Molecular profiling of risk factors for relapse in Japanese patients with stage II colorectal cancer: a retrospective cohort study.

BACKGROUND: The association between the molecular profiles and prognosis of Stage II colorectal cancer remains unclear. This study aimed to examine the risk factors for relapse of Stage II colorectal cancer using molecular profiling. METHODS: We retrospectively enrolled patients with pStage II colorectal cancer who did not receive perioperative adjuvant therapy and whose surgically resected specimens were evaluated using gene expression and whole-exome analyses between January 2014 and December 2018. We evaluated the long-term outcomes and examined the risk factors for relapse-free survival. RESULTS: We evaluated 322 patients with pStage II colorectal cancer, including 126 (39.1%) with right colon cancer. Eighty-seven patients (27.0%) had pT4 tumor, 175 (54.3%) had positive venous invasion, 120 (37.3%) had positive lymphatic invasion, and 68 (21.1%) had perineural invasion. The presence of mutations in key genes for colorectal cancer development based on whole-exome analyses was as follows: APC, 245 (76.1%); TP53, 208 (64.6%); and KRAS, 134 (41.6%). According to the consensus molecular subtype classification based on gene expression, 76 patients (23.6%) had consensus molecular subtype 4 and a significantly lower relapse-free survival than the other patients (5-year relapse-free survival: 83.8% vs. 92.9%, p = 0.017). Perineural invasion (hazard ratio: 5.316, p < 0.001) and consensus molecular subtype 4 (hazard ratio: 2.399, p = 0.020) were identified as independent risk factors for relapse-free survival. CONCLUSIONS: Molecular profiling of Stage II colorectal cancer to assess the risk factors for relapse may contribute to the indication and drug selection for adjuvant chemotherapy.

The KRAS G12D mutation increases the risk of unresectable recurrence of resectable colorectal liver-only metastasis.

PURPOSE: Unresectable recurrence is a critical predictor of outcomes for colorectal cancer patients. We attempted to identify the prognostic factors, especially for unresectable recurrence-free survival (URFS) as a new endpoint, in patients with resectable colorectal liver-only metastasis (CRLOM). METHODS: We investigated patients with resectable CRLOM, who underwent an R0 resection for both CRC and CRLOM between January, 2014 and March, 2019 at a single institution. The exclusion criteria were patients who received neoadjuvant treatment, the absence of data for genetic analyses, and the presence of multiple cancers, synchronous CRC, or familial adenomatous polyposis. The prognostic factors were examined retrospectively using data on pre-hepatectomy factors, including primary tumor molecular profiling results. RESULTS: We analyzed the data of 101 patients who underwent curative-intent surgery for CRLOM. Multivariate analysis revealed that KRAS G12D mutation-positivity (hazard ratio [HR]: 7.69; p < 0.01), RYR2 mutation-positivity (HR: 4.03; p < 0.01), and KRAS G12S mutation-positivity (HR: 3.96; p = 0.03), CA19-9 > 37 U/ml before hepatectomy (HR: 3.62; p < 0.01), and primary tumor pN2 stage (HR: 3.22; p = 0.03) were significant predictors of the URFS. CONCLUSIONS: This is the first study to show that specific KRAS and RYR2 mutations were associated with the URFS.

Short-term and long-term outcomes after robotic radical surgery for rectal gastrointestinal stromal tumor.

