Search

OBJECTIVE: To establish a liquid-biopsy assay to predict response to neoadjuvant therapy (NAT) in esophageal squamous cell carcinoma (ESCC) patients. SUMMARY BACKGROUND DATA: Pretreatment prediction of resistance to NAT is of great significance for the selection of treatment options in ESCC patients. In this study, we comprehensively translated tissue-based microRNA (miRNA) and messenger RNA (mRNA) expression biomarkers into a liquid biopsy assay. METHODS: We analyzed 186 clinical ESCC samples, which included 128 formalin-fixed paraffin-embedded and a matched subset of 58 serum samples, from 2 independent institutions. We performed quantitative reverse-transcription polymerase chain reaction, and developed a resistance-prediction model using the logistic regression analyses. RESULTS: We first evaluated the potential of 4-miRNAs and 3-mRNAs panel, which robustly predicted resistance to NAT (area under the curve [AUC]: 0.85). Moreover, addition of tumor size to this panel increased predictive potential to establish a combination signature (AUC: 0.92). We successfully validated this signature performance in independent cohort, and our model was more accurate when the signature was combined with clinical predictors (AUC: 0.81) to establish a NAT resistance risk (NATRR) model. Finally, we successfully translated our NATRR model into a liquid biopsy assay (AUC: 0.78), and a multivariate regression analysis revealed this model as an independent predictor for response to NAT (odds ratio: 6.10; P < 0.01). CONCLUSIONS: We successfully developed a liquid biopsy-based assay that allows robust prediction of response to NAT in ESCC patients, and our assay provides fundamentals of developing precision-medicine.

Total mesorectal excision is the standard surgical procedure for rectal cancer because it is associated with low local recurrence rates. To the best of our knowledge, this is the first study to use an image-guided navigation system with total mesorectal excision.The impact of innovation is the development of a deep learning-based image-guided navigation system for areolar tissue in the total mesorectal excision plane. Such a system might be helpful to surgeons because areolar tissue can be used as a landmark for the appropriate dissection plane.This was a single-center experimental feasibility study involving 32 randomly selected patients who had undergone laparoscopic left-sided colorectal resection between 2015 and 2019. Deep learning-based semantic segmentation of areolar tissue in the total mesorectal excision plane was performed. Intraoperative images capturing the total mesorectal excision scene extracted from left colorectal laparoscopic resection videos were used as training data for the deep learning model. Six hundred annotation images were created from 32 videos, with 528 images in the training and 72 images in the test data sets. The experimental feasibility study was conducted at the Department of Colorectal Surgery, National Cancer Center Hospital East, Chiba, Japan. Dice coefficient was used to evaluate semantic segmentation accuracy for areolar tissue.The developed semantic segmentation model helped locate and highlight the areolar tissue area in the total mesorectal excision plane. The accuracy and generalization performance of deep learning models depend mainly on the quantity and quality of the training data. This study had only 600 images; thus, more images for training are necessary to improve the recognition accuracy.We successfully developed a total mesorectal excision plane image-guided navigation system based on an areolar tissue segmentation approach with high accuracy. This may aid surgeons in recognizing the total mesorectal excision plane for dissection.

Background Neuroendocrine neoplasm (NEN) is a comparatively rare tumor that has been considered indolent. Due to these characteristics, detailed epidemiological data have not been analyzed in Japan. To elucidate the present status of NEN diagnosis and treatment in Japan, we started a registry cohort study in January 2015. Methods Patients pathologically diagnosed with NENs of the pancreas, gastrointestinal tract, lungs, bronchi, or thymus after January 2012 were enrolled in this registry after the date of ethics review committee approval in each hospital or institute. Follow-up was continued for enrolled patients. Results During 5 years of enrollment between January 2015 and December 2019, a total of 1526 participants from 63 departments were enrolled in this registry (mean, 305.2 participants/year), covering approximately 5.8% of the annual incidence of NENs in Japan. For pancreatic NEN, 41.9% of patients had metastasis and the dominant metastatic site was the liver, at twice the rate of lymph node metastasis in the current registry. In contrast, the frequency of lymph node metastasis from gastrointestinal (GI)-NEN was similar to that of the liver. The distribution of WHO 2019-based grades varied according to the primary site. Low-to-intermediate grade (G1–G2) was dominant for duodenal, jejunal/ileal, rectal, and pancreatic NENs, whereas high grade (G3 or NEC) was dominant for esophageal, stomach, and colon NENs. For PanNENs, G3 and NEC accounted only for 1.6% and 2.9%, respectively. Conclusions These cohort data provide crucial information for clinical research to clarify the characteristics of NENs in Japan.

Anastomotic stricture is a relatively common postoperative complication after esophagectomy. Previous studies have indicated that impaired perioperative blood perfusion at the anastomosis is associated with the occurrence of stricture. Therefore, we analyzed the association between endoscopically assessed blood perfusion during the early postoperative period and anastomotic stricture.This retrospective study evaluated patients who underwent esophagectomy at Tokyo Medical and Dental University between 2010 and 2015. The patients had undergone nasal endoscopy on the 1st and 8th postoperative days. The findings were used to evaluate blood perfusion at the anastomosis and gastric tube, which was classified based on mucosal color as ischemia (white) or congestion (blue or black). Univariate and multivariable logistic regression analyses were performed to identify risk factors for anastomotic stricture.The study included 197 patients and anastomotic stricture was observed in 60 patients (30.4%). The multivariable analysis revealed that postoperative gastric tube congestion was a risk factor for stricture (odds ratio [OR]: 6.440, 95% confidence interval [CI]: 2.660-15.600; p 0.001). Lower risks of anastomotic stricture were associated with pathological stage III-IV disease (OR: 0.325, 95% CI: 0.161-0.656; p = 0.002).This study revealed that endoscopically detected congestion at the anastomosis on the first postoperative day was a risk factor for anastomotic stricture.

