Protocol for a phase II study to evaluate the efficacy and safety of nivolumab as a postoperative adjuvant therapy for patients with esophageal cancer treated with preoperative docetaxel, cisplatin plus 5-fluorouracil treatment (PENTAGON trial).

BACKGROUND: In Japan, preoperative adjuvant chemotherapy followed by surgical resection is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, the risk of recurrence after surgical resection remains high. Although a randomized controlled trial evaluating the efficacy of nivolumab, a fully human monoclonal anti-programmed death 1 antibody, as postoperative adjuvant therapy after neoadjuvant chemoradiotherapy and surgery established its superior efficacy as adjuvant therapy, the efficacy for patients who received preoperative adjuvant chemotherapy has not been demonstrated. This study aims to elucidate the efficacy and safety of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. METHODS: This study is a multi-institutional, single-arm, Phase II trial. We plan to recruit 130 esophageal squamous cell carcinoma patients, who have undergone preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. If the patient did not have a pathological complete response, nivolumab is started as a postoperative adjuvant therapy within 4-16 weeks after surgery. The nivolumab dose is 480 mg/day every four weeks. Nivolumab is administered for up to 12 months. The primary endpoint is disease-free survival; the secondary endpoints are overall survival, distant metastasis-free survival, and incidence of adverse events. DISCUSSION: To our knowledge this study is the first trial establishing the efficacy of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. In Japan, preoperative adjuvant chemotherapy followed by surgery is a well-established standard treatment for resectable, locally advanced esophageal squamous cell carcinoma. Therefore, developing an effective postoperative adjuvant therapy has been essential for improving oncological outcomes.

Impact of treatment guidelines and pivotal clinical trial results on a surgeon's decision regarding treatment for gastric cancer: a retrospective cohort study using the National Clinical Database.

PURPOSES: The present study evaluated the impact of clinical guidelines for gastric cancer surgery on surgeons' choice of procedure in real-world practice. We focused on the 2014 guideline revision recommending laparoscopic surgery and the evidence concerning splenectomy for prophylactic lymphadenectomy reported in 2015 using the National Clinical Database, which is the most comprehensive database in Japan. METHODS: We investigated the monthly percentages of laparoscopic distal gastrectomies performed for stage I gastric cancer (LDG%) and splenectomies performed during total gastrectomy for advanced cancer (TGS%) between 2014 and 2017. We evaluated the descriptive statistics of the time-series changes in the LDG%, TGS%, and annual trends of outcomes. RESULTS: In total, 124,787 patients were enrolled. The mean LDG% and TGS% were 69.8% and 9.2%, respectively. The LDG% and TGS% were 66.4% and 16.7%, respectively, in January 2014 and 73.1% and 5.9%, respectively, in December 2017. LDG% consistently increased, and TGS% showed a consistent downward trend throughout the observation period. There was no significant change in this trend after the publication of the guideline recommendations or clinical trial results. CONCLUSION: No significant changes in surgical procedures were observed after publication of the guidelines or results of clinical trials.

Significance of Preoperative Tooth Loss in Patients Who Underwent Gastrectomy for Gastric Cancer.

Background/Aim: The relationship between gastric cancer and oral health has been reported in several studies. This study aimed to determine the relationship between the postoperative prognosis of gastric cancer and oral health using preoperative tooth loss as a simple index. Patients and Methods: We conducted a single-center retrospective cohort study. Patients were divided into two groups according to the number of tooth losses. The survival curve was constructed using the Kaplan-Meier method. We also performed univariate and multivariate analyses of overall survival based on Cox proportional hazard regression to determine prognostic factors. Results: A total of 191 patients were divided into two groups: those with seven or more tooth losses and those with less than seven tooth losses. The three-year overall survival rate was 71.5% in the group with seven or more tooth losses and 87.0% in the group with less than seven tooth losses. The group with seven or more tooth losses had a significantly lower overall survival rate compared to the group with less than seven tooth losses (p=0.0014). However, in multivariate analysis, tooth loss was not identified as an independent prognostic factor whereas age, clinical T stage, CEA level, and serum albumin level were independent poor prognostic factors. Conclusion: Preoperative tooth loss was not a prognostic factor for gastric cancer after gastrectomy, but tooth loss may be a simple and useful method for evaluating frailty in patients.