BACKGROUND: The optimal approach for ensuring both complete resection and preservation of anal function in rectal gastrointestinal stromal tumor (GIST) remains unknown. The aim of this study was to clarify short-term and long-term outcomes after robotic radical surgery for rectal GIST. METHODS: A total of 13 patients who underwent robotic radical surgery for rectal GIST between December 2011 and April 2022 were included. All robotic procedures were performed using a systematic approach. A supplemental video of robotic radical surgery for rectal GIST is attached. The short-term outcome was the incidence of postoperative complications during the first 30 days after surgery. Surgical outcomes were retrieved from a prospective database. Long-term outcomes, including overall survival and recurrence-free survival, were determined in all patients. RESULTS: Median distance from the tumor to the anal verge was 4.0 cm. Surgical margins were negative in all patients. Two patients underwent neoadjuvant imatinib therapy. All patients underwent sphincter-preserving surgery. None underwent conversion to open or laparoscopic surgery. The incidence of postoperative Clavien-Dindo grade II and grade ≥ III complications was 7.7% and 0%, respectively. The median postoperative hospital stay was 7 days. Twelve patients (92.3%) underwent stoma closure within 5 months of the initial surgery. Median follow-up time was 76 months. The 5-year overall survival and recurrence-free survival rates were both 100%. None of the patients had recurrence. CONCLUSION: Short-term and long-term outcomes after radical robotic surgery for rectal GIST were favorable. Robotic surgery might be a useful surgical approach for rectal GIST.

Risk factors for stoma prolapse after laparoscopic loop colostomy.

BACKGROUND: Stoma prolapse (SP) is a common stoma-related complication, particularly in loop colostomies. This study aimed to investigate potential risk factors for SP development after laparoscopic loop colostomy. METHODS: In total, data from 140 patients who underwent laparoscopic loop colostomy were analyzed between September 2016 and March 2022. Risk factors for SP were investigated retrospectively. RESULTS: The median follow-up duration after colostomy was 12.5 months, and SP occurred in 33 (23.6%) patients. Multivariate analysis showed that being overweight (body mass index ≥ 25; odds ratio [OR], 8.69; 95% confidential interval [CI], 1.61-46.72; p = 0.012) and having a thin rectus abdominis penetration of the stoma (< 8.9 mm; OR, 8.22; 95% CI, 2.50-27.05; p < 0.001) were independent risk factors for SP. Other patient characteristics and surgical factors associated with stoma construction were unrelated to SP development. CONCLUSIONS: Being overweight and the route penetrating the thinner rectus abdominis during stoma construction was associated with a significantly higher incidence of SP after laparoscopic loop colostomy. Selecting a construction site that penetrates the thicker rectus abdominis muscle may be crucial for preventing SP.

Prediction model of the risk for lateral local recurrence in locally advanced rectal cancer without enlarged lateral lymph nodes: Lessons from a Japanese multicenter pooled analysis of 812 patients.

Aim: Although the oncological impact of lateral lymph node dissection on enlarged lateral lymph nodes has been gradually accepted over the last decade, that on lateral lymph nodes without swelling remains doubtful. This study aimed to develop a prediction model for the future risk of lateral local recurrence and to clarify the value of adding lateral lymph node dissection in locally advanced rectal cancer without enlarged lateral lymph nodes. Methods: This retrospective, multi-institutional study recruited 812 patients with cStage II/III low rectal cancer without enlarged lateral lymph nodes <7 mm. Total lateral local recurrence was a hypothetical value of future risk of lateral local recurrence when lateral lymph node dissection was never performed. Results: Overall, total lateral local recurrences were observed in 67 patients (8.3%). In the multivariate analyses, the strongest risk factor for total local recurrences was no preoperative chemoradiotherapy (odds ratio [OR][95%Cl]: 33.2 [4.56-241.7], P < 0.001), followed by tumor distance ≤40 mm (OR [95%Cl]: 2.71 [1.51-4.86], P < 0.001) and lateral lymph node 5-7 mm (OR[95%Cl]: 2.38 [1.26-4.48], P = 0.007). In patients with lateral lymph nodes of 5-7 mm, the total lateral recurrence rate was 4.8% after preoperative chemoradiotherapy. Lateral lymph node dissection could reduce from a total lateral local recurrence of 21.6% to an actual lateral local recurrence of 8.0% in patients without preoperative treatment. Conclusion: We introduce a novel prediction model of future risk of lateral local recurrences, which has the potential to enable us to indicate lateral lymph node dissection selectively according to the patients' risks.