Systemic inflammatory responses play a key role in cancer progression, and detecting the predictive inflammatory response markers is needed. The present study explored inflammatory response markers capable of predicting survival in patients with gastric cancer. We enrolled 264 patients, who underwent curative gastrectomy for clinical stage (cStage) I–III gastric cancer between 2012 and 2015. The cut-off point of eight preoperative inflammatory response markers was determined by receiver operating characteristic (ROC) curve analysis. The marker with the highest Harrell’s concordance index (C-index) was adopted for subsequent univariate and multivariate analyses using the Cox proportional-hazards model. Among eight representative inflammatory response markers, lymphocyte-to-monocyte ratio (LMR; cut-off point, 4.60) achieved the highest C-index (0.633). The 5-year survival rate was significantly worse in patients with LMR

Laparoscopic transhiatal approach to esophagectomy with mediastinal lymphadenectomy usually involves hand-assisted laparoscopic surgery. However, a totally laparoscopic approach can decrease the size of the abdominal wound and curtail the impact on respiration. We present a novel, totally laparoscopic transhiatal technique that may reduce respiratory complications following thoracoscopic esophagectomy. We performed a series of combined, thoracoscopic and laparoscopic, McKeown esophagectomies via a neck-abdominal first approach. Middle and lower mediastinal lymphadenectomy, subtracheal lymph node removal, and esophageal mobilization were performed via a totally laparoscopic transhiatal approach. Subsequently, upper mediastinal lymph nodes were dissected using a thoracoscopic approach. Finally, an esophagogastric anastomosis was constructed in the neck. For the 36 patients in this series, the median values of the total operative duration and the thoracoscopic portion were 499 minutes (range, 315 to 678 min) and 106 minutes (range, 67 to 243 min), respectively. Postoperative pneumonia occurred in 3 (8.3%) patients. Totally laparoscopic transhiatal approach is feasible for esophageal surgery with acceptable short-term outcomes.

We determined the anastomotic site during gastric tube reconstruction in esophagectomy according to the "90-to 60-s rule" using indocyanine green (ICG) fluorescence angiography. We evaluated its safety and efficacy in a prospective multicenter setting. We enrolled 129 patients who underwent subtotal esophagectomy for esophageal cancer. ICG fluorescence angiography was performed after making a wide gastric tube, and the time from the initial enhancement of the right gastroepiploic artery to the tip of the gastric tube was used as a parameter. Esophago-gastro anastomosis was made at the area that was enhanced within 90 s (preferably within 60 s). The enhancement time and the incidence of anastomotic leakage were compared. In all cases, anastomosis was made at the site enhanced within 90 s. Anastomotic leakage was found in only 4 (3.1%) of 129 cases; specifically, it was detected in 3 (2.4%) of 126 cases whose anastomotic site was enhanced within 60 s and in 1 (33.3%) of 3 cases where the enhancement time exceeded 60 s (p = 0.09). Determining the anastomotic site using the 90-to 60-s rule with ICG imaging in gastric tube reconstruction helps reduce the rate of anastomotic leakage.

A 41-year-old woman presented acute cerebral infarction. Transesophageal echocardiography revealed multiple masses only on both surfaces of the aortic valve cusps. There was no primary lesion outside the heart according to various examinations. After treatment for cerebral infarction, we replaced the aortic valve instead of preservation because the intraoperative histological examination reported that malignancy was highly suspected. Contrary to the rapid frozen section diagnosis, histological and immunohistochemical examinations failed to exhibit malignancy. The tumors were composed of atypical large lymphoid cells and they were assessed to be related to T-/natural killer-cells. Furthermore, Epstein–Barr virus related markers were also positive. Her three-year postoperative course was uneventful without chemotherapy. We report an extremely rare case of Epstein–Barr virus-associated T-/natural killer-cell lymphoproliferative disease which formed multiple small tumors on both surfaces of the aortic valve.

We previously reported on the thin membranous dense connective tissue around the esophagus in the upper mediastinum. This time, we histologically investigated the existence of similar structures in the middle and lower mediastinum, caudal to the bifurcation of the trachea. Semi-sequential transverse sections of the mediastinum were obtained from two cadavers. Hematoxylin and eosin staining and Elastica van Gieson staining were performed. In the middle mediastinum, the “visceral sheath” could not be observed completely around the esophagus. In the lower mediastinum, the thin membranous dense connective tissue was observed beneath the pericardium on the ventral side of the esophagus. On the dorsal side of the esophagus, two thin membranous dense connective tissues were similarly observed in two cadavers. One existed between the dorsal side of the esophagus and the three vessels (i.e., the descending aorta, the azygos vein and the thoracic duct) and was integrated with the thin membranous dense connective tissue of the ventral side of the esophagus at the bilateral side of the esophagus. This integrated dense connective tissue reached the left subpleural region and the adventitia of the aorta on the left side and the peripleural and pulmonary hilum on the right side. The other thin membranous dense connective tissue, which represents the “vascular sheath”, was observed between the descending aorta and the thoracic duct. These two thin membranous dense connective tissues, which are considered to represent the visceral sheath and vascular sheath, are thought to be available as optimal dissecting layers for radical esophagectomy.

Background Locoregional steroid injection prevents post-endoscopic submucosal dissection (ESD) esophageal stricture, but histological changes that occur following steroid injection in the human esophagus are unclear. This study investigated the histopathological characteristics caused by locoregional triamcinolone acetonide (TA) injection using human esophagectomy specimens. Methods From January 2014 to December 2019, among 297 patients (373 lesions) who underwent esophageal ESD, 13 patients who underwent additional esophagectomy after ESD were examined. Seven patients (TA group) with wide excisions were injected with TA after ESD and another six patients (Non-TA group) with smaller tumors were not injected with TA. The clinical background of these patients and histopathological features of ESD ulcer scar obtained from esophagectomy specimens were retrospectively investigated. Results The circumferential rate of ESD excision was more than three-quarters in all cases in the TA group, whereas it was less than three-quarters in the Non-TA group. No other statistical difference in the clinical background was found between the two groups. The subepithelial fibrous tissue of the ESD ulcer scar in the TA group was significantly thinner than that in the Non-TA group (P Conclusions Histological finding of thinning of the subepithelial fibrous tissue of ESD ulcer scar in the human esophagus after TA injection was obtained. This suggests that TA suppresses the proliferation of the fibrous tissue of the subepithelial layer to help prevent esophageal stricture after widespread ESD in the human esophagus.

Ulcerative colitis (UC) is an inflammatory bowel disease that causes chronic inflammation in the colon. 5-aminosalicylic acid and immunosuppressive medications such as corticosteroids, immunomodulators, and biologic agents are used to treat these patients. However, patients with UC who receive immunosuppressive medications may be at risk for certain opportunistic infections. Epstein-Barr virus (EBV) is one of those opportunistic infections, and its pathogenic role has been implicated in refractory UC, but its pathogenicity should be further investigated. Here, we report a surgical case of refractory UC that demonstrated a serologically post-infected pattern of EBV at admission but that later had a high load of EBV in both the peripheral blood and colonic mucosa. These findings suggest that EBV may have been reactivated in the colon, after which it damaged the colonic mucosa and aggravated inflammation in this patient with UC. Thus, EBV might lead to severity and a refractory response against corticosteroids and anti-TNFα agents, necessitating emergency surgery. Viral surveillance for EBV in patients with refractory UC may facilitate understanding of the patient's pathophysiology and predicting response to medications, and the development of antiviral intervention for those patients may improve their prognosis.

