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Narrow pelvis, tumor diameter, and obesity have been reported as clinical variables correlated with the difficulty of conventional laparoscopic low anterior resection (Lap-LAR). A two-team transanal total mesorectal excision (TaTME) approach where the transabdominal and TaTME are performed simultaneously might reduce the difficulty associated with these factors. This study aimed to clarify the factors associated with the longer time required for TME (TME time) in conventional Lap-LAR and a two-team approach for TaTME.We analyzed 52 patients with rectal carcinoma treated with Lap-LAR and 35 patients treated with TaTME. We performed simple linear regression analysis to assess the association between TME time and bony pelvic size using 3D pelvimetry, longest tumor diameter, and body mass index (BMI).Linear regression analysis demonstrated a highly significant association between TME time and obstetric conjugate (RA two-team TaTME approach provided a shorter TME time compared to conventional Lap-LAR, regardless of pelvic size and BMI.

Esophagectomy for esophageal carcinoma is associated with higher morbidity and mortality rates than other gastrointestinal surgeries. Smoking is an established risk factor for postoperative complications after esophagectomy. This study aimed retrospectively to investigate the impact of smoking status on short- and long-term outcomes for patients undergoing thoracoscopic esophagectomy in the prone position (TEP) for esophageal carcinoma.In this study, 234 patients with esophageal carcinoma who underwent TEP between 2012 and 2020 were divided into two groups based on smoking status (current or non-current smokers and the Brinkman index) by patients' declarations. Postoperative complications (Clavien-Dindo classification grade ≥2), overall survival (OS), and disease-free survival (DFS) were compared between smoking statuses.The rates of postoperative complications did not differ significantly between the two groups (current smoker vs non-current smoker; Brinkman index ≥800 vs800). The rate of postoperative pneumonia was higher in the combination group of current and higher Brinkman index (≥800) smokers than in the other group (25.0 % vs 11.8 %; P = 0.036). Multivariate analysis showed that smoking status was an independent risk factor for postoperative pneumonia (hazard ratio, 0.41; 95 % confidence interval, 0.18-0.93; P = 0.037). According to the long-term outcomes, no significant differences in OS and DFS were observed between the smoking statuses.The combination of current smoking and heavy smoking history is a risk factor for postoperative pneumonia in patients who have esophageal carcinoma treated with TEP, although no correlation was observed between the long-term outcomes and smoking status.

Background Many patients with esophageal squamous cell carcinoma (ESCC) have obstructive ventilatory disorder (OVD), which is considered a risk factor for postoperative pneumonia. It has been reported that thoracoscopic esophagectomy in the prone position (TEP) is less invasive and is associated with fewer postoperative respiratory complications compared with open esophagectomy. This matched-cohort study aimed to elucidate the safety and oncologic outcomes of ESCC patients with OVD who undergo TEP. Methods In this matched-cohort study, 237 patients with ESCC who underwent TEP between 2010 and 2018 were divided into two groups based on forced expiratory volume in 1 s/forced vital capacity. Postoperative complications (Clavien–Dindo classification grade II or higher), overall survival (OS), and disease-free survival (DFS) were compared between the two groups. Results Based on their propensity scores, 75 patients with normal respiratory function (NRF) and 75 with OVD were selected. The rates of postoperative pneumonia were not significantly different between the two groups (NRF group vs OVD group: 18.7% vs 18.7%; P = 1.000). The rates of recurrent laryngeal nerve palsy and anastomotic leakage were also not significantly different (NRF group vs OVD group: 12.0% vs 18.7%, P = 0.365; 18.7% vs 18.7%, P = 1.000). The 5-year OS and DFS rates in the NRF vs OVD groups were 66.2% vs 54.9% and 63.5% vs 52.9%, respectively, with no significant differences (P = 0.421, 0.197). Conclusions TEP can be safely performed on ESCC patients with OVD and can result in an oncological efficiency equal to that of the NRF group.

Although survival in cases with early recurrence after curative resection of colorectal cancer has been persistently poor, the risk factors for early recurrence remain unknown.A total of 1,043 patients with stage I-III colorectal cancer underwent curative resection at Kobe University Hospital between April 2007 and September 2020. Of these, 122 patients developed recurrence: 57 had early recurrence (1 year after surgery) and 65 patients had late recurrence (≥1 year after surgery). The clinicopathological features were compared between the groups and the risk factors for early recurrence were analyzed.Overall survival both from the date of recurrence and from the date of surgery were significantly worse in the early recurrence group. The proportion of the patients with ≥100 g of intraoperative blood loss, blood transfusion, and postoperative complications were significantly higher in the early recurrence group. R0 resection was achieved more frequently in the late recurrence group. Multivariate analysis revealed that no adjuvant chemotherapy, elevated preoperative CA19-9, blood transfusion, and the occurrence of the postoperative complication were independent risk factors for early recurrence.Early recurrence after curative resection of colorectal cancer was associated with worse overall survival. Adjuvant chemotherapy might be beneficial for patients with risk factors of early recurrence to improve prognosis.