No difference in the incidence of postoperative pulmonary complications between abdominal laparoscopy and laparotomy for minimally invasive thoracoscopic esophagectomy: a retrospective cohort study using a nationwide Japanese database.

INTRODUCTION: There remains a lack of evidence regarding the optimal abdominal approach, including laparoscopy, hand-assisted, and open laparotomy for minimally invasive thoracoscopic esophagectomy. We aimed to compare the incidence of postoperative complications, particularly pulmonary complications, between laparoscopy and open laparotomy for minimally invasive thoracoscopic esophagectomy using nationwide Japanese databases. METHODS: Data from patients in the National Clinical Database (NCD) who underwent thoracoscopic esophagectomy for esophageal cancer were analyzed. The incidence of pulmonary complications was compared between abdominal laparoscopy and laparotomy after matching the propensity scores (PS) from preoperative factors to account for confounding bias. Laparoscopic-assisted surgery (LAS) was also compared to hand-assisted laparoscopic surgery (HALS). RESULTS: Of the 24,790 patients who underwent esophagectomy between 2018 and 2021, data from 12,633 underwent thoracoscopic procedure. The proportion of patients who experienced pulmonary complications did not significantly differ between the laparoscopy group and the laparotomy group after matching (664/3195 patients, 20.8% versus 702/3195 patients, 22.0%; P = 0.25). No difference in the incidence of pulmonary complications was observed among patients treated using the laparoscopic approach (508/2439 patients, 20.8% in the LAS group versus 498/2439 patients, 20.4% in the HALS group; P = 0.72). CONCLUSIONS: We observed no significant difference in the incidence of postoperative pulmonary complications between laparoscopy and laparotomy for thoracoscopic esophagectomy. Short-term outcomes were similar between the laparoscopic-assisted approach and the hand-assisted approach. This study provides valuable insights into the optimal abdominal approach for thoracoscopic esophagectomy using data from a nationwide database that reflect real-world clinical practice.

Impact of Tumor Size on Survival Outcome in Esophageal Squamous Cell Carcinoma After Esophagectomy Following Neoadjuvant Chemotherapy.

BACKGROUND: Large tumor size is a prognostic factor in esophageal squamous cell carcinoma (ESCC). However, the effect of tumor size on outcomes following neoadjuvant chemotherapy (NAC) has not been evaluated. This study aimed to assess the influence of tumor size on prognosis of patients undergoing esophagectomy after NAC. PATIENTS AND METHODS: This study was made up of 272 patients who underwent esophagectomy after NAC at Kobe University Hospital. We evaluated the pathological tumor size and determined the cutoff level for tumor size using receiver operating characteristics analysis to the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. RESULTS: The patients were categorized into two groups: patients with tumor sizes ≥ 36 mm and < 36 mm. Deep pathological tumor invasion and worse histological response to NAC were associated with tumor size ≥ 36 mm. In patients with pT0-1, pT2, and pT4 ESCC, no significant differences in overall survival (OS) rates were observed between the two groups. In patients with pT3, OS of the tumor size ≥ 36 mm group was significantly worse than that of the tumor size < 36 mm group (p < 0.0001). Multivariate analysis in pT3 patients revealed tumor size ≥ 36 mm was an independent risk factor for OS. The 5-year OS rate was 10% in patients with tumor size ≥ 36 mm pT3 ESCC with pathological lymph node metastasis (p < 0.0001). CONCLUSIONS: Tumor size ≥ 36 mm is an independent risk factor for poorer survival in pT3 patients. Furthermore, tumor size ≥ 36 mm with pathological lymph node metastasis in pT3 patients was associated with very poor survival.

Alb-dNLR Score as a Novel Prognostic Marker for Patients With Locally Advanced Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy.

