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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.

Next-generation sequencing (NGS) is an integral part of precision medicine, and its power for detecting comprehensive genetic alterations may contribute to treatment decisions for patients with advanced, recurrent, or metastatic cancer. An NGS oncology panel developed in the U.S. and Europe, which targets cancer-related genes, has been approved in Japan, and testing is becoming more widespread in clinical oncology practice. However, these panels are based on cancer-related genes selected from cancer databases of Westerners. We aimed to develop an onco-panel for Japanese. We designed two High-tech Omics-based Patient Evaluation (HOPE) onco-panels: HOPE onco-panel Solid for solid tumors and HOPE onco-panel Liquid for liquid biopsy. These were based on genomic information of 5,143 cancer cases in the Japanese Cancer Genome Atlas (JCGA), a database of Japanese cancer cases. Their performance was confirmed using clinical data.

Background Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS). Aim This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine. Methods This study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors. Results The incidence of MSI-H was highest in endometrial cancers (26.7%, 20/75), followed by small intestine (20%, 3/15) and colorectal cancers (CRCs)(13.7%, 64/466); the sum of these three cancers (15.6%) was significantly higher than that of other types (2.5%)(P P P = 0.009), and family history, but not with smoking, drinking, or serum hepatitis virus markers. In CRC cases, MSI-H was significantly associated with a family history of LS-related cancer (P P Conclusions MSI-H was predominantly recognized in LS-related cancer cases with specific family histories and younger age. MSI-H was limited to a small proportion in precision medicine especially for non-LS-related cancer cases.

With the progress in cancer immunotherapy using immune checkpoint blockade (ICB) therapy, histological observations of tumor-infiltrating lymphocyte (TIL) status are needed to evaluate the antitumor effect of ICB using imaging analysis software.Formalin-fixed paraffin-embedded sections obtained from colorectal cancer and gastric cancer patients with more than 500 single nucleotide variants were stained with anti-CD8 and anti-PD-1 antibodies. Based on our own algorithm and imaging analysis software, an automatic TIL measurement method was established and compared to the manual counting methods.In the CD8An imaging software-based automatic measurement could be a simple and useful tool for evaluating the therapeutic effect of cancer immunotherapies in terms of TIL status.

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.

Aim Recent reports have described the use and efficacy of several types of transanal tube (TAT) for preventing anastomotic leakage by reducing intraluminal pressure. The aim of this study was to evaluate the safety and efficacy of a newly developed TAT for the prevention of anastomotic leakage after low anterior resection (LAR) for rectal cancer. Method A multicentre confirmatory single-arm trial was designed to evaluate the safety and efficacy of a new TAT after LAR for rectal cancer. A total of 115 patients were registered in the trial at several cancer centres and other hospitals. All patients initially received reconstruction with a stapled anastomosis, but 18 then underwent creation of a diverting stoma. Of the remaining 97 patients, the first 96 were included in the protocol-defined primary analysis set. The primary outcome was the incidence of symptomatic leakage and the secondary endpoint was the incidence of complications associated with use of the TAT. The TAT was placed during LAR without creating a covering stoma and the drain was removed 4 or 5 days postoperatively. Results The rate of symptomatic leakage was 5.2% (95% confidence interval 1.7-11.7), which was significantly lower than the predetermined threshold value of 15.8% (one-sided p-value 0.0013). Only one patient had Grade 3 rectal bleeding that might have been related to use of the TAT. Conclusion This nonrandomized study shows that the TAT appears to be safe and results in lower rates of anastomotic leakage in LAR compared with previous studies.

Lateral lymph node (LLN) metastasis is a determinant of local recurrence in advanced low rectal cancer. Lateral lymph node dissection (LLND) is effective in removing metastatic lymph nodes, and has been shown to have a decreased local recurrence rate. However, because of its complexity and complications it induces, there is still tremendous controversy about its usage. Neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME) are recommended as a conventional treatment for advanced rectal cancer. However, LLN metastasis and local recurrence still occur despite nCRT with TME. In Japan, TME with LLND is the standard surgical treatment for Stage II/III of advanced low rectal cancer. Before surgery, a proper evaluation of LLN status should be performed. Laparoscopic LLND and robotic-assisted LLND are useful for this. More research is necessary to improve the oncological outcomes of LLND. In this review, we retrospectively examine previous reports about LLND, aiming to emphasize its application prospects to improve patient survival and life quality.

