Evaluation of two-stage hepatectomy using portal vein embolization for colorectal liver metastasis: a retrospective nationwide cohort survey in Japan.

INTRODUCTION: Two-stage hepatectomy (TSH) enables patients to undergo surgery for colorectal liver metastasis (CRLM) which one-stage hepatectomy cannot remove. Although the outcome of TSH has been reported, there is no original report from Japan. The aim of this retrospective study was to evaluate the outcome of TSH in Japanese patients with CRLM. METHODS: We conducted a retrospective cohort study using the nationwide database that included clinical information of 12,519 patients treated with CRLM between 2005 and 2017 in Japan. The primary outcome measure was overall survival. The second outcome measure was progression-free survival. Fisher's exact test, chi-squared test and Mann-Whitney U test were conducted to examine an intergroup difference. Univariate and multivariate analyses were performed using Cox regression model. Survival analysis was performed by Kaplan-Meier method and log-rank test. RESULTS: Of the database, 53 patients undergoing TSH using portal vein embolization (PVE) were identified and analyzed. Their morbidity and in-hospital mortality rate at the second hepatectomy were 26.4% and 0.0%. The mean observation period was 21.8 months. The estimated 1-, 3- and 5-year overall survival rate were 92.5%, 70.8% and 34.7%. Multivariate analyses showed that more than 10 liver nodules significantly increased the mortality risk by 4.2-fold (95%CI 1.224-14.99, P= 0.023). Survival analysis revealed that repeat hepatectomy for disease progression after TSH was superior to chemotherapy in overall survival (mean: 49.6 vs. 18.7, months, P= 0.004). CONCLUSION: In the Japanese cohort, TSH was confirmed to be a safety procedure with acceptable survival outcome. More than 10 liver nodules may be a predictor for unfavorable outcome of patients with CRLM undergoing TSH. Furthermore, repeat hepatectomy can be a salvage treatment for resectable intrahepatic recurrence after TSH.

Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201).

BACKGROUND: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes. METHODS: In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery. RESULTS: Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS. CONCLUSION: The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).

Human metaphase II oocytes with narrow perivitelline space have poor fertilization, developmental, and pregnancy potentials.

PURPOSE: To analyze the fertilization, developmental, and pregnancy potentials in oocytes with narrow perivitelline space. METHODS: Perivitelline space (PVS) of oocytes was evaluated at the time of ICSI, and those without sufficient PVS were judged as oocytes with narrow PVS (NPVS oocytes), and those with sufficient PVS formation were judged as oocytes with non-narrow PVS (non-NPVS oocytes). The analysis included 634 NPVS oocytes from 278 cycles and 12,121 non-NPVS oocytes from 1698 cycles. The fertilization and developmental potentials of NPVS and non-NPVS oocytes were compared by calculating odds ratios using a mixed-effects logistic regression model. We also compared the embryo transfer outcomes of those used for single vitrified-warmed blastocyst transfer after developing into the blastocyst stage. RESULTS: NPVS oocytes had higher odds ratios for degeneration (adjusted odds ratio [aOR], 1.555; 95% confidence interval [CI], 1.096-2.206; p = 0.0133) and 0PN (aOR, 1.387; 95% CI, 1.083-1.775; p = 0.0095), resulting in a lower 2PN rate (aOR, 0.761; 95% CI, 0.623-0.929; p = 0.0072). Even embryos with confirmed 2PN had lower odds ratios for cleavage (aOR, 0.501; 95% CI, 0.294-0.853; p = 0.0109) and blastocyst development (Gardner criteria; CC-AA) rates (aOR, 0.612; 95% CI, 0.476-0.788; p = 0.0001). Blastocysts developed from NPVS oocytes had significantly lower odds ratios for clinical pregnancy (aOR, 0.435; 95% CI, 0.222-0.854; p = 0.0156) than those developed from non-NPVS oocytes. CONCLUSIONS: Oocytes with NPVS have low fertilization and developmental potential, as well as low likelihood of pregnancy.

Clinicopathological features and prognosis of primary small bowel adenocarcinoma: a large multicenter analysis of the JSCCR database in Japan.

BACKGROUND: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan. METHODS: We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum. RESULTS: The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA. CONCLUSIONS: Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.

Outcomes of Metastatic and Unresectable Small Bowel Adenocarcinoma in Japan According to the Treatment Strategy: A Nationwide Observational Study.

