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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.

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.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.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.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.

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.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.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.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.

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., Accurate preoperative diagnosis of lateral lymph node metastasis from lower rectal cancer is important to identify patients who require lateral lymph node dissection. Machine learning based on deep learning contributed to the creation of an effective prediction model for lateral lymph node metastasis.

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 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 = 1,485) 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 96.0% in the first group and 94.4% in the second group; 5-year relapse-free survival was 88.1% 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.

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 prognosis in rectal cancer remains unclear. This study evaluated the impact of MFA on long-term outcomes following robotic proctectomy for rectal cancer. Methods Patients who underwent robotic proctectomy 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 the MFA, and long-term outcomes were 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], 0.92; 95% confidence interval [CI], 0.87–0.98; p 2 had a significantly lower 5-year RFS rate (72.6%) than those with MFA ≥ 20.7cm2 (87.0%). Conclusions Smaller MFA was associated with worse RFS in patients undergoing robotic proctectomy for lower rectal cancer. MFA is considered to be a prognostic factor in rectal cancer.

Purpose There are no established treatment strategies for patients with hepatic and pulmonary metastases at the time of primary colorectal cancer (CRC) diagnosis. This study assessed patients undergoing complete resection of primary CRC and hepatic and pulmonary metastases, to evaluate long-term outcomes and clarify clinicopathological factors associated with failure of complete resection. Methods This retrospective analysis enrolled patients at Shizuoka Cancer Center between 2002 and 2018 who underwent colorectal resection with curative intent for primary CRC with hepatic and pulmonary metastases. The curative resection (CR) group comprised patients who underwent complete resection of the primary tumor and metastatic lesions, and the non-curative resection (Non-CR) group consisted of those in whom resection of the metastatic lesions was not performed. Univariate and multivariate analyses were conducted to determine clinicopathological factors associated with non-curative resection. Results Of 26 total patients, the CR and Non-CR groups consisted of 14 (54%) and 12 patients (46%), respectively. In the CR group, the 3-year overall and relapse-free survival rates were 92.9% and 28.6%, respectively. Multivariate analysis showed that pathological stage T4 (odds ratio 8.58, 95% confidence interval 1.13-65.20, p = 0.04) was independently associated with non-curative resection. Conclusion The percentage of patients undergoing complete resection of primary CRC and metastatic lesions was 56%, and the 3-year OS rate was 92.9%. Resection of primary CRC and metastatic lesions was considered to be appropriate in this population, and pathological stage T4 tumor was associated with incomplete resection of metastatic tumors.

We present a very rare case of rectal cancer in a patient with situs inversus totalis (SIT), which is a complete transposition of the thoracic and abdominal viscera. A woman in her 60s visited a local hospital reporting bloody stool and was diagnosed with upper rectal cancer and SIT. We made careful preoperative preparations for the congenital anomaly, and robotic-assisted high anterior resection with D3 lymph node dissection was performed. Although we adopted an unusual six-port placement, the operation was performed safely and efficiently without any adverse events. The patient recovered uneventfully. The pathological specimen was classified as pT3N2bM0 with negative resection margins. Robotic-assisted surgery is advantageous for rectal cancer treatment even when anatomical abnormalities make the surgical procedure more difficult.

The aim of the study was to investigate the effect of chemo-radiation on the genetic and immunological status of rectal cancer patients who were treated with preoperative chemoradiotherapy (CRT). The expression of immune response-associated genes was compared between rectal cancer patients treated (n = 9) and not-treated (n = 10) with preoperative CRT using volcano plot analysis. Apoptosis and epithelial-to-mesenchymal transition (EMT) marker genes were analysed by quantitative PCR (qPCR). Other markers associated with the tumor microenvironment (TME), such as tumor-infiltrating lymphocytes (TIL) and immune checkpoint molecules, were investigated using immunohistochemistry (IHC). The clinical responses of preoperative CRT for 9 rectal cancer patients were all rated as stable disease, while the pathological tumor regression score (TRG) revealed 6 cases of grade2 and 3 cases of grade1. According to the genetic signature of colon cancers, treated tumors belonged to consensus molecular subtype (CMS)4, while not-treated tumors had signatures of CMS2 or 3. CRT-treated tumors showed significant upregulation of EMT-associated genes, such as CDH2, TGF-beta and FGF, and cancer stem cell-associated genes. Additionally, qPCR and IHC demonstrated a suppressive immunological status derived from the upregulation of inflammatory cytokines (IL-6, IL-10 and TGF-beta) and immune checkpoint genes (B7-H3 and B7-H5) and from M2-type macrophage accumulation in the tumor. The induction of EMT and immune-suppressive status in the tumor after strong CRT treatment urges the development of a novel combined therapy that restores immune-suppression and inhibits EMT, ultimately leading to distant metastasis control.

