Effects of the COVID-19 pandemic on short-term postoperative outcomes for colorectal perforation: A nationwide study in Japan based on the National Clinical Database.

Aim: Possible negative effects of the COVID-19 pandemic on short-term postoperative outcomes for colorectal perforation in Japan were examined in this study. Methods: The National Clinical Database (NCD) is a large-scale database including more than 95% of surgical cases in Japan. We analyzed 13 107 cases of colorectal perforation from 2019 to 2021. National data were analyzed, and subgroup analyses were conducted for subjects in prefectures with high infection levels (HILs) and metropolitan areas (Tokyo Met. and Osaka Pref.). Postoperative 30-day mortality, surgical mortality, and postoperative complications (Clavien-Dindo grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. Results: In the NCD, postoperative 30-day mortality occurred in 1371 subjects (10.5%), surgical mortality in 1805 (13.8%), and postoperative complications in 3950 (30.1%). Significantly higher SMRs were found for 30-day mortality in November 2020 (14.6%, 1.39 [95% CI: 1.04-1.83]) and February 2021 (14.6%, 1.48 [95% CI: 1.10-1.96]), and for postoperative complications in June 2020 (37.3%, 1.28 [95% CI: 1.08-1.52]) and November 2020 (36.4%, 1.21 [95% CI: 1.01-1.44]). The SMRs for surgical mortality were not significantly high in any month. In prefectures with HILs and large metropolitan areas, there were few months with significantly higher SMRs. Conclusions: The COVID-19 pandemic had limited negative effects on postoperative outcomes in patients with colorectal perforation. These findings suggest that the emergency system for colorectal perforation in Japan was generally maintained during the pandemic.

Endoscopic treatment of anastomotic leakage after colorectal surgery by using polyglycolic acid sheets and fibrin glue.

We describe the case of a 66-year-old man with an anastomotic fistula after rectal surgery, which was treated colonoscopically using polyglycolic acid sheets and fibrin glue. Polyglycolic acid sheets and fibrin glue have been used in thoracic surgery and otolaryngology to reinforce sutures and prevent air leakage. There have been recent reports of their use in endoscopic surgery for the closure of intraoperative perforations after endoscopic submucosal dissection and for fistula closure after upper gastrointestinal tract surgery. However, anastomotic fistulas in colorectal surgery are difficult to visualize endoscopically and may be difficult to suture with clips due to fibrosis. Polyglycolic acid sheets can be easily trimmed, and the fistula can be easily filled using these sheets; moreover, using fibrin glue to fix the sheets may enable fistula closure in areas that are difficult to visualize endoscopically.

AI diagnosis of heart sounds differentiated with super StethoScope.

In the aging global society, heart failure and valvular heart diseases, including aortic stenosis, are affecting millions of people and healthcare systems worldwide. Although the number of effective treatment options has increased in recent years, the lack of effective screening methods is provoking continued high mortality and rehospitalization rates. Appropriately, auscultation has been the primary option for screening such patients, however, challenges arise due to the variability in auscultation skills, the objectivity of the clinical method, and the presence of sounds inaudible to the human ear. To address challenges associated with the current approach towards auscultation, the hardware of Super StethoScope was developed. This paper is composed of (1) a background literature review of bioacoustic research regarding heart disease detection, (2) an introduction of our approach to heart sound research and development of Super StethoScope, (3) a discussion of the application of remote auscultation to telemedicine, and (4) results of a market needs survey on traditional and remote auscultation. Heart sounds and murmurs, if collected properly, have been shown to closely represent heart disease characteristics. Correspondingly, the main characteristics of Super StethoScope include: (1) simultaneous collection of electrocardiographic and heart sound for the detection of heart rate variability, (2) optimized signal-to-noise ratio in the audible frequency bands, and (3) acquisition of heart sounds including the inaudible frequency ranges. Due to the ability to visualize the data, the device is able to provide quantitative results without disturbance by sound quality alterations during remote auscultations. An online survey of 3648 doctors confirmed that auscultation is the common examination method used in today's clinical practice and revealed that artificial intelligence-based heart sound analysis systems are expected to be integrated into clinicians' practices. Super StethoScope would open new horizons for heart sound research and telemedicine.