BACKGROUND/AIM: The albumin and derived neutrophil-to-lymphocyte ratio (Alb-dNLR) score, which combines an inflammation index with a nutritional index, has recently been reported as a useful prognostic marker in various cancers. However, evaluation of the usefulness of Alb-dNLR score in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (NACRT) has not been reported yet. PATIENTS AND METHODS: This retrospective study included 69 patients with LARC undergoing NACRT followed by surgery between November 2005 and July 2020. The cutoff value of the Alb-dNLR score for relapse-free survival (RFS) was determined using a receiver operating characteristic curve. Patients were divided into high and low Alb-dNLR-score groups and analyzed for RFS and overall survival (OS). RESULTS: A total of 10 patients had high Alb-dNLR scores, and 59 had low Alb-dNLR scores. The high Alb-dNLR-score group had significantly higher rates of open surgery (70.0% vs. 28.8%; p<0.026), greater intraoperative blood loss (2,009 g vs. 421 g; p<0.001), and longer postoperative hospital stays (70 days vs. 42 days, p=0.012) than those of the low-Alb-dNLR-score group. The high Alb-dNLR-score group further demonstrated significantly worse RFS and OS than the low Alb-dNLR-score group (both p<0.001). Multivariate analysis identified the Alb-dNLR score as the most independent prognostic factor for RFS (hazard ratio=5.27; 95% confidence interval=2.09-13.27; p<0.001). CONCLUSION: The Alb-dNLR score is a valuable prognostic marker for predicting the oncological outcomes in patients with LARC undergoing NACRT.

Effectiveness of long-term tube feeding intervention in preventing skeletal muscle loss after minimally invasive esophagectomy.

PURPOSE: Esophageal cancer is a lethal tumor typically treated by neoadjuvant chemotherapy and surgery. For patients undergoing esophagectomy, postoperative enteral nutrition is important in preventing complications. Sarcopenia is associated with poor postoperative outcomes in esophageal cancer. In this study, we evaluated the benefits of tube feeding intervention and compared its short- and long-term outcomes in patients who underwent esophagectomy. METHODS: Propensity score matching was performed in 303 patients who underwent esophagectomy at Kobe University Hospital between 2010 and 2020. Patients were divided into feeding and nonfeeding jejunostomy tube groups (n = 70 each). The feeding jejunostomy tube group was further divided into long-term (≥ 60 days) and short-term (< 60 days) subgroups. The groups were then retrospectively compared regarding postoperative albumin levels, body weight, and psoas muscle area and volume. RESULTS: In the long-term feeding jejunostomy tube group, anastomotic leakage (p = 0.013) and left laryngeal nerve palsy (p = 0.004) occurred frequently. There were no significant between-group differences in postoperative albumin levels, body weight, or psoas muscle area. However, significant psoas muscle volume recovery was confirmed in the long-term jejunostomy tube group at 6 months postoperatively (p = 0.041). CONCLUSIONS: Tube feeding intervention after minimally invasive esophagectomy may attenuate skeletal muscle mass loss and help prevent sarcopenia.

Safety and Efficacy of Neoadjuvant Chemotherapy for Advanced Gastric Cancer in Elderly Patients.

BACKGROUND/AIM: Elderly patients with pathological stage II/III gastric cancer struggle to complete adjuvant chemotherapy. Neoadjuvant chemotherapy (NAC) for treating locally advanced gastric cancer (LAGC) has drawn attention; however, its indication for elderly patients who are vulnerable to chemotherapy is unclear. This study aimed to investigate the feasibility and efficacy of NAC for elderly patients with gastric cancer. PATIENTS AND METHODS: In this study, patients aged ≥75 years who underwent curative gastrectomy for LAGC or adenocarcinoma of the esophagogastric junction between April 2013 and November 2021 were included. Vulnerable patients, with poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 2-3 were also included. The patients were classified into NAC+ (n=20) and NAC - (n=45) groups. The clinicopathological data of the patients were retrospectively investigated. RESULTS: The NAC+ group showed a higher R0 resection rate than the NAC- group (100% vs. 89.1%, p=0.3) and pathological downstaging was achieved in 12 (60%) cases, including five (25%) pathological complete responses. The incidence of adverse events during postoperative chemotherapy was 35%, and the rate of postoperative complications greater than Clavien-Dindo Grade II was comparable between the two groups (35% vs. 46.7%, p=0.43). The NAC+ group showed a higher three-year overall survival rate (75% vs. 36%, p=0.015). CONCLUSION: NAC was feasible and effective for elderly patients including vulnerable patients with LAGC or adenocarcinoma of the esophagogastric junction. It can be considered as treatment option, with a high down staging rate and better survival.

The modified Glasgow prognostic score is a reliable predictor of oncological outcomes in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy.