PURPOSE: Limited information is available regarding the characteristics and outcomes of stage IV small bowel adenocarcinoma (SBA) in Japan. This study examined the clinical and pathological characteristics and outcomes according to the treatment strategies in patients with stage IV SBA. METHODS: This retrospective observational study used the data of patients with jejunal or ileal adenocarcinoma collected by the Small Bowel Malignant Tumor Project of the Japanese Society for Cancer of the Colon and Rectum. Descriptive statistics were expressed as the mean (standard deviation) or median (range). Survival analysis was performed using Kaplan-Meier curves and pairwise log-rank tests. RESULTS: Data from 128 patients were analyzed. The treatment strategies were chemotherapy alone (26 of 128, 20.3%), surgery alone (including palliative surgery; 21 of 128, 16.4%), surgery + chemotherapy (74 of 128, 57.8%), and best supportive care (7 of 128, 5.5%). The median (range) overall survival was 16 (0-125) months overall, and 11 (1-38) months, 8 (0-80) months, 18 (0-125) months, and 0 (0-1) months for the chemotherapy, surgery, surgery + chemotherapy, and best supportive care groups, respectively. Three main categories of chemotherapeutic regimen were used: a combination of fluoropyrimidine and oxaliplatin (F + Ox), fluoropyrimidine and irinotecan (F + Iri), and single-agent fluoropyrimidine. Among patients treated with chemotherapy, the median (range) OS was 16 (1-106) months overall, and 17 (1-87) months, 29 (7-39) months, and 16 (1-106) months in patients treated with fluoropyrimidine, F + Iri, and F + Ox, respectively. CONCLUSION: Patients treated with surgery, chemotherapy, or both had a better prognosis than those who received best supportive care. Among patients who received chemotherapy, survival did not differ according to the chemotherapeutic regimen.

Designing artificial circadian environments with multisensory cares for supporting preterm infants' growth in NICUs.

Previous studies suggest the importance of stable circadian environments for fetuses to achieve sound physiology and intrauterine development. This idea is also supported by epidemiological and animal studies, in which pregnant females exposed to repeated shifting of light-dark cycles had increased rates of reproductive abnormalities and adverse pregnancy outcomes. In response to such findings, artificial circadian environments with light-dark (LD) cycles have been introduced to NICUs to promote better physical development of preterm infants. Such LD cycles, however, may not be fully effective for preterm infants who are less than 30 weeks gestational age (WGA) since they are too premature to be adequately responsive to light. Instead, circadian rhythmicity of incubated preterm infants less than 30 WGA may be able to be developed through stimulation of the non-visual senses such as touch and sound.

Optimal bowel resection margin in colon cancer surgery: prospective multicentre cohort study with lymph node and feeding artery mapping.

Background: There are no standardised criteria for the 'regional' pericolic node in colon cancer, which represents a major cause of the international uncertainty regarding the optimal bowel resection margin. This study aimed to determine 'regional' pericolic nodes based on prospective lymph node (LN) mapping. Methods: According to preplanned in vivo measurements of the bowel, the anatomical distributions of the feeding artery and LNs were determined in 2996 stages I-III colon cancer patients who underwent colectomy with resection margin >10 cm at 25 institutions in Japan. Findings: The mean number of retrieved pericolic nodes was 20.9 (standard deviation, 10.8) per patient. In all patients except seven (0.2%), the primary feeding artery was distributed within 10 cm of the primary tumour. The metastatic pericolic node most distant from the primary tumour was within 3 cm in 837 patients, 3-5 cm in 130 patients, 5-7 cm in 39 patients and 7-10 cm in 34 patients. Only four patients (0.1%) had pericolic lymphatic spread beyond 10 cm; all of whom had T3/4 tumours accompanying extensive mesenteric lymphatic spread. The location of metastatic pericolic node did not differ by the feeding artery's distribution. Postoperatively, none of the 2996 patients developed recurrence in the remaining pericolic nodes. Interpretation: The pericolic nodes designated as 'regional' were those located within 10 cm of the primary tumours, which should be fully considered when determining the bowel resection margin, even in the era of complete mesocolic excision. Funding: Japanese Society for Cancer of the Colon and Rectum.

Correlation between recurrence-free survival and overall survival after upfront surgery for resected colorectal liver metastases.