If patients with surgically resectable colorectal cancershave synchronous colorectal neoplasms that are difficult to remove by endoscopic mucosal resection, preemptive endoscopic submucosal dissection (ESD) can avoid excessive colorectal resection. The aim of this study was to evaluate the efficacy of the strategy of preemptive ESD and surgery for synchronous colorectal neoplasms.Patients who underwent preemptive ESD and surgery for synchronous colorectal neoplasms between September 2002 and December 2017 were enrolled in this retrospective cohort study. The proportion of cases in which extended surgery could be avoided following curative ESD was calculated. Clinicopathological characteristics were evaluated for all patients and long-term outcomes were analyzed for patients who underwent curative ESD and surgery.A total of 45 consecutive patients with 47 endoscopically-resected lesions and 46 surgically-resected lesions were retrospectively evaluated. Curative ESD was achieved in 44 lesions (93.6%) and an extended surgical procedure could be avoided in 42 patients (93.3%). Intraoperative perforation occurred in two lesions (4.3%), delayed perforation in one lesion (2.1%), and delayed bleeding in two lesions (4.3%). Final stages were as follows: stage 0, 3 patients (7.1%); stage I, 23 patients (54.8%); stage II, 3 patients (7.1%); stage III, 12 patients (28.6%); and stage IV, 1 patient (2.4%). The 5-year overall survival rates of patients with all pathological stages, stage 0-II, and stage III-IV were 93.7%, 100%, and 79.1%, respectively.The strategy of preemptive ESD and surgery for synchronous colorectal neoplasms is minimally invasive and has a favorable prognosis.

Urinary dysfunction (UD) remains a significant complication of rectal cancer surgery. In modern surgical treatment for rectal cancer, multiple operative approaches are used. Such approaches include open, laparoscopic, and robotic-assisted surgery; and multiple procedures, including anterior, intersphincteric, and abdominoperineal resection. Thus, modern surgical treatments for rectal cancer have diversified. This study aimed to identify risk factors for early UD (EUD) after total mesorectal excision (TME) and to explore the methods for decreasing postoperative EUD in diverse surgical treatments for rectal cancer. In our retrospective cohort study, we enrolled patients with lower rectal cancer who underwent TME alone at a single high-volume cancer center between 2010 and 2017. EUD was defined as the presence of ≥ 50 mL residual urine volume. Multivariate analysis was performed to determine clinicopathological factors significantly associated with postoperative EUD. Of a total of 337 eligible patients, 32 patients (10%) had postoperative EUD. Multivariate analysis revealed that only the operative approach (laparoscopic surgery: odds ratio [OR], 8.93; 95% confidence interval [CI], 2.94–27.14, open surgery: OR, 11.55; 95% CI 2.10–63.83) was significantly associated with an increase in postoperative EUD. Robotic-assisted surgery was associated with significant reduction in postoperative EUD. Only robotic-assisted surgery was inversely correlated with postoperative EUD. Robotic-assisted surgery may be a useful approach to protect urinary function in lower rectal cancer surgery.

Aim To compare the surgical outcomes of laparoscopic colectomy (LAC) with Japanese D3 dissection for descending colon cancer (DCC) with those of open colectomy (OC). Patients and methods Seventy-two patients who underwent OC or LAC with D3 dissection for clinical stage II/III DCC between September 2002 and June 2019 were evaluated in terms of short-term outcomes. The long-term outcomes of the 59 patients who underwent surgery between September 2002 and June 2016 were evaluated. Results Twenty-six patients underwent OC and 46 patients underwent LAC. The blood loss was significantly less in the LAC group. The complication rate was similar in both groups. The rates of 5-year overall survival (95.8% in the OC group vs. 89.9% in the LAC group) and relapse-free survival (79.2% in the OC group vs. 82.1% in the LAC group) were similar in both groups. Conclusion LAC is an acceptable treatment option for stage II/III DCC.