Although lateral pelvic lymph node dissection (LLND) might be an effective approach for patients with rectal cancer with lateral lymph node metastasis, it is technically challenging because of the anatomical complexity and location of the deep pelvis. An assistance by transanal approach might be useful for a successful LLND.From September 2016 to May 2021, 39 patients with low rectal cancer underwent transanal total mesorectal excision with LLND. Among them, 18 patients underwent LLND using a conventional laparoscopic approach alone, while the remaining 21 underwent LLND using both conventional and transanal approaches. Their clinical outcomes were retrospectively compared.The operation time for LLND on each side was significantly shorter in the transanal group (105 min vs. 54 min, P 0.001). The intraoperative blood loss was also significantly less in the transanal group (40 g vs. 0 g, P = 0.031). The rate of overall postoperative complications ≥ grade II according to the Clavien-Dindo classification was significantly less in the transanal group (66.7% vs. 28.6%, odds ratio: 5.000, 95% confidence intervals: 1.313-19.047, P = 0.040). The number of harvested lateral lymph nodes in both groups was similar (8.5 vs. 8, P = 0.544).The transanal approach for LLND reduced operative time, blood loss, and morbidity compared with the conventional approach alone in a cohort of patients with rectal cancer.

Postoperative complications affect long-term prognosis in patients with esophageal squamous cell carcinoma (ESCC). Although a comprehensive estimator can predict long-term prognosis, the Clavien-Dindo classification system, a widely used approach to evaluate complications, assesses each complication individually. We aimed to clarify the utility of the comprehensive complication index (CCI) on predicting the overall survival (OS) of patients with ESCC following minimally invasive esophagectomy (MIE).This was a retrospective study of patients undergoing MIE for ESCC in the prone position between January 2011 and December 2018. Multivariate analyses using the Cox proportional hazards model were performed to determine independent risk factors for OS.The study cohort included 229 patients who were categorized into patients with CCI values of ≥ 33.7 (CCI high) and 33.7 (CCI low) by receiver-operating characteristic (ROC) curve analysis. There were no significant differences between the two groups according to clinicopathological factors, such as sex, age, tumor location, tumor depth, lymph node metastasis, and neoadjuvant chemotherapy. The intraoperative transfusion rate in the CCI high group was significantly higher than in the CCI low group. The 5 year OS rate was significantly lower in the CCI high group than in the CCI low group (49.5% vs. 65.7%, p = 0.030). By multivariate analyses, age, tumor depth, lymph node metastasis, and the CCI were independent predictors of OS.Comprehensive assessment of postoperative complications using the CCI was useful in predicting OS of patients undergoing MIE for the ESCC.

Technical difficulties are occasionally encountered when performing conventional minimally invasive esophagectomy and robot-assisted minimally invasive esophagectomy in patients with a narrow thoracic cavity. Thoracic cavity-to-cage ratio is an indicator of thoracic cavity length. We hypothesized that the thoracic cavity-to-cage ratio could be a predictor of technical difficulties in conventional minimally invasive esophagectomy and robot-assisted minimally invasive esophagectomy.We evaluated 340 patients who underwent minimally invasive esophagectomy for esophageal squamous cell carcinoma between April 2010 and March 2021. Thoracic cavity-to-cage ratio was calculated as the diameter of the thoracic cavity to that of the thoracic cage at the brachiocephalic vein, tracheal bifurcation, and inferior right pulmonary vein levels. Moreover, thoracic cavity-to-cage ratio score, which is an indicator of the whole thoracic cavity length based on the thoracic cavity-to-cage ratio at the 3 levels, was defined. The thoracic procedure time was considered an indicator of surgical difficulty.We divided the patients into the conventional minimally invasive esophagectomy (n = 295) and robot-assisted minimally invasive esophagectomy (n = 45) groups. The patients in each group were divided into 2 cohorts according to median thoracic procedure time. Based on multivariate analysis, body mass index (P = .0007), clinical N stage (P = .0191), and thoracic cavity-to-cage ratio score (P = .0005) were independent factors for thoracic procedure time in the conventional minimally invasive esophagectomy group. Moreover, thoracic cavity-to-cage ratio at the tracheal bifurcation level (P = .0331) was the only independent factor for thoracic procedure time in the robot-assisted minimally invasive esophagectomy group.Thoracic cavity-to-cage ratio could be a predictor of technical difficulties in both conventional minimally invasive esophagectomy and robot-assisted minimally invasive esophagectomy.

