tumour sites (right-sided colon, left-sided colon or rectum) may have prognostic significance for recurrence-free survival and survival after recurrence, rather than sidedness alone.

Cost-effectiveness of surveillance intervals after curative resection of colorectal cancer.

BACKGROUND: Major guidelines consistently recommend 5 years of postoperative surveillance for patients with colorectal cancer. However, they differ in their recommendations for examination intervals and whether they should vary according to disease stage. Furthermore, there are no reports on the cost-effectiveness of the different surveillance schedules. The objective of this study is to identify the most cost-effective surveillance intervals after curative resection of colorectal cancer. METHODS: A total of 3701 patients who underwent curative surgery for colorectal cancer at the National Cancer Center Hospital were included. A cost-effectiveness analysis was conducted for the five surveillance strategies with reference to the guidelines. Expected medical costs and quality-adjusted life years after colorectal cancer resection were calculated using a state-transition model by Monte Carlo simulation. The incremental cost-effectiveness ratio per quality-adjusted life years gained was calculated for each strategy, with a maximum acceptable value of 43 500-52 200 USD (5-6 million JPY). RESULTS: Stages I, II and III included 1316, 1082 and 1303 patients, respectively, with 45, 140 and 338 relapsed cases. For patients with stage I disease, strategy 4 (incremental cost-effectiveness ratio $26 555/quality-adjusted life year) was considered to be the most cost-effective, while strategies 3 ($83 071/quality-adjusted life year) and 2 ($289 642/quality-adjusted life year) exceeded the threshold value. In stages II and III, the incremental cost-effectiveness ratio for strategy 3 was the most cost-effective option, with an incremental cost-effectiveness ratio of $18 358-22 230/quality-adjusted life year. CONCLUSIONS: In stage I, the cost-effectiveness of intensive surveillance is very poor and strategy 4 is the most cost-effective. Strategy 3 is the most cost-effective in stages II and III.

Lateral pelvic lymph node metastasis in T2 low rectal cancer: is TME alone sufficient for cure?

BACKGROUND: Some patients with even T2 low rectal cancer are known to develop lateral pelvic lymph node metastasis. This study aimed to investigate real-world evidence regarding lateral nodal metastasis on T2 low rectal cancer treatment. METHODS: Consecutive patients with pathological T2 low rectal adenocarcinoma who underwent curative-intent surgery between January 2007 and December 2015 at two Japanese cancer centres dedicated to lateral pelvic lymph node dissection were identified and included in the analysis. Lateral pelvic lymph node metastasis was defined as pathologically confirmed metastatic lateral pelvic lymph node or lateral-local recurrence after primary surgery. RESULTS: A total of 215 consecutive patients, including 101 and 114 patients who did and did not undergo bilateral lateral pelvic lymph node dissection, were included in the analysis. Overall, 19 (8.8%) patients had lateral pelvic lymph node metastasis, including 13 with pathologically confirmed metastatic lateral pelvic lymph node and six with lateral-local recurrence. A total of 10 (4.7%) patients had local recurrence, including six with lateral-local recurrence, two with central-local recurrence and two with anastomotic recurrence. Five/7-year cumulative risks of lateral-local recurrence in patients with and without lateral pelvic lymph node dissection were 1.1/1.1% and 3.9/5.2%, respectively. CONCLUSION: The problem of the relatively high rate of lateral local recurrence remains in treating T2 low rectal cancer with only total mesorectal excision. The selection of high-risk patients of lateral pelvic lymph node metastasis and the indication of additional treatment in T2 low rectal cancer should be discussed further.

A review of 14 cases of perianal Paget's disease: characteristics of anorectal cancer with pagetoid spread.

BACKGROUND: Perianal Paget's disease (PPD) is an intraepithelial invasion of the perianal skin and is frequently associated with underlying anorectal carcinoma. The relatively rare nature of this disease has made it difficult to develop treatment recommendations. This study aims to analyze the clinical and pathological features of perianal Paget's disease (PPD) and to explore rational treatment options and follow-up for this disease. METHODS: The National Cancer Center Hospital database was searched for all cases of perianal Paget's disease diagnosed between 2006 and 2021. In the 14 patients identified, we reviewed the diagnosis, management, and outcomes of adenocarcinoma with pagetoid spread, including suspected or recurrent cases. RESULTS: All 14 cases met the inclusion criteria. The median follow-up period after diagnosis was 4.5 (range, 0.1-13.0) years. Pagetoid spread before initial treatment was suspected in 12 cases (85.7%). Underlying rectal cancer was identified in 6 cases, and no primary tumor was detected in the other 6 cases. Seven patients had recurrent disease, with the median time to recurrence of 34.6 (range, 19.2-81.7) months. The time to the first relapse was 3 months, and that to the second relapse was 6 months. The overall 5-year survival rate was 90.0%. CONCLUSIONS: Endoscopic and radiologic evaluation, as well as immunohistologic examination, should be performed. is to differentiate PPD with and without underlying anorectal carcinoma. The time to first recurrence varies widely, and long-term and regular follow-up for more than 5 years is considered necessary for local recurrence and distant metastasis.