There has been no reliable marker for predicting oncological outcomes in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (NACRT). We retrospectively analyzed 73 patients with LARC who underwent curative surgery after NACRT. The modified Glasgow prognostic score (mGPS) was assessed after NACRT, and clinical outcomes were compared between the high (mGPS = 1 or 2; n = 23) and low (mGPS = 0; n = 50) groups. Body mass index was significantly higher in the low mGPS group. The 5-year disease-free survival (DFS) rate was significantly worse in the high mGPS group than that in the low mGPS group (36.7% vs. 76.6%, p = 0.002). Univariate and multivariate analyses of DFS revealed that mGPS was the most significant predictor (p < 0.001). mGPS appears to be a reliable predictor of oncological outcomes in patients with LARC undergoing NACRT.

Deep Learning-based Image Cytometry Using a Bit-pattern Kernel-filtering Algorithm to Avoid Multi-counted Cell Determination.

BACKGROUND/AIM: In pathology, the digitization of tissue slide images and the development of image analysis by deep learning have dramatically increased the amount of information obtainable from tissue slides. This advancement is anticipated to not only aid in pathological diagnosis, but also to enhance patient management. Deep learning-based image cytometry (DL-IC) is a technique that plays a pivotal role in this process, enabling cell identification and counting with precision. Accurate cell determination is essential when using this technique. Herein, we aimed to evaluate the performance of our DL-IC in cell identification. MATERIALS AND METHODS: Cu-Cyto, a DL-IC with a bit-pattern kernel-filtering algorithm designed to help avoid multi-counted cell determination, was developed and evaluated for performance using tumor tissue slide images with immunohistochemical staining (IHC). RESULTS: The performances of three versions of Cu-Cyto were evaluated according to their learning stages. In the early stage of learning, the F1 score for immunostained CD8+ T cells (0.343) was higher than the scores for non-immunostained cells [adenocarcinoma cells (0.040) and lymphocytes (0.002)]. As training and validation progressed, the F1 scores for all cells improved. In the latest stage of learning, the F1 scores for adenocarcinoma cells, lymphocytes, and CD8+ T cells were 0.589, 0.889, and 0.911, respectively. CONCLUSION: Cu-Cyto demonstrated good performance in cell determination. IHC can boost learning efficiencies in the early stages of learning. Its performance is expected to improve even further with continuous learning, and the DL-IC can contribute to the implementation of precision oncology.

Patients younger than 40 years with colorectal cancer have a similar prognosis to older patients.

PURPOSE: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. In recent years, the proportion of patients diagnosed with CRC at younger ages has increased. The clinicopathological features and oncological outcomes in younger patients with CRC remain controversial. We aimed to analyze the clinicopathological features and oncological outcomes in younger patients with CRC. METHODS: We examined 980 patients who underwent surgery for primary colorectal adenocarcinoma between 2006 and 2020. Patients were divided into two cohorts: younger (< 40 years old) and older (≥ 40 years old). RESULTS: Of the 980 patients, 26 (2.7%) were under the age of 40 years. The younger group had more advanced disease (57.7% vs. 36.6%, p = 0.031) and more cases beyond the transverse colon (84.6% vs. 65.3%, p = 0.029) than the older group. Adjuvant chemotherapy was administered more frequently in the younger group (50% vs. 25.8%, p < 0.01). Relapse-free survival and overall survival were similar between the groups at all stages. Moreover, in stages II and III they were also comparable, regardless of the administration of adjuvant chemotherapy. CONCLUSIONS: Younger patients with CRC have a prognosis equivalent to that of older patients. Further studies are needed to establish the optimal treatment strategies for these patients.

Improvement Effect of Upper Mediastinal Lymphadenectomy During Minimally Invasive Esophagectomy on the Prognosis in Squamous Cell Carcinoma: Efficacy Index and Propensity Score Matching Analyses.