Although a “no-touch isolation” technique is used in colorectal cancer surgery to reduce the risk of metastatic induction, endoscopic resection (ER) prior to surgery may work against this aim. This study evaluated the effects of initial ER on short- and long-term outcomes in T1 colorectal cancer. This retrospective cohort study enrolled patients with pathological T1 colorectal cancer who underwent colorectal surgical resection at a Japanese tertiary cancer center between 2002 and 2012. A total of 548 eligible patients were divided into two groups: patients initially treated using surgical resection with lymph node dissection (LND) (primary group, n = 304) and patients treated using initial ER and additional surgical resection with LND (secondary group, n = 244). The inverse probability of treatment weighting (IPTW) method based on propensity score was used to compare postoperative complications and long-term recurrence. The incidence of postoperative complications with Clavien–Dindo classification grade ≥ II was 10.9% and 7.4% in the primary and secondary groups, respectively (p = 0.16). Multivariate analysis with a logistic proportional hazard regression model using IPTW revealed no significant differences in postoperative complications between the two groups (p = 0.79). During a median follow-up after surgery of 61.4 months, recurrence was observed in 3 (1.0%) and 8 (3.3%) patients, respectively (p = 0.06). Multivariate analysis with a Cox proportional hazard regression model using IPTW revealed no significant differences in recurrence between the two groups (p = 0.07). Our results suggest no significant adverse effects of initial ER prior to surgery on surgical complications and long-term recurrence in T1 colorectal cancer.

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.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.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%) (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.

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.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).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.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.

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

Background Sphincter-preserving operations for ultra-low rectal cancer include low anterior resection 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 performed. We aimed to evaluate whether robotic-assisted surgery is technically superior to laparoscopic surgery for ultra-low rectal cancer. The frequency of conducting low anterior resection by a specific procedure can indicate the technical superiority of that procedure for ultra-low rectal cancer. Thus, we compared the frequency of low anterior resection between robotic-assisted and laparoscopic surgery in cases of sphincter-preserving operations. Methods 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 performed 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

Background. The optimal radical surgical approach for rectal neuroendocrine tumor (NET) is unknown. Methods. This study evaluated the short- and long-term outcomes of 27 patients who underwent robotic radical surgery for rectal NET between 2011 and 2019. Results. The median distance from the lower border of the tumor to the anal verge was 5.0 cm. The median tumor size was 9.5 mm. Six patients (22%) had lymph node metastasis. The incidences of postoperative complications of grade II and grade III or more according to the Clavien–Dindo classification were 11% and 0%, respectively. All patients underwent sphincter-preserving surgery, and no patients required conversion to open surgery. The median follow-up time was 48.9 months, and both the 3-year overall survival and relapse-free survival rates were 100%. Conclusions. Short- and long-term outcomes of robotic surgery for rectal NET tumor were favorable. Robotic surgery may be a useful surgical approach for rectal NET.

An 85‐year‐old woman was admitted to a hospital with abdominal pain. Five years prior to admission, she had a history of hilar cholangiocarcinoma of pStage IIIC. Contrast‐enhanced computed tomography showed a mass between the rectum and uterus as well as bowel obstruction due to the lesion. Colonoscopy showed severe stenosis at the lower rectum and elevation of the submucosal layer with linear erosion. Rectal cancer was suspected, and pelvic recurrence of hilar cholangiocarcinoma or endometrial carcinoma infiltrating the rectum was considered as differential diagnosis. She underwent robot‐assisted low anterior resection combined with partial resection of the uterus. The immunohistopathological findings of the resected specimen favored a diagnosis of metastasis of cholangiocarcinoma, rather than primary rectal cancer or endometrial carcinoma. There were no signs of recurrence after 10 months of follow‐up. Hilar cholangiocarcinoma is a disease with poor prognosis. Recurrence is frequently experienced even after curative resection. Patients with recurrence are rarely candidates for re‐resection. However, better prognosis is reported for those with complete resection., Hilar cholangiocarcinoma is a disease with poor prognosis; recurrences are frequently experienced even after curative resection. However, very few reports focus on resection of the recurrence site. We herein report a unique case of rectal stenosis due to solitary pelvic recurrence of cholangiocarcinoma which was successfully resected.