Appendiceal cancer showing a submucosal tumor-like morphology in the ascending colon on colonoscopy: a case report.

Few reports have described a submucosal tumor (SMT)-like colon tumor together with appendiceal cancer. Moreover, some appendiceal tumors may exhibit a cecal protuberance. Here, we report an uncommon case of appendiceal cancer with an SMT-like tumor, which was a protuberant lesion in the ascending colon. To our knowledge, this is the first report in Japan. Our case was a 50-year-old man with an ascending colon tumor presented at our hospital for further evaluation of this lesion. This was discovered as a cystic lesion near the ascending colon on colonoscopy. Our initial diagnosis was an ascending colon SMT-like tumor, and our treatment strategy was laparoscopic resection. The differential diagnosis was appendiceal cancer or mucocele. Postoperative pathological findings led to a diagnosis of adenocarcinoma of the appendix. The postoperative course was uneventful, and the patient was followed up with computed tomography and blood sampling on an outpatient basis.

New Scale Predicting Distant Recurrence in Locally Advanced Lower Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy.

BACKGROUND/AIM: Neoadjuvant chemoradiotherapy (nCRT) for locally advanced lower rectal cancer (LALRC) is effective in preventing locoregional recurrence; however, it is less effective for preventing distant recurrence. This study aimed to evaluate a new scale for predicting distant recurrence before administering nCRT. PATIENTS AND METHODS: Sixty-three patients underwent nCRT for LALRC between 2009 and 2016 at the Tokyo Women's Medical University. Of these, 51 consecutive patients who underwent curative surgery were enrolled in this study. Patients with ≥cT3 status or cN-positive LALRC were classified into three groups before nCRT based on the neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR): high-risk, NLR ≥3.2 and LMR <5.0; intermediate-risk, NLR <3.2 and LMR ≥5.0 or NLR ≥3.2 and LMR <5.0; and low-risk, NLR <3.2 and LMR ≥5.0. Independent risk factors associated with distant relapse-free survival were analysed using the Cox proportional hazards model. Relapse-free survival from distant metastasis was evaluated using the log-rank test. RESULTS: Patient characteristics and tumour-associated factors were not significantly different between the groups. Distant recurrence in the high-, intermediate-, and low-risk groups was 61.5%, 42.9%, and 20.8% (p=0.046), respectively. In the multivariate analysis, the new scale was an independent risk factor for distant relapse-free survival (high-risk vs. low-risk groups, p=0.004 and intermediate-risk vs. low-risk groups, p=0.055). The 3-year distant relapse-free survival rate in the high-, intermediate-, and low-risk groups was 38.5%, 56.3%, and 81.7% (p=0.028), respectively. CONCLUSION: A new scale combining the pre-nCRT NLR and LMR was independently associated with distant relapse-free survival. The new scale for LALRC may aid selection for total neoadjuvant chemotherapy.

Prognostic risk factors for pT4 colon cancer: A retrospective cohort study.

The present study aimed to clarify the prognostic risk factors for pathological T4 (pT4) colon cancer and provide a basis for improved treatment in affected patients. The current retrospective cohort study included 83 consecutively enrolled patients who underwent curative surgery for primary pT4 colon cancer between January 2014 and December 2021 at Tokyo Medical Women's University (Tokyo, Japan). Oncological outcomes, including recurrence pattern, were compared between patients with pT4a and pT4b colon cancer. Independent risk factors associated with overall survival (OS) and relapse-free survival (RFS) were analyzed using a multivariate Cox regression model. The 3-year OS rates were 85.1 and 95.0% in the pT4a and pT4b groups (P=0.089) and 3-year RFS rates were 64.1 and 60.5% (P=0.589), respectively. Moreover, the 3-year peritoneal recurrence-free survival was 71.0 and 90.2% (P=0.085) in these groups, respectively. Independent risk factors for OS were histology (mucinous or poorly differentiated adenocarcinoma), tumor location (right-sided) and pN status (positive). The risk factors for RFS were histology and pN status. Patients with pT4b colon cancer and R0 resection may not have a poorer prognosis compared with those with pT4a colon cancer. However, patients with pT4a colon cancer tended to have more peritoneal recurrence patterns. Histology and pN status were associated with OS and RFS, and right-sided colon cancer was also a risk factor for OS.