Risk factors for lateral lymph node metastasis based on the molecular profiling of rectal cancer.

AIM: The association between molecular profiles and lateral lymph node metastasis (LLNM) in patients with rectal cancer remains unclear. Therefore, this study aimed to identify the molecular profiles of rectal cancer associated with LLNM. METHOD: We retrospectively examined patients who underwent rectal cancer surgery with lateral lymph node dissection without preoperative treatment and whose surgically resected specimens were evaluated using multiomics-based analyses from 2014 to 2019. We compared the clinical characteristics and molecular profiles of patients with pathological LLNM (pLLNM+) with those of patients without (pLLNM-) and identified risk factors for LLNM. RESULTS: We evaluated a total of 123 patients: 18 with and 105 without pLLNM. The accumulation of mutations in genes key for the development of colorectal cancer were similar between the groups, as was the tumour mutation burden. The distribution of consensus molecular subtypes (CMS) was significantly different between the groups (p = 0.0497). The pLLNM+ patients had a higher prevalance of CMS4 than the pLLNM- patients (77.8% vs. 51.4%). According to the multivariate analysis, the independent risk factors for LLNM were a short-axis diameter of the lateral lymph node of ≥6.0 mm and CMS4; furthermore, the presence of either or both had a sensitivity of 100% for the diagnosis of LLNM. CONCLUSION: Lateral lymph node size and CMS4 are useful predictors of LLNM. The combination of CMS classification and size criteria was remarkably sensitive for the diagnosis of LLNM.

Use of a Powered Circular Stapler Can Prevent Anastomotic Air Leakage in Robotic Low Anterior Resection for Rectal Cancer.

Objectives: Preventing anastomotic complications during rectal cancer surgery is important. Compared with a manual circular stapler, a powered circular stapler is expected to reduce undesirable tension during anastomosis. However, whether a powered circular stapler can reduce anastomotic complications during robotic low anterior resection (Ro-LAR) remains unclear. We aimed to investigate whether the use of a powered circular stapler contributes to safe anastomosis in Ro-LAR. Methods: A total of 271 patients who underwent Ro-LAR for rectal cancer between April 2019 and April 2022 were included. Depending on the type of device employed, patients were divided into a powered circular stapler group (PCSG) and a manual circular stapler group (MCSG). Clinicopathological features and surgical outcomes were compared between the two groups. Results: There were no differences in clinicopathological characteristics and surgical outcomes, except for anastomotic outcomes, between the two groups. Patients with positive air leak tests were significantly more in the MCSG (p=0.026; PCSG, 1.5%; MCSG, 8.0%). Frequencies of anastomotic leakage (p=0.486; PCSG, 6.1%; MCSG, 8.9%) and anastomotic bleeding (p=1.000; PCSG, 0.7%; MCSG, 0.8%) were similar between the two groups. Multivariate analysis showed that the use of a powered circular stapler significantly increased the negative leak tests (p=0.020, odds ratio 6.74, 95% confidence interval 1.35-33.56). Conclusions: Use of a powered circular stapler in Ro-LAR for rectal cancer was significantly associated with a negative air leak test, suggesting that it contributes to stable and safe anastomosis.

The impact of mesorectal fat area on recurrence following total mesorectal excision for lower rectal cancer.