Background/aim Adjuvant chemotherapy for high-risk Stage II colorectal cancer (CRC) is weakly recommended; however, no consensus exists on "high-risk" definition. Prognostic biomarker identification is important for selecting patients with poor prognosis who may benefit from adjuvant chemotherapy. Materials and methods Using Microarray data analyses, ELF3 was identified as a candidate gene highly expressed in Stage II CRC with distant recurrences. ELF3 mRNA expression in 168 Stage II CRC patients was subjected to quantitative RT-PCR analysis and ELF3 protein expression in 185 patients was quantified by immunohistochemical analysis. The relationship between mRNA and protein expression levels and patient characteristics were also investigated. Results The overall recurrence rate and relapse-free survival were significantly poorer in the ELF3 high-expression than the low-expression group at the mRNA and protein levels. High ELF3 mRNA and protein expression levels were independent poor prognostic factors. Conclusion High ELF3 expression was associated with recurrence of Stage II.

Aim To determine acceptable limits of communication delays in telesurgery, we investigated the impact of communication delays under a dynamic environment using a surgical assist robot. Previous studies have evaluated acceptable delays under static environments. Effects of delays may be enhanced in dynamic environments, but studies have not yet focused on this point. Methods Thirty-four subjects with different surgical experience (Group1: no surgical experience; Group2: only laparoscopic surgical experience; Group3: robotic surgery experience) performed 4 tasks under different delays (0, 70, 100, 150, 200, or 300 ms) using a surgical assist robot. Task accomplishment time and total movement distance of forceps were recorded and compared under different communication delays of 0–300 ms. In addition, surgical performance was compared between Group1or Group2 without delay and Group3 with communication delays. Results Significant differences in task accomplishment time were found between delays of 0 and 70 ms, but not between delays of 70 and 100 ms. Thereafter, the greater the communication delay, the longer the task accomplishment time. Similar results were obtained in total movement distance of forceps. Comparisons between Group3 with delay and Group1 or Group2 without delay demonstrated that surgical performance in Group3 with delay was superior or equal to that of Group1 or Group2 without delay as long as the delay was 100 ms or less. Conclusions Communication delays in telesurgery may be acceptable if 100 ms or less. Experienced surgeons with more than 100 ms of delay could outperform less-experienced surgeons without delay.

Objective This study sought to assess the feasibility of diffusion tensor imaging (DTI) to noninvasively evaluate histological grade and lymph node metastasis in patients with rectal carcinoma (RC). Methods Thirty-seven consecutive patients with histologically confirmed RC were examined by 1.5-T MRI. DTI was performed using a single-shot echo-planar imaging sequence with b values of 0 and 1000 s/mm2 and motion-probing gradients in nine noncollinear directions. Fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) maps were compared with histopathological findings. Results The FA values (0.357 ± 0.047) of the RCs were significantly lower than those of the normal rectal wall, muscle, prostate, and uterus (P Conclusions DTI may be clinically useful for the noninvasive evaluation of histological grade and lymph node metastasis in patients with RC.

Currently, there is no consensus for an optimal minimally invasive esophagectomy (MIE) approach. This study aimed to compare hybrid MIE (hMIE) with neck-abdominal first approach to standard open esophagectomy (OE). Data from a cohort of 301 patients were retrospectively analyzed. All participants received either hMIE or OE for the treatment of esophageal squamous cell carcinoma at Tokyo Medical and Dental University between January 2003 and December 2013. Analyses included propensity score matching and the Kaplan–Meier statistical method to determine overall survival (OS) and disease-free survival (DFS) of the cohort. After one-to-one propensity score matching, there were 68 patient pairs. The hMIE group had significantly lower incidence of severe postoperative complications (20.1% vs. 7.4%; p = 0.026) and severe respiratory complications (7.4% vs. 0%; p = 0.058) than the OE group. The 5-year oncological outcomes of the two groups were almost equivalent (OS: OE, 55.0%; hMIE, 69.0%; p = 0.063 and DFS: OE, 54.0%; hMIE, 62.0%; p = 0.28). This study compared hMIE with neck-abdominal first approach to standard OE. The results showed significantly less severe postoperative complications for hMIE with neck-abdominal first approach in comparison with OE, without a compromise in long-term oncological outcomes.

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

We herein evaluated the hemodynamics of a gastric tube in esophagectomy using a new noninvasive blood flow evaluation device utilizing near-infrared spectroscopy. Thirty-two cases of subtotal esophagectomy and gastric tube reconstruction for esophageal cancer were studied. The new device measures the regional tissue saturation of oxygen (rSO2: 0–99%) and total hemoglobin index (T-HbI: 0–1.0) with a small sensor. We measured these values at the antrum (point A), final branch of the right gastroepiploic artery (point B) and planned anastomotic point (point C) before and after gastric tube formation. The values at the three points were compared, and the gradients at the three points from before to after gastric tube formation were compared. The mean values of rSO2 at point A, B, and C before gastric tube formation were 57.2%, 57.8% and 56.0%, and those after formation were 54.6%, 58.0% and 55.8%, respectively. There was no significant difference in the comparison of the rSO2 gradient before and after formation (p = 0.167). The mean values of T-HbI at point A, B, and C before formation were 0.126, 0.178 and 0.211, and those after formation were 0.167, 0.247 and 0.292, respectively. There was no significant difference in the gradient of the increase before and after formation (p = 0.461). A new device has shown that the gastric tube used in our facility is one that maintains tissue saturation of oxygen and does not cause excessive congestion at anastomosis.

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.

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.

We are attempting to develop a navigation system for safe and effective peripancreatic lymphadenectomy in gastric cancer surgery. As a preliminary study, we examined whether or not the peripancreatic dissection line could be learned by a machine learning model (MLM).Among the 41 patients with gastric cancer who underwent radical gastrectomy between April 2019 and January 2020, we selected 6 in whom the pancreatic contour was relatively easy to trace. The pancreatic contour was annotated by a trainer surgeon in 1242 images captured from the video recordings. The MLM was trained using the annotated images from five of the six patients. The pancreatic contour was then segmented by the trained MLM using images from the remaining patient. The same procedure was repeated for all six combinations.The median maximum intersection over union of each image was 0.708, which was higher than the threshold (0.5). However, the pancreatic contour was misidentified in parts where fatty tissue or thin vessels overlaid the pancreas in some cases.The contour of the pancreas could be traced relatively well using the trained MLM. Further investigations and training of the system are needed to develop a practical navigation system.