Multiple intestinal lymphangiomas with episodic hemorrhage requiring partial laparoscopic resection: a case report.

BACKGROUND: Lymphangioma is a non-epithelial tumor marked by aggregates of abnormally dilated lymphatics. Mesenteric occurrences account for < 1% of all cases, and < 0.05% involve the gastrointestinal tract. Most are confined to children, rarely affecting adults. CASE PRESENTATION: Herein, we describe an elderly Japanese woman with anemia, hypoalbuminemia, and episodic bleeding due to multiple intestinal lymphangiomas. Abdominal computed tomography revealed multiple low-density defects of mesentery, with areas of intermediate (T1 images) or high (T2 images) signal intensity similarly dispersed in magnetic resonance scanning sequences. Single-balloon enteroscopy was undertaken, enabling identification and tattooing of a small intestinal bleeding source. Laparoscopy-assisted resection at this site served to control related hemorrhage, removing a histologically confirmed hemolymphangioma. Having recovered uneventfully, the patient remained stable 2 months postoperatively. CONCLUSIONS: Although rare in adults, mesenteric or gastrointestinal lymphangiomas must be considered in a setting of anemia and hypoalbuminemia. Complete resection is advantageous to improve patient symptoms, but limited resection of multiple lesions may be equally effective.

Automated recognition of objects and types of forceps in surgical images using deep learning.

Analysis of operative data with convolutional neural networks (CNNs) is expected to improve the knowledge and professional skills of surgeons. Identification of objects in videos recorded during surgery can be used for surgical skill assessment and surgical navigation. The objectives of this study were to recognize objects and types of forceps in surgical videos acquired during colorectal surgeries and evaluate detection accuracy. Images (n = 1818) were extracted from 11 surgical videos for model training, and another 500 images were extracted from 6 additional videos for validation. The following 5 types of forceps were selected for annotation: ultrasonic scalpel, grasping, clip, angled (Maryland and right-angled), and spatula. IBM Visual Insights software was used, which incorporates the most popular open-source deep-learning CNN frameworks. In total, 1039/1062 (97.8%) forceps were correctly identified among 500 test images. Calculated recall and precision values were as follows: grasping forceps, 98.1% and 98.0%; ultrasonic scalpel, 99.4% and 93.9%; clip forceps, 96.2% and 92.7%; angled forceps, 94.9% and 100%; and spatula forceps, 98.1% and 94.5%, respectively. Forceps recognition can be achieved with high accuracy using deep-learning models, providing the opportunity to evaluate how forceps are used in various operations.

Lateral pelvic lymph nodes for rectal cancer: A review of diagnosis and management.

The current status and future prospects for diagnosis and treatment of lateral pelvic lymph node (LPLN) metastasis of rectal cancer are described in this review. Magnetic resonance imaging (MRI) is recommended for the diagnosis of LPLN metastasis. A LPLN-positive status on MRI is a strong risk factor for metastasis, and evaluation by MRI is important for deciding treatment strategy. LPLN dissection (LPLD) has an advantage of reducing recurrence in the lateral pelvis but also has a disadvantage of complications; therefore, LPLD may not be appropriate for cases that are less likely to have LPLN metastasis. Radiation therapy (RT) and chemoradiation therapy (CRT) have limited effects in cases with suspected LPLN metastasis, but a combination of preoperative CRT and LPLD may improve the treatment outcome. Thus, RT and CRT plus selective LPLD may be a rational strategy to omit unnecessary LPLD and produce a favorable treatment outcome.

Pedunculated early colorectal cancer with nodal metastasis: a case report.

