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Aim We investigated whether or not postoperative complications (POCs) themselves have a negative survival impact or indirectly worsen the survival due to insufficient adjuvant chemotherapy in a pooled analysis of two large phase III studies performed in Japan Patients and methods The study examined the patients who enrolled in 1304, phase III study comparing the efficacy of 6 and 12 months of capecitabine as adjuvant chemotherapy for stage III colon cancer patients and in 882, a phase III study to confirm the tolerability of oxaliplatin, fluorouracil, and l-leucovorin in Japanese stage II/III colon cancer patients. In our study, POCs were defined as the following major surgical complications: anastomotic leakage, pneumonia, bowel obstruction/ileus, surgical site infection, postoperative bleeding, urinary tract infection, and fistula. Patients were classified as those with POCs (C group) and those without POCs (NC group). Results A total of 2095 patients were examined in the present study. POCs were observed in 169 patients (8.1%). The overall survival (OS) rates at 5 years after surgery were 75.3% in the C group and 86.5% in the NC group (p = 0.0017). The hazard ratio of POCs for the OS in multivariate analysis was 1.70 (95% confidence interval, 1.19 to 2.45; p = 0.0040). The time to adjuvant treatment failure (TTF) of adjuvant chemotherapy was similar between the groups, being 68.6% in the C group and 67.1% in the NC group for the 6-month continuation rate of adjuvant chemotherapy. The dose reduction rate of adjuvant chemotherapy and adjuvant treatment suspension rate were also similar between the groups (C vs. NC groups: 45.0% vs. 48.7%, p = 0.3520; and 52.7% vs. 55.0%, p = 0.5522, respectively). Conclusion POCs were associated with a poor prognosis but did not affect the intensity of adjuvant chemotherapy. These results suggested that POCs themselves negatively influence the survival.

There are several reports of hepatic resection for postoperative hepatic metastatic recurrence of esophageal cancer. However, it is unclear whether surgery is the best local treatment for liver metastases. Thus, this study aimed to retrospectively analyze proton beam therapy (PBT) for postoperative liver metastatic recurrence of esophageal cancer without extrahepatic lesions and examine outcomes and adverse events. This single-center historical cohort study selected patients who underwent PBT at our proton therapy center between 2012 and 2018. The patients were selected based on the following criteria: primary esophagus carcinoma was resection and metachronous liver oligometastasis recurrence without extrahepatic tumors and no more than three liver metastases. This study included seven males with a median age of 66 (range, 58–78) years, and 15 lesions were included in the study. The median tumor size was 22.6 (7–55.3) mm. The most frequent dose was 72.6 Gy relative biological effect (RBE)/22 fractions (fr) for four lesions and 64 Gy (RBE)/8 fr for four lesions. The median survival time was 35.5 (13.2–119.4) months. The 1-, 2- and 3-year overall survival (OS) rates were 100%, 57.1% and 42.9%, respectively. The median progression-free survival (PFS) time was 8.7 (1.2–44.1) months. The 1-, 2- and 3-year PFS rates were 28.6%. The 1-, 2- and 3-year local control (LC) rates were 100%. No grade ≥4 radiation-induced adverse events (AEs) were observed. We conclude that PBT can be considered an alternative to hepatic resection for recurrent liver metastases postoperative esophageal cancer.

We investigated the association of the levels of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) with prognosis in patients with stage IV colorectal cancer at diagnosis.In this multicenter retrospective cohort study, patients with serum CEA and CA19-9 measured at diagnosis of stage IV colorectal cancer were included. The cutoff values were 5 ng/ml for CEA and 37 U/ml for CA19-9. Patients were categorized into four groups: those with normal levels for both CEA and CA19-9; those with only an elevated CEA level; those with only an elevated CA19-9 level; and those with elevated levels of both.A total of 825 patients were included. Among them, 132 (16.0%) had normal levels for both markers, 258 (31.3%) had an elevated CEA level only, 33 (4.0%) had an elevated CA19-9 level only, and 402 (48.7%) had elevated levels of both CEA and CA19-9. Compared with patients with normal levels for both CEA and CA19-9, the multivariate hazard ratio for overall survival was 1.24 (95% confidence interval=0.95-1.62, p=0.12) for those with elevated CEA only, 2.04 (95% confidence interval=1.31-3.17, p=0.002) for those with elevated CA19-9 only, and 1.82 (95% confidence interval=1.41-2.32, p0.001) in those with elevation of both CEA and CA19-9.Elevation of CEA alone was not prognostic. Elevation of only CA19-9 at diagnosis was associated with a worse prognosis in patients with stage IV colorectal cancer. The combined measurement of CEA and CA19-9 can be helpful as a predictive tool for the prognosis of stage IV colorectal cancer.