Background Treatment for regional lymph node recurrence after initial treatment for esophageal squamous cell carcinoma (ESCC) differs among institutions. Though some retrospective cohort studies have shown that lymphadenectomy for cervical lymph node recurrence is safe and leads to long-term survival, the efficacy remains unclear. In this study, we investigated the long-term outcomes of patients who underwent lymphadenectomy for regional recurrence after treatment for ESCC. Patients and methods We retrieved 20 cases in which lymphadenectomy was performed for lymph node recurrence after initial treatment for ESCC in our hospital from January 2003 to December 2016. Initial treatments included esophagectomy, endoscopic resection (ER) and chemoradiotherapy/chemotherapy (CRT/CT). Overall survival (OS) and recurrence-free survival (RFS) after lymphadenectomy were calculated by the Kaplan–Meier method. We also used a univariate analysis with a Cox proportional hazards model to determine factors influencing the long-term outcomes. Results The five-year OS and RFS of patients who underwent secondary lymphadenectomy for recurrence after initial treatment were 50.0% and 26.7%, respectively. The five-year overall survival rates of patients who received esophagectomy, ER and CRT/CT as initial treatments, were 40.0%, 75.0% and 50.0%, respectively. The five-year OS rates of patients with Stage I and Stage II-IVB at initial treatments were 83.3% and 33.3%, respectively. Conclusions Lymphadenectomy for regional recurrence after initial treatment for ESCC is effective to some degree. Patients with regional recurrence after initial treatment for Stage I ESCC have a good prognosis; thus, lymphadenectomy should be considered for these cases.

Introduction Clinical sequencing has provided molecular and therapeutic insights into the field of clinical oncology. However, despite its significance, its clinical utility in Japanese patients remains unknown. Here, we examined the clinical utility of tissue-based clinical sequencing with FoundationOne® CDx and FoundationOne® Heme. Between August 2018 and August 2019, 130 Japanese pretreated patients with advanced solid tumors were tested with FoundationOne® CDx or FoundationOne® Heme. Results The median age of 130 patients was 60.5 years (range: 3 to 84 years), and among them, 64 were males and 66 were females. Major cancer types were gastrointestinal cancer (23 cases) and hepatic, biliary, and pancreatic cancer (21 cases). A molecular tumor board had been completed on all 130 cases by October 31, 2019. The median number of gene alterations detected by Foundation testing, excluding variants of unknown significance (VUS) was 4 (ranged 0 to 21) per case. Of the 130 cases, one or more alterations were found in 123 cases (94.6%), and in 114 cases (87.7%), actionable alterations with candidates for therapeutic agents were found. In 29 (22.3%) of them, treatment corresponding to the gene alteration was performed. Regarding secondary findings, 13 cases (10%) had an alteration suspected of a hereditary tumor. Of the 13 cases, only one case received a definite diagnosis of hereditary tumor. Conclusions Our study showed that clinical sequencing might be useful for detecting gene alterations in various cancer types and exploring treatment options. However, many issues still need to be improved.

Background Robot-assisted laparoscopic surgery has several advantages over conventional laparoscopy. However, population-based comparative studies for low anterior resection are limited. This article aimed to compare peri-operative results of robot-assisted low anterior resection (RALAR) and laparoscopy Methods This retrospective cohort study used data from patients treated with RALAR or conventional laparoscopic low anterior resection (CLLAR) between October 2018 and December 2019, as recorded in the Japanese National Clinical Database, a data set registering clinical information, perioperative outcomes, and mortality. Of note, the registry does not include information on the tumour location (centimetres from the anal verge) and diverting stoma creation. Perioperative outcomes, including rate of conversion to open surgery, were compared between RALAR and CLLAR groups. Confounding factors were adjusted for using propensity score matching. Results Of 21 415 patients treated during the study interval, 20 220 were reviewed. Two homogeneous groups of 2843 patients were created by propensity score matching. The conversion rate to open surgery was significantly lower in the RALAR group than in the CLLAR group (0.7 versus 2.0 per cent; P < 0.001). The RALAR group had a longer operating time (median: 352 versus 283 min; P < 0.001), less intraoperative blood loss (15 versus 20 ml; P < 0.001), a lower in-hospital mortality rate (0.1 versus 0.5 per cent; P = 0.007), and a shorter postoperative hospital stay (median: 13 versus 14 days; P < 0.001) compared with the CLLAR group. The CLLAR group had a lower rate of readmission within 30 days (2.4 versus 3.3 per cent; P = 0.045). Conclusion These data highlight the reduced conversion rate, in-hospital mortality rate, intraoperative blood loss, and length of postoperative hospital stay for rectal cancer surgery in patients treated using robot-assisted laparoscopic surgery compared with laparoscopic low anterior resection., A retrospective cohort study was undertaken using data from 20 220 patients who underwent robot-assisted low anterior resection (RALAR) or conventional laparoscopic low anterior resection as recorded in the National Clinical Database in Japan. The data highlight the potential benefit of RALAR in improving the conversion rate to open surgery, in-hospital mortality rate, intraoperative blood loss, and length of postoperative hospital stay for rectal cancer surgery.

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.

Postoperative feeding is administered relatively early in gastric surgery, especially distal gastrectomy, but its feasibility and safety for proximal gastric surgery remains unclear. We retrospectively analyzed 91 consecutive patients who underwent total or proximal gastrectomy between 2014 and 2019. Baseline and perioperative results were prospectively recorded in our dataset. In our clinical pathway, sips of water and a soft diet were allowed on postoperative days 1 and 3. Discharge was set at days 6–8, and clinical pathway completion was defined as discharge by postoperative day 8. Median patient age was 69 years, and 25 patients (27%) were aged ≥ 75 years. Fifty-nine patients (65%) had comorbidities. Esophageal involvement occurred in 12 patients (13%), and there were 28 cases (31%) of pathological stage IA. The open approach was applied in 22 patients (24%), laparoscopy was applied in 53 patients (58%), and the robotic approach was applied in 16 patients (18%). Total gastrectomy was performed in 56 patients (62%) and proximal gastrectomy was performed in 35 patients (38%). Overall and severe (Clavien–Dindo grade III or higher) complications occurred in 24 (26%) and 9 (10%) patients, respectively. There were four cases (4%) of esophagojejunal leakage (three with esophagogastric junction cancer, one with long-term corticosteroid use). Clinical pathway completion was achieved in 66 patients (73%), with readmission of five cases (5%). Early feeding and discharge for total or proximal gastrectomy is feasible and safe as long as it is carefully applied to high-risk patients, but we must be aware of the relatively higher readmission rate of this patient group.

