N 1-Methylpseudouridine substitution enhances the performance of synthetic mRNA switches in cells.

Synthetic messenger RNA (mRNA) tools often use pseudouridine and 5-methyl cytidine as substitutions for uridine and cytidine to avoid the immune response and cytotoxicity induced by introducing mRNA into cells. However, the influence of base modifications on the functionality of the RNA tools is poorly understood. Here we show that synthetic mRNA switches containing N1-methylpseudouridine (m1Ψ) as a substitution of uridine substantially out-performed all other modified bases studied, exhibiting enhanced microRNA and protein sensitivity, better cell-type separation ability, and comparably low immune stimulation. We found that the observed phenomena stem from the high protein expression from m1Ψ containing mRNA and efficient translational repression in the presence of target microRNAs or proteins. In addition, synthetic gene circuits with m1Ψ significantly improve performance in cells. These findings indicate that synthetic mRNAs with m1Ψ modification have enormous potentials in the research and application of biofunctional RNA tools.

Factors affecting R0 resection of colorectal cancer with synchronous peritoneal metastases: a multicenter prospective observational study by the Japanese Society for Cancer of the Colon and Rectum.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.0001], low PCI score (1-6) (OR 20.0; 95% CI 4.8-83.4; p < 0.0001), and high PS (0) (OR 2.40; 95% CI 0.66-8.68; p = 0.18) were independent factors affecting R0/R1 resection. PCI score and PS were also independent factors affecting R0/R1 resection in M1c patients without non-peritoneal distant metastases (n = 59). CONCLUSION: Distant metastases, PCI score, and PS are three factors which affect R0 resection for M1c disease.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer.

The number of deaths from colorectal cancer in Japan continues to increase. Colorectal cancer deaths exceeded 50,000 in 2016. In the 2019 edition, revision of all aspects of treatments was performed, with corrections and additions made based on knowledge acquired since the 2016 version (drug therapy) and the 2014 version (other treatments). The Japanese Society for Cancer of the Colon and Rectum guidelines 2019 for the treatment of colorectal cancer (JSCCR guidelines 2019) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment and to deepen mutual understanding between healthcare professionals and patients by making these guidelines available to the general public. These guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. Controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSCCR guidelines 2019.

[A Case of Intussusception Due to Sigmoid Colon Cancer].

A 78-year-old man was referred to our hospital with diarrhea, melena, and weight loss. During a digital rectal examination, a protuberant mass located 7-8 cm above the anal verge was palpable. Computed tomography(CT)scans of his chest, abdomen, and pelvis revealed an intestinal obstruction with a target sign in the lower rectum, indicating intussusception due to a sigmoid colon mass. A gastrografin enema examination revealed a typical filling defect with a crab claw sign in the rectum. However, the enema did not reduce the intussusception. The surgical findings showed that the sigmoid colon had slipped inside the rectum, consistent with the diagnostic imaging findings. A radical sigmoidectomy(D2)with diverting colostomy was performed to address the unprepared colon with accompanying edema. Pathology of the resected specimen revealed a type 2 tumor measuring 5 cm in size and comprising moderately differentiated adenocarcinoma(pT3pN0M0, pStage Ⅱ). The patient's postoperative course was uneventful, and his stoma was closed 2 months later. Intussusception occurs less frequently in adults than in children. In a case of bowel-within-bowel configuration, in which layers of the bowel are duplicated to form concentric rings, the target-like sign on CT images may be a useful diagnostic marker of colorectal intussusception.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer.

Japanese mortality due to colorectal cancer is on the rise, surpassing 49,000 in 2015. Many new treatment methods have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2016 for the treatment of colorectal cancer (JSCCR Guidelines 2016) were prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding between health-care professionals and patients by making these Guidelines available to the general public. These Guidelines were prepared by consensus reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches, and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these Guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions held by the Guideline Committee, controversial issues were selected as Clinical Questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2016.

Incorporation of serum carcinoembryonic antigen levels into the prognostic grouping system of colon cancer.

