Hiroharu Yamashita

Background: Liquid biopsy using bodily fluids enables noninvasive acquisition of diverse tumor-derived molecules for comprehensive characterization of tumor profiles. Metabolomic analysis, in particular, may accurately reflect disease pathogenesis and holds promise for clinical diagnostic applications. Objective: This study explored metabolic alterations associated with pancreatic ductal adenocarcinoma (PDAC) using non-targeted metabolomic analysis of pancreatic juice to construct a preliminary diagnostic model based on selected metabolites. Methods: Pancreatic juice samples were collected intraoperatively and postoperatively from patients undergoing pancreaticoduodenectomy for PDAC (n = 11) and from those who had non-PDAC diseases, including benign conditions such as chronic pancreatitis and non-pancreatic malignancies such as distal bile duct adenocarcinoma and ampullary adenocarcinoma (n = 14). Non-targeted metabolomic analysis was performed using LC-QTOF-MS. Data were processed using MS-DIAL and MetaboAnalyst, and components showing intergroup differences were selected via PLS-DA. A diagnostic model was constructed using logistic regression based on annotated metabolites. Results: PLS-DA identified 56 discriminative components, of which 19 were successfully annotated. One metabolite was notably increased and 22 were relatively decreased in pancreatic juice of patients with PDAC. Among known metabolites that tended to decrease were isocitric acid, citric acid, and several oxidized fatty acids. A tentative logistic regression-based diagnostic model using these selected metabolites showed moderate discriminative performance. Citric acid was included in the final three-variable model, suggesting its potential as a candidate marker for PDAC discrimination. Conclusions: Pancreatic juice reflects PDAC-associated metabolic changes and may contain candidate diagnostic biomarkers. Metabolites annotated in this study may have potential as novel markers, and further studies on unknown components could help advance PDAC diagnosis and treatment.

Aim: This study explores the evolving landscape of gastrectomy procedures in Japan, based on nationwide surveys conducted in 2014 and 2021. It highlights changes in surgical approaches, including a growing focus on minimally invasive and function‐preserving procedures, as well as the increasing consideration of postoperative quality of life (QOL).Methods: Two nationwide questionnaire surveys were conducted in 2014 and 2021, targeting members of the Japanese Society for Gastro‐surgical Pathophysiology. The surveys covered institutional characteristics, surgical case volumes, procedure preferences for early gastric cancer by tumor location, and emerging topics such as robot‐assisted surgery and sentinel node navigation surgery. Statistical analysis included Fisher's exact test and residual analysis for changes in procedure selection over time.Results: The results indicate a marked shift toward laparoscopic and robot‐assisted gastrectomy, alongside a rise in function‐preserving procedures, particularly proximal gastrectomy and small remnant distal gastrectomy. However, procedures like pylorus‐preserving gastrectomy and vagus nerve preservation, and total gastrectomy with jejunal pouch reconstruction remain underutilized due to concerns regarding unclear benefits, technical complexity, and oncological safety.Conclusion: This study underscores advancements in minimally invasive and function‐preserving gastrectomy procedures in Japan but emphasizes the need for more robust clinical evidence to support the broader adoption of certain procedures. Future research, guided by emerging evaluation tools, is crucial for optimizing surgical outcomes and enhancing QOL for gastric cancer patients.

INTRODUCTION: The prevalence of obesity has increased markedly across the globe over the past several decades. In parallel, the number of metabolic surgeries has risen sharply in recent years, resulting in a growing incidence of concomitant surgical procedures. Obese individuals have an elevated risk of malignancy, partly due to the chronic inflammation associated with excess adipose tissue. A key clinical question arises: How should surgeons manage unexpected pathology identified during the preoperative evaluation of patients with morbid obesity?CASE PRESENTATION: A morbidly obese male patient with a body mass index of 50 underwent evaluation for laparoscopic sleeve gastrectomy (LSG). Preoperative CT and PET-CT revealed a 25-mm retroperitoneal mass adjacent to the left gastric artery. Given the elevated risk of malignancy in obese individuals, it was essential to rule out a malignant process before proceeding with LSG. Thus, we adopted a surgical strategy in which LSG would be performed only if the intraoperative frozen section confirmed the lesion to be benign. The retroperitoneal mass was resected laparoscopically and identified as a benign schwannoma on the intraoperative frozen section, allowing us to proceed with LSG as planned. Retroperitoneal schwannomas are rare and often difficult to diagnose preoperatively, which supports the rationale behind our surgical strategy. To our knowledge, this is the first reported case of concomitant LSG performed following the laparoscopic complete excision of a retroperitoneal schwannoma.CONCLUSIONS: Concomitant procedures performed alongside metabolic surgery may be a viable approach to reduce the overall surgical burden on patients. Given the increased risk of malignancy in morbidly obese individuals, a thorough preoperative evaluation for concomitant malignancies should be considered before bariatric surgery. When an unexpected abdominal pathology is identified on preoperative imaging in obese patients, the intraoperative frozen section analysis of the resected specimen can be a valuable tool to guide surgical decision-making regarding concomitant bariatric surgery.