We investigated the merits and demerits of right cervical open surgery with right trans-cervical pneumomediastinal approach in mediastinoscopic esophagectomy. Ten thoracic esophageal cancer patients were treated using this approach. Under pneumomediastinum via a right neck incision, the right cervical and upper mediastinal paraesophageal lymph nodes were dissected. The left recurrent nerve lymph nodes were dissected using a left trans-cervical pneumomediastinal approach. The subaortic arch to the left tracheobronchial lymph nodes was dissected with a combined right and left trans-cervical crossover approach. The average number of dissected lymph nodes among the right cervical and upper mediastinal paraesophageal lymph nodes identified with a right cervical open/right trans-cervical mediastinoscopic/right thoracoscopic approach was 3.2/4.0/0.6, respectively. The average number of dissected lymph nodes among the subaortic arch to the left tracheobronchial lymph nodes with a right trans-cervical mediastinoscopic/right thoracoscopic approach was 1.5/0.6, respectively. These findings indicate that, without using the right trans-cervical pneumomediastinal approach, it might be impossible to successfully remove some of the right cervical and upper mediastinal paraesophageal lymph nodes and the subaortic arch to the left tracheobronchial lymph nodes lymph nodes. Regarding surgical complications, one case of bilateral recurrent nerve palsy as well as two cases on the right and two cases on the left were noted. Although the rate of recurrent nerve palsy should still be reduced, a bilateral (especially right-sided) trans-cervical pneumomediastinal approach is an available option for achieving sufficient upper mediastinal lymph node dissection and esophagectomy.

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 prospective trial evaluated the feasibility and safety of “mediastinoscopic esophagectomy with lymph node dissection” (MELD). Eligible patients had thoracic esophageal squamous cell carcinoma, excluding T4, a bulky primary lesion or distant metastasis. Ten patients were enrolled and treated between September 2015 and March 2018. Additionally, to verify the integrity of the mediastinal lymph node dissection, thoracoscopic observation and lymph node dissection were followed. The primary end point was the integrity of mediastinal lymph node dissection. The secondary end points were the short-term outcomes, including mortality and morbidity. The median number of dissected lymph nodes in the upper mediastinal to cervical region and middle to lower mediastinal region by mediastinoscopy/thoracoscopy was 27/0.5 and 11.5/0, respectively. The median total operation time was 615 min, the median bleeding amount was 476 ml, and the median postoperative hospital stay was 15.5 days. Regarding complications of more than grade III according to the Clavien–Dindo classification, four had sputum excretion difficulty, one had pneumothorax and one had bilateral recurrent nerve palsy, but none required conversion to thoracotomy, and no operative deaths occurred. Although the rate of recurrent nerve palsy still should be reduced, our mediastinoscopic lymphadenectomy technique is closely similar to radical esophagectomy.

There is no clear evidence on the number of cases required to master the techniques required in robot-assisted surgery for different surgical fields and techniques. The purpose of this study was to clarify the learning curve of robot-assisted rectal surgery for malignant disease by surgical process.The study retrospectively analyzed robot-assisted rectal surgeries performed between April 2014 and July 2020 for which the operating time per process was measurable. The following learning curves were created using the cumulative sum (CUSUM) method: (1) console time required for total mesorectal excision (CUSUM tTME), (2) time from peritoneal incision to inferior mesenteric artery dissection (CUSUM tIMA), (3) time required to mobilize the descending and sigmoid colon (CUSUM tCM), and (4) time required to mobilize the rectum (CUSUM tRM). Each learning curve was classified into phases 1-3 and evaluated. A fifth learning curve was evaluated for robot-assisted lateral lymph node dissection (CUSUM tLLND).This study included 149 cases. Phase 1 consisted of 32 cases for CUSUM tTME, 30 for CUSUM tIMA, 21 for CUSUM tCM, and 30 for CUSUM tRM; the respective numbers were 54, 48, 45, and 61 in phase 2 and 63, 71, 83, and 58 in phase 3. There was no significant difference in the number of cases in each phase. Lateral lymph node dissection was initiated in the 76th case where robot-assisted rectal surgery was performed. For CUSUM tLLND, there were 12 cases in phase 1, 6 in phase 2, and 7 cases in phase 3.These findings suggest that the learning curve for robot-assisted rectal surgery is the same for all surgical processes. Surgeons who already have adequate experience in robot-assisted surgery may be able to acquire stable technique in a smaller number of cases when they start to learn other techniques.

A time interval between diagnosis and surgery for gastric cancer is necessary, although its impact on survival remains controversial. We evaluated the impact of preoperative time interval on survival in gastric cancer patients. We enrolled 332 patients who underwent curative gastrectomy for clinical stage (cStage) I–III gastric cancer between 2012 and 2015. We separately analyzed early- (cStage I) and advanced-stage (cStages II and III) patients. Early-stage patients were divided according to preoperative time interval: short (≤ 42 days) and long (> 42 days) groups. Advanced-stage patients were also divided into short (≤ 21 days) and long (> 21 days) groups. We compared the survival between the short and long groups in early- and advanced-stage patients. The median preoperative time interval was 29 days, and no significant differences were found in patient characteristics between the short and long groups in early- and advanced-stage patients. In early-stage patients, the 5-year survival rates of the short and long groups were 86.5% and 88.4%, respectively (P = 0.917). In advanced-stage patients, the 5-year survival rates were 72.1% and 70.0%, respectively (P = 0.552). In multivariate analysis, a longer time interval was not selected as an independent prognostic factor in early- and advanced-stage patients. In this study, survival difference was not found based upon preoperative time interval. The results do not affirm the delay of treatment without reason, however, imperative extension of preoperative time interval may be justified from the standpoint of long-term survival.

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

Locally recurrent rectal cancer (LRRC) has a tremendous impact on prognosis as well as the quality of life. Because of the low incidence and various recurrence patterns, the treatment outcome of LRRC is not fully elucidated. The current study aimed to evaluate the prognosis and identify the prognosticators in patients with LRRC. We conducted a multicenter study at 24 hospitals in Japan. Patients with primary rectal cancer who underwent curative resection between 1997 and 2012 and developed local recurrence only as a first recurrent event were recruited. The primary outcome of our study was overall survival (OS) after a diagnosis of LRRC. Four hundred and ninety-eight patients were included in the study. Of these, 213 (42.8%) underwent surgical resection; this was associated with the best 5-year OS rate of 52%, followed by carbon ion/proton therapy (44%). Among LRRC patients, undifferentiated type, T4, high CEA level, and high CA19–9 level were independent prognosticators of OS (hazard ratio (HR) = 1.83, P = 0.008, HR = 1.54, P = 0.004, HR = 1.35, P = 0.03, and HR = 1.58, P = 0.003, respectively). This large-scale cohort study showed that surgical resection led to a favorable prognosis compared to other treatments for LRRC. Therefore, surgical resection should be considered whenever feasible for LRRC patients. In addition, undifferentiated type, T4, and tumor marker (CEA and CA19–9) elevation were identified as independent prognostic factors for OS among patients with LRRC.

