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In this study, we aimed to analyse human cancer cell–platelet interactions in functional cell analyses and explore the molecular mechanisms behind tumour progression. Various functional analyses of gastric cancer (GC) cells were performed after direct/indirect co-incubation with platelets derived from GC patients. Further detailed expression and signalling analyses were performed after co-culture with direct and indirect GC cells–platelet contact. Malignant behaviours of cancer cells, such as proliferation, migration, invasion and adhesion, were significantly enhanced after direct co-incubation with platelets. Microarray analyses demonstrated changes in multiple genes, including epithelial–mesenchymal transition (EMT)-related genes. Among them, matrix metalloproteinase 9 was notably upregulated, which was validated by quantitative reverse transcription–polymerase chain reaction and western blot. Further, this change was only observed after direct co-incubation with platelets. This study demonstrated that platelets from GC patients promote malignant behaviours of GC cells through EMT-related signalling, especially by direct contact with tumour cells.

Background Each method of reconstruction after gastrectomy results in a change in the digestive and absorptive status. However, there are few reports on the changes in pancreatic exocrine function after gastrectomy. We conducted this study to investigate the dynamics of pancreatic exocrine function after gastrectomy according to the method of reconstruction performed. Methods The subjects of this study were 45 patients who underwent pancreatic exocrine function tests preoperatively and postoperatively, from among all patients who underwent gastrectomy for gastric cancer at our hospital between September, 2020 and March, 2022. We assessed pancreatic exocrine function using the Pancreatic Function Diagnostant (PFD) test. Result The mean preoperative PFD test result values for the distal gastrectomy (DG) Billroth I reconstruction (B–I) group and the DG Roux-en-Y reconstruction (R–Y) group were 62.6 and 67.3 ( p  = 0.36), respectively, and the mean postoperative PFD test result values for each group were 65.8 and 46.9 ( p  = 0.0094), respectively. A significant decrease in postoperative pancreatic function was observed in the DG R-Y group but not in the DG B–I group. The logistic regression analysis identified that age and the R–Y group were significantly correlated with a 10% decrease in the PFD value after gastrectomy. Conclusions Our study suggests that R–Y reconstruction may result in more impaired pancreatic exocrine function than B–I reconstruction.

BackgroundPancreatectomy is a highly invasive procedure with extensive intraoperative blood loss (IBL) and high risk of postoperative pancreatic fistula (POPF). We conducted an experimental and retrospective clinical study to determine whether the malignant behaviors of pancreatic cancer cells were enhanced by exposure to blood components in vitro and to evaluate the oncological significance of high IBL and POPF in pancreatic cancer.MethodsThis study included 107 patients undergoing radical pancreatectomy in the University of Yamanashi Hospital between 2011 and 2017, classified into high (n = 29) and low (n = 78) IBL groups. In vitro experiments included functional analyses of Panc-1 pancreatic cancer and normal mesothelial cells exposed to patient blood components, and clinical data were used to assess the contribution of IBL and POPF to patient outcomes.ResultsThe migration (p = 0.007), invasion (p < 0.001), and proliferation (p < 0.01) of Panc-1 cells were enhanced with platelet coculture. The ability of Panc-1 cells to adhere mesothelial cells was enhanced by plasma coincubation, especially in the presence of inflammation (p < 0.001). High IBL was associated with worse overall survival (p = 0.007) and increased locoregional recurrence (p = 0.003) in patients. POPF enhanced the negative prognostic significance of high IBL (p < 0.001 for overall survival, p = 0.001 for locoregional recurrence), indicating the oncological negative effects of high IBL and POPF.ConclusionsBlood components, especially platelets, and inflammation enhance the malignant behaviors of pancreatic cancer cells, potentially contributing to poor prognosis for pancreatic cancer patients.