Background: Tumor mutation burden (TMB) is the total exonic mutation count per megabase of tumor DNA. Recent advances in precision medicine occasionally detect Lynch syndrome (LS) by germline sequencing for mismatch-repair (g.MMR) genes but not using TMB. The current study analyzes the utility of TMB in detecting LS. Methods: Whole-exome sequencing (ion-semiconductor sequencing) was performed for somatic and germline DNA from 2,501 various cancer patients to detect TMB and g.MMR sequencing. MMR IHC was conducted when high TMB (≥10) was detected in LS-related cancers with an additional condition of wild-type BRAF in colorectal cancers. Target sequencing and multiplex ligation-dependent probe amplification (MLPA) were further performed for g.MMR genes in MMR-deficient cancers (TMB-based g.MMR target sequencing). We compared universal sequencing and TMB-based target sequencing in their sensitivity for detecting LS. Results: LS was detected in 16 (0.6%) of the 2,501 patients: 1.1% (9/826) of colorectal cancer patients, 16.2% (6/37) of endometrial cancer patients, and 14.3% (1/7) of small intestine cancer patients. TMB-based g.MMR target sequencing (81.3%) showed superior sensitivity for detecting LS than universal g.MMR sequencing (56.3%; P = 0.127) but missed 3 LS patients (1 with a low-TMB cancer, 1 with a BRAF-mutant colorectal cancer, and 1 with an MMR-proficient cancer). Ion-semiconductor sequencing could detect single-nucleotide substitutions but not large deletions. POL-mutated cancers showed extremely high TMBs (48.4–749.2). Conclusions: g.MMR target sequencing, combined with TMB, somatic BRAF mutation, and MMR IHC is an effective strategy for detecting LS. Impact: TMB can be a biomarker for detecting LS in precision medicine.

Many reports demonstrate that a high tumor mutation burden (TMB-H) is closely associated with good prognosis of cancer. However, specific studies investigating the association of various TMB statuses with overall survival in patients with solid tumors are scarce.In the present study, we investigated the association of TMB status with overall survival in 5,072 patients with cancer from the HOPE project and clarified the specific mechanism responsible for the good prognosis of the TMB-H group. All tumors were classified into one of four groups based on TMB: ultralow (UL), low (L), intermediate (I) and high (H).The TMB-H group had a better prognosis than the TMB-I and TMB-L groups, but not than the TMB-UL group. Analyzing the expression of 293 immune response-associated genes, 17 genes were up-regulated in the TMB-H group compared to the TMB-I and TNB-L groups, and two genes [CD274 and interferon-γ (IFNG)] were identified as good prognostic factors. Analysis of immune cell populations inside tumors demonstrated that the frequencies of exhausted CD8One possible mechanism for the good prognosis of the TMB-UL group compared to the TMB-H group might be that the TMB-UL group features a balance between immunosuppression and immunostimulation.

Background Successful achievement of randomized controlled trials (RCTs) is dependent on the acquisition of informed consent (IC) from patients. The aim of this study was to prospectively calculate the proportion of participation in a surgical RCT and to identify the reasons for failed acquisition of IC. Methods A 50-insitution RCT was conducted to evaluate oncological outcomes of open and laparoscopic surgery for stage IV colon cancer (JCOG1107: UMIN-CTR 000000105). The success rate of obtaining IC was evaluated in eight periods between January 2013 and January 2021. In addition, reasons for failed acquisition of IC were identified from questionnaires. Results In total, 391 patients were informed of their eligibility for the trial, and 168 (42%) were randomly assigned to either the laparoscopic surgery group (n = 84) or open surgery group (n = 84). The success rate of IC acquisition ranged from 33 to 58% in three periods. The most common reasons for failed IC acquisition were the patients’ preference for one approach of surgery based on recommendations from referring doctors and family members, and anxiety/unhappiness about randomization. Conclusions The success rate of acquiring IC from patients for an RCT of laparoscopic versus open surgery for stage IV colon cancer was lower than the expected rate planned in the protocol. To obtain the planned rate, investigators should make efforts to inform patients and their families about the medical contributions a surgical RCT can make and recognize that the period in equipoise may be limited.