Evaluation of Recurrence Risk After Curative Resection for Patients With Stage I to III Colorectal Cancer Using the Hazard Function: Retrospective Analysis of a Single-institution Large Cohort.

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 (<0.0015) for 5 years after surgery. The hazard curve for stage II had a peak hazard rate of 0.0046 at 13.7 months, after which the curve had a long hem to the right. The hazard curve for stage III had an earlier and higher peak than that of stage II (0.0105 at 11.6 months), with a long hem to the right. CONCLUSIONS: Changes in recurrence hazard for CRC patients varied considerably by stage. Our findings suggest that short-interval surveillance might be unnecessary for stage I patients for the first 3 years after surgery, whereas short-interval surveillance for the first 3 years should be considered for stage III patients.

Evaluation of the learning curve for robot-assisted rectal surgery using the cumulative sum method.

BACKGROUND: There is no clear evidence on the number of cases required to master the techniques required in robot-assisted surgery for different surgical fields and techniques. The purpose of this study was to clarify the learning curve of robot-assisted rectal surgery for malignant disease by surgical process. METHOD: The study retrospectively analyzed robot-assisted rectal surgeries performed between April 2014 and July 2020 for which the operating time per process was measurable. The following learning curves were created using the cumulative sum (CUSUM) method: (1) console time required for total mesorectal excision (CUSUM tTME), (2) time from peritoneal incision to inferior mesenteric artery dissection (CUSUM tIMA), (3) time required to mobilize the descending and sigmoid colon (CUSUM tCM), and (4) time required to mobilize the rectum (CUSUM tRM). Each learning curve was classified into phases 1-3 and evaluated. A fifth learning curve was evaluated for robot-assisted lateral lymph node dissection (CUSUM tLLND). RESULTS: This study included 149 cases. Phase 1 consisted of 32 cases for CUSUM tTME, 30 for CUSUM tIMA, 21 for CUSUM tCM, and 30 for CUSUM tRM; the respective numbers were 54, 48, 45, and 61 in phase 2 and 63, 71, 83, and 58 in phase 3. There was no significant difference in the number of cases in each phase. Lateral lymph node dissection was initiated in the 76th case where robot-assisted rectal surgery was performed. For CUSUM tLLND, there were 12 cases in phase 1, 6 in phase 2, and 7 cases in phase 3. CONCLUSIONS: These findings suggest that the learning curve for robot-assisted rectal surgery is the same for all surgical processes. Surgeons who already have adequate experience in robot-assisted surgery may be able to acquire stable technique in a smaller number of cases when they start to learn other techniques.

Prognostic impact of conversion hepatectomy for initially unresectable colorectal liver metastasis.

PURPOSE: This study aimed to evaluate the prognostic impact of conversion hepatectomy in patients with initially unresectable colorectal liver metastasis (CRLM) and to identify prognostic factors after conversion hepatectomy. METHODS: Correlations of conversion hepatectomy with relapse-free survival (RFS) and overall survival (OS) were retrospectively investigated in 554 consecutive patients who underwent hepatectomy for CRLM in 2000-2017. Prognostic factors after conversion hepatectomy were examined in multivariable analysis. RESULTS: Five hundred and nine patients (92%) had initially resectable CRLM at diagnosis and underwent hepatectomy (primary resection group) and 45 (8%) underwent conversion hepatectomy following chemotherapy (conversion group). The 5-year RFS was 30.0% in the primary resection group and 19.8% in the conversion group (p = 0.042); the respective 5-year OS rates were 62.0% and 52.4% (p = 0.253). Multivariable analysis did not identify conversion hepatectomy as a significant prognostic factor for RFS (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.64-1.37, p = 0.796) or OS (HR 1.12, 95% CI 0.67-1.79, p = 0.667). In the conversion group, multivariable analysis identified the following independent prognostic factors: timing of liver metastases for RFS (synchronous: HR 3.14, 95% CI 1.20-8.24, p = 0.020) and preoperative CEA level for RFS (> 5 ng/ml: HR 3.10, 95% CI 1.45-6.61, p = 0.003) and OS (> 5 ng/ml: HR 3.29, 95% CI 1.18-9.17, p = 0.023). CONCLUSIONS: RFS and OS rates after conversion hepatectomy were not inferior to those after primary resection in patients with CRLM. Patients with a normal CEA level before hepatectomy can be expected to have good long-term prognosis after conversion hepatectomy.

