Prognostic Impact of Gastroduodenal Artery Involvement in Cancer of the Pancreatic Head.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) contacting major arteries such as the celiac, common hepatic, and superior mesenteric artery is linked to poor prognosis and classified as borderline resectable. Although PDAC involving the gastroduodenal artery (GDA) is considered resectable, the prognostic impact of GDA involvement remains unclear. Here we investigated the prognostic impact of GDA involvement in PDAC after resection. METHODS: This study included 105 patients with resectable PDAC or borderline resectable with portal vein involvement. Patients were divided into two groups: those with tumor-GDA contact ≤ 180° and those with GDA contact > 180°. We evaluated the prognostic impact of GDA involvement between these groups. RESULTS: Both recurrence-free and overall survival after the surgery were significantly poorer with GDA contact > 180° than ≤ 180°. The poorer prognosis with GDA contact > 180° was verified by multivariate analysis and propensity score matching analysis to match patient backgrounds between the groups. The frequency of postoperative distant metastasis was also significantly higher in patients with GDA contact > 180°. CONCLUSIONS: GDA involvement is an independent factor significantly associated with postoperative survival in PDAC, and the poorer prognosis with GDA involvement may be linked to the development of postoperative distant metastasis.

[A Case of Multidisciplinary Treatment for a Recurrent Gastrointestinal Stromal Tumor of the Stomach].

The standard treatment for unresectable or recurrent gastrointestinal stromal tumor(GIST)is tyrosine kinase inhibitor(TKI). It is reported that resection of metastatic lesions after TKI administration prolongs progression free survival, but its influence on overall survival is not clarified. We experienced a case of GIST with peritoneal dissemination for which TKI administration and 2 local resections were effective. The patient was a man in his 70's. We started chemotherapy with imatinib for GIST with peritoneal dissemination. However, it was discontinued due to the occurrence of interstitial pneumonia. Dissemination was evaluated as radically resectable on the images. After the interstitial pneumonia was alleviated, surgery was performed. Although sunitinib was introduced at 2 months postoperatively, recurrent peritoneal dissemination was detected at 32 months postoperatively, and treatment was then changed to regorafenib. Regorafenib treatment reduced the tumor size; however, Grade 3 albuminuria was detected 16 months after treatment initiation and, thus, this treatment was discontinued. Subsequently, the tumor enlarged again. Because there was only 1 recurrent lesion, we performed radical resection. Postoperatively, a reduced dose of regorafenib was re-administered. At present, 9 months after the re-surgery, the patient is alive without recurrence.

[A Case of Myeloid Sarcoma That Primarily Developed in the Spleen].

We report a case of myeloid sarcoma(MS)that primarily developed in the spleen. The patient was a 60s man with a chief complainant of low-grade fever following a dental implant. Although he underwent intensive antibiotic treatment, including levofloxacin, meropenem, and vancomycin, no significant decline in fever was observed. Abdominal contrast-enhanced CT revealed an LDA occupying the majority of his spleen, which was diagnosed as a splenic abscess. Although a CT-guided biopsy and drainage for the spleen were considered, a puncture of the spleen was not performed due to the substantial concern of bleeding. Subsequently, a splenectomy was performed and HE staining revealed mitosis of tumor cells and massive necrosis. Immunohistochemical analysis revealed that the tumor cells were positive for myeloperoxidase, CD43, CD45, and CD68. Finally, the splenic LDA was diagnosed as MS instead of a splenic abscess. He was treated with systemic chemotherapy. MS primarily develops in the spleen is quite rare: we found only 2 case reports of this disease. The prognosis of MS is poor due to the complications of AML. Accordingly, MS should be considered as a differential diagnosis for accurate diagnosis and treatment of splenic LDA.

Skeletal Myoblast Cells Enhance the Function of Transplanted Islets in Diabetic Mice.

Islet transplantation (ITx) is an established and safe alternative to pancreas transplantation for type 1 diabetes mellitus (T1DM) patients. However, most ITx recipients lose insulin independence by 3 years after ITx due to early graft loss, such that multiple donors are required to achieve insulin independence. In the present study, we investigated whether skeletal myoblast cells could be beneficial for promoting angiogenesis and maintaining the differentiated phenotypes of islets. In vitro experiments showed that the myoblast cells secreted angiogenesis-related cytokines (vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and stromal-derived factor-1α (SDF-1α)), contributed to maintenance of differentiated islet phenotypes, and enhanced islet cell insulin secretion capacity. To verify these findings in vivo, we transplanted islets alone or with myoblast cells under the kidney capsule of streptozotocin-induced diabetic mice. Compared with islets alone, the group bearing islets with myoblast cells had a significantly lower average blood glucose level. Histological examination revealed that transplants with islets plus myoblast cells were associated with a significantly larger insulin-positive area and significantly higher number of CD31-positive microvessels compared to islets alone. Furthermore, islets cotransplanted with myoblast cells showed JAK-STAT signaling activation. Our results suggest two possible mechanisms underlying enhancement of islet graft function with myoblast cells cotransplantation: "indirect effects" mediated by angiogenesis and "direct effects" of myoblast cells on islets via the JAK-STAT cascade. Overall, these findings suggest that skeletal myoblast cells enhance the function of transplanted islets, implying clinical potential for a novel ITx procedure involving myoblast cells for patients with diabetes.