Despite the increasing incidence of adenocarcinoma of the esophagogastric junction, laparoscopic proximal gastrectomy with lower esophagectomy (PGLE) is not widely accepted owing to the lack of standardized reconstruction techniques. In this study, we developed a new reconstruction method named y-shaped overlap esophagogastric tube reconstruction, which reproduces an angle of His and a pseudo-fornix, to be used in laparoscopic transhiatal PGLE. This study aimed to determine the feasibility of this novel reconstruction method.This retrospective study included the analysis of short- and mid-term surgical outcomes of 30 consecutive patients with Siewert type II esophagogastric junction adenocarcinoma who underwent laparoscopic PGLE with y-shaped overlap esophagogastric tube reconstruction from April 2015 to August 2020. A novel method was used to form a 6-cm pseudo-fornix and an angle of His using the distal esophagus and a long gastric tube.The median operation time was 369 min, and the median blood loss was 28 mL. The median follow-up period after surgery was 37 months. Although two patients experienced postoperative anastomotic leakage, none of the patients developed stenosis. One patient experienced moderate reflux symptoms, whereas four patients developed moderate reflux esophagitis based on the 1-year follow-up endoscopic examination; the condition of all patients could be efficiently controlled with medication.The short- and mid-term surgical outcomes of y-shaped overlap esophagogastric tube reconstruction reflected the feasibility of this simple technique and suggested its potential utility as a reconstruction alternative for Siewert type II tumors.

BACKGROUND Multidisciplinary treatment for esophageal squamous cell carcinoma (ESCC) has improved outcomes, but the prognosis for ESCC remains poor. Nutritional and inflammatory indicators are reported to be associated with cancer prognosis. The combination of albumin and the derived neutrophil-to-lymphocyte ratio (Alb-dNLR) score was established to measure the immune system and nutritional status. The authors hypothesized that the Alb-dNLR score could be a new reliable prognostic factor for ESCC patients. METHODS The study evaluated 269 patients who underwent esophagectomy between April 2010 and March 2018, including 185 patients who received neoadjuvant chemotherapy. The Alb-dNLR score was calculated using serum albumin and the dNLR. The dNLR was calculated as neutrophils to (leukocyte-neutrophil count). The cutoff values of the albumin and dNLR for overall survival (OS) were determined using the receiver operating characteristic curve. Patients were divided into "high" and "low" groups according to the Alb-dNLR score. RESULTS A high Alb-dNLR score was found in 61 cases (22.7%). The 5-year OS was 34% in the high Alb-dNLR group and 66.2% in the low Alb-dNLR group (p < 0.0001). The 5-year cause-specific survival (CSS) was 51.5% in the high Alb-dNLR group and 74.7% in the low Alb-dNLR group (p < 0.0001). Multivariate analyses demonstrated that the Alb-dNLR score was an independent prognostic factor for OS (hazard ratio [HR], 2.198; 95% confidence interval [CI], 1.460-3.263; p = 0.0002) and CSS (HR, 1.733; 95% CI, 1.035-2.835; p = 0.0371). CONCLUSIONS The Alb-dNLR score is an extremely useful, easy-to-use parameter to predict OS and CSS for ESCC patients.

The list of Topologically significant genes by RNA-Seq analysis

The Wnt/β-catenin signaling pathway plays crucial roles in embryonic development and the development of multiple types of cancer, and its aberrant activation provides cancer cells with escape mechanisms from immune checkpoint inhibitors. E7386, an orally active selective inhibitor of the interaction between β-catenin and CREB binding protein, which is part of the Wnt/β-catenin signaling pathway, disrupts the Wnt/β-catenin signaling pathway in HEK293 and adenomatous polyposis coli (APC)-mutated human gastric cancer ECC10 cells. It also inhibited tumor growth in an ECC10 xenograft model and suppressed polyp formation in the intestinal tract of ApcMin/+ mice, in which mutation of Apc activates the Wnt/β-catenin signaling pathway. E7386 demonstrated antitumor activity against mouse mammary tumors developed in mouse mammary tumor virus (MMTV)-Wnt1 transgenic mice. Gene expression profiling using RNA sequencing data of MMTV-Wnt1 tumor tissue from mice treated with E7386 showed that E7386 downregulated genes in the hypoxia signaling pathway and immune responses related to the CCL2, and IHC analysis showed that E7386 induced infiltration of CD8+ cells into tumor tissues. Furthermore, E7386 showed synergistic antitumor activity against MMTV-Wnt1 tumor in combination with anti-PD-1 antibody. In conclusion, E7386 demonstrates clear antitumor activity via modulation of the Wnt/β-catenin signaling pathway and alteration of the tumor and immune microenvironments, and its antitumor activity can be enhanced in combination with anti-PD-1 antibody.Significance:These findings demonstrate that the novel anticancer agent, E7386, modulates Wnt/β-catenin signaling, altering the tumor immune microenvironment and exhibiting synergistic antitumor activity in combination with anti-PD-1 antibody.

Supplementary Table S1, Table S4, Table S5, Table S6, Table S7. Supplementary Table S1: The list of DEGs by nCounter analysis (|Fold change| > 1.25, P < 0.1). Supplementary Table S4: Top 10 enriched pathways identified by RNA-Seq analysis in MMTV-Wnt1 model. Supplementary Table S5: The result of CIBERSORT analysis. Supplementary Table S6: The lists of antibody for flow cytometry analysis. Supplementary Table S7: Comparison of Physicochemical property between E7386 and C-82.