BACKGROUND: The role of recurrence-free survival (RFS) as a valid surrogate endpoint for overall survival (OS) in patients who underwent upfront surgery for colorectal liver metastases remains uncertain. The aim of the study was to compare the two survival measures in a nationwide cohort of upfront resected colorectal liver metastasis. METHODS: Data from patients with colorectal liver metastases without extrahepatic metastases who underwent curative surgery for liver metastases were retrieved from the Japanese nationwide database (data collection 2005-2007 and 2013-2014). RFS, OS, and survival after recurrence were estimated using the Kaplan-Meier method. The correlation (ρ) between RFS and OS was assessed using the rank correlation method combined with iterative multiple imputation, to account for censoring. As a secondary analysis, the correlation was evaluated according to adjuvant chemotherapy regimen. In sensitivity analysis, the pairwise correlation between RFS and OS was calculated. RESULTS: A total of 2385 patients with colorectal liver metastases were included. In the primary analysis, there was a moderately strong correlation between RFS and OS (ρ = 0.73, 95 per cent c.i. 0.70 to 0.76). The strength of the correlation was similar regardless of the adjuvant treatment regimen (oxaliplatin plus 5-fluorouracil: ρ = 0.72, 0.67 to 0.77; 5-fluorouracil alone: ρ = 0.72, 0.66 to 0.76; observation: ρ = 0.74, 0.69 to 0.78). The mean(s.d.) pairwise correlation coefficient between 3-year RFS and 5-year OS was 0.87(0.06). CONCLUSION: In surgically treated patients with colorectal liver metastases, there was a moderately strong correlation between RFS and OS, which was unaffected by the treatment regimen. Further validation using a trial-level analysis is required.

Comprehensive data of 4502 patients newly diagnosed with colorectal liver metastasis between 2015 and 2017, and prognostic data of 2427 patients newly diagnosed with colorectal liver metastasis in 2013 and 2014: Third report of a nationwide survey in Japan.

To improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. The aim of the study was to evaluate transition in the characteristics and treatment strategy in CRLM patients and analyze prognostic factors using large-scale data. The present study summarizes the data of patients newly diagnosed between 2015 and 2017 and presents prognostic data of patients newly diagnosed in 2013 and 2014. Survival curves were generated by the Kaplan-Meier method and compared by log-rank test. Multivariate analyses were carried out using Cox proportional hazard modeling. The data of 4502 patients newly diagnosed with CRLM between 2015 and 2017 and the prognostic data of 2427 patients diagnosed in 2013 and 2014 are included. Regarding the 2013 and 2014 prognostic data, the 5-year overall survival (OS) rates of patients who underwent hepatectomy alone was 59.8%. Multivariate analyses identified age at diagnosis of CRLM ≥70 years, concomitant extrahepatic metastasis at diagnosis of CRLM, tumor depth of primary lesion ≥subserosa/pericolic or perirectal tissue, mutant KRAS status, number of CRLM ≥5, maximum diameter of CRLM >5 cm, and surgical curability R1/R2 as independent predictors of OS. Analysis of the latest nationwide database of patients diagnosed with CRLM revealed changes in patients and oncological characteristics, a transition in treatment strategy, and different independent prognosticators to those reported previously.

Validation study of the JSHBPS nomogram for patients with colorectal liver metastases who underwent hepatic resection in the recent era - a nationwide survey in Japan.

BACKGROUND: The Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) nomogram was developed to predict disease-free survival in patients with colorectal liver metastases (CRLM) undergoing upfront hepatectomy. However, the utility of the nomogram in patients with resected CRLM remains unknown in the current situation in which treatment strategies are changing with advances in drugs. METHODS: Patients in the initial nomogram cohort (n = 727) and validation cohort (n = 2225) were divided into the upfront hepatectomy and preoperative chemotherapy groups. The nomogram was validated by measuring calibration and discrimination in the two cohorts. Calibration curves were plotted, and survival probabilities were compared. Finally, to quantify the discrimination power, we estimated the concordance index (C-index). RESULTS: In the upfront hepatectomy group, the C-index was 0.63, the suitable cutoff value of the Beppu score was 7, and adjuvant chemotherapy was significantly effective limited to high-risk patients (Beppu score ≥7). The C-index was 0.56 in the preoperative chemotherapy group. CONCLUSIONS: The JSHBPS nomogram remains beneficial for patients undergoing upfront hepatectomy in the recent era but is less effective for patients undergoing hepatectomy after chemotherapy. Patients with a Beppu score ≥7 showed high-risk recurrence, and adjuvant chemotherapy should be recommended for these patients.

Optimal diagnostic criteria for lateral lymph node dissection using magnetic resonance imaging: a multicenter prospective study.