This study aimed to examine the effectiveness of polypectomy with cutting current (PCC) for colorectal polyps, compared with cold snare polypectomy (CSP).The study design was a singlecenter randomized controlled trial. We included patients with one or more non-pedunculated colorectal polyps of 6 mm or more and less than 10 mm. The primary endpoint was the proportion of complete resection of the muscularis mucosae.Twenty-seven patients (37 polyps) were assigned to the CSP group, and 22 (29 polyps) were assigned to the PCC group. The number of polyps that could achieve complete muscularis mucosae resection was 7 (20.0%) in the CSP group and 24 (92.3%) in the PCC group, and the rate of complete muscularis mucosae resection was statistically significantly higher in the PCC group.PCC is a safer procedure because it can remove the muscularis mucosae more reliably.

The incidence of acute cholecystitis has a seasonal peak in summer. However, the reason for such seasonality remains unclear. This retrospective cohort study was performed to examine the association between ambient temperature and acute cholecystitis.We identified admissions for acute cholecystitis from January 2011 to December 2017 from a nationwide inpatient database in Japan. We performed a Poisson regression analysis to investigate the association between ambient temperature and admission for acute cholecystitis with adjustment for relative humidity, national holidays, day of the week, and year. We accounted for clustering of the outcome within prefectures using a generalized estimating equation.We analyzed 601 665 admissions for acute cholecystitis. With an ambient temperature of 5.0 °C-9.9 °C as a reference, Poisson regression showed that the number of admissions increased significantly with increasing temperature (highest above 30 °C; relative risk, 1.35; 95% confidence interval, 1.34-1.37). An ambient temperature of5.0 °C was also associated with higher admission for acute cholecystitis than an ambient temperature of 5.0 °C-9.9 °C (relative risk, 1.23; 95% confidence interval, 1.21-1.25).The present nationwide Japanese inpatient database study showed that high temperature (≥10.0 °C) and low temperature (5.0 °C) were associated with increased admission for acute cholecystitis.

A sheet-like X-ray phantom on which thin Iodine is uniformly coated was developed to facilitate the handling of iodined objects used in any X-ray imaging studies.The most recommendable protocol as follows: (1) prepare undiluted 240 mg/ml Iohexol-based contrast agent and drop around 1.6 g on a horizontal surface. (2) infiltrate the agent into a membrane filter (47 mm in diameter) from the secondary side. (3) one minute later, the excess liquid components should be removed by a softy absorbent paper, and the infiltrated membrane filter should be left until substantially dried.The dried membrane filter can be utilized as a sheet-like X-ray phantom on which the iodine of around 2.45 mg is almost uniformly distributed per 1 cmIn the practical experiments, the X-ray attenuation factor can be controlled by changing the stacking number of the sheet, and the spatial size and form can also be designed by cutting the sheet. This capability is expected to improve the efficiency of any X-ray experiments and quality control works that requires iodined materials.

Purpose The purpose of this study was to clarify the clinical features and outcomes of patients with recurrence after esophagectomy following neoadjuvant chemotherapy (NAC) related to the timing of recurrence. Methods We reviewed 240 consecutive patients who underwent NAC followed by esophagectomy for clinical stage II/III esophageal squamous cell carcinoma between 2009 and 2014. We compared the clinical features and survival after recurrence among groups of patients stratified by the timing of recurrence diagnosis and identified the risk factors for early recurrence (ER). Results Recurrence was identified within 1 year in 61 patients and after 1 year in 23 patients. Significant differences were observed between the patients with recurrence within 1 year (early recurrence; ER) and those with recurrence after 1 year (late recurrence; LR). The ER patients had more advanced tumors and higher pretreatment serum squamous cell antigen (SCC-Ag) levels and less experienced downstaging than patients without recurrence (no recurrence; NR). Overall survival was significantly worse for the ER patients than for the LR patients. Multivariate analysis revealed that cN2-3, increased serum SCC-Ag levels, and clinical response to NAC were independent predictors of ER. Conclusion The ER patients had distinctive clinical features from the LR and NR patients. Extensive lymph node metastasis, an elevated SCC-Ag, and inadequate response to NAC were identified as predictors of ER.

