Preemptive Bundle Therapy for Subclinical Pulmonary Hypertension After Liver Transplant.

OBJECTIVES: After liver transplant, veno-occlusive disease and infectious complications may result from subclinical pulmonary hypertension. In this retrospective study, we investigated whether our preemptive bundle therapy was effective for subclinical pulmonary hypertension and extrasinusoidal platelet aggregation after liver transplant. MATERIALS AND METHODS: After January 2014, nutrition therapy with glutamine, synbiotics, phosphodiesterase 3 inhibitors, prostaglandin E1, prostaglandin I2, closedloop artificial pancreas, and sivelestat has been used to reduce bacterialtranslocation, vascular endothelial cell damage, and extrasinusoidal platelet aggregation, which is administered as preemptive bundle therapy for all livertransplantrecipients. In this study, we evaluated the prognosis of 84 liver transplant recipients who underwent liver transplants through 2018. Subclinical pulmonary hypertension was evaluated in 49 adult liver transplant recipients with an evaluable main pulmonary artery trunk cross-sectional area using enhanced computed tomography in the acute phase after transplant, with 14 of these patients receiving preemptive bundle therapy. RESULTS: Subclinical pulmonary hypertension was reduced in the preemptive bundle therapy group (n = 14) compared with the nontherapy group (n = 35). The preemptive bundle therapy group showed more rapid recovery of platelet, prothrombin time, and bilirubin levels afterlivertransplant compared with the nontherapy group. The prognosis of patients in the preemptive bundle therapy group was significantly better than in the nontherapy group. Extrasinusoidal platelet aggregation was significantly lower in the preemptive bundle therapy group than in the nontherapy group. CONCLUSIONS: Preemptive bundle therapy reduced sinusoidal endothelial cell injury, extrasinusoidal platelet aggregation, and subclinical pulmonary hypertension after liver transplant, resulting in good posttransplant recovery.

Impact of Extravasated Platelet Activation and Podoplanin-positive Cancer-associated Fibroblasts in Pancreatic Cancer Stroma.

BACKGROUND/AIM: The aim of the study was to evaluate the status of extravasated platelet activation (EPA) surrounding podoplanin (PDPN)-positive cancer-associated fibroblasts (CAFs) in pancreatic cancer stroma by neoadjuvant chemotherapy. PATIENTS AND METHODS: A total of 74 patients were enrolled in this study. We investigated CD42b and PDPN expression in the groups of untreated, gemcitabine (GEM) alone, GEM plus S-1 (GS) and GEM plus nab-paclitaxel (GnP). RESULTS: CD42b expression in surrounding CAFs was observed in 58% patients. CD42b expression was significantly correlated with PDPN expression. CD42b-positive cases were significantly lower in the group treated with GnP than in the untreated group and groups treated with GEM alone or GS. PDPN expression was reduced in the GnP group, as revealed by markedly disorganized collagen and a low density of PDPN-positive fibroblasts. There was a significantly lower CD42b expression and fewer PDPN-positive fibroblasts in the GnP group than in untreated, GEM alone, and GS groups, but there was no significant difference between the latter three groups. CONCLUSION: There is a significant association between EPA and PDPN-positive CAFs in pancreatic cancer stroma. Our data suggest that the GnP regimen decreases EPA through PDPN-positive CAF depletion.

Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-paclitaxel Reduces the Number of Cancer-associated Fibroblasts Through Depletion of Pancreatic Stroma.

BACKGROUND: In this study, the effects of neoadjuvant chemotherapy (NAC) on cancer-associated fibroblasts (CAFs) in pancreatic cancer stroma were investigated. MATERIALS AND METHODS: Density of α-smooth muscle actin (αSMA)-positive fibroblasts in resected surgical specimens from untreated patients, patients receiving conventional gemcitabine plus S-1 (GS), and patients receiving gemcitabine plus nab-paclitaxel (GnP) was determined by hybrid cell counting. 18F-Fluorodeoxyglucose positron-emission tomography (FDG-PET) scans and carbohydrate antigen 19-9 (CA19-9) concentrations were used to assess tumor activity before and after chemotherapy in the GnP group. RESULTS: In this retrospective study of 65 patients, αSMA expression was reduced in the GnP group, as revealed by markedly disorganized collagen and a low density of αSMA-positive fibroblasts. There were significantly fewer αSMA-positive fibroblasts in the GnP than in the untreated and GS groups, but there was no significant difference between the latter two groups. αSMA density reflected a decrease in standardized uptake value on FDG-PET, but not CA19-9 concentration, after GnP chemotherapy. CONCLUSION: These data suggest that the GnP regimen induces stromal depletion, resulting in fewer CAFs.