BACKGROUND: LLND in cases with suspected lateral lymph node (LLN) metastasis has been focused on as a novel treatment strategy in recent years. However, the optimal indication for LLND in rectal cancer patients has not been determined. This study aimed to establish the optimal indication for lateral lymph node dissection (LLND) in patients with rectal cancer using magnetic resonance imaging (MRI). METHODS: A total of 209 patients with rectal adenocarcinoma who underwent total mesorectal excision and LLND in 13 hospitals were prospectively registered. By matching the sizes of the harvested LNs and those in magnetic resonance imaging (MRI), the pathological outcome of each LN was confirmed one-by-one. Using parameters of the LLNs in MRI, the optimal diagnostic criteria for LLND were established. RESULTS: Of 3241 harvested LLNs, including 83 metastatic nodes, 1010 (31.1%) were visualized on MRI. Although all parameters assessed showed strong correlations with the presence of metastasis, none of these parameters could discriminate metastatic LLNs from non-metastatic nodes with sufficient sensitivity. However, by using the combination of long axis and short/long ratio in pretreatment MRI, we could establish optimal criteria for LLND. The sensitivity and specificity of the criteria for LLN metastasis were 94.3% and 40.2%, respectively. CONCLUSIONS: In conclusion, we established novel criteria for LLND in rectal cancer patients using MRI. Our criteria will be of great clinical use in determining indications for LLND.

The morphokinetics algorithm based on data from day 5 blastocyst transfer (KIDScoreD5 version 3) is also useful for embryo selection in day 6 blastocyst transfer.

Purpose: To analyze whether the morphokinetics algorithm based on data from day 5 blastocyst transfer (KIDScoreD5 version 3) can predict the pregnancy rate of both day 5 and day 6 blastocyst transfers. Methods: The relationship between KIDScoreD5 and clinical pregnancy rate was evaluated using the Cochran-Armitage test and receiver-operating characteristic (ROC) curve analysis. Results: A positive correlation was observed between the KIDScoreD5 value and clinical pregnancy rate for both day 5 (p = 0.0003) and day 6 blastocysts (p = 0.0019) using the Cochrane-Armitage test. ROC curve analysis showed that the area under the curve (AUC) of KIDScoreD5 for clinical pregnancy was 0.627 (0.575-0.677, p < 0.0001) for day 5 blastocysts and 0.685 (0.571-0.780, p = 0.0009) for day 6 blastocysts. The combined analysis of both day 5 and day 6 blastocysts also showed an AUC of 0.680 (0.636-0.720, p < 0.0001), suggesting that it is possible to select embryos that are more likely to result in pregnancy. Conclusions: KIDScoreD5 could predict pregnancy not only in day 5 blastocysts but also in day 6 blastocysts. When both day 5 and day 6 blastocysts are vitrified, embryo selection by KIDScoreD5 is possible with a high prediction ability of pregnancy.

Management of inguinal lymph node metastases from rectal and anal canal adenocarcinoma.

AIM: The surgical treatment of inguinal lymph node (ILN) metastases secondary to anorectal adenocarcinoma remains controversial. This study aimed to clarify the surgical treatment and management of ILN metastasis according to its classification. METHODS: This retrospective, multi-centre, observational study included patients with synchronous or metachronous ILN metastases who were diagnosed with rectal or anal canal adenocarcinoma between January 1997 and December 2011. Treatment outcomes were analysed according to recurrence and prognosis. RESULTS: Among 1181 consecutively enrolled patients who received treatment for rectal or anal canal adenocarcinoma at 20 referral hospitals, 76 (6.4%) and 65 (5.5%) had synchronous and metachronous ILN metastases, respectively. Among 141 patients with ILN metastasis, differentiated carcinoma, solitary ILN metastasis and ILN dissection were identified as independent predictive factors associated with a favourable prognosis. No significant difference was found in the frequency of recurrence after ILN dissection between patients with synchronous (80.6%) or metachronous (81.0%) ILN metastases. Patients who underwent R0 resection of the primary tumour and ILN dissection had a 5-year survival rate of 41.3% after ILN dissection (34.1% and 53.1% for patients with synchronous and metachronous ILN metastases, respectively, P = 0.55). CONCLUSION: The ILN can be appropriately classified as a regional lymph node in rectal and anal canal adenocarcinoma. Moreover, aggressive ILN dissection might be effective in improving the prognosis of low rectal and anal canal adenocarcinoma with ILN metastases; thus, prophylactic ILN dissection is unnecessary.