PURPOSE: This study aimed to clarify the significance of preoperative serum carcinoembryonic antigen (CEA) on disease-free survival (DFS) in colon cancer and propose a new prognostic grouping system. METHODS: A multiinstitutional retrospective cohort of 7296 colon cancer patients who underwent R0 surgery between 1997 and 2006 was analyzed. We stratified preoperative serum CEA values into three categories (C-stages): C0 (normal CEA), C1A (up to double the cutoff value), and C1B (more than double the cutoff value) and stratified each TNM stage by C-stage. Multivariate analyses using Cox regression models were used to analyze the significance of C-stage on 5-year DFS. RESULTS: CEA level was an independent factor affecting DFS; the 5-year DFS of patients with C0 and C1, as well as those with C1A and C1B, differed significantly (C0 84.6%, C1 69.8%, C1A 72.7%, and C1B 66.4%, P < 0.0001). Additionally, the DFS of pStages IIC and C1B was significantly lower than of pStages IIIA and C0 (65.8 vs. 87.7%, respectively; hazard ratio 3.44, 95% confidence interval 1.97-5.88, P < 0.0001). Moreover, the 5-year DFS of pStages IIIA and C0 or C1A did not differ significantly from pStages I and C1A (87.7 vs. 87.7%, P = 0.90 and 86.4 vs. 87.7%, P = 0.78, respectively). CONCLUSIONS: pStage IIC and C1B disease should be considered candidates for intensive adjuvant chemotherapy. Conversely, pStages IIIA and C0 or C1A could be exempted from adjuvant chemotherapy. Incorporating C-stage into the current TNM staging system may facilitate decision making regarding the use of adjuvant chemotherapy in colon cancer patients.

Risk Factors for the Development of Desmoid Tumor After Colectomy in Patients with Familial Adenomatous Polyposis: Multicenter Retrospective Cohort Study in Japan.

BACKGROUND: Desmoid tumor (DT) is the primary cause of death in patients with familial adenomatous polyposis (FAP) after restorative proctocolectomy. This study aimed to identify risk factors for DT in a Japanese population. METHODS: Clinical data for 319 patients with FAP undergoing first colectomy from 2000 to 2012 were reviewed retrospectively. RESULTS: Two hundred seventy-seven FAP patients were included in this study. Thirty-nine (14.1 %) patients developed DT. Occurrence sites were the intraperitoneal region in 25 (64.1 %) cases, intraperitoneal region and abdominal wall in three (7.7 %), and abdominal wall in nine (23.1 %). The mean period from surgery to DT development was 26.3 months (range 4-120 months). Gender (female vs. male, p = 0.03), age at surgery (>30 vs. ≤30 years, p = 0.02), purpose of surgery (prophylactic vs. cancer excision, p = 0.01), and surgical procedure (proctocolectomy [ileoanal anastomosis (IAA), ileoanal canal anastomosis (IACA), total proctocolectomy (TPC)] vs. total colectomy [ileorectal anastomosis, partial colectomy]; p = 0.03) significantly influenced the estimated cumulative risk of developing DT at 5 years after surgery. Conversely, approach (laparoscopic vs. open, p = 0.17) had no significant effect on the increased risk of DT occurrence. In multivariate analysis, female gender, with a hazard ratio of 2.2 (p = 0.02,) and proctocolectomy (IAA, IACA, TPC), with a hazard ratio of 2.2 (p = 0.03), were independent risk factors for DT incidence after colectomy. CONCLUSIONS: Female gender and proctocolectomy (IAA, IACA, TPC) were independent risk factors for developing DT after colectomy in patients with FAP.

Impact of Lateral Pelvic Lymph Node Dissection on the Survival of Patients with T3 and T4 Low Rectal Cancer.

BACKGROUND: The aim of this study was to clarify the survival benefit of lateral pelvic lymph node dissection (LPLND) for patients with pathological T3 and T4 (pT3/T4) low rectal cancer. METHODS: We evaluated the impact of LPLND on survival for pT3/T4 low rectal cancer patients. The primary endpoint of the study was overall survival (OS). The large-scale database of the Japanese Society for Cancer of the Colon and Rectum registration system was accessed and the data were analyzed using a propensity score matching method based on the likelihood of receiving LPLND. Using seven covariates, the propensity scores were calculated with multivariate logistic regression. A total of 499 propensity score-matched pairs of patients were selected from the entire cohort of 1,840 patients who had received curative resection for pT3/T4 low rectal cancer between 1995 and 2004. RESULTS: In the matched cohort, the 5-year OS of the patients who had and had not undergone LPLND were 68.9 and 62.0 %, respectively (p = 0.013; hazard ratio [HR], 0.755; 95 % confidence interval [CI], 0.604-0.944). The 5-year OS of the patients with node-negative disease who had and had not received LPLND differed statistically significantly (5-year OS were 82.1 and 71.4 %, respectively. p = 0.006; HR, 0.579; 95 % CI 0.389-0.862). However, those with node-positive disease did not differ significantly (5-year OS were 55.5 and 53.8 %, respectively. p = 0.415; HR 0.893; 95 % CI 0.681-1.172). CONCLUSIONS: The impact of LPLND on OS for patients with node-negative pT3/T4 low rectal cancer was suggested in this retrospective cohort study. To determine true benefits and harms of LPLND, further prospective studies may be warranted.