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.

Summary: Background/objective: Paraaortic lymph node (PALN) metastasis influences treatment strategy for colorectal cancer. The aims of this study were to elucidate the diagnostic value of computed tomography (CT) and positron emission tomography (PET) for PALN metastasis from left-sided colorectal cancer. Methods: A total of 108 patients who underwent radical surgery including PALN dissection were included. Size and morphology of PALN were evaluated using CT, and presence of higher FDG uptake was evaluated using PET. Findings of CT and PET were compared with pathological status. Results: The largest major axis ≥11 mm and heterogeneous internal density were predictive factors on multivariate analysis. Eighty five percent of the PALNs ≥11 mm with heterogeneous internal density were pathologically metastatic, whereas 94.1% without them were not metastatic. PET had an accuracy, sensitivity, and specificity of 85.7%, 66.7%, and 94.1%, respectively. In patients with PALNs

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.

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

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.

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.

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.

Mutually exclusive KIT and PDGFRA mutations are considered to be the earliest events in gastrointestinal stromal tumors (GIST), but insufficient for their malignant progression. Herein, we aimed to identify driver genes and signaling pathways relevant to GIST progression. We investigated genetic profiles of 707 driver genes, including mutations, gene fusions, copy number gain or loss, and gene expression for 65 clinical specimens of surgically dissected GIST, consisting of six metastatic tumors and 59 primary tumors from stomach, small intestine, rectum, and esophagus. Genetic alterations included oncogenic mutations and amplification‐dependent expression enhancement for oncogenes (OG), and loss of heterozygosity (LOH) and expression reduction for tumor suppressor genes (TSG). We assigned activated OG and inactivated TSG to 27 signaling pathways, the activation of which was compared between malignant GIST (metastasis and high‐risk GIST) and less malignant GIST (low‐ and very low‐risk GIST). Integrative molecular profiling indicated that a greater incidence of genetic alterations of driver genes was detected in malignant GIST (96%, 22 of 23) than in less malignant GIST (73%, 24 of 33). Malignant GIST samples groups showed mutations, LOH, and aberrant expression dominantly in driver genes associated with signaling pathways of PI3K (PIK3CA, AKT1, and PTEN) and the cell cycle (RB1, CDK4, and CDKN1B). Additionally, we identified potential PI3K‐related genes, the expression of which was upregulated (SNAI1 and TPX2) or downregulated (BANK1) in malignant GIST. Based on our observations, we propose that inhibition of PI3K pathway signals might potentially be an effective therapeutic strategy against malignant progression of GIST., Signaling pathways involved in 65 GIST samples were investigated. Pathways were curated by genetic alterations, including oncogenic mutations and amplification‐dependent expression enhancement for oncogenes, and loss of heterozygosity and expression reduction for tumor suppressor genes. Malignant GIST with metastasis and high‐risk showed mutations, LOH, and aberrant expression dominantly in driver genes associated with signaling pathways of PI3K and the cell cycle.

Objectives To evaluate the relationships between adenine-thymine-rich interactive domain 1A (ARID1A) expression and the clinicopathologic features in T1 colorectal cancer (CRC) and to investigate whether the presence of ARID1A protein is related to genetic changes. Methods We retrospectively studied 219 surgically resected T1 CRCs. ARID1A expression was assessed by immunohistochemical methods, and the correlation between ARID1A expression and clinicopathologic features was evaluated. The relationship between ARID1A expression and 409 cancer-related gene mutations was also evaluated using next-generation sequencing (NGS). Results Immunohistochemical staining indicated negative ARID1A expression in 4.6%. Loss of ARID1A expression was significantly associated with younger age, lymphatic invasion, and lymph node metastasis (LNM). NGS showed that PKHD1, RNF213, and MSH6 mutations were more frequent in ARID1A-negative tumors, whereas KRAS mutations were more common in ARID1A-positive tumors. Conclusions In T1 CRC, negative ARID1A expression was correlated with early onset, lymphatic invasion, and LNM. Mutations in some cancer-related genes were possibly related with ARID1A expression.