BACKGROUND: The mesorectal fat area (MFA) at the tip of the ischial spines on magnetic resonance imaging has been used to characterize mesorectal morphology. Recent studies reported that a larger MFA correlated with difficulties in rectal cancer surgery. However, the relationship between MFA and rectal cancer prognosis remains unclear. This study evaluated the impact of MFA on recurrence following robotic total mesorectal excision (TME) for rectal cancer. METHODS: Patients who underwent robotic TME for lower rectal cancer from December 2011 to December 2016 were enrolled. Cox regression analysis was performed to determine variables associated with relapse-free survival (RFS). Patients were divided into groups based on MFA, and RFS was compared. RESULTS: Of 230 patients, 173 (75.3%) were male. The median age was 63 years, and median MFA was 19.7 cm2. In multivariate analysis, smaller MFA (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.88-0.97; p < 0.01), p/yp stage II (HR, 3.81; 95% CI, 1.40-10.35; p < 0.01), and p/yp stage III (HR, 5.35; 95% CI, 1.88-15.27; p < 0.01) were independently associated with worse RFS. Sex, body mass index, and visceral fat area were not correlated with RFS. In the median follow-up period of 60.8 months, patients with MFA < 19.7 cm2 had a significantly lower 5-year RFS rate (72.7%) than those with MFA ≥ 19.7 cm2 (85.0%). CONCLUSIONS: Smaller MFA was associated with worse RFS in patients undergoing robotic TME for lower rectal cancer. MFA is considered to be a prognostic factor in rectal cancer.

Incidence and clinical significance of 491 known fusion genes in a large cohort of Japanese patients with colorectal cancer.

BACKGROUND: The clinical significance of fusion genes in colorectal cancer remains unclear. The purpose of this study was to determine the incidence of fusion genes in colorectal cancer and explore their clinical significance by screening for common fusion genes in a large Japanese cohort. METHODS: This study involved 1588 patients. The incidence of 491 fusion genes was examined using a designed fusion panel. In addition, the patients were classified into two groups (RSPO fusion-positive or -negative) according to the presence of RSPO fusions, and the clinicopathological and genetic characteristics of both groups were compared. Long-term outcomes were analyzed in patients without distant metastases. RESULTS: Fusion genes were detected in 2% (31/1588) of colorectal cancers. The incidence of RSPO fusions (such as PTPRK-RSPO3 and EIF3E-RSPO2) was 1.5% (24/1588), making them the most common fusions, whereas the incidence of other fusion genes was extremely low. The distribution of consensus molecular subtypes and frequency of APC mutations were significantly different between the RSPO fusion-positive and -negative groups. The 3-year cumulative incidence rate of recurrence was higher in the RSPO fusion-positive group than in the RSPO fusion-negative group (positive, 31.2% vs. negative, 13.5%, hazard ratio = 2.357; p = 0.040). CONCLUSION: Broad screening for fusion genes showed that RSPO fusions were the most common in colorectal cancer, with an incidence of 1.5%. RSPO fusions may be clinically significant in identifying patients at a high risk of recurrence who would be responsive to specific treatments.

Feasibility of two laparoscopic surgeries for colon cancer performed by the same surgeon on a single day.

BACKGROUND: Although the proportion of laparoscopic colectomies (LCs) for colon cancer is increasing, the feasibility of the same surgeon performing two LCs on a single day remains unknown. This study was conducted to clarify the feasibility of this practice by evaluating short-term and long-term outcomes. METHODS: This retrospective analysis enrolled patients with pathological stage I-III colon cancer who underwent LC at the Shizuoka Cancer Center between 2010 and 2020. Patients were divided into two groups based on the timing of the surgery for the surgeon. The first group (n = 1485) comprised patients who underwent LC as the first surgery of the day for the surgeon. The second group (n = 163) comprised patients who underwent LC as the second LC of the day for the surgeon. Propensity score matching was performed to balance the baseline characteristics of the first and second groups. The short-term and long-term outcomes of the two groups were compared. RESULTS: After propensity score matching, there were no significant differences in the incidence of postoperative complications of Clavien-Dindo classification grade II or higher between the first (10.4%, 17/163) and second groups (5.5%, 9/163). There were no significant differences in other perioperative outcomes, including operative time, intraoperative blood loss, and incidence of conversion to open surgery, between the two groups. Regarding long-term outcomes, there were no significant differences in overall survival or relapse-free survival between the two groups both in the full cohort and in the propensity score-matched cohort. In the propensity score-matched cohort, 5-year overall survival was 92.7% in the first group and 94.4% in the second group; 5-year relapse-free survival was 87.1% and 90.3%, respectively. CONCLUSION: Our results suggest that the same surgeon performing two LCs for colon cancer on a single day is feasible in terms of short-term and long-term outcomes.