Supplementary Materials and Methods

Background/Aim: Neoadjuvant chemotherapy (NAC) for advanced gastric cancer (GC) and esophagogastric junction cancer (EGC) is expected to effectively control the tumor; however, histological tumor response and immune function markers as prognostic factors for NAC remain unknown. This study assessed the prognostic significance of histological response and immune function markers in patients undergoing NAC for GC and EGC. Patients and Methods: Forty-two patients who underwent NAC followed by surgical resection for operable advanced GC or EGC from January 2007 to December 2019 were divided into two groups based on histological response. Overall survival (OS), tumor response, and immune function markers, such as the neutrophil/lymphocyte ratio (NLR), were the outcomes analyzed. Results: The 5-year OS for Grade 2b-3 (n=10, responder group) according to the Japanese Gastric Cancer Classification was 72.0% with a favorable prognosis, compared with 33.3% for Grade 0-1a (n=18), and 46.8% for Grade 1b-2a (n=14) in the non-responder group. There was no significant difference in the background between the two groups regarding clinical status or immune function markers. In a multivariate analysis of immune function markers, the NLR value before NAC was significantly associated with prognosis (p=0.048). Patients with an NLR value

Background/Aim: The safety of gastrectomy for patients receiving antithrombotic agents remains unclear. This retrospective cohort study sought to compare outcomes between patients who did and did not receive antithrombotic agents. Patients and Methods: This single-center retrospective cohort study included 548 patients who underwent gastrectomy for primary gastric adenocarcinoma from January 2011 to December 2019. The surgical outcomes were compared between two groups according to whether they received antithrombotic therapy (n=121) or not (n=427). Results: Among the entire cohort, the patients in the antithrombotic therapy group were significantly older than those who did not receive this therapy and had significantly higher postoperative complication rates than those who did not (33.1% vs. 23.9%; p=0.046). However, after propensity score matching, no significant difference in the postoperative complication rate was observed between the two groups. Conclusion: Despite having a high risk for postoperative complications, patients receiving antithrombotic therapy can safely undergo gastric resection.

Rectal or anal canal adenocarcinoma with inguinal lymph node metastasis (ILNM) is rare and is associated with poor prognostic outcomes. This study aimed to elucidate the clinical significance of neoadjuvant therapy followed by selective inguinal lymph node dissection and total mesorectal excision for rectal or anal canal adenocarcinoma with clinically suspected ILNM.This study enrolled 15 consecutive patients who underwent neoadjuvant therapy and curative resection for rectal or anal canal adenocarcinoma with clinically suspected ILNM between 2005 and 2019 at a single institution. Inguinal lymph node dissection was selectively performed on the side of suspected metastasis before neoadjuvant therapy. Short- and long-term outcomes were retrospectively reviewed.Out of the15 patients, 11 were treated with neoadjuvant chemoradiation, three with chemotherapy, and one with chemoradiation followed by chemotherapy. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans were performed after neoadjuvant therapy in 14 patients. Five patients had negative FDG accumulation in inguinal lymph nodes on FDG-PET scan, and their inguinal lymph nodes were also pathologically negative for metastasis. Of the nine patients who had positive FDG accumulation, four had pathologically positive inguinal lymph nodes. Seven patients (46.7%) had inguinal seroma postoperatively. Five-year-overall survival was 77.5%, and 5-year-relapse-free survival was 64.2%. No patient had a recurrence in the inguinal region.In patients with rectal or anal canal adenocarcinoma associated with clinical ILNM, radical resection with neoadjuvant therapy provides a good long-term survival.

Laparoscopic local resection for gastrointestinal stromal tumors (GISTs) near the esophagogastric junction (EGJ) increases the risk of injuring the EGJ. We investigated the safety of laparoscopic local resection for GISTs near the EGJ according to the distance from the EGJ to the tumor edge. We retrospectively evaluated 40 patients who had undergone laparoscopic local resection for GISTs near the EGJ between January 2009 and December 2019. After excluding 1 patient who had undergone right colectomy at the same time, 39 patients were classified according to distance of the GIST from the EGJ in the Near group (0–2.0 cm; n = 16) and the Far group (2.1–5.0 cm; n = 23). We found no marked differences in the operation time, blood loss, length of postoperative hospital stay, or postoperative complication rate in the two groups. Anastomotic leakage occurred with a tumor located on the EGJ. Three tumors recurred in the Near group, and all of them were located on the EGJ. Except for GISTs located on the EGJ, laparoscopic local resection for GISTs near the EGJ can be performed safely with few postoperative complications and a low risk of recurrence.

