Tumor-infiltrating B cells producing antitumor active immunoglobulins in resected HCC prolong patient survival Tumor-infiltrating B cells producing antitumor active immunoglobulins in resected HCC prolong patient survival

Allograft fibrosis still remains a critical problem in transplantation, including heart transplantation. The IL-13/TGF-β1 interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-β1 interaction prevents allograft fibrosis.

The aim of this study was to assess the value of ¹⁸F-FDG PET/CT for quantitative assessment of hepatic metabolism in patients with different stages of liver fibrosis/cirrhosis. ¹⁸F-FDG PET/CT scans of 37 patients either with or without liver fibrosis/cirrhosis, classified according to the METAVIR score (F0-F4) obtained from histopathological analysis of liver specimen, were analyzed retrospectively and classified as follows: no liver fibrosis (F0, n = 6), mild liver fibrosis (F1, n = 11), advanced liver fibrosis (F2, n = 6), severe liver fibrosis (F3, n = 5), and liver cirrhosis (F4, n = 11). The liver-to-blood ratio (LBR, scan time corrected for a reference time of 75 min) was compared between patient groups. Patients with liver fibrosis or cirrhosis (≥ F1; LBR 1.53 ± 0.35) showed a significant higher LBR than patients with normal liver parenchyma (F0, 1.08 ± 0.23; P = 0.004). In direct comparison, LBR increased up to the advanced stage of liver fibrosis (F2; 2.00 ± 0.40) and decreased until liver cirrhosis is reached (F4, 1.32 ± 0.14). Functional changes in liver parenchyma during liver fibrosis/cirrhosis affect hepatic glucose metabolism and significantly differ between stages of liver fibrosis/cirrhosis, classified according to the METAVIR scoring system, as demonstrated by LBR quantification by ¹⁸F-FDG PET/CT.

This study was performed to assess the 2006 introduced ENETS TNM-classification with respect to patient survival and surgical approach for patients who underwent surgery for a neuroendocrine tumor of the pancreas (PNET). Between 2001 and 2010 38 patients after resection of a PNET were investigated regarding tumor localization and size. Further, patient survival with regards to the new TNM-classification, the operation methods and immunohistochemical markers was analyzed. The estimated mean survival time of the 38 patients was 91 ± 10 months (female 116 ± 9, male 56 ± 14 months; p = 0.008). The 5-year survival rate was 63.9%. Patient survival differed significantly depending on tumor size (pT1 107 ± 13, pT2 94 ± 16, pT3 44 ± 7 and pT4 18 ± 14 months; P = 0.006). Patients without lymph node metastasis survived significantly longer compared to patients with positive lymph node status (108 ± 9 vs. 19 ± 5 months; P < 0.001). However, survival in patients with and without distant metastasis did not differ significantly (92 ± 11 vs. 80 ± 23 months; P = 0.876). Further, the tumor grading significantly influenced patient survival (G1 111 ± 12, G2 68 ± 12 and G3 21 ± 14 months; P = 0.037). As part of the TNM-classification especially lymph node status and also tumor size and grading were identified as important factors determining patient survival. Further, gender was demonstrated to significantly influence survival time. If an R0 resection was achieved in patients with distant metastases patient survival was comparable to patients without metastasis.

The purpose of this study was to elucidate whether DC NK lectin group receptor-1 (DNGR-1)-dependent cross-presentation of dead-cell-associated antigens occurs after transplantation and contributes to CD8⁺ T cell responses, chronic allograft rejection (CAR), and fibrosis. BALB/c or C57BL/6 hearts were heterotopically transplanted into WT, Clec9a^−/−, or Batf3^−/− recipient C57BL/6 mice. Allografts were analyzed for cell infiltration, CD8⁺ T cell activation, fibrogenesis, and CAR using immunohistochemistry, Western blot, qRT²-PCR, and flow cytometry. Allografts displayed infiltration by recipient DNGR-1⁺ DCs, signs of CAR, and fibrosis. Allografts in Clec9a^−/− recipients showed reduced CAR (p < 0.0001), fibrosis (P = 0.0137), CD8⁺ cell infiltration (P < 0.0001), and effector cytokine levels compared to WT recipients. Batf3-deficiency greatly reduced DNGR-1⁺ DC-infiltration, CAR (P < 0.0001), and fibrosis (P = 0.0382). CD8 cells infiltrating allografts of cytochrome C treated recipients, showed reduced production of CD8 effector cytokines (P < 0.05). Further, alloreactive CD8⁺ T cell response in indirect pathway IFN-γ ELISPOT was reduced in Clec9a^−/− recipient mice (P = 0.0283). Blockade of DNGR-1 by antibody, similar to genetic elimination of the receptor, reduced CAR (P = 0.0003), fibrosis (P = 0.0273), infiltration of CD8⁺ cells (p = 0.0006), and effector cytokine levels. DNGR-1-dependent alloantigen cross-presentation by DNGR-1⁺ DCs induces alloreactive CD8⁺ cells that induce CAR and fibrosis. Antibody against DNGR-1 can block this process and prevent CAR and fibrosis.

Electrochemotherapy (ECT) is a novel non-thermal ablative technique that combines chemotherapy and the application of electric pulses for reversible cell membrane electroporation. This method was recently performed in the treatment of deep-seated liver tumors during open surgery but experience about percutaneous ECT is rare and further developments like combination of percutaneous ECT with stereotactic navigated devices may be very promising. We report on a case of a 4.7 × 4.5 × 3.5 cm unresectable HCC at the hepatic hilum adjacent to the major vessels and the bile duct that was successfully treated using percutaneous ECT in combination with stereotactic navigation. Follow-up imaging 6 weeks and 6 months after ECT showed complete response.