Clinicopathological Factors Associated with Recurrence and Prognosis after R0 Resection for Stage IV Colorectal Cancer with Peritoneal Metastasis.

BACKGROUND/AIMS: Peritoneal metastasis (PM) is a well-known predictor of poor prognosis. This study aims at identifying factors affecting recurrence and prognosis after R0 resection for colorectal cancer (CRC) with synchronous PM. METHODS: A multi-institutional, retrospective analysis of 172 patients with R0 surgery for CRC with PM was conducted. Clinicopathological variables were analyzed for their significance in contributing toward recurrence and prognosis. RESULTS: Lymph node (LN) metastasis was an independent factor affecting recurrence as indicated by logistic regression analyses. The following factors were independent predictors of poor prognostic using the Cox proportional hazard model: LN metastasis, no postoperative adjuvant chemotherapy, five or fewer dissected LNs, and preoperative high serum carbohydrate antigen 19-9 levels. Of the patients undergoing postoperative adjuvant chemotherapy, no significant differences were observed in recurrence rate and disease-free interval between those with intensive adjuvant chemotherapy and those with non-intensive chemotherapy. After R0 surgery for PM, 90 patients (76.3%) experienced recurrence by 18 months, and hematogenous recurrence occurred significantly more often than peritoneal recurrence. CONCLUSION: Harvesting of more than 5 LNs and administration of postoperative adjuvant chemotherapy after R0 surgery are recommended for prognosis improvement. Intensive follow-up should be performed within 18 months after R0 surgery for CRC with synchronous PM.

New Staging System for Colorectal Cancer Patients with Synchronous Peritoneal Metastasis in Accordance with the Japanese Classification of Colorectal Carcinoma: A Multi-Institutional Study.

BACKGROUND: Peritoneal metastasis of colorectal cancer (CRC) is often discovered during initial surgery. The aim of this study is to propose a new staging system that could be used to help determine the management of CRC patients. METHODS: We evaluated a total of 766 Stage IV CRC patients with synchronous peritoneal metastasis. According to the Japanese classification, we divided the peritoneal metastasis into P1, P2, and P3. We distinguished distant metastasis from liver metastasis and peritoneal metastasis. According to the Cox proportional hazard model, we constructed a new staging group. RESULTS: According to a comparison of the R2 statistics, the combination of liver metastasis and peritoneal metastasis was selected as the final variables. Next, we defined P1H(-) as Grade A, P2H(-) as Grade B, and other groups as Grade C. Our proposed new stage (Akaike Information Criteria [AIC] 7,338.82; concordance index [c-index] 0.644; R2 0.123) could thus divide the patients into different prognostic groups more clearly than the current Japanese classification (AIC 7,373.89; c-index 0.619; R2 0.097). CONCLUSION: Our proposed new staging system is very simple and easy for general surgeons to follow. This system is useful for determining the appropriate operative strategy for CRC patients with peritoneal metastasis and for estimating the patients' prognosis.

Gender differences in colorectal cancer survival in Japan.

BACKGROUND: A gender difference in survival has been documented in colorectal cancer (CRC) patients, although the underlying mechanism remains undefined. This study aimed to gain improved insight into this difference, with a special focus on improved cancer-specific survival. METHODS: The study population consisted of 82,402 patients with invasive CRC who had undergone surgery in Japan between 1985 and 2004. To estimate improved survival, multivariate adjustment using patient demographics and tumor characteristics was performed. RESULTS: Patient characteristics changed over time. The 5-year survival rates increased from 66.5 to 76.3 % during the study period. Higher survival rates persisted in women over time (multivariate-adjustment model-hazard ratio [HR] 0.87, 95 % confidence interval [CI] 0.85-0.90). Patients who received surgery during the period 2000-2004 had significantly longer survival than those during the period 1985-1989 (men: HR 0.70, 95 % CI 0.67-0.74; women: HR 0.72, 95 % CI 0.67-0.76). However, there was no gender difference regarding improved survival. CONCLUSIONS: A reduced risk of cancer-specific death for women relative to men persisted over time; however, enhancement of survival was equally observed in both genders. Identification of factors associated with gender differences and changes over time in CRC survival may serve as targets for further improvement.

Proposal of new classification for stage III colon cancer based on the lymph node ratio: analysis of 4,172 patients from multi-institutional database in Japan.