Purpose Rectal or anal canal adenocarcinoma with inguinal lymph node metastasis (ILNM) is rare and is associated with poor prognostic outcomes. This study aimed to elucidate the clinical significance of neoadjuvant therapy followed by selective inguinal lymph node dissection and total mesorectal excision for rectal or anal canal adenocarcinoma with clinically suspected ILNM. Methods This study enrolled 15 consecutive patients who underwent neoadjuvant therapy and curative resection for rectal or anal canal adenocarcinoma with clinically suspected ILNM between 2005 and 2019 at a single institution. Inguinal lymph node dissection was selectively performed on the side of suspected metastasis before neoadjuvant therapy. Short- and long-term outcomes were retrospectively reviewed. Results Out of the15 patients, 11 were treated with neoadjuvant chemoradiation, three with chemotherapy, and one with chemoradiation followed by chemotherapy. Six patients had negative fluorodeoxyglucose (FDG) accumulation in inguinal lymph nodes on preoperative FDG-positron emission tomography (FDG-PET) scan, and their inguinal lymph nodes were also pathologically negative for metastasis. Of the nine patients who had positive FDG accumulation, four had pathologically positive inguinal lymph nodes. Seven patients (46.7%) had inguinal seroma postoperatively. Five-year-overall survival was 77.5%, and 5-year-relapse-free survival was 64.2%. No patient had a recurrence in the inguinal region. Conclusion In patients with rectal or anal canal adenocarcinoma associated with clinical ILNM, radical resection with neoadjuvant therapy provides a good long-term survival.

Purpose: Despite the increasing incidence of adenocarcinoma of the esophagogastric junction, laparoscopic proximal gastrectomy with lower esophagectomy (PGLE) is not widely accepted owing to the lack of standardized reconstruction techniques. In this study, we developed a new reconstruction method named y-shaped overlap esophagogastric tube reconstruction, which reproduces an angle of His and a pseudo-fornix, to be used in laparoscopic transhiatal PGLE. This study aimed to determine the feasibility of this novel reconstruction method.Methods: This retrospective study included the analysis of short- and mid-term surgical outcomes of 30 consecutive patients with Siewert type II esophagogastric junction adenocarcinoma who underwent laparoscopic PGLE with y-shaped overlap esophagogastric tube reconstruction from April 2015 to August 2020. A novel method was used to form a 6-cm pseudo-fornix and an angle of His using the distal esophagus and a long gastric tube.Results: The median operation time was 369 min, and the median blood loss was 28 mL. The median follow-up period after surgery was 37 months. Although two patients experienced postoperative anastomotic leakage, none of the patients developed stenosis. One patient experienced moderate reflux symptoms, whereas four patients developed moderate reflux esophagitis based on the 1-year follow-up endoscopic examination; the condition of all patients could be efficiently controlled with medication.Conclusion: The short- and mid-term surgical outcomes of y-shaped overlap esophagogastric tube reconstruction reflected the feasibility of this simple technique and suggested its potential utility as a reconstruction alternative for Siewert type II tumors.

No study has focused on the safety and feasibility of our previously developed open-window suturing technique to close mucosal defects on the pancreatic side after endoscopic submucosal dissection from the opened duodenal wall. This study aimed to evaluate the safety and usefulness of laparoscopic endoscopic cooperative surgery for duodenal tumors for treating superficial non-ampullary duodenal epithelial tumors on the pancreatic side of the duodenum.This retrospective study included 61 consecutive patients who underwent surgery during August 2014-November 2021. After dissection when the tumor was on the pancreatic side, we sutured the mucosal defect from the opened duodenal wall. A preoperative endoscopic pancreatic stent was placed for tumors within 1 cm of the ampulla of Vater. The surgical outcomes were compared between tumors on the pancreatic and non-pancreatic sides.There were 27 and 34 patients with tumors on the pancreatic and non-pancreatic sides, respectively. The patient characteristics were similar. Preoperative pancreatic stents were placed in four patients in the pancreatic side group. The median operative time was significantly longer on the pancreatic side than in the non-pancreatic side group (241 vs. 209 min, P = 0.02). In one patient in the pancreatic side group, an intraoperative injury of the ampulla of Vater was successfully treated with intraoperative management. There were no significant differences in the incidence of postoperative grade II or higher complications between the groups.Laparoscopic endoscopic cooperative surgery for duodenal tumors for treating superficial non-ampullary duodenal epithelial tumors on the pancreatic side is safe and feasible.

The Wnt/β-catenin signaling pathway plays crucial roles in embryonic development and the development of multiple types of cancer, and its aberrant activation provides cancer cells with escape mechanisms from immune checkpoint inhibitors. E7386, an orally active selective inhibitor of the interaction between β-catenin and CREB binding protein, which is part of the Wnt/β-catenin signaling pathway, disrupts the Wnt/β-catenin signaling pathway in HEK293 and adenomatous polyposis coli (APC)-mutated human gastric cancer ECC10 cells. It also inhibited tumor growth in an ECC10 xenograft model and suppressed polyp formation in the intestinal tract of ApcMin/+ mice, in which mutation of Apc activates the Wnt/β-catenin signaling pathway. E7386 demonstrated antitumor activity against mouse mammary tumors developed in mouse mammary tumor virus (MMTV)-Wnt1 transgenic mice. Gene expression profiling using RNA sequencing data of MMTV-Wnt1 tumor tissue from mice treated with E7386 showed that E7386 downregulated genes in the hypoxia signaling pathway and immune responses related to the CCL2, and IHC analysis showed that E7386 induced infiltration of CD8+ cells into tumor tissues. Furthermore, E7386 showed synergistic antitumor activity against MMTV-Wnt1 tumor in combination with anti-PD-1 antibody. In conclusion, E7386 demonstrates clear antitumor activity via modulation of the Wnt/β-catenin signaling pathway and alteration of the tumor and immune microenvironments, and its antitumor activity can be enhanced in combination with anti-PD-1 antibody. Significance: These findings demonstrate that the novel anticancer agent, E7386, modulates Wnt/β-catenin signaling, altering the tumor immune microenvironment and exhibiting synergistic antitumor activity in combination with anti-PD-1 antibody.