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.

A depth of submucosal invasion (DSI) of ≥1000 μm is an important risk factor for lymph node metastasis (LNM) in patients with submucosal invasive (pT1) colorectal cancer (CRC), according to the European Society of Gastrointestinal Endoscopy and the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines. According to the latter, if the location of the muscularis mucosae in the invasive area is not confirmed, the DSI can be measured from the surface. In these cases, a ‘remaining intramucosal lesion’ (rIL), which is in the invasive area, is sometimes observed. To avoid over-measuring the DSI, we proposed a ‘modified DSI’ (mDSI), which excludes the rIL from the JSCCR DSI. We investigated the characteristics and effectiveness of the rIL and mDSI by grouping cases with polypoid growth (PG) and non-polypoid growth (NPG) histologically. Three hundred and thirty-nine consecutive patients with pT1 CRC were examined. LNM was detected in 37 cases. The distribution of the DSI and rIL was significantly higher in PG than in NPG cases (P

This study aimed to examine the risk factors for surgical site infection (SSI) and the association of that with recurrence in JCOG0212. The results for secondary endpoints showed that compared with the mesorectal excision (ME) alone group, ME with lateral lymph node dissection (LLND) group showed significantly longer operative time and significantly higher blood loss. These results suggested that LLND was a risk factor for SSI. All 701 patients registered in JCOG0212 were analyzed in this study. Wound infection was defined as incisional/deep SSI, and pelvic abscess and anastomotic leakage were defined as organ/space SSI. The risk factors for the incidence of SSI and the effect of SSI on relapse-free survival (RFS) were investigated. Multivariable odds ratio of Grade 2 or higher all SSI was 0.58 [95% Confidence interval: 0.36–0.93] for female (vs. male) and that of Grade 2 or higher incisional/deep SSI was 2.24 [1.03–4.86] for blood infusion. For RFS, patients with Grade 3 or higher all SSI showed poor prognosis (multivariable hazard ratio: 1.66 [1.03–2.68]). LLND is not significant factor for the incidence of all SSI. Male sex might be a risk factor of Grade 2 or higher SSI, and blood transfusion is a possible risk factor of Grade 2 or higher incisional/deep SSI. Grade 3 or higher all SSI might be a significant worse prognostic factor for lower rectal cancer.

Background The JCOG0212 trial was a randomized controlled trial comparing mesorectal excision alone to mesorectal excision with lateral lymph node dissection for stage II/III lower rectal cancer patients without clinical lateral lymph node enlargement. This study aimed to identify clinicopathological prognostic factors for relapse-free survival and overall survival of lower rectal cancer in the trial. Methods Prospective data were selected from 663 patients with complete data. Uni and multivariable Cox regression model was applied to evaluate the preoperative and the combined preoperative and postoperative factors, respectively. Preoperative factors included age, sex, performance status, clinical T, clinical N and operative procedures. Postoperative factors included histological grade, pathological T, number of metastatic lymph nodes and number of dissected lymph nodes. No patient received neoadjuvant treatment. Results Regarding preoperative factors, multivariable analysis revealed that performance status 1 (vs. 0: HR 2.079, P = 0.0041) and cT4a (vs. cT2–3: HR 2.721, P = 0.0002) were independent risk factors for relapse-free survival, and those for overall survival were male (vs. female: HR 1.660, P = 0.0228) and cT4a (vs. cT2–3: HR 2.486, P = 0.0473). The only independent preoperative risk factor common for relapse-free survival and overall survival was cT4a. Taking preoperative and postoperative factors together, the number of metastatic lymph nodes was the only independent risk factor common for relapse-free survival and overall survival. Conclusions Clinical stage II/III lower rectal cancer patients with cT4a should be a target of therapeutic development of neoadjuvant therapy. Postoperatively, intensive chemotherapy should be investigated for patients with more metastatic lymph nodes.

