松本 志郎

BACKGROUND AND PURPOSE: The peritoneal cavity constitutes a unique immune microenvironment that critically influences the pathobiology of peritoneal metastasis (PM). This study aimed to clarify the mechanisms by which local immune alterations affect the efficacy of intraperitoneal (IP) chemotherapy for PM from gastric cancer (GC). METHOD: Peritoneal lavage or ascitic fluid was obtained from 42 patients with GC and PM treated with IP paclitaxel (PTX) in combination with systemic oxaliplatin and oral S-1. Serial samples from 31 patients were analyzed after 1-3 cycles of chemotherapy. Immune cell subsets were evaluated using multicolor flow cytometry with monoclonal antibodies, and the functional properties of peritoneal eosinophils were assessed using gene expression profiling and cytotoxicity assays. RESULTS: IP chemotherapy was associated with decreased CD4(+) T cells and increased CD11b(+) myeloid cells. Notably, many patients, particularly those with negative cytology (CY0), exhibited striking recruitment of CD66b(+) CD16(-) CD193(+) Siglec-F(+) eosinophils into the peritoneal cavity. Eosinophil expansion was correlated with improved clinical outcomes. Post-treatment eosinophils displayed an activated, partially degranulated phenotype with elevated CD11b and CD63 expression and distinct messenger RNA signatures compared with circulating eosinophils. Peritoneal eosinophils demonstrated the ability to induce apoptosis in GC cells. CONCLUSION: IP PTX promotes the recruitment and activation of eosinophils with potent antitumor activity in the peritoneal cavity. Early post-treatment abdominal eosinophilia is a robust prognostic biomarker and may represent a promising therapeutic target to enhance the efficacy of IP chemotherapy in patients with PM from GC.

BACKGROUND: Patients with advanced gastric cancer (GC) with peritoneal involvement have a dismal prognosis. Recent clinical trials have shown that anti-Claudin18.2 (CLDN18.2) antibody (zolbetuximab) enhances survival in patients with GC expressing high levels of CLDN18.2. However, the effectiveness of the zolbetuximab in patients with peritoneal metastases (PMs) remains unclear. In this study, we aimed to evaluate the expression of CLDN18.2 in disseminated lesions to assess the clinical utility of zolbetuximab in the treatment of GC with PM. METHODS: In 42 patients diagnosed with stage IV GC with PM, biopsy samples from the primary tumors and peritoneal metastatic nodules were collected and immunostained using the specific antibody (43-14A, Ventana). The expression of CLDN18.2 was comparatively evaluated based on staining intensity and the proportion of positive cells. RESULTS: Positive immunoreactivity of CLDN18.2 was observed in 37 (88%) of the primary tumors. Specifically, CLDN18.2 positivity was identified in 26 (62%) or 12 (29%) patients based on moderate to strong membrane staining in at least 40% or 75% of tumor cells, respectively. In comparison, the staining intensity in tumor cells was consistently reduced in PM across all patients. CLDN18.2 expression was absent in PM of 29 (69%) patients, while 3 (7.1%) cases were determined to be CLDN18.2-positive based on a cutoff value of 40% for high staining. This trend was particularly pronounced in cases with undifferentiated type and human epidermal growth factor receptor 2 (HER-2) negative primary tumors. CONCLUSIONS: Although CLDN18.2 expression in PM mirrored that in primary lesions, the levels were generally reduced. When zolbetuximab is used for GC patients with peritoneal involvement, it is preferable to assess the expression of CLDN18.2 in the disseminated lesions.