BACKGROUND: The effect of lymphadenectomy around the recurrent laryngeal nerve (RLN) in open esophagectomy has been demonstrated with the efficacy index (EI). However, it remains unclear whether this effect exists for minimally invasive esophagectomy (MIE) in the prone position. The purpose of this study was to clarify whether the upper mediastinal lymphadenectomy contributed to improved prognosis in patients with esophageal squamous cell carcinoma. STUDY DESIGN: This study included 339 patients with esophageal squamous cell carcinoma treated with MIE in the prone position at Kobe University or Hyogo Cancer Center, Japan, from 2010 to 2015. EIs for each station, correlations between metastatic lymph nodes around the left RLN and RLN palsy, and survival of patients with and without upper mediastinal lymphadenectomy were investigated. RESULTS: Among 297 patients treated with upper mediastinal lymphadenectomy, Clavien- Dindo grade ≥ II left RLN palsy occurred in 59 patients (20%). Overall, EIs for the right RLN (7.4) and left RLN (6.6) were higher than EIs for other stations. For patients with upper-third or middle-third tumors, the trend was stronger. Left RLN palsy was more likely in patients with metastatic lymph nodes around the left RLN than in those without (44% vs 15%, p < 0.0001). After propensity score-matching, 42 patients were included in each group with and without upper mediastinal lymphadenectomy. In survival analyses, the 5-year overall survival rates were 55% vs 35% and cause-specific survival rates were 61% vs 43% for the patients with and without upper mediastinal lymphadenectomy respectively. Significant differences were confirmed in survival curves (overall survival: p = 0.03; cause-specific survival: p = 0.04, respectively). CONCLUSIONS: Upper mediastinal lymphadenectomy contributes to improved prognosis with high EIs in MIE in the prone position.

Safety of Laparoscopic Gastrectomy for Advanced Gastric Cancer With Greater than Serosal Invasion Depth.

BACKGROUND/AIM: There are several concerns about oncological contamination and technical difficulty in the laparoscopic approach for locally advanced gastric cancer. We aimed to determine the safety and usefulness of laparoscopic gastrectomy for patients with advanced gastric cancer with tumor depth greater than serosal invasion. PATIENTS AND METHODS: Sixty-two laparoscopic and 82 laparotomy gastric cancer cases surgically diagnosed as serosal or other organ invasions intraoperatively between 2011 and 2021 were included. The laparoscopic and open gastrectomy results were compared by propensity score matching using stage, preoperative chemotherapy, curative resection, surgical technique, and age as explanatory variables and laparoscopy and open resection as outcome variables. RESULTS: No difference in median operative time (341 vs. 386 minutes, p=0.24) was observed, but median blood loss (0 vs. 510 ml, p<0.001) and blood transfusion requirement (9.5 vs. 43%, p<0.001) were lower in the laparoscopic group. No difference was observed between the two groups regarding complications. Furthermore, 3-year overall survival was also similar (43 vs. 42%, p=0.74). CONCLUSION: The laparoscopic surgery results are comparable to those of open surgery in treating gastric cancer with T4a or greater depth. In addition, it is minimally invasive with less blood loss, making it a standard approach.

Efficacy and Postoperative Outcomes of Laparoscopic Retrosternal Route Creation for the Gastric Conduit: Propensity Score-Matched Comparison to Posterior Mediastinal Reconstruction.

BACKGROUND: Retrosternal reconstruction has lower risks for severe postoperative morbidities, such as gastro-tracheal fistula or esophageal hiatal hernia. We have previously reported the laparoscopic retrosternal route creation (LRRC) method, but its safety and efficacy remain unclear. METHODS: In total, 374 patients with esophageal carcinoma who underwent minimally invasive McKeown esophagectomy in the prone position between 2010 and 2021 were retrospectively reviewed. We performed a propensity score-matched analysis with the simple, nearest-neighbor method and no calipers to compare postoperative outcomes and reconstructed gastric conduit functionality between patients who underwent LRRC and counterparts who underwent posterior mediastinal reconstruction. RESULTS: After matching, 62 patients were included in the laparoscopic retrosternal group (LR group) or posterior mediastinal group (PM group). No significant differences were observed between the groups, apart from the number of robot-assisted surgeries, the extent of lymph node dissection, and the method of cervical anastomosis. There were no significant differences in the incidence of Clavien-Dindo grade ≥ 2 complications. Gastro-tracheal fistula (n = 1) and esophageal hiatal hernia (n = 2) occurred in the PM group but not in the LR group. There were no differences in the incidence of pulmonary embolism between the groups (5% vs. 5%). The postoperative anastomotic stenosis rate was similar (16% vs. 27%, p = 0.192). Endoscopic findings of reflux esophagitis (modified Los Angeles classification ≥ M) at 1 year after surgery were significantly better in the LR group (p = 0.037). CONCLUSIONS: LRRC for gastric conduit reconstruction is safe and valuable. It is associated with good reconstructed gastric conduit function.

Feasibility and safety of robotic surgery for low rectal cancer combined with transanal total mesorectal excision.