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

Risk stratification in Stage II and III colorectal cancer (CRC) patients is critical, as it allows patient selection for adjuvant chemotherapy. In view of the inadequacy of current clinicopathological features for risk-stratification, we undertook a systematic and comprehensive biomarker discovery effort to develop a risk-assessment signature in CRC patients. The biomarker discovery phase examined 853 CRC patients, and identified a gene signature for predicting recurrence-free survival (RFS). This signature was validated in a meta-analysis of 1212 patients from nine independent datasets, and its performance was compared against established prognostic signatures and consensus molecular subtypes (CMS). In addition, a risk-prediction model was trained (n = 142), and subsequently validated in an independent clinical cohort (n = 286). As a result, this mesenchymal-associated transcriptomic signature (MATS) identified high-risk CRC patients with poor RFS in the discovery (hazard ratio [HR]: 1.79), and nine validation cohorts (HR: 1.86). In multivariate analysis, MATS was the most significant predictor of RFS compared to established prognostic signatures and CMS subtypes. Intriguingly, MATS robustly identified CMS4-subtype in multiple CRC cohorts (AUC = 0.92-0.99). In the two clinical cohorts, MATS stratified low and high-risk groups with a 5-year RFS in the training (HR: 4.11) and validation cohorts (HR: 2.55), as well as predicted response to adjuvant therapy in Stage II and III CRC patients. We report a novel prognostic and predictive biomarker signature in CRC, which is superior to currently used approaches and have the potential for clinical translation in near future.

The treatment for desmoid-type fibromatosis involves surgical resection and medication therapy, but the standard treatment has not yet been established. In the West, the usefulness of radiation therapy has been reported. We encountered a patient with desmoid-type fibromatosis in the pelvis who was treated by radiation and medication therapies and achieved a good tumor reduction effect. The patient was a 70-year-old man. He had a 6-year history of pain in the right leg and had a palpable mass on the right side of the anus; he was admitted to our department. CT showed a 12×7×12 cm mass in the pelvis, and CT-guided needle biopsy revealed a desmoid-type fibromatosis. Because tumor exclusion resulted in obstruction of the rectum, radiation therapy(60 Gy in 30 Fr)was started after performing transverse colon colostomy; simultaneous medication therapy with a COX-2 inhibitor and the anti-allergic agent tranilast was administered. Cystic degeneration was observed 5 months after the end of radiation therapy, and after 12 months, the tumor volume had halved. Around 28 months after the end of radiation therapy, medication treatment has been continued with slow contraction.

In accordance with guidelines, most patients with T1 colorectal cancers (CRC) undergo surgical resection with lymph node dissection, despite the low incidence (∼10%) of metastasis to lymph nodes. To reduce unnecessary surgical resections, we used artificial intelligence to build a model to identify T1 colorectal tumors at risk for metastasis to lymph node and validated the model in a separate set of patients.We collected data from 3134 patients with T1 CRC treated at 6 hospitals in Japan from April 1997 through September 2017 (training cohort). We developed a machine-learning artificial neural network (ANN) using data on patients' age and sex, as well as tumor size, location, morphology, lymphatic and vascular invasion, and histologic grade. We then conducted the external validation on the ANN model using independent 939 patients at another hospital during the same period (validation cohort). We calculated areas under the receiver operator characteristics curves (AUCs) for the ability of the model and US guidelines to identify patients with lymph node metastases.Lymph node metastases were found in 319 (10.2%) of 3134 patients in the training cohort and 79 (8.4%) of /939 patients in the validation cohort. In the validation cohort, the ANN model identified patients with lymph node metastases with an AUC of 0.83, whereas the guidelines identified patients with lymph node metastases with an AUC of 0.73 (P.001). When the analysis was limited to patients with initial endoscopic resection (n = 517), the ANN model identified patients with lymph node metastases with an AUC of 0.84 and the guidelines identified these patients with an AUC of 0.77 (P = .005).The ANN model outperformed guidelines in identifying patients with T1 CRCs who had lymph node metastases. This model might be used to determine which patients require additional surgery after endoscopic resection of T1 CRCs. UMIN Clinical Trials Registry no: UMIN000038609.

Background and objectives: Adenocarcinoma of the esophagogastric junction (AEG) has a complicated surgical anatomy, due to which it sometimes induces excessive intraoperative blood loss that necessitates intraoperative blood transfusion (BTF). However, few reports have focused on the impact of BTF on the survival outcomes of patients with AEG. We aimed to evaluate the impact of BTF on AEG prognosis. Materials andMethods: We included 63 patients who underwent surgical resection for AEG at our hospital between January 2010 and September 2020. Clinicopathological characteristics and survival outcomes were compared between patients with (n = 12) and without (n = 51) BTF. Multivariate analysis was performed to identify the independent prognostic factors for overall survival. Results: None of the patients who underwent minimally invasive surgery received BTF. Patients who received BTF had a significantly worse 5-year survival rate than those who did not (67.8% vs. 28.3%, p = 0.001). BTF was an independent risk factor for overall survival (hazard ratio: 3.90, 95% confidence interval 1.30–11.7), even after patients who underwent minimally invasive surgery were excluded. Conclusions: BTF adversely affected the survival outcomes of patients with AEG who underwent curative surgery. To avoid BTF, surgeons should strive to minimize intraoperative bleeding.

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.

Postoperative urinary dysfunction is a major complication of rectal cancer surgery. A randomized controlled trial (JCOG0212) concluded that the noninferiority of mesorectal excision alone to mesorectal excision with lateral lymph node dissection was not confirmed in terms of relapse-free survival.Eligibility criteria included histologically proven clinical stage II/III rectal cancer, a main lesion located in the rectum with the lower margin below the peritoneal reflection, and the absence of lateral lymph node enlargement. After confirming R0 resection by mesorectal excision, patients were randomized intraoperatively. The residual urine volume was measured three times. Urinary dysfunction was defined as ≥50 mL residual urine occurring at least once or no measurement of residual urinary volume. This trial was registered with the UMIN Clinical Trials Registry, number C000000034.In the mesorectal excision alone and the mesorectal excision with lateral lymph node dissection groups, the incidence of early urinary dysfunction were 58% and 59%, respectively. A tumor location in the lower rectum (vs. upper rectum) and a blood loss of ≥500 mL (vs.500 mL) were associated with an increased risk of early urinary dysfunction. However, only blood loss was independently predictive of early urinary dysfunction (relative risk, 1.25 [95% CI: 1.10-1.55], p = .04).Mesorectal excision with lateral lymph node dissection is not associated with a significant increase in the incidence of urinary dysfunction. Urinary dysfunction is associated with tumor location and blood loss.