Purpose This study aimed to compare motions of the laparoscope tip during a laparoscopic task in a training box using a recent joystick-guided robotic scope holder to those manipulated by human scopists. We hypothesized that laparoscopic manipulation could be positively affected by robotic scope holders due to the elimination of unintentional movement. Methods Twelve surgeons participated as operators, and eight medical doctors participated in this study. Among the human scopists, five were trained surgeons and three were novices who had no experience with laparoscopic surgery. A validated laparoscopic task was used to evaluate the path length of the laparoscope tip using an optical position tracker and operative time. The operators performed the designated camera task under three different laparoscopic manipulations: using a joystick-guided robotic scope holder, expert human scopists, and novice scopists. Results The median path lengths (cm) of the laparoscopic tip were 94.0, 110.0, and 122.2 in the robotic scope holder, expert, and novice groups, respectively. The path lengths in the robotic scope holder group were significantly shorter than those in the other groups (P < .01). The median operative times (seconds) were 136.6, 66.4, and 62.3 in the robotic scope holder, expert, and novice groups, respectively. The operative time of the robotic scope holder group was significantly longer than that of the other groups (P < .001). Conclusion A robotic scope holder can provide shorter camera movement owing to the stable holding and intentional scope manipulation by the operator, although it requires a longer operative time than a human assistant.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignant disease. This study examined whether the platelet-to-lymphocyte ratio (PLR) can be used as a biomarker to evaluate prognosis in patients with advanced ESCC following neoadjuvant chemotherapy (NAC) and undergoing minimally invasive esophagectomy (MIE).We examined 174 patients between January 2010 and December 2015 at the Kobe University. Of these, 121 were treated with NAC. The PLR cutoff was determined through receiver-operating characteristic curve analysis. Univariate and multivariate analyses were conducted to identify prognostic factors for overall survival (OS).The PLR cutoff for OS in 121 patients was 169.6. Patients with PLR ≥169.6 had worse 5-year OS rates (31.1%) than those with a PLR169.6 (61.1%, p=0.001). Multivariate analysis revealed that a PLR of ≥169.6 was an independent factor for poor prognosis.PLR is an independent prognostic factor for patients with ESCC after NAC and MIE.

This study aimed to identify prognostic factors for adenocarcinoma of the esophagogastric junction (AEG) in Siewert type II and characterize the population whose prognosis is expected to improve.We retrospectively reviewed a database of 68 AEG type II patients who had undergone surgical curative resection without preoperative treatment.Although patients with pathological N0 (pN0) showed favorable 3-year disease-free survival (91%), patients with pN1-3 had poor outcomes (42%, 23%, and 10%). Multivariate analyses showed that the only independent prognostic factor was lymph node metastasis, and that tumor depth (cT3-4) and tumor size (≥4 cm) were correlated closely with lymph node metastasis.Surgical curative resection without preoperative treatment is insufficient to treat AEG type II with lymph node metastasis. Among AEG patients, those with the high-risk factors of preoperative tumor depth (T3-4) or/and size (≥4 cm) might need intensive multimodal treatment, including perioperative adjuvant chemotherapy.

Background: With the aging population, more patients are expected to receive antithrombotic treatment. Although many studies have investigated the perioperative management of antithrombotic therapy, few have targeted gastrectomy. Hence, the safety of gastrectomy for patients receiving antithrombotic agents remains unclear. This retrospective cohort study sought to compare outcomes between patients who did and did not receive antithrombotic agents.Methods: This single-center retrospective cohort study included 548 patients who underwent gastrectomy for primary gastric adenocarcinoma from January 2011 to December 2019. Patients were subsequently classified into two groups according to whether they received antithrombotic therapy (n = 121) or not (n = 427), after which surgical outcomes were compared. Propensity score analysis was performed based on age, sex, body mass index, open versus laparoscopic surgery, and total versus distal gastrectomy. After propensity score matching, 121 patients were included in each group.Results: Among the entire cohort, receiving antithrombotic therapy group was significantly older than those who did not (age ≥ 75 years, 48% vs. 33%; p ≤ 0.0001). Those receiving antithrombotic therapy had significantly higher postoperative complication rates than those who did not (33.1% vs. 23.9%; p = 0.046). After matching, no significant difference in the postoperative complication rate was observed between both groups.Conclusion: Despite having a high risk for postoperative complications, patients receiving antithrombotic therapy can safely undergo gastric resection.