BACKGROUND: Pedunculated polyps are more likely to be amenable to complete resection than non-pedunculated early colorectal cancers and rarely require additional surgery. We encountered a patient with a pedunculated early colorectal cancer that consisted of poorly differentiated adenocarcinoma with lymphatic invasion. We performed an additional bowel resection and found nodal metastasis. CASE PRESENTATION: A 43-year-old woman underwent colonoscopy after a positive fecal occult blood test. The colonoscopist found a 20-mm pedunculated polyp in the descending colon and performed endoscopic resection. Histopathologic examination revealed non-solid type poorly differentiated adenocarcinoma. The lesion invaded the submucosa (3500 µm from the muscularis mucosa) and demonstrated lymphatic invasion. In spite of the early stage of this cancer, the patient was considered at high risk for nodal metastasis. She was referred to our institution, where she underwent bowel resection. Although there was no residual cancer after her endoscopic resection, a metastatic lesion was found in one regional lymph node. The patient is undergoing postoperative adjuvant chemotherapy, and there has been no evidence of recurrence 3 months after the second surgery. CONCLUSIONS: Additional bowel resection is indicated for patients with pedunculated polyps and multiple risk factors for nodal metastasis, such as poorly differentiated adenocarcinoma and lymphatic invasion. We encountered just such a patient who did have a nodal metastasis; herein, we report her case history with a review of the literature.

Stage II colon cancer staging using the number of retrieved lymph nodes may be superior to current TNM staging for prognosis stratification: the Japanese study group for postoperative follow-up of colorectal cancer.

PURPOSE: The purpose of the study was to compare staging of stage II colon cancer using the number of retrieved lymph nodes (RN) to current TNM staging for stratification of prognosis. METHODS: The subjects were 6307 patients with stage II colon cancer who underwent curative resection at 24 Japanese institutions. The cutoff for the number of RN was established using Akaike information criterion (AIC) values for relapse-free survival (RFS) and overall survival (OS). Comparison of survival using TNM and T + RN (TRN) staging was performed using a Cox proportional hazards regression model. RESULTS: AIC was lowest for 14 retrieved lymph nodes for RFS and OS. This number was used as the cutoff. In multivariate analysis, age (≥ 69), male gender, V1, CEA (> 5), pT (T4a, T4b), and RN-L were independent factors associated with RFS and OS. Six combinations of pT and RN categories were used to establish three subgroups: TRN stages IIA, IIB, and IIC. The 5-year RFS was 83.9%, 72.3%, and 71.8% in TNM stages IIA, IIB, and IIC; and 86.0%, 76.9%, and 60.3% in TRN stages IIA, IIB, and IIC. The 5-year OS was 90.0%, 81.3%, and 82.6% for the TNM stages; and 91.6%, 85.0%, and 71.9% for the TRN stages. The AIC for RFS was lower for TRN (22,318.2) than for TNM (22,390.6), and that for OS was also lower for TRN (16,285.3) than for TNM (16,355.1). CONCLUSION: Stage II colon cancer staging using the number of retrieved lymph nodes may be superior to current TNM staging for prognosis stratification.

Object and anatomical feature recognition in surgical video images based on a convolutional neural network.

PURPOSE: Artificial intelligence-enabled techniques can process large amounts of surgical data and may be utilized for clinical decision support to recognize or forecast adverse events in an actual intraoperative scenario. To develop an image-guided navigation technology that will help in surgical education, we explored the performance of a convolutional neural network (CNN)-based computer vision system in detecting intraoperative objects. METHODS: The surgical videos used for annotation were recorded during surgeries conducted in the Department of Surgery of Tokyo Women's Medical University from 2019 to 2020. Abdominal endoscopic images were cut out from manually captured surgical videos. An open-source programming framework for CNN was used to design a model that could recognize and segment objects in real time through IBM Visual Insights. The model was used to detect the GI tract, blood, vessels, uterus, forceps, ports, gauze and clips in the surgical images. RESULTS: The accuracy, precision and recall of the model were 83%, 80% and 92%, respectively. The mean average precision (mAP), the calculated mean of the precision for each object, was 91%. Among surgical tools, the highest recall and precision of 96.3% and 97.9%, respectively, were achieved for forceps. Among the anatomical structures, the highest recall and precision of 92.9% and 91.3%, respectively, were achieved for the GI tract. CONCLUSION: The proposed model could detect objects in operative images with high accuracy, highlighting the possibility of using AI-based object recognition techniques for intraoperative navigation. Real-time object recognition will play a major role in navigation surgery and surgical education.

Feasibility of Pooled One-Step Nucleic Acid Amplification for Molecular Staging of Pathologically Node-Negative Colon Cancer: A Prospective Multicenter Study.

