川平 洋

BACKGROUND: Recent studies reveal that during trogocytosis plasma membranes are frequently transferred upon cell-to-cell contact, and that this phenomenon plays an important role in the modulation of anti-tumor immune response. However, the accompanying physiological roles in the tumor microenvironment are poorly understood. METHODS & RESULTS: Human gastric cancer cell line OCUM-1 was co-cultured with T cells whose plasma membrane was stained with PKH26. Flow-cytometric analysis revealed that OCUM-1 was positive for PKH26 at one hour and the positive rate increased over time. The acquisition of PKH26 was dependent on cell-to-cell contact and suppressed when T cells were fixed. OCUM-1 came to express various immunological synapse molecules after 10 hours of co-culture (positive rate, CD45:73.6±7.9%, CD3: 35.5±10.1%, CD4: 15.3±14.7%, CD8: 7.7±2.4%, CD11a: 8.1±4.3%, CD11b: 3.4±1.9%). We focused on CD11a which belongs to β2 integrins and aids immune cell adherence to endothelial cells. After co-culture with activated T cells (LAK), the expression level of CD11a on OCUM-1 was accelerated (with T cells: 19.1±13.4%, with LAK: 75.2±11.8%) and the adhesion rate on endothelial cells increased in a CD11a dependent manner (adhesion rate, single-culture: 2.0±0.64%, co-culture: 6.3±2.0%, co-culture (pre-treat with CD11a antibody): 2.3±1.4%, n=10, single-culture vs co-culture, p<0.0001; co-culture vs pre-treat with CD11a antibody, p<0.0001). CONCLUSION: These results suggest that acquisition of CD11a from T cells by trogocytosis enables cancer cells to increase adhesive properties towards endothelial cells, which may result in intravenous metastasis promotion.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with diabetes mellitus (DM), and their prognosis remains particularly poor. Metformin, a widely used antidiabetic agent, has demonstrated anti-tumor effects through multiple mechanisms and has been associated with improved outcomes in various malignancies. In this study, we investigated retrospectively survival outcomes and intra-tumoral infiltration patterns of various immune cells in diabetic patients who underwent curative resection of PDAC, comparing those who received metformin with those who did not. METHODS: A total of 65 diabetic patients who underwent curative resection for invasive PDAC were retrospectively analyzed. Among them, 17 patients received metformin, while 48 did not. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups. Following propensity score matching, tumor-infiltrating CD3(+) and CD8(+) T cells were assessed by immunohistochemistry (IHC), and their densities were compared between metformin users and non-users. RESULTS: Patients in the metformin group showed significantly prolonged RFS [hazard ratio (HR) =0.42, P=0.03] and OS (HR =0.421, P=0.03) compared to those in the non-metformin group. Multivariate analysis identified metformin use as an independent prognostic factor for both RFS (HR =0.40, P=0.02) and OS (HR =0.21, P=0.02). The survival benefit of metformin was particularly evident in patients who underwent upfront surgery, whereas not significant in those who received neoadjuvant therapy. Immunohistochemical analysis revealed a significantly higher density of CD8(+) T cells (650.7 vs. 269.9/mm2, P<0.001) with an increased CD8/CD3 ratio in resected tumors from metformin-treated patients compared to non-users (58.9% vs. 44.8%, P<0.001). This trend was kept in patients who underwent upfront surgery, while less pronounced in patients treated with neoadjuvant therapy. CONCLUSIONS: Metformin may enhance the infiltration of cytotoxic CD8(+) T cells into the tumor microenvironment and improve the prognosis of diabetic patients with PDAC, particularly in those undergoing upfront surgical resection.

PURPOSE: There is limited awareness of work-related musculoskeletal disorders (MSDs) in Japan, despite the high ergonomic risks for surgeons. We conducted this study to investigate the prevalence, characteristics, and impact of MSDs on Japanese general surgeons. METHODS: An electronic survey of 136 general surgeons at a Japanese university hospital network used a modified Nordic Musculoskeletal Questionnaire to assess demographics, work factors, MSD symptoms, psychological distress, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and their impact. RESULTS: Based on a 56.6% response rate, we found a high prevalence of chronic (37.7%) and acute (51.9%) MSDs. These disorders frequently impacted surgeons' work (30.0%) and daily life (39.0%), leading to time off (5.2%) and medical intervention (28.6%). Both MSD types correlated significantly with the use of NSAIDs and psychological distress. Notably, neck pain was strongly associated with the use of NSAIDs. The proportion of minimally invasive surgical procedures performed each week was associated significantly with acute, but not chronic, MSDs. CONCLUSIONS: MSDs are highly prevalent among Japanese surgeons, impacting their physical and psychological health. The high symptom prevalence and the strong association between neck pain and NSAID reliance underscore the urgent need for ergonomic interventions and preventive strategies in surgical practice to protect this essential workforce.

Abstract The advent of Artificial Intelligence (AI)-based object detection technology has made identification of position coordinates of surgical instruments from videos possible. This study aimed to find kinematic differences by surgical skill level. An AI algorithm was developed to identify X and Y coordinates of surgical instrument tips accurately from video. Kinematic analysis including fluctuation analysis was performed on 18 laparoscopic distal gastrectomy videos from three expert and three novice surgeons (3 videos/surgeon, 11.6 h, 1,254,010 frames). Analysis showed the expert surgeon cohort moved more efficiently and regularly, with significantly less operation time and total travel distance. Instrument tip movement did not differ in velocity, acceleration, or jerk between skill levels. The evaluation index of fluctuation β was significantly higher in experts. ROC curve cutoff value at 1.4 determined sensitivity and specificity of 77.8% for experts and novices. Despite the small sample, this study suggests AI-based object detection with fluctuation analysis is promising because skill evaluation can be calculated in real time with potential for peri-operational evaluation.

