Pancreatectomy in patients with HD

Background : Several reports have shown the high mortality rate of pancreatic resection in patients with hemodialysis (HD), however, its long-term outcome remains unclear. In this study, we examined cases of pancreatic resection in patients with HD and conducted a literature review. Methods : Four patients with HD who underwent pancreatic resection from 2004 to 2019 were enrolled. To compare the clinicopathological variables of HD and non-HD patients, 161 non-HD patients who had undergone surgical resection for pancreatic cancer were enrolled. Results : Among four cases of pancreatic resection with HD, three cases were malignant diseases. All patients with HD had some co-morbidities (100% in HD group, 45.3% in the non-HD group) and postoperative complications (100% in the HD group, vs 46.6% in the non-HD group). Although one patient had severe postoperative complications and length of postoperative hospital stay was longer, the 30- and 90-day mortality rates were both 0% in patients with HD. However, three cases in the HD group (75%) died approximately 6 months after surgery, including one cancer-related death. Conclusions : Pancreatic surgery in patients with HD should be carefully indicated, especially pancreaticoduodenectomy or total pancreatectomy, because of the poor prognosis induced by non-cancer-related causes of death

The Fragility of Cryopreserved Insulin-producing Cells Differentiated from Adipose-tissue-derived Stem Cells

The aim of our study is to determine whether insulin-producing cells (IPCs) differentiated from adipose-tissue-derived stem cells (ADSCs) can be cryopreserved. Human ADSCs were differentiated into IPCs using our two-step protocol encompassing a three-dimensional culture and xenoantigen-free method. Thereafter, IPCs were frozen using three different methods. First, IPCs were immediately frozen at −80°C (−80°C group). Second, IPCs were initially placed into a Bicell freezing container before freezing at −80°C (BICELL group). Third, a vitrification method for oocytes and embryos was used (CRYOTOP group). Cell counting kit-8 (CCK-8) assay showed that cell viability was decreased in all groups after cryopreservation (P < 0.01). Corroboratively, the amount of adenosine triphosphate was markedly decreased after cryopreservation in all groups (P < 0.01). Immunofluorescence staining showed a reduced positive staining area for insulin in all cryopreservation groups. Furthermore, 4′,6-diamidino-2-phenylindole and merged immunofluorescence images showed that cryopreserved cells appeared to be randomly reduced in the −80°C group and CRYOTOP group, while only the central region was visibly reduced in the BICELL group. Using immunohistochemical staining, IPCs after cryopreservation were shown to be positive for cleaved caspase-3 antibody in all groups. Finally, insulin secretion following glucose stimulation was significantly reduced in IPCs from all groups after cryopreservation (P < 0.01). In conclusion, IPCs may be too fragile for cryopreservation with accomplished methods and further investigations for a suitable preservation method are required

Fibrinogen–platelet ratio and pancreatic cancer

Background : Several prognostic factors were reported in pancreatic cancer. The fibrinogen–platelet ratio (FPR) was reported as a prognostic factor of resectable gastric cancer. In this report, the FPR was evaluated in patients with resectable pancreatic cancer. Methods : Between 2004 and 2019, 163 patients with curative resection for pancreatic cancer were enrolled. Cases of non-curative resection were excluded. The FPR was calculated using the preoperative plasma fibrinogen and the platelet counts and the cut-off value was determined by receiver operating characteristic (ROC) curve analysis. The patients were divided into high and low FPR groups according to this cut-off value. Results : The cut-off value of FPR was 25.2. Among age, sex, body mass index (BMI), and surgical factors including surgery type, volume of blood loss and surgery time, there was no significant difference between the two groups. Patients in the low FPR group had significantly better overall survival (OS) and relapse-free survival (RFS) compared with the high FPR group (P 300 U / ml, and receipt of adjuvant chemotherapy were independent risk factors for OS and DFS. Conclusions : The FPR might be a prognostic factor for patients with resectable pancreatic cancer

CRP–albumin ratio and pancreatic cancer

Background : The C-reactive protein (CRP)–albumin ratio (CAR) was reported as a prognostic factor of resectable hepatocellular carcinoma. The aim of this study was to analyse the significance of CAR in resectable pancreatic cancer. Patients and Methods : 163 patients with curative resection for pancreatic cancer were enrolled in this retrospective study. Cases of non-curative resection were excluded. The CAR was calculated with the preoperative plasma CRP and albumin values, with a cut-off value of 0.06, as calculated in a previous report. Results : Patients in the low CAR group had significantly better overall survival (OS) and disease-free survival (DFS) compared with the high CAR group (P 300 U / ml and receipt of adjuvant chemotherapy were independent risk factors for OS and DFS. High CAR was significantly associated with advanced T stage. Conclusion : The CAR might be a prognostic factor for patients with resectable pancreatic cancer