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

This is a prospective observational cohort study aiming to include 4000 patients with stages I to III colon cancer treated at 35 specialist institutions in Japan, South Korea, Germany, Russia, Lithuania and Taiwan. The anatomical distribution of lymph nodes and feeding arteries are investigated using surgical specimens according to pre-specified categorizing methods using intraoperative anatomical markings. Primary analyses are performed to identify the general principles of metastatic lymph node distribution in terms of its relation to the location of the primary tumor and feeding arteries. Secondary analyses will be used to estimate prognostic outcomes according to bowel resection length and central radicality and will be used to evaluate the quality of resected surgical specimens. Through in-depth lymph node mapping, standardized criteria for the definite area of ‘regional’ lymph node resection in routine surgical procedures can be identified, which is expected to contribute to international standardization in colon cancer surgery (ClinicalTrials.gov NCT02938481)., The T-REX study is an international initiative to determine standardized criteria for regional lymph node resection in colon cancer surgery using in-depth lymph node mapping.

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

Despite the frequent detection of KRAS driver mutations in patients with colorectal cancer (CRC), no effective treatments that target mutant KRAS proteins have been introduced into clinical practice. In this study, we identified potential effector molecules, based on differences in gene expression between CRC patients carrying wild-type KRAS (n = 390) and those carrying KRAS mutations in codon 12 (n = 240). CRC patients with wild-type KRAS harboring mutations in HRAS, NRAS, PIK3CA, PIK3CD, PIK3CG, RALGDS, BRAF, or ARAF were excluded from the analysis. At least 11 promising candidate molecules showed greater than two-fold change between the KRAS G12 mutant and wild-type and had a Benjamini-Hochberg-adjusted P value of less than 1E-08, evidence of significantly differential expression between these two groups. Among these 11 genes examined in cell lines transfected with KRAS G12 mutants, BMP4, PHLDA1, and GJB5 showed significantly higher expression level in KRAS G12A, G12D, and G12V transfected cells than in the wild-type transfected cells. We expect that this study will lead to the development of novel treatments that target signaling molecules functioning with KRAS G12-driven CRC.

Objectives Preoperative colonoscopy is often incomplete for stenotic colorectal cancers (CRC). This prospective observational study aimed to evaluate the ability of an ultrathin colonoscope (UTC) to inspect the whole colon by passing through the stenotic CRC. Methods All patients who underwent preoperative colonoscopy for stenotic CRCs at Shizuoka Cancer Center were examined for eligibility. If a standard colonoscope (PCF-H290ZI) could not pass because of a stenosis, the patients were recruited. All of the eligible patients were prospectively enrolled when informed consent could be obtained, and complete colonoscopy was attempted again using an UTC (PCF-PQ260L). Patients with stent placement and those requiring right hemicolectomy were not recruited. Primary endpoints were pass-through and cecal intubation rates. The detected synchronous neoplasias (adenomas and cancers) and their pathological findings after resection were evaluated. Results A total of 100 patients were enrolled between September 2017 and February 2019. The mean age was 65.6 ± 10.8 years, and 59% were male. The pass-through and cecal intubation rates were 67% (67/100) and 58% (58/100), respectively. Synchronous lesions located proximal to the stenoses were detected in 65.5% (38/58) of the complete colonoscopies, with a total of 86 lesions, including 18 advanced neoplasias with three invasive cancers. Conclusion When standard colonoscopy cannot pass through stenotic CRC, ultrathin colonoscopy can be considered as an option to inspect the whole colon proximal to the stenosis because treatment strategy can potentially be changed by detecting synchronous neoplasias proximal to the stenosis before surgery. (UMIN000028505).

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.