BACKGROUND: We retrospectively examined the optimal lymph node ratio (LNR) cutoff value and attempted to construct a new classification using the LNR in stage III colon cancer. METHODS: The clinical and pathological data of 4,172 patients with histologically proven lymph node metastasis who underwent curative surgery for primary colon cancer at multiple institutions between 1995 and 2004 were derived from the multi-institutional database of the Japanese Society for Cancer of the Colon and Rectum (JSCCR). We determined independent prognostic factors and constructed a new classification using these factors. Finally, we compared the discriminatory ability between the new classification and the TNM seventh edition (TNM 7th) classification. RESULTS: The optimal LNR cutoff value was 0.18. Multivariate analysis revealed that year of surgery, age, gender, histological type, TNM 7th T category, lymphatic invasion, venous invasion, TNM 7th N category, and LNR were found to be significant independent prognostic factors. We attempted to construct a new classification based on the combination of TNM 7th T category and LNR. As a result, the cancer-specific survivals were well stratified (P < .0001). According to the Akaike's information criteria value, the new classification was judged to be superior to the TNM 7th classification with respect to both a better fit and lower complexity. CONCLUSIONS: The optimal LNR cutoff value that was found using the Japanese multi-institutional database and the new classification using LNR are considered to be extremely significant. Therefore, these findings strongly support the application of LNR in the stage classification in stage III colon cancer.

Validation and Modification of the Japanese Classification System for Liver Metastases from Colorectal Cancer: A Multi-institutional Study.

BACKGROUND: A Japanese multicenter study disclosed four prognostic indicators of colorectal cancer liver metastases: ≥5 hepatic tumors (HT), HT size > 5 cm, nodal status (N2) of primary cancer, and the presence of extrahepatic metastases (EM). The Japanese classification was then defined as Stage A, HT1 (≤4 lesions and ≤5 cm) and N0/1; Stage B, HT2 (≥5 lesions or >5 cm) and N0/1, or HT1 and N2; and Stage C, HT2 and N2, HT3 (≥5 lesions and >5 cm) with any N, or EM1 (presence of EM) with any HT/N. This study aimed to validate the prognostic reliability in a recent population and to develop a modified staging system that divided Stage C patients. METHODS: A total of 1185 patients diagnosed with liver metastases between 2007 and 2008 were enrolled in the study. According to the classification, 358, 257, and 570 patients were categorized as Stages A, B, and C, respectively. Stage C was further divided into two groups: Stage C-I, HT3 and N0/1, HT2 and N2, or HT1 and EM1; and Stage C-II, HT3 and N2, or HT2/3 and EM1. RESULTS: Cumulative overall survival curves for Stages A, B, and C were significantly different between each two stages (p < 0.0001, p < 0.0001). The modified system discriminated patients with a relatively better outcome (Stage C-I) from desperate patients (Stage C-II) (p < 0.0001). CONCLUSIONS: The Japanese classification system was adequately validated in a recent population, and the modified system is useful in risk stratification of Stage C cases.

Influence of extent of lymph node dissection on survival for patients with pT2 colon cancer.

PURPOSE: The optimal extent of lymph node dissection for early-stage colon cancer (CC) remains undefined. This study assessed the influence of the extent of lymph node dissection on overall survival (OS) in patients with pT2 CC. METHODS: We retrospectively examined data from the multi-institutional registry system of the Japanese Society for Cancer of the Colon and Rectum and used a propensity score matching method to balance potential confounders of lymph node dissection. We extracted 463 matched pairs from 1433 patients who underwent major resections for pT2 CC between 1995 and 2004. RESULTS: Lymph node metastasis was found in 301 (21.0%) of 1433 patients with pT2 CC. In this cohort, significant independent risk factors for lymph node metastasis were lymphatic invasion and venous invasion. Patients who underwent D3 or D2 lymph node dissection did not significantly differ in OS, either among the propensity score-matched cohort (estimated hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.536-1.346, P = 0.484) or in the cohort as a whole (HR 0.720, 95% CI 0.492-1.052, P = 0.089). CONCLUSIONS: For patients with pT2 CC, D3 lymph node dissection did not add to OS. D2 lymph node dissection may be adequate for pT2 CC.

Oncological benefit of primary tumor resection with high tie lymph node dissection in unresectable colorectal cancer with synchronous peritoneal metastasis: a propensity score analysis of data from a multi-institute database.