Impact of using a perioperative artificial endocrine pancreas in pancreatic resection

Aim: Pancreatectomy causes both hyperglycemia, secondary to surgical stress, and pancreatic diabetes, which leads to difficult-to-control postoperative blood glucose levels. We investigated whether using an artificial pancreas perioperatively to provide appropriate blood glucose control could reduce postoperative complications following pancreatectomy. Methods: We retrospectively enrolled 52 patients who underwent pancreatectomy at Tokushima University Hospital from 2015 to 2019. The most recent 26/52 patients received perioperative blood glucose control using an artificial pancreas. Postoperative blood glucose control with manual insulin injections based on a sliding scale was performed in the earlier 26 patients (controls). We compared surgical outcomes between the artificial pancreas group and the control group. Results: There was no significant difference in patients' white blood cell or neutrophil counts, prognostic nutritional index, neutrophil-lymphocyte ratio, and C-reactive protein-to-albumin ratio on postoperative day 1; however, lymphocyte counts were higher in the artificial pancreas group. The number of serious complications of Clavien-Dindo grade >IIIa was significantly lower in the artificial pancreas group (P < .05). Conclusions: Using an artificial pancreas for perioperative blood glucose control in patients undergoing pancreatectomy decreased the number of serious complications through proper management of blood glucose levels without hypoglycemia, and may influence peripheral lymphocytes

Nrf2 signaling in sorafenib-resistant HCC

Background and aim As a multiple tyrosine kinase inhibitor, sorafenib is widely used to treat hepatocellular carcinoma (HCC), but patients frequently face resistance problems. Because the mechanism controlling sorafenib-resistance is not well understood, this study focused on the connection between tumor characteristics and the Nrf2 signaling pathway in a sorafenib-resistant HCC cell line. Methods A sorafenib-resistant HCC cell line (Huh7) was developed by increasing the dose of sorafenib in the culture medium until the target concentration was reached. Cell morphology, migration/invasion rates, and expression of stemness-related and ATP-binding cassette (ABC) transporter genes were compared between sorafenib-resistant Huh7 cells and parental Huh7 cells. Next, a small interfering RNA was used to knock down Nrf2 expression in sorafenib-resistant Huh7 cells, after which cell viability, stemness, migration, and ABC transporter gene expression were examined again. Results Proliferation, migration, and invasion rates of sorafenib-resistant Huh7 cells were significantly increased relative to the parental cells with or without sorafenib added to the medium. The expression levels of stemness markers and ABC transporter genes were up-regulated in sorafenib-resistant cells. After Nrf2 was knocked down in sorafenib-resistant cells, cell migration and invasion rates were reduced, and expression levels of stemness markers and ABC transporter genes were reduced. Conclusion Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant HCC cells

Significance of frailty in prognosis after surgery in patients with pancreatic ductal adenocarcinoma

Background: Frailty is an important consideration for older patients undergoing surgery. We aimed to investigate whether frailty could be a prognostic factor in patients with pancreatic ductal adenocarcinoma who underwent pancreatic resection. Methods: One hundred and twenty patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma were enrolled. Frailty was defined as a clinical frailty scale score ≥4. Patients were divided into frailty (n = 29) and non-frailty (n=91) groups, and clinicopathological factors were compared between the two groups. Results: The frailty group showed an older age, lower serum albumin concentration, lower prognostic nutritional index, larger tumor diameter, and higher rate of lymph node metastasis than the non-frailty group (p < 0.05). Neutrophil–lymphocyte ratio and modified Glasgow prognostic score tended to be higher in the frailty group. Cancer-specific and disease-free survival rates were significantly poor in the frailty group (p < 0.05). With a multivariate analysis, frailty was an independent prognostic factor of cancer-specific survival. Conclusions: Frailty can predict the prognosis of patients with pancreatic ductal adenocarcinoma who undergo pancreatic resection

Newly Generated 3D Schwann-Like Cell Spheroids From Human Adipose-Derived Stem Cells Using a Modified Protocol