Summary Background Adjuvant chemotherapy with oral fluoropyrimidine alone after D3/D2 lymph node dissection improves disease-free survival and overall survival in patients with stage III colon cancer. Adjuvant S-1 has been shown to be non-inferior to uracil and tegafur plus leucovorin in terms of disease-free survival. This study aims to confirm the non-inferiority of S-1 compared with capecitabine as adjuvant treatment in patients with stage III colorectal cancer. Methods This study was an open-label, non-inferiority, randomised, phase 3, multicentre trial done in 56 Japanese centres to assess the non-inferiority of S-1 to capecitabine as adjuvant chemotherapy. Eligible patients were aged 20–80 years with stage III colorectal adenocarcinoma, as defined by the presence of an inferior margin of the primary tumour above the peritoneal reflection; R0 resection; and colectomy with D3 or D2 lymph node dissection. Patients were randomly assigned (1:1) to receive eight courses of capecitabine (1250 mg/m 2 orally twice daily, days 1–14, every 21 days) or four courses of S-1 (40 mg/m 2 orally twice daily, days 1–28, every 42 days). Randomisation was done via phone call, fax, or web-based systems to the Japan Clinical Oncology Group Data Center and used a minimisation method with a random component adjusted by institution, tumour location (colon vs rectosigmoid and upper rectum), number of positive lymph node metastases (≤3 vs ≥4), and surgical technique (conventional vs non-touch isolation). The primary endpoint was disease-free survival with a non-inferiority margin for the hazard ratio (HR) set at 1·24, analysed by intention to treat. This trial was registered with UMIN Clinical Trial Registry, number UMIN000003272. Findings Between March 1, 2010, and Aug 23, 2013, 1564 patients were randomly assigned to capecitabine (n=782) or S-1 (n=782), all of whom were included in the efficacy analysis; 777 patients in the capecitabine group and 768 in the S-1 group were included in the safety analysis. At the prespecified second interim analysis after final accrual, 258 (48%) of 535 required events were reported, and the Data and Safety Monitoring Committee recommended early publication because S-1 could not show non-inferiority compared with capecitabine for disease-free survival. With a median follow-up of 23·7 months (IQR 14·1–35·2), 3-year disease-free survival was 82·0% (95% CI 78·5–85·0) for the capecitabine group and 77·9% (74·1–81·1) for the S-1 group (HR 1·23, 99·05% CI 0·89–1·70; one-sided p non-inferiority =0·46). The most frequent grade 3 or higher adverse events in the capecitabine group were hand–foot skin reactions (123 [16%] of 777 patients), and in the S-1 group were diarrhoea (64 [8%] of 768 patients) and neutropenia (61 [8%]). There was one ( Interpretation Adjuvant capecitabine remains one of the standard treatments for stage III colorectal cancer in Japan; S-1 is not recommended. Funding National Cancer Center and Ministry of Health, Labour and Welfare of Japan.

In cadavers, even Thiel-embalmed cadavers, the arteries (especially the thoracic aorta) are extremely collapsed. This is in marked contrast to the state of the arteries in a living body. Aortic inflation is necessary to improve this unfavorable situation for anatomical observation or dissection. To inflate the aorta, we injected 500 ml of hot liquid agar into the aorta using a 18-Fr catheter inserted into the common femoral artery and subclavian artery. The injected agar then rapidly cools to room temperature and solidifies. As a result, the thoracic aorta remains sufficiently and constantly inflated in the mediastinum. This method is not only easy and inexpensive, but also useful and effective for achieving a life-like anatomy in cadavers used in surgical training for operations involving mediastinal organs, with the exception of the heart and great vessels.

Mesorectal excision with lateral lymph node dissection is the standard treatment for locally advanced low rectal cancer in Japan. However, the safety and feasibility of laparoscopic lateral lymph node dissection remain to be determined.The purpose of this study was to evaluate the safety and feasibility of laparoscopic versus open lateral lymph node dissection for locally advanced low rectal cancer.This was a retrospective cohort study using an exact matching method.We conducted a multicenter study of 69 specialized centers in Japan.Patients with consecutive midrectal or low rectal adenocarcinoma cancer stage II to III who underwent mesorectal excision with curative intent between 2010 and 2011 were recruited.Short-term and oncological outcomes were compared between the laparoscopic and open-surgery groups.Of the 1500 eligible patients, 676 patients who underwent lateral lymph node dissection were analyzed, including 137 patients who were treated laparoscopically and 539 patients who were treated with open surgery. After matching, the patients were stratified into laparoscopic (n = 118) and open-surgery (n = 118) groups. Operative times in the overall cohort were significantly longer (461 vs 372 min) in the laparoscopic versus the open-surgery group. In the laparoscopic group, the blood loss volume was significantly smaller (193 vs 722 mL), with fewer instances of blood transfusion (7.3% vs 25.5%) compared with the open-surgery group. The postoperative complication rates were 35.8% and 43.6% for the laparoscopic and open-surgery groups (p = 0.10). The 3-year relapse-free survival rates were 80.3% and 72.6% for the laparoscopic and open-surgery groups (p = 0.07).The study was limited by its retrospective design and potential selection bias.Laparoscopic lateral lymph node dissection is safe and feasible for cancer stage II to III low rectal cancer and is associated with similar oncological outcomes as open lateral lymph node dissection. See Video Abstract at http://links.lww.com/DCR/A334.

This study was designed to establish clinical outcomes after aortic valve replacement (AVR) with On-X bileaflet mechanical heart valve. Between 2006 and 2014, AVR was performed to 686 patients. Of them, 78 patients using On-X valve were enrolled. The mean age was 65 ± 11 years (ranged 33–85); 65% were men; and 81% were in sinus rhythm preoperatively. Calcific or degenerative tricuspid aortic valve was present in 73%. Concomitant procedures included coronary artery bypass grafting (22%), Bentall (8%), mitral valve procedure (3%) and other (9%). They postoperatively received lower dose warfarin [international normalized ratio (INR), 1.5–2.0] and 100 mg aspirin daily. The follow-up duration averaged 5 years (386.6 patient-years). The follow-up rate was 97.3%. In-hospital mortality rates were 3.8% (n = 3). Late mortality rates were 2.6% per patient-years (n = 10). Five-year Kaplan–Meier survival rates were 84%. Freedom from major adverse valve-related stroke and cerebral bleeding events was 93.3% (n = 5, 1.29% per patient-years) and 98.6% (n = 1, 0.26% per patient-years, mild subdural hematoma). The incidence of stroke was two patients of transient ischemic attack, two patients of paralytic event, one patient of asymptomatic stroke (self-interruption of anticoagulation). The median INR was 1.92 ± 0.53, ranged from 1.00 to 8.98 (n = 1181) and 51% of all measured INR values were in the therapeutic range of 1.5–2.0. AVR using On-X valve with low target INR regimen and low-dose aspirin resulted in a significantly low risk of bleeding.