Granulocyte-macrophage colony-stimulating factor-containing medium treatment after thawing improves blastocyst-transfer outcomes in the frozen- thawed blastocyst-transfer cycle.

PURPOSE: To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-containing medium could improve embryo-transfer outcomes in frozen-thawed blastocyst transfer. METHODS: Patients who underwent frozen-thawed blastocyst transfer (430 women, aged 30-39 years, 566 cycles) were analyzed. Frozen-thawed blastocysts were cultured in GM-CSF-containing medium or control medium for 3-5 h, followed by transfer to the uterus. The embryo-transfer outcomes in the two groups were measured and compared, and a propensity score matching (1:1) method was used to balance the differences in baseline characteristics. We analyzed 213 matched samples. RESULTS: In patients who underwent frozen-thawed blastocyst transfer with GM-CSF, the percentage of human chorionic gonadotropin-positive cases, biochemical pregnancies, clinical pregnancies, ongoing pregnancies, and live birth rates was 60.6%, 7.98%, 52.6%, 42.9%, and 40.9%, respectively, as compared with 45.1%, 3.29%, 41.8%, 31.1%, and 30.5%, respectively, for the control groups. The rates of human chorionic gonadotropin positivity (odds ratio [OR]: 1.87, 95% confidence interval: [CI]: 1.27-2.75), biochemical pregnancy (2.55, 1.04-6.29), clinical pregnancy (1.54, 1.05-2.27), ongoing pregnancy (1.64, 1.13-2.41), and live birth (1.67, 1.14-2.45) were significantly higher in the GM-CSF group than the control group. The incidence of pregnancy loss (22.3% vs. 27.0%) did not significantly differ between the groups. CONCLUSION: The use of a GM-CSF-containing medium for blastocyst-recovery culture improved the live birth rate as a result of increased implantation rate in the frozen-thawed blastocyst-transfer cycle. The use of GM-CSF-containing medium following blastocyst thawing could be an effective choice for improving the blastocyst-transfer outcomes.

Optimizing nodal and staging classification in low rectal cancers with lateral node metastasis: multicentre retrospective cohort study.

BACKGROUND: Patients with lateral node metastasis in low rectal cancers have a poor prognosis. However, variability in patient survival in terms of lateral metastatic status has not been thoroughly investigated. This study was conducted to assess the prognostic value of lateral node involvement and to review nodal classification. METHODS: Patients with stage III low rectal cancers who underwent lateral node dissection were retrospectively reviewed. Two cohorts were set: the first one (1995-2006) was selected using a Japanese multi-institutional database and was used for development of a new nodal system, and the second (2007-2013) was collected from referral institutions for validation of findings. Variables correlated with poor prognosis were investigated. Next, a modified classification of lateral-positive nodal cancers was created. Finally, this new classification was compared with TNM and Japanese classification-based systems according to the Akaike information criterion (AIC) and concordance index (c-index). RESULTS: Overall, 742 and 508 patients were selected for cohorts 1 and 2, respectively. Based on the analyses on cohort 1, patients with two or more lateral metastatic nodes partially spreading into regions outside of internal iliac area exhibited poor prognosis; accordingly, a modified N classification was created, where TNM-N1 and N2a cancers with this feature were upgraded, respectively, to N2a and N2b. The modified N classification yielded the most favourable indices (AIC = 2661.08; c-index = 0.6477) compared with the TNM (AIC = 2662.36; c-index = 0.6457) and Japanese classification-based systems (AIC = 2684.06; c-index = 0.6302). All findings were confirmed by analysing cohort 2. CONCLUSION: A modified nodal system is proposed to account for the significance of lateral node metastasis.

Characteristics of anal canal cancer in Japan.

Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi-institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above-mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b.

Prospective observational study of the efficacy of oral uracil and tegafur plus leucovorin for stage II colon cancer with risk factors for recurrence using propensity score matching (JFMC46-1201).