Here, we investigated the clinicopathological and mutation profiles of colorectal cancer (CRC) with POLE mutations. Whole‐exome sequencing was performed in 910 surgically resected primary CRCs. Tumors exceeding 500 counts of nonsynonymous single nucleotide variants (SNVs) were classified as hypermutators, whereas the remaining were classified as nonhypermutators. The hypermutators were subdivided into 2 groups. CRCs harboring more than 20% C‐to‐A and less than 3% C‐to‐G transversions were classified as POLE category tumors, whereas the remaining were classified as common‐hypermutators. Gene expression profiling (GEP) analysis was performed in 892 (98.0%) tumors. Fifty‐seven (6.3%) and 10 (1.1%) tumors were classified common‐hypermutators and POLE category tumors, respectively. POLE category tumors harbored a significantly higher SNV count than common‐hypermutators, and all POLE category tumors were associated with exonuclease domain mutations, such as P286R, F367C, V411L, and S297Y, in the POLE gene. Patients with POLE category tumors were significantly younger than those with nonhypermutators and common‐hypermutators. All POLE mutations in the early‐onset (age of onset ≤50 years old) POLE category (7 tumors) were P286R mutations. GEP analysis revealed that PD‐L1 and PD‐1 gene expression levels were significantly increased in both common‐hypermutators and POLE category tumors compared with those in nonhypermutators. CD8A expression was significantly upregulated in POLE category tumors compared with that in nonhypermutators. Thus, we concluded that CRCs with POLE proofreading deficiency had characteristics distinct from those of other CRCs. Analysis of POLE proofreading deficiency may be clinically significant for personalized management of CRCs.

Background: In node-positive colon cancer, the impact of MLN size on prognosis is controversial. The aim of this study was to clarify the impact of metastatic lymph node (MLN) size on long-term outcomes in patients undergoing curative resection for pStage III colon cancer.Methods: This study enrolled patients who underwent curative colectomy for pStage III colon cancer between January 2013 and December 2015. All eligible 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; and Group D, ≥ 15 mm. We performed univariate and multivariate analysis using Cox proportional hazard regression models to identify clinicopathological factors affecting recurrence-free survival (RFS).Results: A total of 209 patients were analyzed. We evaluated 7305 LNs, of which 644 were metastatic. The 5-year RFS rates of Groups A, B, C, and D were 82.3%, 74.6%, 74.5%, and 60.7%, respectively. In univariate analysis, age older than 70 years, Group D (largest MLN ≥ 15 mm), and the absence of adjuvant chemotherapy were significantly associated with RFS. In multivariate analysis, Group D (hazard ratio [HR], 3.95; 95% confidence interval [CI], 1.34–11.65; p=0.01) and the absence of adjuvant chemotherapy (HR, 2.44; 95% CI, 1.26-4.72; pConclusion: A maximum MLN ≥ 15 mm was significantly associated with worse RFS in stage III colon cancer. Bulky MLNs might be a poor prognostic factor in node-positive colon cancer.

Although robotic surgery for rectal cancer can overcome the shortcomings of laparoscopic surgery, studies focusing on abdominoperineal resection are limited. The aim of this study was to compare the operative outcomes between robotic and laparoscopic abdominoperineal resection. This retrospective cohort study was conducted from April 2010 to March 2020. Patients with rectal cancer who underwent robotic or laparoscopic abdominoperineal resection without lateral lymph node dissection were enrolled. The perioperative and oncological outcomes were compared. We evaluated 33 and 20 patients in the robotic and laparoscopic groups, respectively. The median operative time and blood loss were comparable between the two groups. No significant differences in the overall complication rates were noted, whereas the rates of urinary dysfunction (3% vs. 26%, p = 0.02) and perineal wound infection (9% vs. 35%, p = 0.03) in the robotic group were significantly lower in comparison to the laparoscopic group. The median postoperative hospital stay was significantly shorter in the robotic group (8 days vs. 11 days, p

Clinical evidence demonstrating risk factors for anastomotic leakage including robotic staplers has remained limited, even though the use of robotic surgery has increased substantially. The purpose of this study was to evaluate the effects of robotic staplers on symptomatic anastomotic leakage in robotic low anterior resection for rectal cancer. A total of 427 consecutive patients with primary rectal cancer who underwent robotic low anterior resection without diverting stoma were investigated retrospectively. Symptomatic anastomotic leakage was defined as anastomotic leakage of Clavien–Dindo Grade ≥ II. We compared the symptomatic anastomotic leakage rates between manual and robotic staplers using propensity score matching and investigated the risk factors for symptomatic anastomotic leakage. After propensity score matching, 168 pairs of manual and robotic stapler cases were selected. The symptomatic anastomotic leakage rate was significantly higher for manual staplers (6.5%) than for robotic staplers (1.2%, p = 0.02). In a multivariate analysis, the use of a manual stapler (p = 0.04, OR 4.86, 95% CI 1.08–21.8) and anastomosis