Various predictors of the difficulty of total mesorectal excision for rectal cancer have been described. Although a bulky mesorectum was considered to pose technical difficulties in total mesorectal excision, no studies have evaluated the influence of mesorectum morphology on the difficulty of total mesorectal excision. Mesorectal fat area at the level of the tip of the ischial spines on magnetic resonance imaging was described as a parameter characterizing mesorectum morphology. This study aimed to evaluate the influence of clinical and anatomical factors, including mesorectal fat area, on the difficulty of total mesorectal excision for rectal cancer. This study enrolled 98 patients who underwent robotic-assisted laparoscopic low anterior resection with total mesorectal excision for primary rectal cancer, performed by a single expert surgeon, between 2010 and 2015. Magnetic resonance imaging-based pelvimetry data were collected. Linear regression was performed to determine clinical and anatomical factors significantly associated with operative time of the pelvic phase, which was defined as the time interval from the start of rectal mobilization to the division of the rectum. The median operative time of the pelvic phase was 68 min (range 33–178 min). On univariate analysis, the following variables were significantly associated with longer operative time of the pelvic phase: male sex, larger tumor size, larger visceral fat area, larger mesorectal fat area, shorter pelvic outlet length, longer sacral length, shorter interspinous distance, larger pelvic inlet angle, and smaller angle between the lines connecting the coccyx to S3 and to the inferior middle aspect of the pubic symphysis. On multiple linear regression analysis, only larger mesorectal fat area remained significantly associated with longer operative time of the pelvic phase (p = 0.009). Mesorectal fat area may serve as a useful predictor of the difficulty of total mesorectal excision for rectal cancer.

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

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.

The TRICC0808 trial is a phase II multi-institutional trial that investigated the efficacy of preoperative mFOLFOX6 + bevacizumab (BV) therapy for liver-only metastasis that is unsuitable for upfront resection. The R0 resection rate in the efficacy analysis has been reported to be 44.4%, and the final analysis for survival was conducted (data fixation on February 16, 2015). Six cycles of mFOLFOX6 + BV therapy were applied to patients with liver-only metastases, which were > 5 cm in diameter or more than four tumors (H2 and H3), and hepatectomy was performed if possible. Primary and secondary endpoints were the R0 hepatectomy rate and overall survival (OS), respectively. Of 46 patients registered, OS was analyzed for 45 patients in whom the 3-year OS rate from the starting date of chemotherapy was 44.0% with a 33.6-month median survival time (MST). The 3-year OS rate of 31 patients with hepatectomy, including resection after an additional chemotherapy, was 61.3% with a 43.1-month MST, which was significantly better than 0% of the 3-year OS rate with a 21.0-month MST of 14 patients without hepatectomy (p value

Surgical treatment for colorectal cancer has been approached by various treatment strategies. Among them, laparoscopic surgery, trans-anal total mesorectal excision(TaTME)and robot-assisted surgery are nowbeing the newstandard. Moreover, in Japan, lateral lymph node dissection for lower rectal cancer has been performed as a standard treatment. In this article, we introduce some evidences obtained by clinical trials to date on these topics for colorectal cancer.

Anastomotic leakage after low anterior resection for rectal cancer is a critical problem. Many risk factors have been suggested and surgical techniques have improved, but anastomotic leakage remains a major postoperative challenge. This study sought to create a nomogram for precise prediction of anastomotic leakage after low anterior resection for rectal cancer. We used data of 936 patients that had been prospectively collected by the Japanese Society for Colon and Rectal Cancer between June 2010 and February 2013. Risk factors for anastomotic leakage were identified by multivariate logistic regression analysis and used to create a nomogram. The performance of the nomogram was evaluated by using a bootstrapped-concordance index and calibration plots. Sex, preoperative serum albumin, tumor location and diameter, and simultaneous resection of other organs were identified as significantly associated factors that could be combined for accurate prediction of anastomotic leakage. We created a nomogram for anastomotic leakage by using these risk factors. The area under the curve was 0.72 (95% confidence interval 0.67–0.76). The nomogram had a bootstrapped-concordance index of 0.72 and was well calibrated. Our nomogram was a useful tool for precise prediction of anastomotic leakage after low anterior resection for rectal cancer.

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.