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.

Treatment of rectal cancer with postoperative pelvic recurrence may complicate infection and may be difficult to treat. We experienced 2 cases complicated with sepsis due to infection in the pelvic local recurrence in which radiation therapy was performed and they were shifted to outpatient molecular-targeted drug therapy. Case 1 involved a 58-year-old woman. In December 2011, colostomy and chemotherapy were performed for locally advanced rectal cancer. In June 2012, we performed low anterior resection. In January 2014, chemotherapy was started for pelvic recurrence. She discontinued treatment for 4 months due to personal circumstances. Recurrence was worsened, and infection caused sepsis and she was admitted to the hospital in February 2017. Infection was not improved with antibiotic drugs, and radiation therapy(60 Gy/30 times)was performed. Infection was improved, and panitumumab monotherapy was started and she was discharged. Case 2 involved a 61-year-old man. In February 2014, a lower anterior resection for rectal cancer was performed. In September 2015, chemotherapy was started for pelvic recurrence. In November 2016, chemotherapy was discontinued due to esophageal variceal rupture. Recurrence was worsened, and infection caused sepsis and he was admitted to the hospital in May 2017. Radiation therapy(50 Gy/20 times)was performed after colostomy. Infection was improved, and cetuximab monotherapy was started and he was discharged.

Background We conducted a randomized controlled trial (JCOG0212) to determine whether the outcome of mesorectal excision (ME) alone for rectal cancer is not inferior to that of ME with lateral lymph node dissection (LLND). The present study focused on male sexual dysfunction after surgery. Methodology Eligibility criteria included clinical stage II/III rectal cancer, the lower margin of the lesion below the peritoneal reflection, the absence of lateral pelvic lymph node enlargement, and no preoperative radiotherapy. After confirmation of R0 resection by ME, patients were intraoperatively randomized. Questionnaires using the International Index of Erectile Function (IIEF-5) about the sexual function of men were collected before and 1 year after surgery. Sexual dysfunction incidence was defined as the ratio of patients showing sexual dysfunction after surgery relative to the number who had no erectile dysfunction before surgery. Results Among 701 patients enrolled between June 2003 and August 2010, 472 males were included. Among them, 343 (73%) completed preoperative and postoperative questionnaires. According to the study protocol, the incidences of sexual dysfunction in patients who underwent ME alone and ME with LLND were 68% (17/25; 95%CI, 47–85%) and 79% (23/29; 95%CI, 60–92%), respectively (p = 0.37). Incidences of sexual dysfunction in patients with no or only mild erectile dysfunction before surgery who underwent ME alone and ME with LLND were 59% (48/81) and 71% (67/95), respectively (p = 0.15). Multivariate analysis identified age as the only risk factor for sexual dysfunction after surgery (p = 0.02). Conclusions LLND may not increase sexual dysfunction incidence after rectal cancer surgery. This incidence is associated with increased age. This trial is registered with ClinicalTrials.gov , number NCT00190541 and University Hospital Medical Information Network Clinical Trials Registry, number C000000034.

In cases of carcinoma in the remnant stomach (CRS), the lymphatic flow may be altered by the initial surgery. In this study of CRS after gastrectomy, we investigated how the regions of lymph node metastasis and changes in lymphatic flow depend on initial disease status. The study included 76 patients with CRS who underwent gastrectomy between September 2002 and November 2014. We analyzed and compared the clinicopathological factors and survival periods between patients after distal gastrectomy for malignant disease (group M, 33 patients) and patients after distal gastrectomy for benign disease (group B, 43 patients). The depth of tumor invasion was more advanced in group B (T1/T2/T3/T4: group M 18/1/7/7, group B 8/11/8/16; P = 0.002). However, the degree of lymph node metastasis did not differ significantly between the two groups. The incidence of lymph node metastasis was high at stations 2 (19 %), 4sa (17 %), 10 (25 %), 11p (19 %), and 11d (27 %) in group M and 1 (14 %), 3 (23 %), and 4sb (15 %), and the mesojejunal lymph node (21 %) in group B. Lymph node dissection was highly beneficial at station 3, station 7, and the mesojejunum in both groups, but not at stations 10 or 11d. As compared with group B, group M showed higher incidences of lymph node metastasis in the greater curvature, splenic hilum, and lymph nodes along the splenic artery, suggesting the predominance of lymphatic flows from the greater curvature to the splenic hilum and from the remnant stomach to the splenic artery.

The standard treatment for locally advanced gastric cancer differs across the world. In western countries, perioperative chemotherapy or postoperative adjuvant chemoradiotherapy are the preferred treatment options, whereas in Asia, D2 gastrectomy followed by postoperative adjuvant chemotherapy is standard. In Japan, adjuvant chemotherapy with S-1 is the standard treatment for pStage II gastric cancer, whereas adjuvant chemotherapy with a doublet regimen is preferred for pStage III gastric cancer. The efficacy of preoperative neoadjuvant chemotherapy using S-1 plus cisplatin, has been investigated in selected patients with expected poor survival outcomes. To expand the indications for neoadjuvant chemotherapy, a clinical trial investigating the efficacy of preoperative S-1 plus oxaliplatin in patients with cStage III (cT3-4N1-3) gastric cancer (JCOG1509) is ongoing in Japan. The addition of immune checkpoint inhibitors to cytotoxic chemotherapy also seems promising and is being investigated in international randomized clinical trials. Although we have to await the final results of these studies, preoperative neoadjuvant chemotherapy is a promising treatment strategy and likely to become standard treatment for locally advanced gastric cancer in Japan.

Interest in minimally invasive surgery has increased in recent decades. Robotic-assisted laparoscopic surgery(RALS)was introduced as the latest advancement in minimally invasive surgery. RALS has the potential to provide better clinical outcomes in rectal cancer surgery, allowing for precise dissection in the narrow pelvic space. In addition, RALS represents an important advancement in surgical education with respect to use of the dual-console robotic surgery system. Because the public health insurance systems in Japan have covered the cost of RALS for rectal cancer since April 2018, RALS has been attracting increasingly more attention. Although no overall robust evidence has yet shown that RALS is superior to laparoscopic or open surgery, the current evidence supports the notion that technically demanding subgroups(patients with obesity, male patients, and patients treated by extended procedures)may benefit from RALS. Technological innovation is a constantly evolving field. Several companies have been developing new robotic systems that incorporate new technology. This competition among companies in the development of such systems is anticipated to lead to further improvements in patient outcomes as well as drive down the cost of RALS, which is one main concern of this new technique.