Endoscopic tattooing failure by deep mural injection or tattoo leakage-induced massive staining causes localization errors or decreased laparoscopic visualization. To overcome these, we developed a novel tattoo needle with comparatively shorter needle (length, 2.5 mm) and minimal-caliber catheter (volume, 0.3 mL). The single-center, prospective observational study aimed to determine the efficacy and safety of a small-doze endoscopic tattooing prior to laparoscopic surgery for colorectal cancer, using the needle. Patients with colorectal cancer indicated for laparoscopic surgery were recruited. With the novel needle, a single tattoo was created at the anterior wall close to the lesion. During laparoscopic surgery, surgeons assessed the tattoo visibility, tattoo leakage, and the disturbance of laparoscopic view by tattoo leakage. The primary endpoint was an accurate localization by visible tattoo. Secondary endpoints were adverse events related to tattooing, the need for intraoperative endoscopy, and tattoo leakage. A total of 383 tattoos in 358 patients were analyzed. Accurate tumor localization rate was 96.6% (95% confidence interval [CI]: 94.3–98.0%). No adverse events occurred. Intraoperative colonoscopy was performed in 7 (1.8%) patients with invisible tattoo. Tattoo leakage was found in 4.2% (95%CI: 2.6–6.7%), and leakage disturbed the laparoscopic view of the surgical plane in 0.7% (95%CI: 0.3–2.3%). Prior to laparoscopic surgery for colorectal cancer, our endoscopic tattooing with a standardized protocol using a novel needle is considered a simple, highly reliable localization technique with an extremely safe profile, which would be valuable to reduce physician’s efforts and redundant medical resources. Trial registration number UMIN000021012. Date of registration: June 2016

The optimal surgical approach for clinical T4 (cT4) rectal cancer is unknown. This study was conducted to clarify short- and long-term outcomes of robotic surgery for cT4 rectal cancer. In our retrospective cohort study, we enrolled patients who underwent robotic surgery for cT4 rectal cancer within 15 cm from the anal verge between 2011 and 2018. The short- and long-term outcomes were evaluated. Of a total of 122 eligible patients, 70 (57%) had cT4a tumors and 52 (43%) had cT4b tumors. Thirty-five patients (29%) had distant metastasis and 21 (17%) underwent preoperative chemoradiotherapy. Thirty-four patients (28%) underwent combined resection of adjacent organs and 43 (35%) underwent lateral lymph node dissection. The median operative time was 288 min and the median blood loss was 11 ml. No patients required conversion to open surgery. The incidences of postoperative complications of grades II, III, and IV or more according to the Clavien–Dindo classification were 17.2%, 3.5%, and 0%, respectively. Seventy-three patients (60%) had pathological T4 tumors, and the incidence of positive resection margins was 4.9%. The median follow-up time was 42.9 months. The 3-year overall survival, disease-free survival, and cumulative local recurrence rates were 87.5%, 70.4%, and 4.0%, respectively. The short- and long-term outcomes of robotic surgery for cT4 rectal cancer were favorable. Robotic surgery is considered to be a useful approach for cT4 rectal cancer.

Scientific evidence supporting robotic-assisted laparoscopic surgery (RALS) for rectal cancer remains inconclusive because most previous reports were retrospective case series or case-control studies, with few reports focusing on long-term oncological outcomes with a large volume of patients. The aim of this study was to clarify the short- and long-term outcomes of a large number of consecutive patients with rectal cancer who underwent RALS in a single high-volume center. The records of 551 consecutive patients who underwent RALS for rectal adenocarcinoma between December 2011 and March 2017 were examined to reveal the short-term outcomes. The oncological outcomes of the 204 patients who underwent surgery between December 2011 and March 2014 were evaluated. Most patients had tumors located in the lower or mid-rectum (86.0%). Only 7.6% of patients underwent neoadjuvant chemoradiotherapy. Lateral lymph node dissection was performed for 191 patients (34.7%). The median operative time was 257 min, median blood loss was 10 mL, and no transfusions were needed. No conversion to open surgery was necessary. Eighteen patients (3.3%) had Clavien-Dindo grade III postoperative complications. Six patients (1.1%) had positive resection margins. The mean follow-up duration of the 204 patients was 43.6 ± 9.8 (months). The 5-year cancer-specific survival rate for stage I/II/III/IV was 100%/100%/100%/not reached, respectively. The 5-year relapse-free survival rate for stage I/II/III/IV was 93.6%/75.0%/77.6%/ not reached, respectively. The rate of local recurrence was 0.5%. Our results suggest that RALS is technically feasible for rectal cancer and has good short- and long-term outcomes.