Several retrospective studies have demonstrated the safety and technical feasibility of robotic-assisted laparoscopic surgery (RALS). The aim of the present study was to clarify the advantages of RALS for rectal cancer by comparing its short-term outcomes with those of conventional laparoscopic surgery (CLS).Between April, 2010 and April, 2015, a total of 974 patients underwent proctectomy for rectal cancer. After the exclusion of those who underwent open surgery, high anterior resection, lateral lymph node dissection, or multiple resection, 442 patients were enrolled in this study, including 203 who underwent RALS and 239 who underwent CLS. We compared the short-term outcomes of these two groups.There was no case of conversion to open surgery in the RALS group, but 8 (3.3 %) cases in the CLS group (p = 0.009). Operative time was not significantly different, but blood loss was significantly less in the RALS group than in the CLS group (p 0.001). The postoperative hospital stay was shorter in the RALS group than in the CLS group (p 0.001). The rate of urinary retention was significantly lower in the RALS group than in the CLS group (p = 0.018).The short-term outcomes in this series provide further evidence that RALS may be superior to CLS for rectal cancer.

The aim of the present study was to clarify the advantages of robotic-assisted laparoscopic lateral lymph node dissection (RALLD) for rectal cancer by comparing its short-term outcomes with those of open lateral lymph node dissection (OLLD) in a large series from a single center. In terms of RALLD for advanced lower rectal cancer, there are only a few reports with a small number of cases in retrospective, non-comparative studies.From April 2010 to July 2014, a total of 177 patients underwent rectal cancer surgery with lateral lymph node dissection. Four patients who underwent conventional laparoscopic lateral lymph node dissection were excluded. Thus, 173 patients were enrolled, with 85 RALLD and 88 OLLD cases. Perioperative outcomes, postoperative complications, and pathological results were compared between the groups.No conversion to open surgery was necessary in the RALLD group. The rate of sphincter-preserving procedure was significantly higher in the RALLD group than in the OLLD group (p = 0.007). Operative time was significantly longer in the RALLD group than in the OLLD group (p = 0.007). Blood loss was significantly less in the RALLD group than in the OLLD group (p0.001). The rates of wound infection, small bowel obstruction, anastomotic leakage, and urinary retention were significantly lower in the RALLD group than in the OLLD group. Numbers of harvested lymph nodes and positive resection margin rates showed no significant differences.The short-term outcomes of RALLD may be superior to those of OLLD for advanced lower rectal cancer.

There is an increased risk of developing metachronous colorectal cancer (CRC) in the remnant colorectum after surgical resection of CRC. We evaluated the incidence of metachronous advanced neoplasia (AN) after surgery for CRC according to resection type and synchronous AN.This cohort study included patients who underwent surgical resection for initial CRC at a tertiary cancer center in Japan between September 2002 and December 2012. The cumulative probability of metachronous AN was calculated using the Kaplan-Meier method and was evaluated by the log-rank test.Metachronous AN was detected in 145 of 1731 included patients, and the 5-year cumulative probability of metachronous AN was 13.1%. There was no significant difference in the incidence of metachronous AN in the right-sided colorectal resection versus left-sided colorectal resection (LCR) groups (log-rank test P = .151), whereas the incidence of metachronous AN was significantly higher in patients with synchronous AN (log-rank test P .001). In subgroup analysis of patients according to resection type and synchronous AN, the LCR group with synchronous AN showed a significantly higher incidence of metachronous AN than the other groups (log-rank test P .001).We found that synchronous AN, but not resection type, was independently associated with the incidence of metachronous AN in patients who underwent surgical resection of CRC. In addition, subjects with synchronous AN after LCR had a potentially increased risk for metachronous AN. Thus, it may be useful to perform risk stratification according to synchronous AN and resection type.

The safety and feasibility of laparoscopic reoperation for anastomotic leakage remain unclear.A total of 3321 patients underwent laparoscopic surgery for primary colorectal cancer at a tertiary referral center from September 2002 to May 2016. Of these, 31 patients who underwent reoperation for treatment of anastomotic leakage were enrolled in this study and divided into two reoperation groups: laparoscopic (n = 15) and open (n = 16). Data regarding patient demographics, operative outcomes, morbidity, length of hospital stay, mortality, and stoma closure after reoperation in the two groups were compared.No significant difference was observed in the primary surgery procedure between the two groups. Estimated blood loss (1 vs 9 mL, P = 0.020), total postoperative complications (26.7% vs 68.8%, P = 0.032), wound infection (0.0% vs 31.2%, P = 0.043), and postoperative hospital stay (18 vs 31 days, P = 0.017) were significantly better in the laparoscopic group than in the open group. Although the rate of stoma closure after reoperation was higher in the laparoscopic group, the difference was not significant (86.7% vs 62.5%, P = 0.220).Laparoscopic reoperation exhibited better short-term outcomes than open reoperation for selected patients with anastomotic leakage.