The eighth edition of the American Joint Committee on Cancer (AJCC) tumor node metastasis (AJCC-TNM 8th) system adopted the newly separate post-neoadjuvant pathologic stage group (ypTNM). However, it is not compatible with the Japanese pathologic classification after neoadjuvant chemotherapy (JPN-CT-pTNM). The aim of this study is to clarify the subjects of the AJCC-ypTNM 8th and propose a unification of the AJCC and Japanese systems to create novel AJCC-CT-pTNM 8th.Participants were 304 esophageal squamous cell carcinoma (ESCC) patients who underwent neoadjuvant chemotherapy followed by 3 stage esophagectomy between 2010 and 2019. Predictive probabilities of pN, pM in AJCC-ypTNM 8th and JPN-CT-pTNM 11th systems were evaluated to propose novel system.In training data from 234 patients, the overall survival rate was statistically better for ypStage IIIA than ypStage II (P = 0.040) resulting in staging inversion in AJCC-ypTNM 8th. Predictive probability of pathological N status in AJCC-ypTNM 8th (Akaike Information Criterion: AIC = 979.53) was superior to that in JPN-CT-pTNM 11th (AIC = 999.07). In AJCC-ypTNM 8th, 71% (15/21) of ypM1 diseases were supraclavicular lymph nodes (No. 104 L/N as regional in JPN-CT-pTNM 11th) metastases with considerably good prognosis. The predictive probability of the novel AJCC-CT-pTNM 8th [unification of ypStage II and IIIA, conversion of supraclavicular L/Ns metastases from ypM to ypN] (AIC = 1054.24) was superior to that of the existing AJCC-ypTNM 8th (AIC = 1070.74). The feasibility of novel system was validated using test data from 70 patients.Unification of the AJCC and Japanese systems yields a simpler and more precise predictive system after neoadjuvant chemotherapy.

Background Lateral pelvic lymph node metastasis impairs the oncological outcomes of patients with rectal cancer. Although lateral pelvic lymph node dissection (LLND) might be an effective procedure for such patients, the associated risk factors for postoperative complications are unknown. Patients and methods The operative outcomes of 21 patients undergoing unilateral LLND and 26 patients undergoing bilateral LLND for rectal cancer were compared. The risk factors for complications were evaluated using a logistic regression model. Results Univariate and multivariate analyses revealed that a longer operative time (≥480 min) was the most important risk factor for grade II or more postoperative complications according to the Clavien-Dindo classification (odds ratio=6.58; 95% confidence interval=1.35-32.1; p=0.020). A bilateral procedure was not a significant risk factor for postoperative complications. Conclusion Surgeons should make efforts to shorten the operative time to reduce the risk of postoperative complications.

Minimally invasive esophagectomy (MIE) for esophageal cancer patients with sarcopenia is associated with a high risk of perioperative complications; however, the relationship between sarcopenia and the survival of esophageal cancer patients remains controversial. In this study, we aimed to develop a stratifying marker for sarcopenia to precisely predict patients' prognosis.We retrospectively studied 135 patients who underwent thoracoscopic esophagectomy at Kobe University Hospital from 2011 to 2015 and who were preoperatively diagnosed with or without sarcopenia based on the Asian Working Group for Sarcopenia index. Creatinine levels and albumin as measures of skeletal muscle volume and nutritional status, respectively, were used to develop a marker to be used for stratifying sarcopenic patients based on prognosis.Of the 135 patients, 35 were diagnosed with sarcopenia and 100 were not. We combined the creatinine and albumin levels (Cr × Alb) as a stratifying marker for sarcopenia, and extracted sarcopenic patients with values below the Cr × Alb cut-off as the actual sarcopenic group. The 5-year overall survival (OS) rates of the actual and non-actual sarcopenic groups were 28.9% and 58.9%, respectively (p = 0.0005), and the 5-year disease-free survival rate of the actual sarcopenic group was 34.1%, and 62.8% (p = 0.0106) for the non-actual sarcopenic group. This stratified sarcopenia model was an independent prognostic factor and was superior to sarcopenia alone for OS.In patients undergoing MIE, preoperative measurement of Cr × Alb may be a prognostic stratification marker for patients with sarcopenia.

