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Background The mechanisms by which neutrophils acquire pro-tumor properties remain poorly understood. In pancreatic cancer, cancer-associated fibroblasts (CAFs) may interact with neutrophils, directing them to promote tumor progression. Methods To validate the association between CAFs and neutrophils, the localization of neutrophils was examined in clinically resected pancreatic cancer specimens. CAFs were produced by culturing in cancer-conditioned media, and the effects of these CAFs on neutrophils were examined. In vitro migration and invasion assays assess the effect of CAF-activated neutrophils on cancer cells. The factors secreted by the activated neutrophils were also explored. Finally, pirfenidone (PFD) was tested to determine whether it could suppress the pro-tumor functions of activated neutrophils. Results In pancreatic cancer specimens, neutrophils tended to co-localize with IL-6-positive CAFs. Neutrophils co-cultured with CAFs increased migratory capacity and prolonged life span. CAF-affected neutrophils enhance the migratory and invasive activities of pancreatic cancer cells. IL-8 is the most upregulated cytokine secreted by the neutrophils. PFD suppresses IL-8 secretion from CAF-stimulated neutrophils and mitigates the malignant traits of pancreatic cancer cells. Conclusion CAFs activate neutrophils and enhance the malignant phenotype of pancreatic cancer. The interactions between cancer cells, CAFs, and neutrophils can be disrupted by PFD, highlighting a potential therapeutic approach.

Background Internationally, evidence supporting robotic liver resection (RLR) has gradually increased in recent years. However, a standardized protocol for RLR remains lacking. This study describes a surgical protocol and the initial outcomes of RLR in a high-volume center for robotic hepatopancreatobiliary surgery in Japan. Methods Patients were placed in the reverse Trendelenburg position, with a supine position for anterolateral tumors and left lateral position for posterosuperior tumors. Our standard RLR protocol involved a two-surgeon technique. Liver parenchymal transection was performed by an assistant using the clamp crush technique with a console, with or without a laparoscopic Cavitron ultrasonic surgical aspirator (CUSA). Surgical techniques, including the tips, tricks, and pitfalls of RLR, are also demonstrated. Results We performed 113 RLR at our institution for common primary diseases, including hepatocellular carcinoma ( n  = 52, 46.0%) and metastatic tumors ( n  = 48, 42.5%) between July 2022 and December 2024. The median operative time and estimated blood loss were 156 min (interquartile range [IQR], 121–209 min) and 20 mL (IQR, 0–100 mL), respectively. During liver parenchymal transection, a laparoscopic CUSA was used in 59 patients (52.2%), and a water-jet scalpel was used in 12 patients (10.6%). The incidence of mortality, major complications, and bile leakage was 0%, 6.2%, and 2.7%, respectively. The median hospital stay was 7 days (IQR, 6–9 days). Conclusions We successfully introduced an RLR program using the two-surgeon technique. Safe implementation of RLR can be achieved upon completion of the training program and thorough understanding of the surgical protocols.

Background/Objectives: Although neoadjuvant chemotherapy (NAC) is not universally recommended for resectable pancreatic ductal adenocarcinoma (PDAC), NAC with gemcitabine plus S-1 (NAC-GS) has become a commonly used regimen for resectable PDAC in Japan. Furthermore, the impact of achieving textbook outcomes (TO) in patients receiving NAC-GS remains unclear. Methods: This retrospective study included 265 patients who were diagnosed with resectable PDAC at our institution between January 2009 and December 2023. Patients were categorized into two groups: the NAC-GS group (n = 81; 2019–2023) and the upfront surgery (UFS) group (n = 164; 2009–2018). After comparing the clinical outcomes between groups, multivariate analyses for survival were performed. Additionally, outcomes stratified by the achievement of the modified TO were analyzed in the NAC-GS group. Results: The completion rate of NAC-GS was 90.1%. Patients in the NAC-GS group exhibited significantly longer survival than those in the UFS group (2-year recurrence-free survival: 61.4% vs. 37.9%, p < 0.01; 2-year overall survival: 83.2% vs. 61.2%, p < 0.01). Multivariate analyses identified lymph node metastasis, NAC-GS induction, and completion of adjuvant chemotherapy as factors significantly associated with improved survival. Moreover, among patients who received NAC-GS, those who achieved modified TO demonstrated significantly longer survival than those who did not. Conclusions: This study demonstrated the clinical efficacy of NAC-GS in patients with resectable PDAC. Induction of NAC-GS was significantly associated with improved long-term outcomes. In multidisciplinary treatment strategies for PDAC, achieving a modified TO may lead to improved survival of patients undergoing NAC-GS.