The purpose of this study was to identify the size criteria of lateral lymph node metastasis in lower rectal cancer both in patients who underwent preoperative CRT and those who did not. This study enrolled 150 patients who underwent resection for primary lower rectal adenocarcinoma with lateral lymph node dissection between 2013 and 2015. Patients were divided into two groups: the CRT group, treated with preoperative chemoradiotherapy before surgery, and the non-CRT group, treated with surgery alone. The short-axis diameter of each dissected lateral lymph node was measured. Receiver-operating characteristic curves were generated to reveal the optimal cutoff values for determining lateral lymph node metastasis in both groups. In the non-CRT group (n = 131), the ROC curve demonstrated that the optimal cutoff value for determining metastasis was 6.0 mm, with a sensitivity of 78.5% and specificity of 82.9%, and the AUC was 0.845. In comparison, in the CRT group (n = 19), the optimal cutoff value was 5.0 mm, with a sensitivity of 71.4% and specificity of 85.3% and an AUC of 0.836. The cutoff size for determining lateral lymph node metastasis was smaller in the CRT group than in the non-CRT group.

The purpose of this study is to clarify the optimal extent of lymph node dissection for colon cancer by evaluating the distributions of lymph node metastases and lymph node size according to tumor location and T stage. This study enrolled 662 patients who underwent curative resection for primary colon cancer between 2013 and 2015. Lymph node regions were classified into pericolic, intermediate, and main nodes. The short-axis diameter of each dissected lymph node was measured. The distributions of lymph node metastases and lymph node size were evaluated according to tumor location and T stage. In the overall cohort, the incidence of metastases in pericolic nodes located more than 5 cm but no more than 10 cm from tumor and in pericolic nodes located more than 10 cm from tumor was 3.6 and 0.2%, respectively. More than 2% of patients with ≥ T2 tumor had metastases in main lymph nodes, and no patients with T1 tumor had metastases in main lymph nodes. Only 0.7% of patients with T1 tumor had lymph node metastases in pericolic nodes located more than 5 cm from the tumor. Both metastatic and non-metastatic lymph node sizes were significantly larger in right-sided colon cancer than in left-sided colon cancer, and both metastatic and non-metastatic lymph node sizes were significantly larger in ≥ T2 tumor than in T1 tumor. It is necessary to resect 10 cm of normal bowel both proximal and distal to the tumor and to perform D3 lymph node dissection for ≥ T2 colon cancer.

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.

Para-aortic lymph node (PALN) metastasis from colorectal cancer is rare and often not suitable for surgery. However, in selected patients, radical resection may bring about longer survival. The aim of this study was to evaluate long-term outcomes of resection of left-sided colon or rectal cancer with simultaneous PALN metastasis. The study included 2122 patients with left-sided colon or rectal cancer (30 patients with and 2092 patients without PALN metastasis) who underwent resection with curative intent between 2002 and 2013. Clinicopathological characteristics, long-term outcomes of resection, and factors related to poor postoperative survival in patients with PALN metastasis were investigated. Of a total of 2122 total patients, 16 of 50 patients (32.0%) with lymph node metastasis at the root of the inferior mesenteric artery had PALN metastasis. The 5-year overall survival rates for 18 patients who underwent R0 resection and 12 patients who did not were 29.1 and 10.4%, respectively (p = 0.017). Factors associated with poor postoperative survival among patients who underwent R0 resection were presence of conversion therapy, lack of adjuvant chemotherapy, carcinoembryonic antigen >20 ng/mL, and lateral lymph node metastasis in rectal cancer patients. The 5-year recurrence-free survival rate was 14.8%. Although recurrence was frequent, R0 resection for left-sided colon or rectal cancer with PALN metastasis was associated with longer survival than R1/R2 resection. Furthermore, the 5-year overall survival rate in the R0 group was relatively favorable for stage IV. Therefore, R0 resection may prolong survival compared with chemotherapy alone in selected patients.