Purpose: The prevention of osteoporosis is a particularly relevant issue for gastric cancer survivors. We investigated the relationship between postoperative physical activity and the change of bone mineral density (BMD) in patients with gastric cancer.Methods: Patients who underwent radical gastrectomy for gastric cancer were enrolled in this single-center prospective cohort study. Physical activity was evaluated using the International Physical Activity Questionnaire Short Form at postoperative month (POM) 6 and patients were classified into high, middle, and low physical activity groups accordingly. The primary outcome was the change in BMD from baseline at POM 12, which was expressed as a percentage of the young adult mean (YAM). The YAM of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. Results: One hundred ten patients were enrolled in this study. The physical activity level at POM6 was classified as high (n=50; 45%), middle (n=25; 23%), and low (n=35; 32%). The mean decrease of YAM% was 5.1% in the lumbar spine and 4.2% in the femoral neck at POM 12. A multivariable-adjusted logistic regression model revealed that low physical activity at POM 6 was a significant risk factor for BMD loss at POM 12 (odds ratio, 3.63; 95% confidence interval, 1.45–9.11; p=0.006).Conclusion: Low physical activity after gastrectomy is an independent risk factor for decreased BMD at POM12. The introduction of exercise may prevent osteoporosis after the surgical treatment of gastric cancer.

Primary tumor resection (PTR) before commencing systemic chemotherapy in patients with stage IV colorectal cancer and unresectable metastases (mCRC) remains controversial. This study aimed to assess whether PTR before systemic chemotherapy is associated with mortality in mCRC patients, after adjusting for confounding factors, such as the severity of the primary tumor and metastatic lesions. We analyzed hospital-based cancer registries from nine designated cancer hospitals in Fukushima Prefecture, Japan. Patients were divided into two groups (PTR and non-PTR), based on whether PTR was performed as initial therapy for mCRC or not. The primary outcome was all-cause mortality. Kaplan–Meier survival analysis was performed, and survival estimates were compared using the log-rank test. Adjusted hazard ratios were calculated using Cox regression to adjust for confounding factors. All tests were two-sided; P-values

Purpose This study aims to investigate the influence of time-intensity curves (TICs) on the shapes using a dynamic contrast-enhanced magnetic resonance imaging (MRI) study depending on the Cartesian and radial orders for benign and cancerous breast tumors. Methods Based on kinetic curve parameters, the signal intensities of six concentration gradients comprising two benign and four cancer models were used. The study aimed to construct a dynamic simulated image by creating a digital phantom image according to the following steps: (1) creating a simple numerical phantom, (2) setting the signal intensity in the contrast area, (3) creating the k-space in each time phase, (4) extracting data from k-space in each time phase, (5) filling in the k-space and adding data to the k-space assembly, and (6) creating a magnitude image. The TICs of Cartesian (centric and sequential) and radial (full-length [RFL] and half-length [RHL]) orders were created and sigmoid curve fitting was performed to compare these curves. Maximum slope (MS, s−1), width of the response (WOR, s), and primary signal response (PSR) were then calculated. Phase encode steps were set for 512 and 256. Results MS was significantly decreased by radial order in the cancer model. No change was observed in WOR in Cartesian order, whereas RFL and RHL orders increased in the cancer models. PSR increased remarkably in the radial orders of cancer models. The difference in the fill slope in radial orders was remarkable when the TIC was steeper compared with when it was gentle, especially RHL. In WOR, both radial RFL and RHL were well matched except for the one benign model, and the shape of radial TIC was similar to sequential order as compared to centric order in 256 steps. Conclusion The effects of Cartesian and radial orders on the patterns of TICs in a dynamic contrast-enhanced MRI study of benign and cancerous breast tumors were revealed. Interestingly, the TIC gradient of radial orders became gentler, particularly in the breast cancer MRI.