Abstract Background Osteopenia reflects frailty and has been shown to be associated with outcomes in cancer patients. This study was undertaken to examine whether osteopenia is an independent prognostic factor in patients with esophageal cancer after resection. Methods A total of 214 patients who underwent surgery for esophageal cancer were analyzed retrospectively. Bone mineral density (BMD) of the 11th thoracic vertebra was measured by computed tomography scan, and patients classified into osteopenia and normal BMD groups with BMD <160 Hounsfield units as the cutoff. Clinicopathological data and prognosis were analyzed. Results The 5‐year survival rate was 55.4% for the osteopenia group and 74.7% for the normal BMD group with a significantly worse prognosis in the osteopenia group (p = 0.0080). In multivariable analysis, osteopenia was a significant independent risk factor associated with overall survival (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.27–3.34, and p = 0.0151) along with R1/2 resection (HR 3.02, 95% CI 1.71–5.18, and p = 0.0002). Conclusion In patients with esophageal cancer undergoing resection, osteopenia may be a surrogate marker for frailty and an independent predictor of prognosis.

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.

BACKGROUND: Adjuvant nivolumab therapy has become the standard therapy for patients with localized advanced esophageal cancer with non-pathological complete response after neoadjuvant chemoradiotherapy followed by curative surgery. However, the necessity of this therapy for patients after neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen followed by surgery is unclear, and the prognosis of grouping based on the presence or absence of pathological tumor and lymph node findings has not been analyzed. Therefore, our study aimed to address these questions. METHODS: This retrospective cohort study included patients with cT1N1-3M0 and cT2-3N0-3M0 esophageal cancer according to the Japanese Classification of Esophageal Cancer, 11th edition, who received NAC with DCF followed by curative surgery between 2008 and 2020 at Jichi Medical University Hospital. We divided patients with ypT0-3N0-3M0 into four histological groups, namely ypT0N0, ypT+N0, ypT0N+, and ypT+N+, and we evaluated overall survival as the primary outcome and the prognostic relationship of lymph node metastasis as the secondary outcome. RESULTS: A total of 101 patients were included in this study. Kaplan-Meier analysis showed that the curves of the ypT0N0 and ypT+N0 groups were almost identical, while they differed from the other two groups. The hazard ratio of ypN+ was 4.44 (95% confidence interval: 2.03-9.71; P<0.001). CONCLUSIONS: The prognosis of the ypT+N0 group after NAC with DCF followed by surgery was similar to that of pathological complete remission. Grouping patients according to pathological lymph node status is a reasonable predictor of prognosis.

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.

In this study, the relationship between gaze patterns, task duration, and years of experience, which are commonly used to define and evaluate expert surgeons in laparoscopic surgery, was identified. Ten surgeons with 1-28 years of experience and six inexperienced students were included. Subjects used forceps to repeat the task of suturing a suture pad. Each subject wore an eye-marking recorder, and gaze points were recorded and analyzed. No significant relationship between task duration and gaze pattern was observed. However, there was a significant relationship between a surgeon's years of experience and the percentage of time spent gazing at the forceps. Subjects with more years of experience operated without looking at the forceps and fixed their gaze on the operational target. Therefore, when analyzing laparoscopic gazing patterns, it may be more appropriate to define an "expert" based on the years of experience rather than task duration.

BACKGROUND: Despite recent progress in systemic chemotherapy, the prognosis of patients with peritoneal metastases from gastric cancer is still poor. Efficacious intraperitoneal and systemic combination chemotherapy regimens to treat patients with peritoneal metastases have recently been developed. CASE PRESENTATION: A 74-year-old man with gastric cancer T4b (transverse mesocolon) N3 M1 (peritoneum) received combination chemotherapy with intraperitoneal administration of paclitaxel, intravenous oxaliplatin, and oral S-1. Eight courses of combined chemotherapy had remarkable anti-tumor effects on the primary lesion, lymph node metastases, and peritoneal metastases. Total gastrectomy with regional lymph node dissection was performed. Pathological examination revealed no viable tumor cells in the resected specimens. After gastrectomy, the patient received 25 courses of the same chemotherapy without oxaliplatin and has no evidence of recurrence 24 months later. DISCUSSION: Therapeutic approaches including systemic chemotherapy, extended resection, and heated intraperitoneal chemotherapy have been used to treat patients with peritoneal metastases. Repeat therapy with intraperitoneal paclitaxel has been used recently. Intraperitoneal administration of paclitaxel results in prolonged retention in the peritoneal cavity with effects against peritoneal metastases. Repeated administration of paclitaxel does not cause adhesions in the peritoneal cavity. When combination chemotherapy is effective, salvage gastrectomy is a promising option with minimal morbidity and mortality. CONCLUSION: Combined chemotherapy with intraperitoneal paclitaxel and systemic chemotherapy followed by gastrectomy is a promising strategy for patients with advanced gastric cancer and peritoneal metastases.