What qualifies as optimal lymph node (LN) dissection in the surgical management of splenic flexure colon cancer (SFCC) still remains controversial because few studies have evaluated the distribution of LN metastasis of SFCC. The aim of this study was to clarify detailed distribution of LN metastasis and long-term outcomes of SFCC. This retrospective study enrolled patients who had curative colectomy for primary transverse or descending colon cancer of pathological stage I, II, or III at a single high-volume cancer center between April 2002 and December 2018. The 538 eligible patients were divided into three groups: patients with SFCC (SFCC group, n = 168), patients with proximal transverse colon cancer (PTCC group, n = 290), and patients with distal descending colon cancer (DDCC group, n = 80). LNs were classified into horizontal (pericolic) and vertical (intermediate and main) nodes. Intermediate and main LN station numbers were defined according to the Japanese Society for Cancer of the Colon and Rectum classification. Distributions of LN metastasis and long-term outcomes were compared. In the SFCC group, the mean age was 67.3 ± 10.5 years and 110 patients (65.5%) were male. The proportion of patients with LN metastasis in the intermediate or main region was significantly lower in the SFCC group (8%) than in the PTCC (37%) (p

We present a case of rectal cancer with rare variations of the left renal vessels. A man in his 60s underwent endoscopic mucosal resection for an Ip-type lesion in the upper rectum. Histologically, the lesion was a well-differentiated adenocarcinoma that had invaded the deep submucosal layer. Therefore, additional resection of the rectum with regional lymph node dissection was recommended. Preoperative CT revealed rare variations of the left renal vessels. There were two left renal arteries and veins; the caudal left renal artery and vein were located between the inferior mesenteric artery and the abdominal aorta. During the operation, these renal vessels were confirmed, and laparoscopic high anterior resection was performed safely without any injury to these renal vessels. To avoid the risk of unexpected intraoperative injuries, it is important to preoperatively check whether there are any variations in the renal vessels, even before colorectal surgery.

Persistent descending mesocolon (PDM) is typically asymptomatic. However, features such as adhesion and variations in vessel anatomy could affect the surgical techniques for colorectal cancer (CRC). This study aimed to investigate the frequency and radiological features of PDM. Short-term outcomes after conventional laparoscopic surgery (CLS) for CRC with PDM were also investigated to assess the feasibility of CLS and identify strategies for minimally invasive surgery (MIS) in CRC with PDM. Patients who underwent MIS, including CLS and robot-assisted laparoscopic surgery (RALS), for left-sided CRC between April 2016 and June 2019, were investigated. PDM was defined as the existence of the right border of the descending colon inside the right border of the left kidney based on preoperative computed tomography findings. Radiological findings of 837 patients were examined, and PDM was found in 19 (2.3%) patients. Radiality of the inferior mesenteric artery (IMA) was found in 5 of 19 (26.3%) PDM cases, which was significantly higher than that in non-PDM cases. The median lengths between the IMA and inferior mesenteric vein (IMV) and between the IMV and descending colon in PDM cases were 14.8 mm and 17.2 mm, respectively, which were significantly shorter than those in non-PDM cases. Short-term outcomes were evaluated only in CLS cases since the rate of hybrid surgery among RALS cases differed between non-PDM and PDM cases (0% vs. 44.4%), which would affect the surgical outcomes. The short-term outcomes in 447 CLS cases were similar between PDM and non-PDM cases. The frequency of extracorporeal division of the left colic artery (LCA) and IMV was significantly higher in PDM than in non-PDM cases (70.0% vs. 5.7%). This radiological definition of PDM was feasible. CLS for left-sided CRC with PDM was feasible, and dividing the LCA and IMV extracorporeally would be vital for safe surgery.

Polysplenia syndrome is a rare congenital disease characterized by variable thoracic and abdominal anomalies. A man in his 70s was diagnosed with rectal cancer by close exploration for fecal occult blood. A barium enema revealed a type 1 rectal tumor andwith non-rotation of intestine. CT revealed multiple abnormalities: a polyspleen, preduodenal portal vein, congenital absence of the pancreatic tail, bilateral superior vena cava, andbilateral bilobedlung. Basedon these findings, the patient was diagnosedas having rectal cancer with polysplenia syndrome andtreatedwith robotic assistedlaparoscopic low anterior resection. At operation, the whole colon was located in the left side of the abdominal cavity. The whole colon adhered with each other. The ileocecum adheredto the front of the aorta andthe right iliac artery. In the pelvis, anatomical abnormality was not detectedandrectal mobilization andresection was performedas usual. The patient hadno signs of recurrence of the rectal cancer. This is the first case presentation of laparoscopic low anterior resection in a patient with rectal cancer and polysplenia syndrome.