INTRODUCTION: The aim of this study is to characterize health related quality of life (HRQOL) in Japanese patients after bladder cancer surgery and to perform cross-cultural comparison between Japanese and American patients. METHODS: Firstly, we cross-sectionally assessed HRQOL of 371 patients in Japan using the Bladder Cancer Index (BCI-Japanese). HRQOL of the four groups of patients (native bladder without intravesical therapy, native bladder with intravesical therapy, cystectomy with ileal conduit, and cystectomy with neobladder) were assessed. Secondly, we compared the Japanese with the American cohort (n = 315) from the original BCI paper. After adjusting for age and gender, the differences in each BCI subdomain score was analyzed. RESULTS: Among Japanese patients, the urinary domain function score was significantly lower among the cystectomy with neobladder group, compared to the cystectomy with ileal conduit group (p

The clipping method is widely used in endoscopic hemostasis for colonic diverticular hemorrhage. Recently, rebleeding was shown to be less common in ligation therapy than in clipping. Ligation methods include endoscopic band ligation (EBL) and endoscopic detachable snare ligation (EDSL). No studies have compared procedure times for EBL and EDSL. The present study aimed to compare EDSL and EBL in terms of procedure time.In this single-center retrospective observational cohort study, we evaluated the data of 39 patients who underwent EBL or EDSL for colonic diverticular hemorrhage. The primary and secondary outcomes measured were the total procedure time and early rebleeding rate, respectively.Among the 39 patients included in the study, 18 underwent EBL, and 21 underwent EDSL for hemostasis. The median total pro- cedure times for the EBL and EDSL groups were 50 (range, 30-80) minutes and 35 (range, 18-55) minutes, respectively, demonstrating that the total colonoscopy time was significantly shorter in the EDSL group (P.001). The early rebleeding rate was 11.1% (2/18) in the EBL group and 4.8% (1/21) in the EDSL group (P = .246).Important improvements in procedure time were achieved in the EDSL group. Based on our results, we believe that EDSL may reduce patient and endoscopist burden.

There are no existing reports on proton beam therapy (PBT) for local control (LC) of liver metastasis of colorectal cancer (LMCRC). We calculated the LC rate of PBT for LMCRC and explored the influence of each factor on the LC rate.Cases in which PBT was performed at our center between 2009 and 2018 were retrospectively selected from the database. Patients with LMCRC without extrahepatic lesions and no more than three liver metastases were included. Effectiveness was assessed based on LC, overall survival (OS), and progression-free survival (PFS) rates. Adverse events (AEs) are described. Factors that may be related to LC were also investigated.This study included 23 men and 18 women, with a median age of 66 (range 24-87) years. A total of 63 lesions were included in the study. The most frequent dose was 72.6 Gy (relative biological effectiveness)/22 fractions. The median follow-up period was 27.6 months. The 3‑year LC, OS, and PFS rates were 54.9%, 61.6%, and 16.7%, respectively. Our multivariate analysis identified the distance between the tumor and the gastrointestinal (GI) tract as a factor associated with LC (P = 0.02). No grade ≥ 3 AEs were observed. None of the patients experienced liver failure during the acute or late phase.Care must be taken with tumors that have reduced planning target volume coverage owing to organs at risk restrictions, especially in tumors near the GI tract.

Introduction We validated a Japanese version of the Bladder Cancer Index (BCI) as a tool for measuring health-related quality of life (HRQOL) in bladder cancer patients treated with various surgical procedures. Methods The reliability and validity of the Japanese BCI were examined in 397 Japanese patients with bladder cancer via cross-sectional analysis. The patients simultaneously completed the Short Form (SF)-12, EQ-5D, and the Functional Assessment of Cancer Therapy-General and Bladder (FACT-G and FACT-BL). The differences in BCI subscales among various treatment groups were analyzed. Results This study involved 397 patients (301 males and 96 females), with a mean age of 70 years and a median disease duration of 29 months (IQR: 12–66 months). Of these patients, 221 underwent transurethral resection of a bladder tumor, and 176 patients underwent radical cystectomy (ileal conduit: 101 patients, ileal neobladder: 49, and ureterostomy: 26). Cronbach’s alpha coefficient was ≥ 0.78 for all subscales, except the bowel bother subscale. Despite moderate correlations being detected between the function and bother score in urinary and bowel domains, the sexual function score was inversely correlated with the sexual bother score (r = − 0.19). A missing value percentage of > 15% was associated with old age (p Conclusions Although revisions are needed to make it easier for elderly patients to comprehend, we confirmed the reliability and validity of the Japanese BCI. The Japanese BCI could be used for cross-cultural assessments of HRQOL in bladder cancer patients.