Preoperative Nutritional Scores as Host-Related Prognostic Factors for Both Overall Survival and Postoperative Complications in Patients With Stage II to III Colorectal Cancer.

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 últimas etapificaciones T-N-M, tanto el estado nutricional como inflamatorio han sido descritos como factores pronósticos en cáncer de esófago, hepático y pancreático. Sin embargo en cáncer colorectal solo la edad y la raza son enumerados como factores pronósticos.OBJETIVO:Evaluar la importancia pronóstica de los scores nutricionales e inflamatorias para los resultados posoperatorios en pacientes con cáncer colorrectal.DISEÑO:Estudio retrospectivo utilizando una base de datos.AJUSTE:Centro oncológico teciario en Japón.PACIENTES:Fueron incluidos en el estudio 1880 pacientes, consecutivos, con cancer colorectal etapa II y III sometidos a reseeción curativa en el National Cancer Center Hospital entre 2004 y 2012. Se aplicaron dos scores: nutricional (índice nutricional pronóstico y puntuación del estado nutricional) e inflamatorias (Glasgow modificada, proporción de neutrófilos a linfocitos, de plaquetas a linfocitos y de proteína C reactiva a albúmina).PRINCIPALES MEDIDAS DE RESULTADO:Evaluar scores nutricional e inflamatorio con sobrevida y complicaciones postoperatoria.RESULTADOS:Después de ajustar los factores clínicos y patológicos clave mediante análisis multivariable, dos scores nutricionales (índice nutricional pronóstico y puntuación del estado nutricional de control) y dos inflamatorias (proporción de neutrófilos a linfocitos y proporción de proteína C reactiva a albúmina) fueron pronósticos independientes factores para la sobrevida. Con respecto a la capacidad discriminativa, las curvas de características operativas del receptor, dependientes del tiempo y el índice de concordancia de Harrell, revelaron que el índice nutricional pronóstico y del estado nutricional de control eran superiores a las cuatro inflamatorias para predecir la sobrevida general. Los análisis de regresión logística multivariable también revelaron que el índice nutricional pronóstico, el estado nutricional de control y la relación proteína C reactiva / albúmina fueron predictores independientes de complicaciones postoperatorias.LIMITACIONES:Estudio de tipo retrospectivo.CONCLUSIONES:Los scores nutricionales preoperatorias son factores pronósticos prometedores relacionados con la sobrevida y las complicaciones postoperatorias en pacientes con cáncer colorrectal en estadio II y III. Consulte Video Resumen en http://links.lww.com/DCR/B587.

Circumferential Resection Margin Status as a Predictive Factor for Recurrence in Preoperative MRI for Advanced Lower Rectal Cancer Without Preoperative Therapy.