Peripheral nerve injury (PNI) is a relatively frequent type of trauma that results in the suffering of many patients worldwide every year. Schwann cells (SCs) are expected to be applied in cell therapy because of their ability to promote peripheral nerve regeneration. However, the lack of clinically renewable sources of SCs hinders the application of SC-based therapies. Adipose-derived stem cells (ADSCs) have generated great interest in recent years because of their multipotency and ease of harvest, and they have already been verified to differentiate into Schwann-like cells (SLCs) in vitro. However, the efficiency of differentiation and the functions of SLCs remain unsatisfactory. We newly generated three-dimensional (3D) SLC spheroids from ADSCs using a modified protocol with human recombinant peptide (RCP) petaloid μ-piece. Morphological analysis, gene expression analysis by qRT-PCR, ELISA measurement of the secretion capabilities of neurotrophic factors, and neurite formation assay were performed to evaluate the functions of these 3D SLCs in vitro. Motor function recovery was measured in a sciatic nerve injury mouse model to analyze the nerve regeneration-promoting effect of 3D SLCs in vivo. The differentiation efficiency and the secretion of neurotrophic factors were enhanced in 3D SLCs compared with conventional SLCs. 3D SLCs could more effectively promote neurite growth and longer neurite extension in a neuron-like SH-SY5Y model. Additionally, 3D SLCs had a better therapeutic effect on nerve regeneration after transplantation into the sciatic nerve injury mouse model. These findings demonstrated that the potential of ADSC-derived SLCs to promote nerve regeneration could be significantly increased using our modified differentiation protocol and by assembling cells into a 3D sphere conformation. Therefore, these cells have great potential and can be used in the clinical treatment of PNI

The interaction between cancer associated fibroblasts and tumor associated macrophages via the osteopontin pathway in the tumor microenvironment of hepatocellular carcinoma

Background: Cancer-tumor associated macrophage (TAM)-cancer associated fibroblast (CAF) interactions are an important factor in the tumor microenvironment of hepatocellular carcinoma. Materials and Methods: Hepatic stellate cells (HSCs) were cultured with cancer cell-conditioned medium (Ca.-CM), TAM-CM and CAF-CM, and the expression of CAF markers were evaluated by RT-PCR. Whether HSCs cultured with Ca.-CM, TAM-CM and CAF-CM contributed to the enhanced malignancy of cancer cells was examined using proliferation, invasion and migration assays. Furthermore, the differences between these three types of CM were evaluated using cytokine arrays. Results: HSCs cultured with Ca.-CM, TAM-CM and CAF-CM showed significantly increased mRNA expression of αSMA, FAP and IL-6. All HSCs cultured with each CM exhibited significantly increased proliferation, invasion and migration of cancer cells. The osteopontin concentration was significantly higher in HSCs cultured with TAM-CM than the other CAF-CMs. Osteopontin inhibition significantly reduced osteopontin secretion from HSCs cultured with TAM-CM and suppressed the proliferation and invasion of cancer cells enhanced by HSCs cultured with TAM-CM. Conclusions: We observed enhanced osteopontin secretion from TAMs, and this increased osteopontin further promoted osteopontin secretion from HSCs cultured with TAM-CM, leading to increased malignancy. For the first time, we demonstrated the importance of cancer-TAM-CAF interactions via osteopontin in hepatocellular carcinoma

Effect of TU-100 on Peyer's patches in a bacterial translocation rat model

Background: Daikenchuto (TU-100), a Japanese herbal medicine, is widely used for various gastrointestinal diseases. We have previously reported that TU-100 suppresses CPT-11-induced bacterial translocation (BT) by maintaining the diversity of the microbiome. In this study we show that TU-100 modulates the immune response during BT by inducing PD-1 expression in Peyer's patches. Methods: Eighteen male Wistar rats were divided into four groups: a control group; a control + TU-100 group, given TU-100 1000 mg/kg orally for 5 d; a BT group, given CPT-11 250 mg/kg intra-peritoneal for 2 d; and a TU-100 group, given TU-100 1000 mg/kg orally for 5 d with CPT-11 250 mg/kg intra-peritoneal on days 4 and 5. Results: The size of Peyer's patch was significantly bigger in the BT group compared to the control group (9.0 × 104 µm2 vs 29.4 × 104 µm2, P < .05), but improved in the TU-100 group (15.4 × 104 µm2, P < .005). TU-100 significantly induced PD-1 expression in Peyer's patch compared to the control group and the BT group (control vs BT vs TU-100 = 4.3 ± 4.9 vs 5.1 ± 10.3 vs 17.9 ± 17.8). The CD4+ cells were increased in the BT group (P < .05) compared to the control group but decreased in the TU-100 group. The Foxp3+ cells were increased in the BT group compared to the control group (P < .05), and further increased in the TU-100 group compared to the BT group. CPT-11 significantly increased TLR4, NF-κβ, TNF-α mRNA expressions in the BT group. TU-100 cotreatment significantly reversed these mRNA expressions. Conclusion: TU-100 may have a protective effect against BT through PD-1 expression in Peyer's patch