•This study demonstrated the effects of sarcopenia in colorectal cancer recurrence.•In our cohort with colorectal cancer, preoperative sarcopenia was associated with prognosis.•Even in participants with preoperative sarcopenia, the prognosis improved in the sarcopenia-improved group at the time of recurrence.•Not only preoperative but also postoperative nutritional interventions are important in sarcopenia. Nutritional status significantly influences postoperative prognosis in gastrointestinal cancers. It has been evaluated using sarcopenia before treatments such as surgery and chemotherapy, despite constant changes in nutritional status. We consider that nutritional status at cancer recurrence is one of the important factors that affect treatment choice and intensity. This study evaluated the prognostic effects of improved postoperative nutritional status for people with colorectal cancer recurrence. We enrolled 209 participants with pathologically confirmed stage II or III colorectal cancer who underwent radical resection. Sarcopenia was diagnosed using the psoas muscle index obtained from analysis of three-dimensional computed tomographic images. We adopted the cutoff value that was proposed by Hamaguchi et al. (psoas muscle index < 6.36 cm2/m2 for men and < 3.92 cm2/m2 for women). Evaluation was performed before surgery and at the time of recurrence. Participants with preoperative sarcopenia who relapsed were divided into two groups at the time of recurrence: sarcopenia continuation and sarcopenia improvement. We compared the prognosis of the two groups and examined the effect of postoperative nutritional improvement. Among the 209 participants, 81 (38.8%) had preoperative sarcopenia; this group had significantly lower overall survival than those without sarcopenia (P = 0.028). Colorectal cancer recurred in 48 participants. Of those 46, sarcopenia was evaluated at the time of recurrence; 19 of those 46 had preoperative sarcopenia. Preoperative sarcopenia did not affect the cancer recurrence ratio (sarcopenia, 23.5%; non-sarcopenia, 21.3%; P = 0.893). The sarcopenia-improvement group had higher overall survival than the sarcopenia-continuation group (P = 0.042). Among participants with preoperative sarcopenia, the prognosis at the time of recurrence improved for the sarcopenia-improvement group compared to the sarcopenia-continuation group. In people with colorectal cancer and sarcopenia, nutritional management is important not only before but also after surgery.

Background Cancer-associated fibroblasts exhibit diversity and have several subtypes. The underlying relationship between the diversity of cancer-associated fibroblasts and their effect on gastric cancer progression remains unclear. In this study, mesenchymal stem cells were differentiated into cancer-associated fibroblasts with gastric cancer cell lines; clinical specimens were used to further investigate the impact of cancer-associated fibroblast diversity on cancer progression. Methods Nine gastric cancer cell lines (NUGC3, NUGC4, MKN7, MKN45, MKN74, FU97, OCUM1, NCI-N87, and KATOIII) were used to induce mesenchymal stem cell differentiation into cancer-associated fibroblasts. The cancer-associated fibroblasts were classified based on ACTA2 and PDPN expression. Cell function analysis was used to examine the impact of cancer-associated fibroblast subtypes on cancer cell phenotype. Tissue samples from 97gastric patients who underwent gastrectomy were used to examine the clinical significance of each subtype classified according to cancer-associated fibroblast expression. Results Co-culture of mesenchymal stem cells with nine gastric cancer cell lines revealed different subtypes of ACTA2 and PDPN expression in differentiated cancer-associated fibroblasts. Cancer-associated fibroblast subtypes with high ACTA2 plus PDPN expression levels significantly increased gastric cancer cell migration, invasion, and proliferation. The cancer-associated fibroblast subtype with ACTA2 plus PDPN expression was an independent prognostic factor along with lymph node metastasis for patients who had gastric cancer and were undergoing surgery. Conclusions Cancer-associated fibroblasts are educated by gastric cancer cells during the development of cancer-associated fibroblast diversity. Differentiated cancer-associated fibroblasts with distinct expression patterns could affect gastric cancer progression and enable prognostic stratification for gastric cancer.

Peritoneal metastasis is a lethal manifestation of gastric cancer, with poor prognosis and limited treatment options. A targeted drug delivery system minimizing systemic toxicity is urgently needed. Given that platelets form stable aggregates with gastric cancer cells, we explored their feasibility as a drug carrier. We engineered paclitaxel‐loaded platelets and assessed their antitumor efficacy using human gastric cancer cell lines. To evaluate therapeutic performance in vivo, a murine model of peritoneal metastasis was established with BALB/c‐Slc‐nu/nu mice. Paclitaxel was administered intraperitoneally at 25 mg/kg per week in both the free paclitaxel and paclitaxel‐loaded platelets groups, via injection every 7 days for a total of 8 times. Paclitaxel‐loaded platelets exhibited strong adhesion to gastric cancer cells, efficiently delivering paclitaxel intracellularly. Functional assays confirmed platelet activation capacity was preserved post drug loading. In vitro, paclitaxel‐loaded platelets significantly inhibited tumor cell viability (p < 0.001). In vivo, they markedly reduced systemic drug exposure (p < 0.047) and significantly improved antitumor efficacy and survival versus free paclitaxel (p < 0.001). Our findings highlight platelets as a novel drug delivery system for peritoneal metastasis in gastric cancer. Leveraging their tumor‐homing properties and biocompatibility, this approach enables targeted intraperitoneal chemotherapy, representing a promising strategy for this treatment‐refractory disease. Paclitaxel‐loaded platelets effectively target gastric cancer peritoneal metastasis, demonstrating enhanced antitumor efficacy, reduced systemic drug distribution, and improved survival, offering a promising novel treatment option.