High-mobility group box 1 fragment ameliorates chronic pancreatitis induced by caerulein in mice.

BACKGROUND: Chronic pancreatitis (CP) is a progressive disease characterized by pancreatic fibrosis for which effective treatment options are lacking. Mesenchymal stem cells (MSCs) have shown potential for fibrosis treatment but face limitations in clinical application. The high-mobility group box 1 (HMGB1) fragment mobilizes MSCs from bone marrow into the blood and has emerged as a promising therapeutic agent for tissue regeneration in various pathological conditions. The aim of this study was to investigate the potential therapeutic effects of systemic administration of the HMGB1 fragment in a mouse model of CP. METHODS: A caerulein-induced CP mouse model was used, and the HMGB1 fragment was administered by tail vein injection. Parameters such as body weight, pancreatic tissue damage, fibrosis, inflammatory cytokine expression, and collagen-related gene expression were evaluated using various assays, including immunohistochemistry, real-time PCR, serum analysis, and single-cell transcriptome analysis. And the migration of MSCs to the pancreas was evaluated using the parabiosis model. RESULTS: Administration of the HMGB1 fragment was associated with significant improvements in pancreatic tissue damage and fibrosis. It suppressed the expression of inflammatory cytokines and activated platelet-derived growth factor receptor-α+ MSCs, leading to their accumulation in the pancreas. The HMGB1 fragment also shifted gene expression patterns associated with pancreatic fibrosis toward those of the normal pancreas. Systemic administration of the HMGB1 fragment demonstrated therapeutic efficacy in attenuating pancreatic tissue damage and fibrosis in a CP mouse model. CONCLUSION: These findings highlight the potential of the HMGB1 fragment as a therapeutic target for the treatment of CP.

Clinical Impact of Ischemic Time of the Pancreas or Kidney Graft on Simultaneous Pancreas-Kidney Transplantation: A Single-Institution Study in Japan.

BACKGROUND: Total ischemic time (TIT) potentially affects graft survival in organ transplantation. However, in simultaneous pancreas-kidney (SPK) transplantation, the impact of TIT of the pancreas (P-TIT) and kidney graft (K-TIT) on posttransplant outcomes remains unclear. This study investigated the impact of P-TIT and K-TIT on postoperative outcomes in patients after SPK at our institution in Japan. PATIENTS AND METHODS: This study included 52 patients who underwent SPK at our hospital from April 2000 to March 2022. Of this patient group, the 52 patients were divided into a short P-TIT group (n = 25), long P-TIT group (n = 27), short K-TIT group (n = 42), and long K-TIT group (n = 10). Short- and long-term postoperative outcomes were compared between the groups. RESULTS: The long K-TIT group had a significantly higher rate of patients who did not urinate intraoperatively (50% vs 7%; P = .0007) and those requiring postoperative hemodialysis (80% vs 38%; P = .0169), as well as a significant longer duration of postoperative hemodialysis (97 ± 147 days vs 6 ± 9 days; P = .0016). These were not significantly different between the short and long P-TIT groups. Kidney or pancreas graft survival was not significantly different between the short and long P-TIT or K-TIT groups. CONCLUSIONS: Patients with prolonged K-TIT during SPK exhibited poor short-term outcomes, but no significant influence of K-TIT was identified on long-term outcomes. The P-TIT did not affect any significant outcomes. These results indicate that shortening K-TIT may improve short-term outcomes after SPK.

Efficacy of Autologous Skeletal Myoblast Cell Sheet Transplantation for Liver Regeneration in Liver Failure.

BACKGROUND: No effective therapies have yet been established for liver regeneration in liver failure. Autologous skeletal myoblast cell sheet transplantation has been proven to improve cardiac function in patients with heart failure, and one of the mechanisms has been reported to be a paracrine effect by various growth factors associated with liver regeneration. Therefore, the present study focused on the effect of myoblast cells on liver regeneration in vitro and in vivo. METHODS: We assessed the effect of myoblast cells on the cells comprising the liver in vitro in association with liver regeneration. In addition, we examined in vivo effect of skeletal myoblast cell sheet transplantation in C57/BL/6 mouse models of liver failure, such as liver fibrosis induced by thioacetamide and hepatectomy. RESULTS: In vitro, the myoblast cells exhibited a capacity to promote the proliferation of hepatic epithelial cells and the angiogenesis of liver sinusoidal endothelial cells, and suppress the activation of hepatic stellate cells. In vivo, sheet transplantation significantly suppressed liver fibrosis in the induced liver fibrosis model and accelerated liver regeneration in the hepatectomy model. CONCLUSIONS: Autologous skeletal myoblast cell sheet transplantation significantly improved the liver failure in the in vitro and in vivo models. Sheet transplantation is expected to have the potential to be a clinically therapeutic option for liver regeneration in liver failure.