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 RESECCIÓN CIRCUNFERENCIAL COMO FACTOR PREDICTIVO DE RECURRENCIA EN LA RESONANCIA MAGNÉTICA PREOPERATORIA, PARA EL CÁNCER RECTAL BAJO AVANZADO SIN TERAPIA PREOPERATORIA: En Japón, la escisión mesorrectal total con disección de ganglios linfáticos laterales y sin terapia preoperatoria, es el tratamiento estándar para el cáncer rectal bajo avanzado. Aunque se han reportado resultados oncológicos a largo plazo con terapia preoperatoria, basada en el estado del margen de resección circunferencial en la resonancia magnética preoperatoria, se desconocen los resultados sin terapia preoperatoria.Este estudio evaluó los resultados oncológicos a largo plazo de cirugía radical sin terapia preoperatoria, en cáncer rectal bajo avanzado, basado en el estado del margen de resección circunferencial en la resonancia magnética preoperatoria, con el objetivo de definir poblaciones de pacientes apropiadas para terapia preoperatoria.Este análisis retrospectivo comparó los resultados oncológicos a largo plazo con resonancia magnética preoperatoria, en pacientes con cáncer rectal bajo.Los pacientes fueron identificados a través de una base de datos administrada por nuestro instituto.Se incluyeron un total de 338 pacientes con cáncer rectal bajo, que se sometieron a cirugía radical entre 2000 y 2014 en el Hospital Nacional del Centro de Cáncer, sin terapia preoperatoria.El resultado principal fue la supervivencia libre de recaídas.La mediana del período de seguimiento fue de 61,7 meses (rango, 3-153 meses). Las tasas de supervivencia sin recaídas a cinco años, con margen de resección circunferencial predicho por resonancia magnética, en pacientes negativos y pacientes positivos fueron 76.0% y 55.6% (p <0.001), respectivamente. Los análisis univariados y multivariados revelaron estadio pN (razón de riesgo [HR], 2.35; intervalo de confianza [IC] del 95%, 1.470-3.770; p <0.001), invasión linfática (HR, 2.03; IC del 95%, 1.302-3.176; p = 0.002), invasión venosa (HR, 2.15; IC 95%, 1.184-3.9; p = 0.01), procedimiento quirúrgico (HR, 1.72; IC 95%, 1.115-2.665; p = 0.01) y circunferencial predicho por resonancia magnética en margen de resección (HR, 1.850; IC 95%, 1.206-2.838; p = 0.0051), como factores de riesgo independientes, para la recurrencia postoperatoria.Este estudio fue retrospectivo en diseño.El margen de resección circunferencial predicho de resonancia magnética, se asoció con una supervivencia libre de recaída sin terapia preoperatoria, lo que indica su potencial para uso en la selección de la terapia óptima preoperatoria. Consulte Video Resumen en http://links.lww.com/DCR/B335.

Surveillance of patients with stage I or II colorectal cancer in Japan: a JCOG study group questionnaire survey.

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.

Comparison of model fit and discriminatory ability of the 8th edition of the tumor-node-metastasis classification and the 9th edition of the Japanese classification to identify stage III colorectal cancer.

BACKGROUND: The most widely accepted staging system for colorectal cancer (CRC) is the tumor-node-metastasis (TNM) classification. In Japan, the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (JCCRC) system is used. The two systems differ mainly in relation to tumor deposits (TD) and metastasis in the regional lymph nodes along the main feeding arteries and lateral pelvic lymph nodes (N3). Here, we investigated the prognostic ability of the two systems for stage III CRC. METHODS: We reviewed 696 consecutive patients who underwent curative resection of stage III CRC at the National Cancer Center Hospital between May 2007 and April 2014. We examined the clinicopathological features of CRC and predicted overall survival (OS) and relapse-free survival (RFS) according to the 8th TNM and 9th JCCRC systems. The systems were compared using Akaike's information criterion (AIC), Harrell's concordance index (C-index), and time-dependent receiver-operating characteristic (ROC) curves. RESULTS: The 9th JCCRC system was more clinically effective according to AIC (OS, 1199 vs. 1206; RFS, 2047 vs. 2057), showed better discriminatory ability according to the C-index (OS, 0.65 vs. 0.62; RFS, 0.62 vs. 0.58), and its time-dependent ROC curve was superior compared with the 8th TNM system. CONCLUSION: These results suggest that the 9th JCCRC system has superior discriminative ability to the 8th TNM system, because the 9th JCCRC accounts for the presence of TD and N3 disease, which were both significant predictors of poor prognosis. Reconsidering the clinical value of these two factors in the TNM system could improve its clinical significance.

A randomized controlled trial comparing primary tumour resection plus chemotherapy with chemotherapy alone in incurable stage IV colorectal cancer: JCOG1007 (iPACS study).

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.

Japanese Evidences on Nerve-Preserving Lateral Pelvic Lymh Node Dissection for Rectal Cancer: Major Historical Milestones and Clinical Impact: The Past, Present and Future.

In Japan, the standard treatment for advanced low rectal cancer has been total mesorectal excision (TME) + lateral pelvic lymph node dissection (LLND). On the other hand, in the West, preoperative chemoradiotherapy (CRT) + TME has been established as the standard. Japanese surgeons developed nerve-preserving LLND that could reduce complications associated with extended dissection. The Japan Clinical Oncology Group (JCOG)0212 trialinvestigated on the outcomes of so-called prophylactic LLND in patients without evident lateral lymph node metastasis in preoperative diagnostic imaging. Data from the JCOG0212 trial demonstrated scientific validity of the theory and practice of the Japanese approach. Data from the JCOG0212 trial supported the validity and safety of the Japanese approach, that is, TME + LLND for low rectal cancer without routine use of preoperative CRT. For future direction, modern approach for rectal cancer should involve both of the Eastern and Western strategies by combining LLND and CRT.