PurposePostoperative pancreatic fistula (POPF) is one of the major complications in patients who undergo distal pancreatectomy (DP). Recently, dividing the pancreas by stapler is a commonly performed technique, however, POPF still occurs. Therefore, the purpose of this study was to investigate the risk factors for POPF after DP using a triple-row stapler.MethodsA total of 75 patients underwent DP using a triple-row stapler (Endo GIA™ Reloads with Tri-Staple™ Technology 60 mm; COVIDIEN, North Haven, CT, USA) at Yamanashi University from December 2012 to December 2016. The clinical risk factors for POPF after DP using a triple-row stapler were identified based on univariate and multivariate analyses.ResultsClinical POPF (ISGPF Grade B and C) was seen in 7 of 75 patients (9.3%). The body mass index (BMI) was significantly higher in the patients with POPF (26.8 ± 0.5 kg/m2) compared with the patients without POPF (21.4 ± 0.4 kg/m2; a cut-off value; 25.7 kg/m2). In addition, the patients with POPF were significantly younger than the patients without POPF (56.4 ± 5.6 vs 67.0 ± 1.5; a cut-off value was 57.0 years old).ConclusionsBMI and age were found to be significant risk factors for POPF after DP using a triple-row stapler.

BackgroundThe present study aimed to determine the ability of diagnosing malignancy and predicting malignant transformation in patients with IPMN using carcinoembryonic antigen (CEA) level in the pancreatic juice.MethodsWe enrolled patients with IPMN who underwent endoscopic retrograde pancreatography (ERP) between 2002 and 2018. We examined the ability of diagnosing malignancy in 63 patients who underwent surgery (surgical group). Furthermore, we examined the value of predicting malignant transformation in 52 patients who underwent follow-up for over 1 year after ERP (follow-up group).ResultsIn the surgical group, the overall sensitivity and specificity of CEA level (≥ 97 ng/ml) in the pancreatic juice for diagnosing malignancy were 45% and 100%, respectively. The specificity was excellent for all IPMN types; however, the sensitivity was highest in main duct type, followed by mixed type and branch duct type. In the follow-up group, malignant transformation was observed in four patients (7.7%) during the follow-up, and the median time until malignant transformation was 58 months. High CEA level in the pancreatic juice demonstrated a statistically significant difference in multivariate analysis and was found to be an independent predictor of malignant transformation (hazard ratio 17; P = 0.02). The cumulative malignant transformation rate was significantly higher in the high CEA group than that in the low CEA group (5-year cumulative malignant transformation rates, 69% vs. 0%, P < 0.001).ConclusionsCarcinoembryonic antigen level in the pancreatic juice is useful not only in diagnosing malignancy but also in predicting future malignant transformations in IPMN patients receiving follow-up.

Aim The prevalence of kyphosis is increasing with increasing life expectancy. One of the most notable gastrointestinal complications is gastroesophageal reflux disease (GERD) in patients with kyphosis. In this study, we investigated the association between kyphosis and the incidence of postoperative GERD in patients who underwent proximal gastrectomy (PG), a procedure with a particularly high risk of GERD. Methods In total, 54 consecutive patients who underwent PG between 2009 and 2023 met the inclusion criteria. The thoracic/lumbar angle ratio (T/L ratio) derived from sagittal computed tomography was performed to preoperatively assess kyphosis, defined as a T/L ratio ≥ 1.25. Results Fifteen patients (27.8%) had kyphosis. Overall, postoperative GERD occurred in seven patients (13.0%). Preoperative albumin levels were significantly lower in the Kyphosis group than in the Normal group (p = 0.03), whereas other clinical characteristics showed no significant differences between the two groups. The incidence of postoperative GERD was significantly higher in the Kyphosis group than in the Normal group (33.3% vs. 5.1%, p = 0.01). Postoperative reflux symptoms also were more frequently observed in the Kyphosis group than in the Normal group (60.0% vs. 16.0%, p = 0.13). Kyphosis was one of the independent predictive factors for postoperative GERD (Odds ratio, 18.7; 95% confidence interval, 1.46–240; p = 0.02) in the multivariate analysis. Conclusion Kyphosis was significantly associated with the occurrence of postoperative GERD in patients who underwent PG. Alternative preventive measures may be considered when patients with kyphosis undergo PG. This study examined the relationship between kyphosis and postoperative gastroesophageal reflux disease (GERD) after proximal gastrectomy using a kyphosis definition that is familiar to surgeons for preoperative assessment. Multivariate analysis revealed that kyphosis is an independent risk factor for GERD after proximal gastrectomy.