Long-term outcomes of upfront robotic rectal cancer surgery: a single-center, retrospective cohort study in Japan.

PURPOSE: The purpose of this study was to evaluate the long-term outcomes of robotic rectal cancer surgery and to examine the risk factors for recurrence. METHODS: In a high-volume center in Japan, we retrospectively enrolled patients with pStage I-III rectal cancer within 15 cm of the anal verge who underwent robotic surgery from 2011 to 2017. Almost all patients underwent upfront surgery, and lateral lymph-node dissection (LLND) was performed for patients with locally advanced lower rectal cancer. We evaluated the 5-year overall survival (OS), relapse-free survival (RFS), and cumulative local recurrence (LR) rates and examined the risk factors for the RFS. RESULTS: We evaluated 488 patients who underwent robotic rectal cancer surgery, including 5.1% who underwent preoperative chemoradiotherapy to obtain clear resection margins and 33.6% who underwent LLND. There were 203, 87, and 198 patients with pStage I, II, and III, respectively, and the positive resection margin rate was 1.0%. The 5-year OS, RFS, and LR rates were 95.5%, 81.7%, and 2.2%, respectively. The independent risk factors for the RFS were the presence of venous invasion, extramural tumor deposits without lymph-node structure, and pT ≥ 3. CONCLUSION: This study demonstrated the favorable long-term outcomes of robotic rectal cancer surgery.

Risk factors for and longitudinal course of male sexual dysfunction after robotic rectal cancer surgery.

AIM: The aim of this work was to investigate the risk factors associated with the incidence of sexual dysfunction in patients who underwent robot-assisted surgery with several treatment options, such as neoadjuvant chemoradiotherapy and lateral lymph node dissection, and clarify the longitudinal course of erectile function in risk groups. METHOD: A total of 203 male patients who underwent robot-assisted total mesorectal excision for rectal cancer between 2013 and 2019 were included. The risk factors for erectile and ejaculatory dysfunction as well as the longitudinal course of erectile function were retrospectively investigated in all cohorts and several risk groups, including those who underwent neoadjuvant chemoradiotherapy, lateral lymph node dissection and adjuvant chemotherapy. Erectile dysfunction was assessed using the International Index of Erectile Function and ejaculatory dysfunction was assessed using original questions. The survey was performed preoperatively and at 3, 6 and 12 months postoperatively. RESULTS: Erectile and ejaculatory dysfunction occurred in 46.8% and 15.7% of the patients, respectively. Multivariate analysis showed that neoadjuvant chemoradiotherapy was an independent risk factor for erectile dysfunction. Erectile function recovered longitudinally to the preoperative level overall, as well as in lateral lymph node dissection and postoperative adjuvant chemotherapy subgroups; however, recovery was poor in the neoadjuvant chemoradiotherapy group, even at 12 months postoperatively. CONCLUSION: Neoadjuvant chemoradiotherapy was found to be a risk factor for erectile dysfunction after robot-assisted surgery for rectal cancer. Erectile function recovered postoperatively in patients undergoing lateral lymph node dissection; however, those receiving neoadjuvant chemoradiotherapy showed poor recovery, even at 12 months postoperatively.

Consensus molecular subtyping improves the clinical usefulness of canonical tumor markers for colorectal cancer.