The optimal extent of lymph node dissection for ampullary carcinoma is controversial. The aim of this study was to investigate the efficacy of lymph node dissection for ampullary carcinoma. Between 2000 and 2020, a total of 75 patients undergoing radical resection for ampullary carcinoma were included. The efficacy index (EI) was calculated by multiplication of the frequency of lymph node metastasis (LNM) at the station and the 5-year survival rate of patients with metastasis at the station. Out of 75 patients, 14 had LNM. The EI for the peri-pancreatic head (station 13 and 17) and superior mesenteric artery (station 14) lymph node were 4.4 and 3.5, respectively. Whereas the peri-gastric (station 5 and 6), common hepatic artery (station 8), and liver hilum (station 12) lymph node stations had zero EI. Although the number of patients with the station 16 dissected was small (9%), the para-aortic (station 16) lymph nodes had the highest EI of 14.3 despite being distant lymph nodes. We identified the distribution of LNM and survival benefit of lymph node dissection for ampullary carcinoma. Our results suggest that the optimal extent of lymph node dissection for ampullary carcinoma could be reconsidered.

Dendritic cells (DCs) transduced with replication-deficient, wild-type human p53-expressing adenovirus Ad-p53 (Ad-p53 DCs) induce p53-targeting cytotoxic T lymphocytes (CTLs). However, the antitumor efficacy of Ad-p53 DCs is diminished by weak p53 immunogenicity in tumor cells and poor immune responses. We developed a p53-armed oncolytic adenovirus, OBP-702, to induce tumor-specific p53 expression and antitumor immune response, suggesting a role for OBP-702 in enhancing the antitumor efficacy of Ad-p53 DCs. The combined effect of Ad-p53 DCs and OBP-702 was investigated using murine colon cancer (CC) tumor models. Ad-p53 DCs were obtained by stimulating bone marrow-derived cells with granulocyte-macrophage colony-stimulating factor, interleukin-4, and Ad-p53. Subcutaneous tumor models of CT26 (p53 wild-type) and MC38 (p53 mutant-type) murine CC cell lines were used to evaluate the therapeutic potential of combination therapy in the terms of tumor growth, abscopal effect, antitumor immune response, and presentation of p53 peptides in tumor cells. Combination therapy with Ad-p53 DCs and OBP-702 significantly suppressed the growth of p53-intact CT26 tumors at treated and untreated sites by inducing tumor-infiltration of CD8+ CTLs and CD11c+ DCs. OBP-702-infected tumor cells presented human p53 epitopes in the context of major histocompatibility complex molecules, which were recognized by CTLs induced by Ad-p53 DCs. Combination therapy significantly suppressed the growth of p53-mutant MC38 tumors by activating the antitumor immune response. Our results suggest that OBP-702-mediated presentation of p53 epitopes on tumor cells enhances the antitumor efficacy of Ad-p53 DCs against murine CC tumors by attracting p53-targeting CTLs.

Background Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate among all cancers; hence, multidisciplinary treatment is essential for patients with PDAC. Although the resectability status, tumour marker, KRAS circulating tumour DNA (mut KRAS -ctDNA) mutations, and GATA binding 6 (GATA6) expression status are promising prognostic biomarkers, their effective integration before and after surgery remains unclear. Methods In this retrospective cohort study, patients with PDAC who had undergone radical resection were enrolled, and pre- and postoperative independent factors associated with poor prognosis were identified using Cox hazard modelling. Risk stratification systems were developed using the identified prognostic factors and investigated for the ability to predict prognosis. Results A total of 91 patients with PDAC were included (median follow-up duration, 28 months). Borderline resectable or locally advanced cancer at diagnosis, elevated carbohydrate antigen 19–9 (CA19-9) level, and mut KRAS -ctDNA-positive status were identified as independent preoperative factors associated with poor prognosis. The postoperative factors significantly associated with shorter overall survival were low GATA6 expression, elevated CA19-9 level, and mut KRAS -ctDNA-positive status. Finally, the preoperative and postoperative risk scoring systems developed using Cox modelling hazard ratio values could significantly stratify prognosis after curative resection for PDAC. Conclusion A risk stratification system based on liquid biopsy, specialised for each phase (pre- and post-surgery), has been proven to be a useful, simple, and practical prognostic prediction clinical tool to determine the optimal multidisciplinary treatment protocol for PDAC.