The safety and feasibility of robotic-assisted multivisceral resection for locally advanced rectal cancer remain unclear. The aim of this study was to assess the short-term outcomes of this procedure at our institution. From December 2011 to December 2016, patients who underwent robotic-assisted multivisceral resection for rectal cancer were investigated. Patient demographics, treatment characteristics, perioperative outcomes, and pathological results were evaluated retrospectively. There were 31 patients; 17 men (54.8%) and 14 women (45.2%), with a median age of 65 years (range 40–82 years). Twenty-one patients (67.7%) had a cT4 tumor, 9 patients (29.0%) had a pT4b tumor, and all patients except one (96.8%) underwent complete resection of the primary tumor with negative resection margins. Eleven patients (35.5%) received neoadjuvant chemoradiation. The most commonly resected organ was the vaginal wall (n = 12, 38.7%), followed by the prostate (n = 10, 32.3%). Lateral lymph node dissection was performed in 20 patients (64.5%). The median operative time was 394 min (range 189–549 min), and the median blood loss was 41 mL (range 0–502 mL). None of the patients received intraoperative blood transfusions or required conversion to open. Overall, postoperative complications occurred in 11 patients (35.5%). The most frequent complication was urinary retention (n = 5, 16.1%), and none of the patients developed serious complications classified as Clavien–Dindo grades III–V. Robotic-assisted multivisceral resection for rectal cancer is safe and technically feasible.

Background The possible benefits of the surgical resection of multiple metastases in rare sites from colorectal cancer (CRC) are still unclear. Therefore, more cases are needed to investigate the surgical outcomes of these diseases. A very rare case in which the simultaneous resection of both the metachronous retroperitoneal lymph node and pancreatic metastases from rectal cancer was successfully performed is reported. Case presentation A 68-year-old man had undergone low anterior resection for rectal cancer. Eight months later, computed tomography showed an enlarged lymph node located below the aortic bifurcation and a pancreatic head tumor. Positron emission tomography showed increased focal uptake in these two lesions. With a diagnosis of retroperitoneal lymph node metastasis from rectal cancer and primary pancreatic cancer or pancreatic metastasis from rectal cancer, resection of the enlarged retroperitoneal lymph node and pancreaticoduodenectomy were performed. The pathological examination showed that both resected lesions were metastases from the primary rectal cancer. After the metastasectomy, the patient was given systemic chemotherapy, which was discontinued due to an adverse event. He was then followed up routinely without any medication. Sixty-nine months after the metastasectomy, he is alive without any indication of recurrence. Conclusions Thus, even with metastases from CRC located in rare sites, an acceptable outcome can be expected following curative surgical resection in carefully selected patients. Whenever possible, an aggressive surgical approach should be included in the multimodality treatment of metastatic CRC.

Currently, when the colon is used for reconstruction after esophagectomy, the supercharge technique is occasionally employed. At our institution, we perform esophagectomy using a procedure in which the laparoscopic transhiatal approach and digestive reconstruction precede the specimen resection. In addition, a retrosternal route is selected for reconstruction. We have devised an intrathoracic supercharge technique for this type of esophagectomy. Two patients whose stomachs were not available for reconstruction underwent subtotal esophagectomy with this supercharge technique. In these cases, the right-side colon was pulled up via a retrosternal route for reconstruction, and anastomoses were performed between the ileocolic artery and right internal thoracic artery, and between the ileocolic vein and superior vena cava, without microsurgery in the pleural space after removing the esophagus. This supercharge technique has the advantage of being less cumbersome, and we consider it to be suitable for esophageal reconstruction.

574 Background: Peritoneal metastasis (PM) in patients diagnosed with colon cancer is associated with a poor prognosis. We aimed to analyze prognostic factors associated with PM in patients diagnosed with colorectal cancer (CRC). Methods: We evaluated 237 patients who underwent surgery between 2002 and 2016 for CRC with PM. The extent of PM was evaluated using the Peritoneal Cancer Index (PCI). Clinicopathological variables, PCI score, surgical curability, and the administration of postoperative chemotherapy were evaluated. Overall survival was analyzed using the Kaplan-Meier method. Multivariate analysis was performed to assess the prognostic value of these variables, using the Cox regression model. Results: Our patients included 119 men and 118 women with a median age of 64 (range: 21–90) years. The primary tumor sites were the right-sided colon (n = 103), left-sided colon (n = 84), and rectum (n = 50). The median PCI score was 4 (range: 1–30). Synchronous PM was detected at the time of diagnosis of the primary tumor in 165 patients (69.6%). Distant metastases except peritoneal metastases was detected in 137 patients (57.8%). R0 resection was performed in 62 patients (19.0%). Postoperative chemotherapy was performed in 165 patients (69.6%). The median survival time in all patients was 19.4 (range: 0–30) months, and the five-year overall survival rate was 16.3%. Multivariate analysis revealed that PCI ≤ 5 (hazard ratio [HR]: 2.56, 95% confidence interval [CI]: 1.56-4.32, P < 0.01); the absence of distant metastasis, except peritoneal metastasis (HR: 1.65, CI: 1.15-2.40, P < 0.01); R0 resection (HR: 4.21, CI: 2.44-7.50, P < 0.01) affected the survival rate. Conclusions: Our results show that a low PCI, the absence of distant metastasis except peritoneal metastasis, and R0 resection are prognostic factors in patients diagnosed with PM-CRC.