Transcriptome-based classification, such as consensus molecular subtyping, is expected to be applied to colorectal cancer (CRC). However, the relationship between molecular profiles and classical tumor markers, which are already used in clinical practice, has not been analyzed in a large cohort and remains unclear. We classified more than 1,500 Japanese patients with CRC based on consensus molecular subtyping and investigated the clinically available blood carcinoembryonic antigen (CEA) concentrations of each subgroup. To precisely distinguish CRCs, we allocated them to five subgroups, including tumors that were difficult to classify using the consensus molecular subtypes (CMSs), and extracted a heterogeneous population with somatic mutations and expression profiles that differed from those of the CMSs 1-4. For patients allocated to the CMS4 subgroup of stage III CRCs, elevated blood CEA concentrations may identify a subgroup with highly aggressive disease and contribute to improving therapeutic decisions. Furthermore, gene expression and pathway analyses of tumor and non-tumor tissues revealed that tumor immunity was "cold" in this subgroup with high CEA concentrations. The combination of emerging molecular profiling and classical tumor markers may have greater clinical utility than either used alone.

Lymph node metastasis in T1 colorectal cancer with the only high-risk histology of submucosal invasion depth ≥ 1000 µm.

PURPOSE: The number of patients undergoing additional surgery after endoscopic resection (ER) for T1 colorectal cancer (CRC) is increasing. Regarding high-risk histology of lymph node metastasis (LNM) in T1 CRC, a submucosal invasion depth ≥ 1000 µm (T1b) alone may be related to a low incidence of LNM. This study was conducted to clarify the incidence of LNM and to identify factors associated with LNM in T1 CRC with high-risk histology characterized only by T1b. METHODS: We retrospectively investigated patients with pathological T1b CRC who underwent colorectal resection between 2010 and 2020. Patients were divided into two groups with high-risk histology: those in whom the only high-risk feature was T1b (low-risk T1b group, n = 263), and those with T1b as well as lymphovascular invasion, tumor budding, or poorly differentiated or mucinous adenocarcinoma (high-risk T1b group, n = 289). The incidences of LNM and recurrence were compared. Multivariate analysis was performed to identify factors associated with LNM in the low-risk T1b group. RESULTS: The incidences of LNM were 3.8% and 21.6% in the Low- and High-risk T1b groups, respectively (p < 0.01), while the 5-year recurrence rates in the two groups were 0.6% and 3.4%, respectively (p = 0.10). Multivariate analysis revealed that only a predominant histological type of moderately differentiated adenocarcinoma (p = 0.04) was independently associated with LNM in the low-risk T1b group. CONCLUSION: When considering the omission of additional surgery after ER in cases of T1 CRC whose only high-risk histological feature is T1b, attention should be paid to the predominant histological type.

Comparison between robotic-assisted and laparoscopic sphincter-preserving operations for ultra-low rectal cancer.

Aim: Sphincter-preserving operations for ultra-low rectal cancer include low anterior and intersphincteric resection. In low anterior resection, the distal rectum is divided by a transabdominal approach, which is technically demanding. In intersphincteric resection, a perineal approach is used. We aimed to evaluate whether robotic-assisted surgery is technically superior to laparoscopic surgery for ultra-low rectal cancer. We compared the frequency of low anterior resection in cases of sphincter-preserving operations. Method: We investigated 183 patients who underwent sphincter-preserving robotic-assisted or laparoscopic surgery for ultra-low rectal cancer (lower border within 5 cm of the anal verge) between April 2010 and March 2020. The frequency of low anterior resection was compared between laparoscopic and robotic-assisted surgeries. The clinicopathological factors associated with an increase in performing low anterior resection were analyzed by multivariate analyses. Results: Overall, 41 (22.4%) and 142 (77.6%) patients underwent laparoscopic and robotic-assisted surgery, respectively. Patient characteristics were similar between the groups. Low anterior resection was done significantly more frequently in robotic-assisted surgery (67.6%) than in laparoscopic surgery (48.8%) (P = 0.04). Multivariate analyses showed that tumor distance from the anal verge (P < 0.01) and robotic-assisted surgery (P = 0.02) were significantly associated with an increase in the performance of low anterior resection. The rate of postoperative complications or pathological results was similar between the groups. Conclusion: Compared with laparoscopic surgery, robotic-assisted surgery significantly increased the frequency of low anterior resection in sphincter-preserving operations for ultra-low rectal cancer. Robotic-assisted surgery has technical superiority over laparoscopic surgery for ultra-low rectal cancer treatment.