Background A 4-week administration of tegafur/gimeracil/oteracil (S-1) followed by a 2-week rest is the standard adjuvant chemotherapy for surgically resected advanced gastric cancer. This study aimed to evaluate the oncological feasibility of a 2-week S-1 administration followed by a 1-week rest, which is frequently applied in clinical practice to reduce toxicity and improve drug adherence. Methods We retrospectively enrolled patients with stage II/III gastric cancer who received S-1 adjuvant chemotherapy following radical gastrectomy from 2006 to 2016 in three institutions. Two-week and 4-week regimen cohorts were compared for relative dose intensity (RDI) as a primary outcome, and treatment completion rate, adverse event incidence, overall survival (OS), and relapse-free survival (RFS) as secondary outcomes. Confounders were adjusted for using propensity score matching (PSM). Results One hundred and thirty-four patients received the 2-week regimen and 121 patients received the 4-week regimen. Ninety-five patients were extracted from each group after PSM. The RDIs of S-1 in the 2-week and 4-week cohorts were 73.5 and 69.9%, respectively (p = 0.35), which were not significantly different. The treatment completion rate (54.7 vs. 53.7%, p = 1.0), incidence of grade ≥3 adverse events (7.4 vs. 12.6%, p = 0.33), 3-year OS (76.4 vs. 82.7%, p = 0.78), and 3-year RFS (71.3 vs. 73.4%, p = 0.70) did not significantly differ between both cohorts. Conclusions The 2-week S-1 adjuvant chemotherapy could not improve drug adherence in terms of RDI, but its relapse rates were not significantly different compared with those of the 4-week regimen. The 2-week regimen might be considered as an option depending on the patient’s status.

Introduction: The prognosis of adolescent and young adult (AYA) patients with colorectal cancer (CRC) is still unclear. The aim of this study was to investigate the clinical features and prognosis in AYA patients compared with middle- aged patients. Methods: Participants were identified from a clinical database of the multicenter cohort in Japan. The AYA group was defined as those

TPS479 Background: The standard treatment for locally advanced proximal gastric cancer invading the greater curvature is “open total gastrectomy combined with splenectomy” (OTG+S) aiming for whole clearance of the splenic hilar lymph nodes. However, its pertinent postoperative severe complication (e.g. pancreatic fistula) is problematic. An objective of this study is to evaluate the safety of “laparoscopic or robotic total gastrectomy with spleen-preserving splenic hilar dissection” (LRSHD) as a new treatment option which has a potential to reduce surgical morbidity, subsequently to replace the current standard treatment, OTG+S. Methods: This is a multicenter single-arm phase II trial. The main eligibility criteria are as follows; clinical T2-4a resectable locally advanced proximal gastric adenocarcinoma that invades the greater curvature; without obvious lymph node metastasis at the splenic hilum nor direct invasion to the spleen/splenogastric ligament. Protocol treatment is laparoscopic or robotic total gastrectomy with splenic hilar lymph node dissection (D2 + No.10 lymphadenectomy according to the Japanese guidelines) in which the spleen is preserved with skeletonizing the splenic vessels. Quality control of surgery is assured by surgeon’s qualification and central peer review of intraoperative photo at the splenic hilum after dissection. The primary endpoint is the proportion of postoperative pancreatic fistula and/or intra-abdominal abscess formation with Clavien-Dindo Grade III or higher (within 30 days after surgery). Secondary endpoints are intraoperative blood loss, operation time, mortality, overall postoperative complication, number of yield splenic hilar nodes, number of metastatic splenic hilar nodes, conversion to splenectomy, conversion to laparotomy, relapse-free survival, and overall survival. Sample size was set as 85 patients to obtain 80% power considering that 15% of patients are judged as unresectable intraoperatively, with the hypothesis that the primary endpoint would have an expected value of 7% and a threshold value of 16% in one-sided alpha of 0.1. Planned accrual period is 5 years. The accrual began in August 2019. As of August 2022, 53 of the planned 85 patients (62.4%) have been enrolled. When the safety of LRSHD is proved by this study, a non-inferiority phase III trial will be consequently launched. Clinical trial registry number: UMIN000037580. Clinical trial information: UMIN000037580 .