BACKGROUND: Although conventional one-step nucleic acid amplification (OSNA) is a useful molecular-staging method, its complexity hinders its use in clinical practice. A pooled approach for OSNA (pOSNA) has been evaluated for its feasibility in pathologically node-negative colon cancer (pNNCC) for molecular staging of lymph node metastasis in clinical practice. METHODS: Subjects were patients diagnosed with clinical stage II-IIIA colon cancer between January 2017 and September 2018. pOSNA involved harvesting pericolic lymph nodes from fresh surgical specimens, cutting them in half, placing 50% of the nodes in a single test tube, and performing the OSNA assay. The remaining halved pericolic, intermediate, and main lymph nodes were submitted for histopathologic examination, with metastasis determined by hematoxylin and eosin staining of a cut surface of each node. RESULTS: Of the 98 enrolled patients, 92 formed the analysis set. The mean number of harvested lymph nodes per case was 24.3 (range 5-66) and the mean number of lymph nodes used for pOSNA analysis was 6.9 (range 1-35). The concordance rate, sensitivity, and specificity between methods were 89.1%, 84.6% (95% confidence interval [CI] 0.80-0.91), and 90.9% (95% CI 0.88-0.94), respectively. The pOSNA upstaging rate for node-negative patients was 9.1% (6/66), and pOSNA returned false-negative results in 15.4% of node-positive cases (4/26). CONCLUSIONS: pOSNA demonstrated an upstaging rate for pNNCC equivalent to that in previous studies, suggesting its feasibility for molecular staging of pNNCC in clinical practice.

Generation of human induced pluripotent stem cell-derived liver buds with chemically defined and animal origin-free media.

Advances in organoid technology have broadened the number of target diseases and conditions in which human induced pluripotent stem cell (iPSC)-based regenerative medicine can be applied; however, mass production of organoids and the development of chemically defined, animal origin-free (CD-AOF) media and supplements are unresolved issues that hamper the clinical applicability of these approaches. CD-AOF media and supplements ensure the quality and reproducibility of culture systems by lowering lot-to-lot variations and the risk of contamination with viruses or toxins. We previously generated liver organoids from iPSCs, namely iPSC-liver buds (iPSC-LBs), by mimicking the organogenic interactions among hepatocytes, endothelial cells (ECs), and mesenchymal cells (MCs) and recently reported the mass production of iPSC-LBs derived entirely from iPSCs (all iPSC-LBs), which should facilitate their large-scale production for the treatment of liver failure. However, in previous studies we used media originating from animals for differentiation except for the maintenance of undifferentiated iPSCs. Therefore, we developed a CD-AOF medium to generate all iPSC-LBs. We first developed a CD-AOF medium for hepatocytes, ECs, and stage-matched MCs, i.e., septum transversum mesenchyme (STM), in 2D cultures. We next generated all iPSC-LBs by incubating individual cell types in ultra-low attachment micro-dimple plates. The hepatic functions of all iPSC-LBs generated using the CD-AOF medium were equivalent to those of all iPSC-LBs generated using the conventional medium both in vitro and in vivo. Furthermore, we found that this CD-AOF medium could be used in several cell culture settings. Taken together, these results demonstrate the successful development of a CD-AOF medium suitable for all iPSC-LBs. The protocol developed in this study will facilitate the clinical applicability of all iPSC-LBs in the treatment of liver diseases.

Superior prognosis stratification for stage III colon cancer using log odds of positive lymph nodes (LODDS) compared to TNM stage classification: the Japanese study group for postoperative follow-up of colorectal cancer.

OBJECTIVES: The aim of this study is to examine whether prognosis stratification in staging of Stage III colon cancer using T factor and log odds of positive lymph nodes (LODDS) categories is superior to that of the TNM staging system. MATERIALS AND METHODS: The subjects were 5,919 patients with Stage III colon cancer who underwent curative resection at 24 Japanese institutions. Univariate analysis of LODDS categories and clinicopathologic factors was conducted using a Cox proportional hazards regression model for cancer-specific survival (CSS). Independent prognostic factors for CSS were extracted in multivariate analysis using factors with significance in univariate analysis. Effect sizes of risk factors for CSS were compared using the LogWorth statistic. Combinations of T factor and LODDS categories were used to create L-stage subgroups A, B and C. Stratification of prognosis with L-stage and TNM was compared using the Akaike information criterion (AIC). RESULTS: In multivariate analysis, LODDS was identified as an independent prognostic factor, together with age, maximum tumor diameter, histopathological grade, L, V, pT, and pN. The LogWorth of LODDS was 17.149, which was the second highest after pT (31.562), and that of pN was 7.434. The 5-year CSS was 96.5%, 88.5%, and 66.6% in TNM stages IIIA, IIIB, and IIIC, respectively, and 96.0%, 87.6%, and 59.3% in L-stage A, B, and C, respectively (p < 0.0001). AICs for TNM and L-stage were 14,795.5 and 14,707.8, respectively. CONCLUSIONS: Prognosis stratification of the stage classification for Stage III colon cancer was superior with L-stage compared to TNM stage classification.

Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells.

Organoid technology provides a revolutionary paradigm toward therapy but has yet to be applied in humans, mainly because of reproducibility and scalability challenges. Here, we overcome these limitations by evolving a scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive "reverse" screen experiments, we identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass producing homogeneous and miniaturized liver buds on a clinically relevant large scale (>108). Vascularized and functional liver tissues generated entirely from iPSCs significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacturing platform for multicellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations.

Prediction of lateral pelvic lymph node metastasis from lower rectal cancer using magnetic resonance imaging and risk factors for metastasis: Multicenter study of the Lymph Node Committee of the Japanese Society for Cancer of the Colon and Rectum.

PURPOSE: The goal of the study was to examine prediction of lateral pelvic lymph node (LPLN) metastasis from lower rectal cancer using a logistic model including risk factors for LPLN metastasis and magnetic resonance imaging (MRI) clinical LPLN (cLPLN) status, compared to prediction based on MRI alone. METHODS: The subjects were 272 patients with lower rectal cancer who underwent MRI prior to mesorectal excision combined with LPLN dissection (LPLD) at six institutes. No patients received neoadjuvant therapy. Prediction models for right and left pathological LPLN (pLPLN) metastasis were developed using cLPLN status, histopathological grade, and perirectal lymph node (PRLN) status. For evaluation, data for patients with left LPLD were substituted into the right-side equation and vice versa. RESULTS: Left LPLN metastasis was predicted using the right-side model with accuracy of 86.5%, sensitivity 56.4%, specificity 92.7%, positive predictive value (PPV) 61.1%, and negative predictive value (NPV) 91.2%, while these data using MRI cLPLN status alone were 80.4, 76.9, 81.2, 45.5, and 94.5%, respectively. Similarly, right LPLN metastasis was predicted using the left-side equation with accuracy of 83.8%, sensitivity 57.8%, specificity 90.4%, PPV 60.5%, and NPV 89.4%, and the equivalent data using MRI alone were 78.4, 68.9, 80.8, 47.7, and 91.1%, respectively. The AUCs for the right- and left-side equations were significantly higher than the equivalent AUCs for MRI cLPLN status alone. CONCLUSIONS: A logistic model including risk factors for LPLN metastasis and MRI findings had significantly better performance for prediction of LPLN metastasis compared with a model based on MRI findings alone.

Efficacy and safety of neoadjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and levofolinate for T3 or T4 stage II/III rectal cancer: the FACT trial.

PURPOSE: A multicenter phase II clinical study was performed in patients with T3 or T4 stage II/III rectal cancer to evaluate the efficacy and safety of neoadjuvant chemotherapy with 5-fluorouracil, levofolinate, and oxaliplatin (mFOLFOX6). METHODS: Patients received four 2-week cycles of mFOLFOX6 therapy (oxaliplatin at 85 mg/m2 + leucovorin at 200 mg/m2 + fluorouracil as a 400 mg/m2 bolus followed by infusion of 2400 mg/m2 over 46 h, all on Day 1). They were evaluated by computed tomography after completion of the fourth cycle. If there was no disease progression, two additional cycles were administered and then surgery was performed. Adjuvant chemotherapy was generally administered for 6 months using appropriate regimens at the discretion of the physician. RESULTS: mFOLFOX6 therapy was given to 52 patients with locally advanced rectal cancer. The preoperative response rate was 48.8% and the operation rate was 80.8%. Serious adverse events of Grade 3-4 were neutropenia (n = 5), leukopenia (n = 1), thrombocytopenia (n = 1), febrile neutropenia (n = 1), nausea (n = 1), vomiting (n = 1), and peripheral neuropathy (n = 2). The R0 resection rate, pathologic complete response rate, and sphincter preservation rate were 91.0, 11.9, and 73.8%, respectively. Postoperative complications were tolerable. CONCLUSIONS: The present results suggested that neoadjuvant therapy with mFOLFOX6 is safe and effective, representing a reasonable treatment option for locally advanced rectal cancer.