INTRODUCTION: Gastric adenocarcinomas with low grade atypia may be difficult to diagnose as gastric cancer by preoperative biopsy. We report an extremely well-differentiated adenocarcinoma (EWDA) of the stomach which appeared like a submucosal tumor diagnosed by preoperative endoscopic submucosal dissection. PRESENTATION OF CASE: A 70-year-old male was referred with a 3-month history of a submucosal-appearing lesion in the gastric wall found on endoscopy. Biopsies of the lesion were performed and were inconclusive for neoplasia. Endoscopic ultrasonography showed a low echoic tumor growing into the fourth layer of the gastric wall. It was difficult to identify the tumor by repeat biopsy. Endoscopic submucosal dissection of the lesion was performed and revealed adenocarcinoma, and laparoscopic total gastrectomy was performed. Histopathologic evaluation showed that the tumor was stage IIA (T3N0M0). There is no recurrence 12 months after resection. DISCUSSION: Gastric EWDAs are rare lesions, accounting for 0.6% of all gastric cancers. It is difficult to diagnose gastric EWDA especially if it appears like a submucosal tumor. This lesion was finally diagnosed by endoscopic submucosal dissection. CONCLUSION: Endoscopic submucosal dissection may facilitate establishing the preoperative diagnosis of a tumor thought to be a gastric EWDA based on its endoscopic appearance and pathological findings.

81歳女性。大腸癌検診にて便潜血反応陽性を指摘され、精査目的に当院へ紹介となった。大腸内視鏡では肛門管に黒色の隆起性結節を認め、腰椎麻酔下で結節の切除生検を行い、病理組織学的に直腸肛門部悪性黒色腫と診断された。以後、腹腔鏡下腹会陰式直腸切断術、D2郭清を施行し、左側にS状結腸の人工肛門を作製した。術後経過は良好で、再発や転移はみられていない。

53歳女。13歳時に虫垂切除術の既往があった。今回、右下腹部痛が出現し、前医にて腹壁の肉芽腫性病変を伴う慢性炎症と診断され当院紹介となった。初診時、右下腹部の虫垂炎の手術瘢痕部に一致して、軽度の圧痛を有する5cm大の腫瘤を認め、腹部CTでは右腹直筋の外縁、内外腹斜筋、腹横筋の移行部に腫瘤を認めた。Schloffer腫瘍と診断して腹壁腫瘍切除術を施行し、腫瘤は3.5cmの膿瘍と肉芽組織を伴う瘢痕組織で、病理診断は縫合糸によるSchloffer腫瘍であった。術後経過は良好で、第12病日に退院となった。

We present three patients with T2 acinar cell carcinomas (ACC) (two of which were small) and discuss their clinical and pathological features. Case 1: A 34 year-old woman had a 2.6 cm iso- or hyperdense tumor. Enucleation was performed but final diagnosis was ACC and a pylorus preserving pancreaticoduodenectomy was performed. Case 2: A 35 year-old woman was found to have a 4.5 cm hypervascular tumor in the tail of the pancreas. Distal pancreatectomy was performed. Case 3: A 61 year-old man suffered from acute pancreatitis and was found to have an encapsulated 2.5 cm hypervascular tumor in the head of pancreas. Pylorus-preserving pancreaticoduodenectomy was performed. These three patients with T2 ACCs had common characteristics including well-demarcated exophytic tumors with slow and limited progress, distinctively different from large ACCs and pancreatic ductal adenocarcinomas. ACCs are important in the differential diagnosis of homogeneously or heterogeneously enhancing small pancreatic tumors.