743 Background: The first choice of treatment for locally recurrent rectal cancer is surgical resection. However, the operation is often difficult with high perioperative risk. For surgically unfit cases, proton beam therapy (PBT) is proposed as the treatment option. However, its efficacy for locally recurrent rectal cancer remains unclear. Therefore, this study aimed to evaluate the efficacy and safety of PBT for locally recurrent rectal cancer. Methods: A total of 23 patients with locally recurrent rectal cancer who received PBT were retrospectively evaluated, from November 2005 to July 2014. Patients with single lesion, who refuse the radical surgical therapy, or who were considered unfit for the operation were included in this study. All patients were treated with 2.8Gy relative biological effectiveness (RBE)/fraction. Twenty-five irradiations were performed, with a total irradiation of 70Gy RBE. Unfit for operation criteria include invasion to the vertebra higher than the third sacrum or lateral lymph node recurrence after a lateral lymph node dissection. To assess the safety of PBT, adverse events were evaluated by using the Common Terminology Criteria for Adverse Effects (CTCAE version4.0). To assess the efficacy, the overall and relapse-free survival rates and local control rate were evaluated. Results: Sixteen patients were unfit for operation, and seven refused surgery. Three patients experienced Grade 3 late adverse events in the CTCAE (two ileum fistula and one urinary tract obstruction). The median follow-up time was 28.9 months. The 5-year overall and relapse-free survival rates were 47.6% and 20.2%, respectively. Fifteen patients (65.2%) showed distant metastasis or regrowth at the locally recurrent site. The 5-year local control rate was 39.0%. Ten patients (43.4%) showed regrowth at the proton beam irradiation site. Conclusions: PBT was relatively effective for locally recurrent rectal cancer with manageable adverse effects. Therefore, PBT may be considered as the therapeutic option for selected locally recurrent rectal cancer patients.

756 Background: Conventional laparoscopic surgery (CLS) for rectal cancer has several inherent technical difficulties, including a limited range of motion of the instruments.Robot-assisted laparoscopic surgery (RALS) has some technical advantages over CLS because it improves dexterity with an increased range of movements at the tips of the instruments. The purpose of this study was to evaluate the short-term and oncological outcomes of RALS for rectal cancer, including robotic, autonomic nerve-preserving, lateral lymph node dissection (RALLD), a new, technically challenging procedure. Methods: Between December 2011 and August 2017, 607 consecutive patients underwent RALS for rectal cancer. Surgical outcomes, pathological results, and oncological results were investigated retrospectively. Results: There were 403 males and 204 females; 577 patients had adenocarcinoma, 19 had carcinoid tumor, 8 had GIST, and 2 had other malignant tumor. The types of procedures performed were: 453 anterior resections, 93 intersphincteric resections, and 61 abdominoperineal resections. RALLD was performed in 202 patients (33.3%). Preoperative chemoradiotherapy was performed in 34 patients. The overall median operative time was 257(109-683) min. In cases without RALLD, the median operative time was 217 (109-545) min, while median operative time was 420 (162-683) min with RALLD. None of the cases was converted to an open or laparoscopic procedure.There was no surgical mortality. The overall complication rate for Clavien-Dindo classification grade III-IV was 3.0%. The oncological results for 279 patients with primary rectal adenocarcinoma, operated before December 2014 was also investigated (Stage I/II/III 115/48/116). The 5-year overall survival was 96.6%, the 3-year relapse free survival was 88.3%, and 3-year local relapse free survival was 98.5%. The 3-year RFS of pStage I/II/III was 96.2/89.6/79.6% respectively. Conclusions: RALS for rectal cancer is a feasible procedure with low morbidity and a low conversion rate, and acceptable oncological results.