Controlling nutritional status (CONUT) score as a preoperative risk assessment index for older patients with colorectal cancer.

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.

Preoperative T staging of colon cancer using CT colonography with multiplanar reconstruction: new diagnostic criteria based on "bordering vessels".

PURPOSE: 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. METHODS: 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. 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. CONCLUSIONS: Our newly developed criteria are useful for preoperative T staging, particularly for distinguishing T3 from T2 and T4.

[Postoperative Dysfunction and Quality of Life in Patients with Rectal Cancer].

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.

Lung exposure to lipopolysaccharide causes atherosclerotic plaque destabilisation.

Epidemiological studies have implicated lung inflammation as a risk factor for acute cardiovascular events, but the underlying mechanisms linking lung injury with cardiovascular events are largely unknown.Our objective was to develop a novel murine model of acute atheromatous plaque rupture related to lung inflammation and to investigate the role of neutrophils in this process.Lipopolysaccharide (LPS; 3 mg·kg(-1)) or saline (control) was instilled directly into the lungs of male apolipoprotein E-null C57BL/6J mice following 8 weeks of a Western-type diet. 24 h later, atheromas in the right brachiocephalic trunk were assessed for stability ex vivo using high-resolution optical projection tomography and histology. 68% of LPS-exposed mice developed vulnerable plaques, characterised by intraplaque haemorrhage and thrombus, versus 12% of saline-exposed mice (p=0.0004). Plaque instability was detectable as early as 8 h post-intratracheal LPS instillation, but not with intraperitoneal instillation. Depletion of circulating neutrophils attenuated plaque rupture.We have established a novel plaque rupture model related to lung injury induced by intratracheal exposure to LPS. In this model, neutrophils play an important role in both lung inflammation and plaque rupture. This model could be useful for screening therapeutic targets to prevent acute vascular events related to lung inflammation.

Laparoscopic radical right hemicolectomy for cecal cancer and middle colic artery aneurysm.

BACKGROUND: Middle colic artery (MCA) aneurysms are very rare and exclusively reported with symptoms or rupture. We report successful laparoscopic elective surgery for both cecal cancer and MCA aneurysm in an 87-year-old man who presented with bloody stools. METHODS: Diagnostic colonoscopy revealed a cecal tumor 40 mm in diameter that was histologically confirmed as a well-differentiated adenocarcinoma. The three-phase dynamic computed tomography showed a cecal tumor without any metastasis and an MCA aneurysm 10 mm in diameter. Radical right hemicolectomy with D3 lymph node dissection that included the MCA aneurysm was performed. The postoperative course was uneventful, and the patient survived without recurrence. CONCLUSIONS: Even though the present patient was very elderly, the postoperative course of laparoscopic radical surgery for both an MCA aneurysm and cecal cancer was uneventful with good short-term outcomes.

Impact of D3 lymph node dissection on survival for patients with T3 and T4 colon cancer.

PURPOSE: The clinical significance of D3 lymph node dissection for patients with colon cancer remains controversial. This study aims to clarify the impact of D3 lymph node dissection on survival in patients with colon cancer. METHODS: This is a retrospective cohort study from a prospectively registered multi-institutional database of colorectal cancer in Japan. Propensity score matching method was applied to balance potential confounders of the treatment. A cohort of 10,098 patients who underwent radical colectomy for pT3 and pT4 colon cancer between 1985 and 1994 were identified. A total of 3,425 propensity score matched pairs were extracted from the entire cohort. The primary outcome measure was overall survival (OS). RESULTS: In the entire cohort, there was a statistically significant difference in overall survival (OS) between the patients who had D3 and D2 lymph node dissection (p = 0.00003). The estimated hazard ratio (HR) for OS of patients who had D3 versus D2 lymph node dissection was 0.827 (95 % confidence interval, 0.757 to 0.904). In the matched cohort, there was also a significant difference in OS between the two groups (p = 0.0001), and the estimated HR for OS was 0.814 (95 % confidence interval, 0.734 to 0.904). CONCLUSIONS: We found D3 lymph node dissection for pT3 and pT4 colon cancer to be associated with a significant survival advantage in a large-scale database, even after adjusting potential confounders of lymph node dissection. This finding may provide a rationale for D3 lymph node dissection in radical surgery for pT3 and pT4 colon cancer.