The important risk factor for lateral pelvic lymph node metastasis of lower rectal cancer is node-positive status on magnetic resonance imaging: study of the Lymph Node Committee of Japanese Society for Cancer of the Colon and Rectum.

PURPOSE: This study seeks to evaluate lateral pelvic lymph node (LPLN) and perirectal lymph node (PRLN) status on magnetic resonance imaging (MRI) as potential risk factors for lymph node metastasis. METHODS: The subjects were 394 patients with lower rectal cancer who underwent MRI prior to mesorectal excision (combined with lateral pelvic lymph node dissection in 272 patients) at 6 institutes. No patients received neoadjuvant therapy. Cases were classified as cN(+) and cN(-) based on the short axis of the largest lymph node ≥5 and <5 mm, respectively. LPLN and PRLN status and other clinicopathologic factors were analyzed by multivariate logistic regression. The importance of identified risk factors for lymph node metastasis was examined using the area under the curve (AUC). RESULTS: Independent risk factors for right LPLN metastasis included histopathological grade (G3 + G4), pPRLN(+), M1, cLPLN(+) [odds ratio (OR) 10.73, 95 % confidence interval (CI) 4.59-27.1], and those for left LPLN metastasis were age (<64), histopathological grade (G3 + G4), pPRLN(+), and cLPLN(+) (OR 24.53, 95 % CI 9.16-77.7). ORs for cLPLN(+) were highest. The AUCs for right and left cLPLN status of 0.7484 (95 % CI 0.6672-0.8153) and 0.7904 (95 % CI 0.7088-0.8538), respectively, were significantly higher than those for other risk factors. In contrast, the ORs for cPRLN(+) and cPRLN status of 2.46 (95 % CI 1.47-4.18) and 0.6396 (95 % CI 0.5917-0.6848) were not much higher than for other factors. CONCLUSIONS: An LPLN-positive status with a short axis ≥5 mm on MRI is an important predictor of LPLN metastasis, but PRLN status is not a strong predictor of PRLN metastasis.

Diagnosis of lateral pelvic lymph node metastasis of T1 lower rectal cancer using diffusion-weighted magnetic resonance imaging: A case report with lateral pelvic lymph node dissection of lower rectal cancer.

The present study presented a 35-year-old female patient in whom fecal occult blood was detected in a medical check-up. Colonoscopy revealed a superficial elevated-type tumor with central depression in the lower rectum. The tumor was diagnosed as T1 deep invasive cancer. No swollen lymph nodes or distant metastasis were found on computed tomography or [18F]-fluorodeoxyglucose-positron emission tomography with computed tomography. However, a swollen right lateral pelvic lymph node (LPLN; short axis 4 mm) was revealed on magnetic resonance imaging (MRI). This lymph node exhibited high intensity on diffusion-weighted imaging (DWI), suggesting metastasis. Low anterior resection, regional lymph node dissection and right LPLN dissection (LPLD) were performed. Histological analysis revealed metastasis in the right LPLN, as suggested by the high DWI intensity. The indication for LPLD in the current Japanese guidelines is based on the tumor location and depth of invasion (≥T3), however, not on the status of LPLN metastasis in pre-operative evaluation. The present case was cT1, which is not included in this indication. DWI is sensitive for the diagnosis of lymph node metastasis of colorectal cancer, although inflammation-induced swelling of lymph nodes in advanced rectal cancer may cause a false-positive result, which is uncommon in T1 cases. Therefore, an LPLN with a high intensity DWI signal in T1 cases is likely to be metastasis-positive. Pre-operative DWI-MRI may be useful for identifying LPLN metastasis when planning the treatment strategy in these cases. The present study suggested reinvestigation of the indication for LPLD with inclusion of LPLN status on pre-operative imaging.