Open surgery may no longer be a control arm of minimally invasive surgery for gastric cancer

We investigated the tumor immune response in gastric cancer patients receiving third-line nivolumab monotherapy to identify immune-related biomarkers for better patient selection. Nineteen patients (10 males, median age 67 years) who received nivolumab as a third- or later-line therapy were enrolled. We analyzed the tumor immune response in durable clinical benefit (DCB) and non-DCB patients. Pre-treatment and early-on-treatment tumor transcriptomes were examined, and gene expression profiles, immunograms, and T cell receptor (TCR) repertoire were analyzed. DCB was observed in 15.8% of patients, with comparable secondary endpoints (ORR; objective response rate, OS; overall survival, PFS; progression-free survival) to previous trials. The immunograms of individual subjects displayed no significant changes before or early in the treatment, except for the regulatory T cell (Treg) score. Moreover, there were no consistent alterations observed among cases experiencing DCB. The intratumoral immune response was suppressed by previous treatments in most third- or later-line nivolumab recipients. TCR repertoire analysis revealed newly emerged clonotypes in early-on-treatment tumors, but clonal replacement did not impact efficacy. High T cell/Treg ratios and a low UV-radiation-response gene signature were linked to DCB and treatment response. This study emphasizes the tumor immune response’s importance in nivolumab efficacy for gastric cancer. High T cell/Treg ratios and specific gene expression signatures show promise as potential biomarkers for treatment response. The tumor-infiltrating immune response was compromised by prior treatments in third-line therapy, implying that, to enhance immunotherapeutic outcomes, commencing treatment at an earlier stage might be preferable. Larger cohort validation is crucial to optimize immune-checkpoint inhibitors in gastric cancer treatment.

Background: We investigated the tumor immune response in gastric cancer patients receiving third line nivolumab monotherapy to identify immune-related biomarkers for better patient se-lection. Methods: Nineteen patients (10 males, median age 67 years) who received nivolumab as a third or later line therapy were enrolled. We analyzed the tumor immune response in durable clinical benefit (DCB) and non-DCB patients. Pre-treatment and early-on-treatment tumor transcriptomes were examined, and gene expression profiles, immunograms, and T cell receptor (TCR) repertoire were analyzed. Results: DCB was observed in 15.8% of patients, with comparable secondary endpoints (ORR, OS, PFS) to previous trials. Individual immunograms showed no significant changes before and ear-ly-on-treatment, nor consistent alterations among DCB cases. The intratumoral immune response was suppressed by previous treatments in most third or later line nivolumab recipients. TCR repertoire analysis revealed newly emerged clonotypes in on-treatment tumors, but clonal re-placement did not impact efficacy. High T cells/Tregs ratios and a low UV radiation response gene signature were linked to DCB and treatment response. Conclusions: This study emphasizes the tumor immune response's importance in nivolumab ef-ficacy for gastric cancer. High T cells/Tregs ratios and specific gene expression signatures show promise as potential biomarkers for treatment response. Larger cohort validation is crucial to optimize immune checkpoint inhibitors in gastric cancer treatment.

Background: The systemic inflammatory response following surgery as well as that of malignant disease itself is associated with a hypercoagulable state, and thromboprophylaxis is thus recommended during postoperative management of cancer patients. However, limited information is available on the prevalence of preoperative deep vein thrombosis (DVT) and its risk factors in surgical candidates, especially those receiving operations for benign diseases.Methods: This is a retrospective observational study with data of all patients scheduled for elective general surgery between January 2011 and September 2020, undergoing lower extremity venous ultrasonography as preoperative screening for DVT. The prevalence of preoperative asymptomatic DVT was estimated and its associations with clinical variables were evaluated.Results: Among 1512 patients included in the study, 161 (10.6%) had asymptomatic DVT before surgery. DVT prevalence was 13.7% in patients with malignant disease, while it was 8.6% in those with benign disease. The site of the thrombus was distal type in 141 (87.6%) patients, most commonly in the soleal vein. Advanced age (>70 years), female sex, and decreased hemoglobin level were significantly associated with preoperative asymptomatic DVT by multivariate analysis. The odds ratio for advanced age was the highest and rose as age increased. Malignant disease was not an independent risk factor for preoperative DVT.Conclusion: This study showed the prevalence of asymptomatic DVT to be equal in patients with and without malignant disease undergoing elective general surgery. Preoperative DVT assessment is necessary regardless of the disease indicated for surgery, especially in patients with the risk factors identified in this study.

Fujisaki M, et al. J Gastric Cancer. 2022 Jul;22(3):235-247. https://doi.org/10.5230/jgc.2022.22.e23