PURPOSE: Laparoscopic surgery for low rectal cancer is often challenging. Transanal total mesorectal excision (TaTME) and robotic surgery have been introduced to overcome the technical difficulties in laparoscopic surgery and achieve more favorable outcomes. Hybrid robotic surgery, which combines TaTME with the abdominal robotic approach, incorporates the advantages of each of these surgical techniques and might achieve less invasive and safer surgery. This study evaluated the safety and feasibility of hybrid robotic surgery with TaTME (hybrid TaTME). METHODS: We retrospectively reviewed 162 TaTME cases performed at our department from September 2016 to May 2022. Among them, 92 cases of conventional TaTME and 30 of hybrid TaTME were eligible. We used propensity score matching analysis (PSM) to adjust for patients' characteristics and compared the short-term outcomes of the two treatment groups. RESULTS: Twenty-seven cases in each group were extracted using PSM. The operation time in hybrid TaTME was comparable to that in conventional TaTME. There was no significant difference in the postoperative hospital stay between the two groups. Other intra- and post-operative outcomes were also comparable between the two groups. Furthermore, no significant differences were observed between the two groups in the curative resection and recurrence rates. CONCLUSION: Hybrid TaTME for low rectal cancer was as favorable as conventional TaTME in producing satisfactory short-term outcomes. However, furthermore, larger-scale studies conducted over longer study periods are needed to evaluate the validity of the findings.

Learning Curve for Transanal Total Mesorectal Excision for Low Rectal Malignancy.

BACKGROUND: Although transanal total mesorectal excision (TaTME) is a promising treatment for low rectal cancer, it is considered technically demanding, and the number of cases required to become proficient in TaTME remains unknown. The purpose of this study was to assess the TaTME learning curve based on the total mesorectal excision completion time. STUDY DESIGN: This retrospective analysis comprised 128 individuals who received TaTME between September 2016 and December 2021. The cumulative sum method was used to generate the learning curve. The duration of the procedure from the beginning to the end of the circumferential rendezvous was used to define the total mesorectal excision completion time. RESULTS: The learning curve consists of 3 phases: phase I (learning phase: cases 1 to 38), phase II (consolidation phase: cases 39 to 70), and phase III (maturing phase: cases 71 to 128). As the phases varied, both the overall operative time and total mesorectal excision completion time decreased considerably. Through the 3 phases of TaTME, intraoperative adverse events decreased, and in phase III, none occurred. Only 1 instance of local recurrence occurred during phase III, and none occurred during phase I or II. CONCLUSIONS: After 70 operations, the surgeon could join the mastery phase of TaTME based on the total mesorectal excision completion time. After the mastering phase began, there were no intraoperative negative occurrences. From the beginning, the oncological safety could be guaranteed.

Evaluation of the Efficiency of a Joystick-Guided Robotic Scope Holder Compared to That of Human Scopists: A Prospective Trial.

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.

Significance of Wnt/ß-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer.

Although a therapeutic response to neoadjuvant chemoradiotherapy (NACRT) is important to improve oncological outcomes after surgery in patients with locally advanced rectal cancer, there is no reliable predictor for this. The Wnt/ß-catenin signal is known to be crucial for the tumorigenesis of colorectal cancer. This study aimed to investigate the association of Wnt/ß-catenin signal activation with a pathological response to NACRT. The immunohistochemical expression of nuclear and membranous ß-catenin was analyzed in biopsy samples obtained from 60 patients with locally advanced rectal cancer who received curative surgery following NACRT. The association of Wnt/ß-catenin signal activation with their clinical outcomes was investigated. Notably, the body mass index of these patients was significantly higher in the low nuclear ß-catenin expression group. Moreover, patients in the high nuclear ß-catenin expression group tended to have more advanced disease and a higher rate of positive vascular invasion than those in the low expression group. Furthermore, the rate of good histological responses was significantly higher in the low nuclear ß-catenin expression group (72% vs. 37.1%, p < 0.01). Overall, relapse-free survival tended to be better in patients with low nuclear/high membranous ß-catenin expression (n = 9) than in other individuals (n = 51) (p = 0.093 and p = 0.214, respectively). Activation of the Wnt/ß-catenin signal pathway represented by nuclear ß-catenin accumulation was significantly associated with a poor response to NACRT in patients with rectal cancer. Analysis of nuclear ß-catenin accumulation before starting treatment might help predict the therapeutic response to NACRT.