Long-term outcomes of D2 vs. D3 lymph node dissection for cT2N0M0 colorectal cancer: a multi­institutional retrospective analysis.

BACKGROUND: According to Japanese guidelines, D2 or D3 lymph node dissection (LND) is indicated for cT2N0M0 colorectal cancer (CRC). In this study, we retrospectively compared the long-term outcomes between D2 and D3 LND among patients with cT2N0M0 CRC. METHODS: Our sample included 515 patients from the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer database, who underwent surgical resection for cT2N0M0 CRC between January 2009 and December 2012, 195 (37.9%) of whom underwent D2 LND and 320 (62.1%) D3 LND. The D2 and D3 groups were retrospectively compared in terms of long-term outcomes including overall survival (OS) and relapse-free survival (RFS). The prognostic factors for these outcomes were also evaluated. RESULTS: The D2 group had significantly older patients and higher proportion of men than the D3 group. The rates of OS (5-year OS; 94.8% in the D3 group vs. 93.4% in the D2 group, p = 0.38) and RFS (5-year RFS; 89.3% in the D3 group vs. 89.1% in the D2 group, p = 0.91) were comparable for both groups. On multivariate analysis, age ≥ 80 years was significantly associated with poor OS. The extent of LND was not associated with either OS or RFS. Long-term outcomes were similar between the two groups, independent of tumor location. CONCLUSION: The long-term outcomes did not differ between the D2 and D3 groups and the extent of LND was not associated with prognosis for cT2N0M0 CRC. Therefore, D2 LND may be sufficient for cT2N0N0 CRC treatment.

Comprehensive genetic characterization of rectal cancer in a large cohort of Japanese patients: differences according to tumor location.

BACKGROUND: In clinical practice, rectal cancer (RC) is classified according to tumor location. However, RC's genetic characteristics according to tumor location remain unclear. Therefore, we aimed to compare RC's genetic characteristics according to tumor location. METHODS: In 611 patients with surgically resected RC, we performed genetic analyses and compared the results between low and other RCs. Low RC was defined according to the European Society for Medical Oncology (ESMO) guidelines and Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (JCCRC). RESULTS: KRAS mutation accumulation was significantly higher in low RC under the ESMO classification. Gene expression levels significantly differed between the groups for CTNNB1, KRAS, and ERBB2, under the ESMO classification and for TP53, KRAS, and ERBB2 under the JCCRC. Under the JCCRC, low RC had a significantly higher prevalence of fusion genes, such as EIF3E-RSPO2, PTPRK-RSPO3, and VTI1A-TCF7L2. Consensus molecular subtype (CMS) distribution was significantly different between the groups under both classifications. In particular, low RC had lower and higher frequencies of CMS2 and CMS4, respectively. CMS2 and CMS4 frequencies in low RC were 14.8% and 41.5% under the ESMO classification and 14.5% and 41.6% under the JCCRC, respectively. Multivariate Cox regression analysis demonstrated that pT3-4, pN1-2, and CMS4 were associated with poor relapse-free survival. CONCLUSIONS: Low RC exhibited distinct genetic characteristics from other RCs. In particular, CMS4 was more frequent in low RC and was a risk factor for poor prognosis. These findings potentially avail further information regarding tumor biology and could lead to improvements in RC treatment.

The Impact of Metastatic Lymph Node Size on Long-term Outcomes for pStage III Colon Cancer.