The prognosis of gastric cancer patients with positive lavage cytology without gross peritoneal dissemination (P0CY1) is poor. The survival benefit of gastrectomy for these patients has not been established.In this population-based cohort study, we investigated the impact of radical gastrectomy with lymph node dissection for P0CY1 patients. Patients who were diagnosed with Stage IV gastric cancer from 2008 to 2015 in all nine cancer-designated hospitals in a tertiary medical area were listed. Patients who were diagnosed with histologically proven adenocarcinoma in both the primary lesion and lavage cytology during the operation or a diagnostic laparoscopic examination were enrolled. Patients with a gross peritoneal lesion or other metastatic lesions were excluded. The primary outcome was the adjusted hazard ratio (aHR) of gastrectomy for overall survival. We also evaluated the survival time in patients who underwent gastrectomy or chemotherapy in comparison to patients managed without primary surgery or with best supportive care.One hundred patients were enrolled. The aHR (95% confidence interval) of gastrectomy was 0.677 (0.411-1.114, p = 0.125). The median survival time in patients who received gastrectomy (n = 74) was 21.7, while that in patients managed without primary surgery (n = 30) was 20.5 months (p = 0.155). The median survival time in patients who received chemotherapy (n = 76) was 23.0 months, while that in patients managed without chemotherapy was 8.6 months (p 0.001).Gastrectomy was not effective for improving the survival time in patients with P0CY1 gastric cancer. Surgeons should prioritize the performance of chemotherapy over surgery as the initial treatment.

Background There are a few established prognostic factors for stage IV colorectal cancer. Thus, this study aimed to evaluate the impact of histological subtypes on prognosis and metastatic patterns in patients with stage IV colorectal cancer. Methods This was a population-based, multicenter, cohort study. We included consecutive patients diagnosed with stage IV colorectal cancer between 2008 and 2015 at all designated cancer hospitals in Fukushima prefecture, Japan. Patients were classified into two groups according to histological subtypes as follows: poorly differentiated adenocarcinoma (Por), mucinous adenocarcinoma (Muc), or signet-ring cell carcinoma (Sig) and well (Wel) or moderately differentiated adenocarcinoma (Mod). We evaluated the relationship between these histological groups and survival time. After adjusting for other clinical factors, we calculated the hazard ratio for Por/Muc/Sig. Results A total of 1,151 patients were enrolled, and 1,031 and 120 had Wel/Mod and Por/Muc/Sig, respectively. The median overall survival was 19.2 and 11.9 months for Wel/Mod and Por/Muc/Sig, respectively (p < 0.001). The adjusted hazard ratio for Por/Muc/Sig with regard to survival time was 1.42 (95% confidence interval: 1.13–1.77). Por/Muc/Sig had a lower incidence of liver and lung metastases and a higher incidence of peritoneal dissemination and metastasis to rare organs, such as the bone and brain. Conclusions The Por/Muc/Sig histological subtype was an independent prognostic factor for poor prognosis among patients with stage IV colorectal cancer. The histological subtype may be useful for predicting the prognosis of patients with stage IV colorectal cancer and designing the treatment strategy.

Background/aim We investigated the clinical impact of the primary tumor site in stage IV colorectal cancer (CRC). Patients and methods In this statewide multicenter retrospective cohort, patients with stage IV CRC from nine hospital-based cancer registries across the Fukushima Prefecture (2008-2015) were categorized based on three primary tumor sites: right colon cancer (RCC), left colon cancer (LCC), and rectal cancer. Overall survival was assessed using Cox regression analysis. Results A total of 1,211 patients were included. The most common clinical symptom was obstruction in LCC and bleeding in rectal cancer. Liver metastases were multiple and larger in LCC, while lung metastases were multiple in rectal cancer. Compared to LCC, the adjusted hazard ratio (HR) for overall survival was 1.19 [95% confidence interval (CI)=1.01-1.39, p=0.032] in RCC and 1.03 (95% CI=0.86-1.23, p=0.77) in rectal cancer. Conclusion RCC was independently associated with a worse prognosis in stage IV CRC.