BACKGROUND: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. We compared the effects of surgery with and without oral uracil and tegafur plus leucovorin (UFT/LV) in patients with high-risk stage II CC, adjusting for potential risk factors. METHODS: We enrolled patients with histologically confirmed stage II colon adenocarcinoma with at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. Patients chose to be non-randomized or randomized to undergo surgery alone (NR-Group S or R-Group S) or surgery followed by 6 months of UFT/LV (NR-Group U or R-Group U). The primary endpoint was disease-free survival (DFS) after adjusting for previously reported risk factors using propensity score matching (1:2) and inverse probability of treatment weighting (IPTW) in the non-randomized arm. RESULTS: Overall, 1,902 (98%) and 36 (2%) patients were enrolled in the non-randomized and randomized arms, respectively. There were too few patients in the randomized arm and these were therefore excluded from the analysis. Of the 1,902 patients, 402 in NR-Group S and 804 in NR-Group U were propensity score-matched. The 3-year DFS rate (95% confidence interval) was significantly higher in NR-Group U (80.9% [77.9%-83.4%]) than in NR-Group S (74.0% [69.3%-78.0%]) (hazard ratio, 0.64 [0.50-0.83]; P = 0.0006). The 3-year overall survival rate was not significantly different between NR-Group S and NR-Group U. Significantly higher 3-year DFS (P = 0.0013) and overall survival (P = 0.0315) rates were observed in NR-Group U compared with NR-Group S using IPTW. CONCLUSIONS: Adjuvant chemotherapy with UFT/LV showed a significant survival benefit over surgery alone in patients with high-risk stage II CC characterized by at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019) (UMIN Clinical Trials Registry: UMIN000007783 , date of registration: 18/04/2012).

A randomized controlled trial of surgery and postoperative modified FOLFOX6 versus surgery and perioperative modified FOLFOX6 plus cetuximab in patients with KRAS wild-type resectable colorectal liver metastases: EXPERT study.

PURPOSE: To clarify the efficacy of perioperative chemotherapy for the patients with resectable colorectal liver metastases (CLM), we conducted a multicenter randomized phase III trial to compare surgery followed by postoperative FOLFOX regimen with perioperative FOLFOX regimen plus cetuximab in patients with KRAS wild-type resectable CLM. METHODS: Patients who had KRAS wild-type resectable CLM having one to eight liver nodules without extrahepatic disease were randomly assigned to the postoperative chemotherapy group, wherein up-front hepatectomy was performed followed by 12 cycles of postoperative modified FOLFOX6, and the perioperative chemotherapy group (experimental), wherein six cycles of preoperative modified FOLFOX6 plus cetuximab were performed followed by hepatectomy and six cycles of postoperative modified FOLFOX6 plus cetuximab. The primary endpoint was progression-free survival (PFS). RESULTS: There were 37 patients in postoperative chemotherapy group and 40 patients in the perioperative chemotherapy group who were analyzed. Baseline characteristics were well-balanced between groups. The PFS and overall survival (OS) showed no significant difference (PFS, hazard ratio 1.18 [95% confidence interval 0.69-2.01], P = 0.539: OS, 1.03 [0.46-2.29], P = 0.950). In the postoperative chemotherapy group, 35.1% had a 3-year PFS, and 86.5% had a 3-year OS. Meanwhile, in the perioperative chemotherapy group, 30.0% had a 3-year PFS, and 74.4% had a 3-year OS. CONCLUSION: There was no difference in survival found between the group of the perioperative chemotherapy plus cetuximab and that of the postoperative chemotherapy in the cohort of our study. The study was registered in the University Hospital Medical Information Network (UMIN000007787).

A nationwide, multi-institutional collaborative retrospective study of colorectal neuroendocrine tumors in Japan.

AIM: Neuroendocrine tumors (NETs) are one of the subtypes of neuroendocrine neoplasms and are defined as epithelial neoplasms with predominant neuroendocrine differentiation. The aim of this study was to clarify the clinicopathological characteristics of colorectal NETs through a nationwide retrospective study in Japan. METHODS: This multicenter retrospective cohort study of NETs in Japan was conducted by the study group of the Japanese Society for Cancer of the Colon and Rectum. In this study, we aimed to clarify the characteristics of Japanese patients with colorectal NETs. This cohort study included patients with colorectal NETs who were treated from January 2011 to December 2015. RESULTS: Most NETs developed in the lower rectum. Predictive factors of lymph node metastasis included size (>10 mm), depth of invasion (muscular propria or greater), NET grade (NET G2), depressed lesion of the tumor, and lymphovascular infiltration. In particular, depressed lesion of the tumor and lymphovascular infiltration were independent predictive factors of lymph node metastasis. The presence of an increased number of these predictive factors increased the lymph node metastasis rate. CONCLUSION: Surgical resection with lymph node dissection is considered in the colorectal NETs patients with predictive factors of lymph node metastasis, the number of which is correlated with incidence of lymph node metastasis.