We conducted a prospective clinical control study to identify the best imaging technology among three-dimensional (3-D) high-definition (HD) stereovision and two-dimensional (2-D) ultra-high-resolution (4 K) technology and confirm their effects on surgical outcomes of laparoscopic gastrectomy for gastric cancer. From April 2018 to August 2019, 50 patients were randomly classified into two groups based on the imaging technology (3-D/HD group = 25, 2-D/4 K = 25). After excluding eight patients based on laparoscopic findings, 42 patients were analyzed (3-D/HD group = 21, 2-D/4 K = 21). The primary endpoint was the operative time; the secondary endpoints were blood loss, postoperative infectious complications, and postoperative hospital stay. The patients’ backgrounds were similar (sex, age, body mass index [BMI], stage, procedure, and extent of lymph node dissection). There were no significant differences in operative time (252 vs. 238 min, P = 0.70), total blood loss, postoperative infectious complications, and postoperative hospital stay between the two groups. However, video analysis of surgeries revealed a significantly shortened median operative time (18 vs. 25 min, P = 0.04) in the suturing step with 3-D/HD; the median number of camera cleaning procedures during suprapancreatic lymph node dissection was significantly lower with 2-D/4 K than with 3-D/HD (n = 4.4 vs. 2.8, P = 0.02). 3-D/HD and 2-D/4 K laparoscopic radical gastrectomies provide similar surgical outcomes. However, the 3-D monitor reduces suturing time during reconstruction, while the 4 K monitor reduces the number of camera cleaning procedures during lymphadenectomy. Registered in the University Hospital Medical Information Network Clinical Trials Registry (identification number 000029227).

Although transperineal minimally invasive abdominoperineal resection (tp-APR) based on the concept of transanal total mesorectal excision has recently been used for rectal cancer, the operative procedure has not been standardized to date due to its technical difficulty. The tp-APR procedure used by the authors for a male patient with low rectal cancer is presented in this video.

Background Recently to improve depth perception, the performance of three-dimensional (3D) laparoscopic surgeries has increased. However, the effects of laparoscopic training using 3D are still unclear. This study aimed to clarify the effects of using a 3D monitor among novices in the early phase of training. Methods Participants were 40 novices who had never performed laparoscopic surgery (20 medical students and 20 junior residents). Three laparoscopic phantom tasks (task 1: touching markers on a flat disk with a rod; task 2: straight rod transfer through a single loop; and task 3: curved rod transfer through two loops) in the training box were performed ten times, respectively. Performances were recorded by an optical position tracker. The participants were randomly divided into two groups: one group performed each task five times initially under a 2D system (2D start group), and the other group performed each task five times under a 3D system (3D start group). Both groups then performed the same task five times. After the trial, we evaluated the performance scores (operative time, path length of forceps, and technical errors) and the learning curves for both groups. Results Scores for all tasks performed under the 3D system were significantly better than scores for tasks using the 2D system. Scores for each task in the 2D start group improved after switching to the 3D system. However, scores for each task in the 3D start group were worse after switching to the 2D system, especially scores related to technical errors. Conclusions The stereoscopic vision improved laparoscopic surgical techniques of novices from the early phase of training. However, the performance of novices trained only by 3D worsened by changing to the 2D environment.

Introduction Three-dimensional (3D) laparoscopic vision can improve depth perception. However, it is a question whether 3D vision can improve motion in the depth direction. The aim of this study was to compare the impact of 3D vision on forceps motion in the depth and horizontal directions. Methods All data were obtained from our previous two studies, where, in total, 40 novices and 20 moderately experienced surgeons participated. A simple phantom task was performed in a training box. The participants were randomly assigned to two groups. Specifically, one group performed the task five times initially under a two-dimensional (2D) system, and the other group started under a 3D system. Both groups then performed the same task five times under the alternative system. Performances were recorded by an optical position tracker. We separately evaluated forceps motion in the x-, y-, and z-axis directions. Results Compared with the findings for 2D vision, the forceps path lengths were significantly decreased among novices and moderately experienced surgeons in almost all tasks under 3D vision. In a comparison of the path length ratio (3D/2D) in each direction, larger reduction was observed for the depth direction among novices, whereas no significant directional difference was noted among moderately experienced surgeons. Conclusions For novices, 3D laparoscopic vision improves depth perception and may give shorter forceps movement in the depth direction even for simple tasks.

Situs inversus totalis (SIT) is a rare congenital anomaly in which the organs are transposed from the normal to the opposite side. Occasionally, we encounter a patient with a combination of this condition and gastric cancer. Several cases of laparoscopic distal gastrectomy for gastric cancer in such patients have been reported. However, there is no report of totally laparoscopic total gastrectomy (TLTG) for such patients. We present a case of advanced gastric cancer with SIT that was successfully treated by TLTG involving radical lymph node dissection. A 63-year-old woman who presented with hematemesis was admitted to our hospital. She was diagnosed with advanced gastric cancer. Endoscopic findings revealed that tumor invasion was to the depth of the muscularis propria. Computed tomography (CT) showed a lack of lymph node swelling or distant metastasis. She was also diagnosed with SIT (a characteristic of Kartagener syndrome). Total gastrectomy was deemed necessary and we planned laparoscopic surgery. We carefully analyzed the location of abdominal organs from a preoperative examination, including three-dimensional reconstruction images from CT. In this operation, we reversed the normal positions of the surgeon, assistant, nurse, and trocar sites to accommodate the inverted abdominal locations of organs. TLTG was completed safely without any postoperative complications. Three-dimensional reconstruction images from CT and the inverse transposition of our usual intraoperative positions led to a smooth operation. TLTG may be not only a minimally invasive, but also a useful option for gastric cancer cases exhibiting SIT.