Aim: To clarify the impact of metastatic lymph node size on long-term outcomes in patients undergoing curative colectomy for pathological stage III colon cancer. Patients and Methods: This study enrolled patients who underwent curative colectomy for pStage III colon cancer between January 2013 and December 2015. All patients were divided into four groups based on the short-axis diameter of the largest MLN: Group A, <5 mm; Group B, ≥5 mm and <10 mm; Group C, ≥10 mm and <15 mm; Group D, ≥15 mm. Results: A total of 209 patients were analyzed. The 5-year recurrence-free survival rates of Groups A, B, C, and D were 82.3%, 74.6%, 74.5% and 60.7%, respectively. In multivariate analysis, Group D (hazard ratio=3.95; 95% confidence interval, 1.34-11.65; p=0.01) was independently associated with worse RFS. Conclusion: Bulky MLNs might be a poor prognostic factor in node-positive colon cancer.

The Effectiveness of Machine Learning in Predicting Lateral Lymph Node Metastasis From Lower Rectal Cancer: A Single Center Development and Validation Study.

AIM: Accurate preoperative diagnosis of lateral lymph node metastasis (LLNM) from lower rectal cancer is important to identify patients who require lateral lymph node dissection (LLND). We aimed to create an effective prediction model for LLNM using machine learning by combining preoperative information. METHODS: We retrospectively examined patients who underwent primary rectal cancer surgery with unilateral or bilateral LLND between April 2010 and March 2020 at a single institution. Using the machine learning software "Prediction One" (Sony Network Communications), we developed a prediction model in the training cohort that included 267 consecutive patients (500 sides) from April 2010. Clinicopathological data obtained from the preoperative examinations were used as the learning items. In the validation cohort that included subsequent patients until March 2020, we compared the discriminating powers of the prediction model and the conventional method using the short-axis diameter of the largest lateral lymph node, as detected on magnetic resonance imaging. RESULTS: The area under the receiver operating characteristic curve (AUC) of the prediction model was 0.903 in the validation cohort comprising 56 patients (107 sides). This indicated significantly higher predictive power than that of the conventional method (AUC = 0.754; P = .022). Using the cutoff values defined in the training cohort, the accuracy, sensitivity, and specificity of the prediction model were 80.4%, 90.0%, and 79.4%, respectively. The model was able to correctly predict four of five sides comprising LLNM with the short-axis diameters ≤4 mm. CONCLUSION: Machine learning contributed to the creation of an effective prediction model for LLNM.

Neoadjuvant chemoradiotherapy for borderline resectable low rectal cancer: short- and long-term outcomes at a single Japanese center.

PURPOSE: Rectal cancers pose a threat to the mesorectal fascia or invade neighboring structures or organs. Some tumors are potentially resectable but are likely to be positive at the resection margin for cancer involvement and are thus recognized as "borderline resectable (BR)" tumors. This study aimed to clarify the short- and long-term outcomes of neoadjuvant chemoradiotherapy (nCRT) for BR low rectal cancer at a single Japanese center. METHODS: Data of 55 patients, who received nCRT followed by BR low rectal cancer surgery between April 2010 and December 2019, were evaluated for the short-term outcomes. The oncological outcomes of 42 patients who underwent surgery between April 2010 and December 2018 were evaluated. RESULTS: Thirty-six (65.5%) patients had cT4 tumors, and 53 (96.4%) patients had a clinical-stage III or IV. Lateral lymph node dissection was performed in 42 (76.4%) patients. The incidence of severe post-operative complications (Clavien-Dindo grade ≥ III) was 18.2%. Fifty-two (94.5%) patients had a pathological negative resection margin. The 3-year overall survival rate, disease-free survival rate, and cumulative incidence of local recurrence were 100%, 70.3%, and 5.3%, respectively. CONCLUSION: The short- and long-term outcomes of nCRT for BR low rectal cancer were acceptable. In particular, reasonable local control was achieved.