BACKGROUND: Peritoneal metastasis is recognized as a predictor of poor prognosis in patients with colorectal cancer, and whether surgical intervention for peritoneal metastasis has any clinical benefit has remained controversial. The purposes of this study were to identify prognostic factors in cases of unresectable colorectal cancer with synchronous peritoneal metastasis and to clarify the impacts of primary tumor resection with high tie lymph node dissection. METHODS: A multi-institutional retrospective analysis was conducted of 579 patients who underwent resection of the primary tumor for unresectable colorectal cancer with peritoneal metastasis between 1991 and 2007. For these 579 patients, clinicopathological variables were analyzed for prognostic significance using Cox proportional hazards model and propensity score analysis to mitigate the selection bias. RESULTS: Multivariate analysis revealed hematogenous metastasis (p < 0.001), histology of the tumor (p = 0.006), postoperative chemotherapy (p < 0.001), and lymph node dissection (p = 0.001) as independent prognostic factors. In the propensity-matched cohort, patients treated with high tie lymph node dissection showed a significantly better overall survival than those with low tie lymph node dissection (median overall survival 13.0 vs. 11.5 months; p = 0.041). CONCLUSIONS: It is suggested that primary tumor resection with high tie lymph node dissection favorably affects survival, even in unresectable colorectal cancer with peritoneal metastasis.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) Guidelines 2014 for treatment of colorectal cancer.

Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms among women and the third largest number among men. Many new methods of treatment have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2014 for treatment of colorectal cancer (JSCCR Guidelines 2014) have been prepared as standard treatment strategies for colorectal cancer, to eliminate treatment disparities among institutions, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding among health-care professionals and patients by making these guidelines available to the general public. These guidelines have been prepared as a result of consensuses reached by the JSCCR Guideline Committee on the basis of careful review of evidence retrieved by literature searches and taking into consideration the medical health insurance system and actual clinical practice in Japan. They can, therefore, be used as a guide for treating colorectal cancer in clinical practice. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions of the Guideline Committee, controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories, on the basis of consensus reached by Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2014.

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.

Enhancing the objectivity of the Japanese classification of peritoneal metastases from colorectal cancer.

OBJECTIVE: The Japanese classification of peritoneal metastases from colorectal cancer is easy to use for general surgeons in routine clinical practice. However, the objectivity of this classification has not been determined. This study aimed to clarify the objectivity of the Japanese classification of peritoneal metastases from colorectal cancer. METHODS: The data of patients with Stage IV colorectal cancer between 1991 and 2007 in 16 hospitals, who were members of the Japanese Society for Cancer of the Colon and Rectum, were investigated. The size, number and extent (nine areas) of peritoneal metastases according to the Japanese classification (P1, P2 and P3) were investigated using Akaike's information criterion. RESULTS: Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 had hematogenous metastases. The minimum Akaike's information criterion was obtained with the cutoff value of one area for P1 metastasis and two or more areas for P2 metastasis (P < 0.0001). When P2 metastasis was compared with P3 metastasis, the cutoff value of the number of peritoneal metastases was 10. CONCLUSIONS: The present study proposes a revision that would give objectivity to the present Japanese classification as follows: P1 is defined as peritoneal metastases 20 mm or smaller confined to one area; P2 is defined as 10 or fewer peritoneal metastases disseminated in two or more areas, or peritoneal metastases confined to one area but the size is >20 mm and P3 is defined as >10 peritoneal metastases disseminated in two or more areas.

Outcomes of surgery without HIPEC for synchronous peritoneal metastasis from colorectal cancer: data from a multi-center registry.

BACKGROUND: Preoperative detection of small peritoneal metastases is difficult, and a convenient method is required to decide the nature of procedures subsequent to initial exploratory surgery. The aim of this study was to validate the Japanese classification of peritoneal metastasis from colorectal cancer. METHODS: This retrospective study analyzes data from a multi-center registry. Factors affecting the extent of peritoneal metastasis, macroscopic radical resection and prognosis were analyzed using data from patients with colorectal cancer and synchronous peritoneal metastasis. Peritoneal metastasis was classified depending on extent into three groups (P1-P3). RESULTS: Among 60,176 patients with colorectal surgery, 3,075 (5.1 %) had synchronous peritoneal metastasis. Tumor location on the right side (P < 0.0001), histological grade (P = 0.0014) and distant metastasis (P < 0.0001) were associated with the extent of peritoneal metastasis. Gender (P = 0.041), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis according to the present classification (P < 0.0001) and the period when the patient underwent the operation (operative period; P < 0.0001) were independently associated with macroscopic radical resection. Cox proportional hazards model disclosed that gender (P = 0.0046), tumor location (P = 0.032), age (P = 0.048), histological grade (P < 0.0001), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis (P < 0.0001), and macroscopic radical resection (P < 0.0001) were independent prognostic factors. CONCLUSIONS: Macroscopic radical resection was an independent prognostic factor even without hyperthermic intraperitoneal chemotherapy. The referral of patients without distant metastasis to centers with experienced peritoneal surgeons might be a potential option if the peritoneal metastasis is unresectable in general hospitals.