Introduction Postoperative pancreatic fistula (POPF) is a critical complication occurring with a high incidence after distal pancreatectomy. To minimize the risk of POPF, we developed an innovative pancreas ligation device capable of closing the pancreatic stump without causing traumatic injury to the pancreatic duct and artery. We conducted an ex vivo follow-up study to compare the pressure resistance of the pancreas ligation device with that of a regular linear stapler. Materials and methods The pancreases were excised from 20 pigs and divided into two groups: ligation group (n = 10) and stapler group (n = 10). Distal pancreatectomy was performed, and the pancreatic stump was closed using either a pancreas ligation device or a regular linear stapler. The main pancreatic duct was cannulated with a 4-French catheter connected to a cannula and syringe filled with contrast medium. Using fluoroscopy detection, pressure resistance was defined as the maximum pressure without leakage from the pancreatic stump. Results No significant differences were found between the two groups regarding sex, age, body weight, or pancreatic thickness. In the ligation group, no leakage was observed at the stump in any pancreas. However, in the stapler group, six of 10 pancreases showed leakage at the staple line or into the parenchyma. Pressure resistance was significantly higher in the ligation group than in the stapler group (median: 42.8 vs. 34.3 mmHg, P = 0.023). Conclusions These findings suggest the effectiveness of a pancreas ligation device in reducing the incidence of POPF after distal pancreatectomy. Our ligation device is expected to be a useful alternative to a linear stapler for pancreatic stump closure.

INTRODUCTION: Computer-aided diagnostic systems are emerging in the field of gastrointestinal endoscopy. In this study, we assessed the clinical performance of the computer-aided detection (CADe) of colonic adenomas using a new endoscopic artificial intelligence system. METHODS: This was a single-center prospective randomized study including 415 participants allocated into the CADe group (n = 207) and control group (n = 208). All endoscopic examinations were performed by experienced endoscopists. The performance of the CADe was assessed based on the adenoma detection rate (ADR). Additionally, we compared the adenoma miss rate for the rectosigmoid colon (AMRrs) between the groups. RESULTS: The basic demographic and procedural characteristics of the CADe and control groups were as follows: mean age, 54.9 and 55.9 years; male sex, 73.9% and 69.7% of participants; and mean withdrawal time, 411.8 and 399.0 s, respectively. The ADR was 59.4% in the CADe group and 47.6% in the control group (p = 0.018). The AMRrs was 11.9% in the CADe group and 26.0% in the control group (p = 0.037). CONCLUSION: The colonoscopy with the CADe system yielded an 11.8% higher ADR than that performed by experienced endoscopists alone. Moreover, there was no need to extend the examination time or request the assistance of additional medical staff to achieve this improved effectiveness. We believe that the novel CADe system can lead to considerable advances in colorectal cancer diagnosis.

INTRODUCTION: An eyeglass gaze camera and a skeletal coordinate camera without sensors attached to the operator's body were used to monitor gaze and movement during a simulated surgical procedure. These new devices have the potential to change skill assessment for laparoscopic surgery. The suitability of these devices for skill assessment was investigated. MATERIAL AND METHODS: Six medical students, six intermediate surgeons, and four experts performed suturing tasks in a dry box. The tip positions of the instruments were identified from video recordings. Performance was evaluated based on instrument movement, gaze, and skeletal coordination. RESULTS: Task performance time and skeletal coordinates were not significantly different among skill levels. The total movement distance of the right instrument was significantly different depending on the skill level. The SD of the gaze coordinates was significantly different depending on skill level and was less for experts. The expert's gaze stayed in a small area with little blurring. CONCLUSIONS: The SD of gaze point coordinates correlates with laparoscopic surgical skill level. These devices may facilitate objective intraoperative skill evaluation in future studies.

Introduction Although new techniques and devices have been introduced, the incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy remains high. To reduce the risk of POPF, we developed an innovative ligation band and conducted this pilot study to assess the possibility of reducing the incidence of POPF and pancreatic necrosis after distal pancreatectomy. Methods Distal pancreatectomy was performed in three pigs. In two animals, ligation of the pancreas was performed while maintaining arterial blood flow to the stump, and in one animal, the arterial blood flow was occluded. After ligation, the pancreas was sharply divided. Animals were sacrificed seven days later, and the remnant pancreas was assessed histologically. POPF was defined as amylase in ascites > 3x the preoperative serum amylase level. The following equation was used to quantify the extent of necrotic tissue: necrotic tissue residual rate = necrotic tissue area/ cross-sectional area. Results All animals survived, and no POPF developed. For two animals in which arterial blood flow to the stump was maintained, necrotic tissue residual rates at the ligation line were 24% and 31%. At the pancreatic stump, necrotic tissue residual rates were 37% and 50%. In the animal in which arterial blood flow to the stump was occluded, the necrotic tissue residual rate at the ligation line was 83% and that at the pancreatic stump was 78%, both higher than that in animals in which arterial blood flow was maintained. In all animals, there was no injury to pancreatic tissue at the ligation line. Conclusion The pancreas ligation band can potentially prevent POPF after distal pancreatectomy by atraumatic ligation, and the band ligates the pancreatic stump while maintaining arterial blood flow and limiting pancreatic necrosis.