Background There are several reports on the safety and feasibility of pancreatoduodenectomy (PD) without reconstruction of the small remnant pancreas. However, a few studies have explored central pancreatectomy (CP) for non-reconstructed small remnant pancreases after PD. This study presents a case of CP without pancreatic reconstruction after PD. Case presentation A 58-year-old man with cerebral palsy underwent PD for distal cholangiocarcinoma. Three years postoperatively, a 12-mm tumor was detected in the remnant pancreatic body and diagnosed as a pancreatic neuroendocrine neoplasm. Surgical resection was performed, because the tumor was enlarged and chemotherapy resistant. The afferent loop with pancreatojejunostomy anastomosis was dissected, and CP, including pancreatojejunostomy anastomosis, was performed. Given the remnant pancreas was hard and atrophic, the pancreatic tail was transected using a stapler without reconstructing the small remnant pancreas. The patient experienced no postoperative complications including postoperative pancreatic fistula, and the endocrine function of the pancreas was preserved. Conclusions We present a case of remnant pancreatic CP that did not require reconstruction after PD. Preservation of the small remnant pancreas without reconstruction during CP may be feasible to maintain endocrine function in select patients after PD.

Induced pluripotent stem (iPS) cells are generated from mouse and human somatic cells by the forced expression of defined transcription factors. Although most somatic cells are capable of acquiring pluripotency with minimal gene transduction, the poor efficiency of cell reprogramming and the uneven quality of iPS cells are still important problems. In particular, the choice of cell type most suitable for inducing high-quality iPS cells remains unclear. Here, we generated iPS cells from PDGFRα+ Sca-1+ (PαS) adult mouse mesenchymal stem cells (MSCs) and PDGFRα⁻ Sca-1⁻ osteo-progenitors (OP cells), and compared the induction efficiency and quality of individual iPS clones. MSCs had a higher reprogramming efficiency compared with OP cells and Tail Tip Fibroblasts (TTFs). The iPS cells induced from MSCs by Oct3/4, Sox2, and Klf4 appeared to be the closest equivalent to ES cells by DNA microarray gene profile and germline-transmission efficiency. Our findings suggest that a purified source of undifferentiated cells from adult tissue can produce high-quality iPS cells. In this context, prospectively enriched MSCs are a promising candidate for the efficient generation of high-quality iPS cells.

An energy-efficient building ventilation system is presented that integrates semi-transparent organic photovoltaic (OPV) technology and solar chimney technology. It achieved a wind velocity of 0.25 m/s and electric power generation of about 1.03 W at an artificial light intensity of 320 W/m2, which corresponds to cloudy weather. These results support the basic study of systems combining ventilation and power generation. The integration of solar chimney ventilation with OPV power generation could be a promising system for energy savings in the future. The proposed integration could contribute to the generation of sustainable and renewable energy.

By recalling gustatory memories, it is possible to generate vivid gustatory perceptions in the absence of gustatory inputs. This gustatory image influences our gustatory processing. However, the mechanism of the “top-down” modulation of gustatory perception in the human is still unclear. Our findings propose a new perspective on the neural basis of gustatory processing. Although gustatory imagery and gustatory perception shared common parts of neural substrates, there was an asymmetrical topography of activation in the insula: the left insula was predominantly activated by gustatory imagery tasks. In addition, the middle and superior frontal gyri were not activated by gustatory perception but they participated in the generation of gustatory hallucinations. These regions in the frontal cortex may mediate the “top-down” control of retrieving gustatory information from the storage of long-term memories.