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Background: Radiofrequency ablation (RFA) is an established treatment option for malignancies located in the liver. RFA-induced irreversible coagulation necrosis leads to the release of danger signals and cellular content. Hence, RFA may constitute an endogenous in situ tumor vaccination, stimulating innate and adaptive immune responses, including tumor-antigen specific T cells. This may explain a phenomenon termed abscopal effect, namely tumor regression in untreated lesions evidenced after distant thermal ablation or irradiation. In this study, we therefore assessed systemic and local immune responses in individual patients treated with RFA. Methods: For this prospective clinical trial, patients with liver metastasis from colorectal carcinoma (mCRC) receiving RFA and undergoing metachronous liver surgery for another lesion were recruited (n = 9) during a 5-year period. Tumor and non-malignant liver tissue samples from six patients were investigated by whole transcriptome sequencing and tandem-mass spectrometry, characterizing naturally presented HLA ligands. Tumor antigen-derived HLA-restricted peptides were selected by different predefined approaches. Further, candidate HLA ligands were manually curated. Peripheral blood mononuclear cells were stimulated in vitro with epitope candidate peptides, and functional T cell responses were assessed by intracellular cytokine staining. Immunohistochemical markers were additionally investigated in surgically resected mCRC from patients treated with (n = 9) or without RFA (n = 7). Results: In all six investigated patients, either induced immune responses and/or pre-existing T cell immunity against the selected targets were observed. Multi-cytokine responses were inter alia directed against known tumor antigens such as cyclin D1 but also against a (predicted) mutation contained in ERBB3. Immunohistochemistry did not show a relevant influx of immune cells into distant malignant lesions after RFA treatment (n = 9) as compared to the surgery only mCRC group (n = 7). Conclusions: Using an individualized approach for target selection, RFA induced and/or boosted T cell responses specific for individual tumor antigens were more frequently detectable as compared to previously published observations with well-characterized tumor antigens. However, the witnessed modest RFA-induced immunological effects alone may not be sufficient for the rejection of established tumors. Therefore, these findings warrant further clinical investigation including the assessment of RFA combination therapies e.g., with immune stimulatory agents, cancer vaccination, and/or immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Intestinal transplantation has evolved into an established treatment for patients with intestinal failure. Although acute rejection episodes are reversible, late onset and chronic rejections remain major prognostic factors. We describe here our experience with endoscopic and histologic long-term monitoring through a cutaneous enterostomy. Between 1989 and 2003, 24 intestinal transplants were performed. After revascularization and reconstruction of proximal intestinal continuity, a side-to-end ileo-enterostomy was performed 20 cm from the stoma and the terminal allograft ileostomy left in the abdominal wall. Approximately after 2 months, in eight patients (nine transplants), the stoma was excluded from the gastrointestinal continuity, allowing ongoing endoscopy and histologic examination. Of 280 forceps biopsies, 64 (23%) were performed through the ‘blind ostomy’. Eleven acute allograft rejections were diagnosed between days 3 and 51, with two episodes in three cases. Through the ‘blind ostomy’, a late mild acute rejection was diagnosed in five instances, three to 37 months after transplantation. In all these patients, basal immunosuppression was intensified. Chronic rejection was seen in three cases 4–26 months after transplantation. In one of the three patients, chronic rejection was diagnosed from the excluded blind enterostomy. A long-term cutaneous enterostomy, even if disconnected from the intestinal continuity, enables simple long-term monitoring of small bowel allografts. [ABSTRACT FROM AUTHOR]

Nocardiosis is a localized or disseminated bacterial infection caused by aerobic Actinomyces that commonly affects immunocompromised hosts. The aim of this study was to retrospectively review clinical course and outcome of nocardiosis in solid organ recipients at our centre. Five cases of nocardiosis were identified in a series of more than 4000 consecutive solid organ transplants performed at Innsbruck university hospital during a 25-year period. Of the five patients with nocardiosis, two had undergone multivisceral, one liver, one kidney and one lung transplantation. Three patients with Nocardia asteroides infection were treated successfully and recovered from their infectious disease, however, one lost his renal graft following withdrawal of immunosuppression. The lung recipient recovered from nocardiosis but died later on from Pseudomonas pneumonia. One multivisceral recipient died from Nocardia farcinica-disseminated infection. Nocardiosis is a rare, difficult-to-diagnose-and-treat complication following solid organ transplantation. Intestinal recipients might be at increased risk to develop this infection. [ABSTRACT FROM AUTHOR]

Liver splitting increased the number of grafts for paediatric recipients. Usually the two left lateral segments are given to a child and the remaining liver to an adult recipient. Splitting into a right and a left lobe may allow a small adult to benefit from the left lobe while the right lobe goes to another adult recipient. Splitting of paediatric grafts, however, has rarely been performed. We here report on a case where the liver from a 9-year-old donor wasex situsplit along the principal fissure creating a right and left lobe which provided grafts for two children aged 2 and 3 years. Immunosuppression consisted of Tacrolimus-based triple drug therapy. Recovery was completely uneventful in both children who are alive and well with normally functioning grafts 11 months following transplantation. These cases demonstrate the feasibility of splitting even paediatric grafts for two small children. [ABSTRACT FROM AUTHOR]

Fungal infections still represent a serious complication after organ transplantation. Early diagnosis and aggressive treatment are crucial. Because of the many diagnostic problems involved, we present a case of mucormycosis - primarily affecting the paranasal sinuses with later intracranial extension - in a highly immunized recipient of a third renal transplant. Although fun gal infection was suspected from various imaging techniques, only the detection of typical fun gal hyphae in the infected tissue was diagnostic. Neither the blood tests and cerebrospinal fluid examinations performed nor cultures from maxillary sinus fluid were of any diagnostic help. Surgical debridement from a transnasal as well as an intracranial approach and systemic amphotericin B together with the discontinuation of immunosuppression after removal of the rejected graft were able to save the patient. This case stresses the importance of early diagnosis that can only be made from tissue biopsies and allows appropriate timely treatment. [ABSTRACT FROM AUTHOR]

Anatomical abnormalities of the liver are extremely rare. Although the majority of cases with an accessory liver are not detected, it can give rise to various clinical symptoms like recurrent abdominal pain and impaired liver function. Here we present the first case of orthotopic liver transplantation in a patient with hepatic ischemia caused by complete vascular occlusion due to a twisted accessory liver lobe. Although rare, an accessory liver lobe may cause serious and life-threatening problems and should therefore be kept in mind in patients presenting with acute abdominal pain. [ABSTRACT FROM AUTHOR]