Tenofovir alafenamide prophylaxis post-liver transplantation: a real-world study in patients with chronic kidney disease.

Background & aims: Tenofovir alafenamide fumarate (TAF) was shown equally efficacious in suppressing hepatitis B virus (HBV) but with less renal toxicity than tenofovir disoproxil fumarate (TDF). The aim of this real-world study was to evaluate renal function in post-liver transplantation (LT) patients that changed TDF with TAF. Methods: The TAF group (n=17) included patients who switched to TAF due to low (<60 ml/min/1.73m2) Glomerular Filtration Rate (GFR). The control group included patients that remained on TDF (n=30), although some (n= 14) had chronic kidney disease (CKD) (TDF-CKD group). GFR was assessed using: i) MDRD-6 variable; ii) CKD-EPI formula; iii) radionuclide technique (rGFR). Results: There were no significant differences between the two groups except for the presence of diabetes and follow-up period, which were more common and shorter, respectively, in the TAF group (35% vs. 10%, p=0.03; 13.7 vs. 35.5 months, p<0.001). At the end of follow-up there were no significant changes in renal function between the TAF and the TDF group or TDF-CKD group, although the numerical change in rGFR in the latter comparison was greater in the TAF group (ΔrGFR 3 vs. -2.14 ml/min, p=0.26). The use of everolimus was associated with improvement in renal function (ΔrGFR 2 vs. -7.75 ml/min, p=0.06 [TAF vs. TDF group]; 2 vs. -12 ml/min, p=0.01 [TAF vs. TDF-CKD group]). There were no TAF- related side effects or cases of HBV recurrence. Conclusion: Conversion to TAF in post-LT patients who develop CKD does not lead to improvement of kidney function after a period of one year.

Case report: Sclerosed hemangioma of the liver: A diagnostic challenge.

Hemangiomas are the most common noncystic benign hepatic tumors and are usually incidentally discovered during routine radiological examinations. The diagnosis of hepatic hemangiomas with a typical presentation is generally easy with plain and cross-sectional imaging; however, it can be complicated when hemangiomas undergo histological changes such as fibrosis. Sclerosed hepatic hemangioma (SHH) is the extreme presentation of this fibrotic process. These atypical lesions can be misdiagnosed as primary hepatic malignancies or metastasis. Their diagnosis is established by histological examination. We report the case of a patient with an SHH, which was misdiagnosed as an intrahepatic cholangiocarcinoma. This article's aim is to draw attention to this infrequent pathology and underline the features of this benign tumor that could suggest its diagnosis prior to surgery to avoid unnecessary hepatic resections.

Long-Term (≥25 Years) Kidney Allograft Survivors: Retrospective Analysis at a Single Center.

INTRODUCTION: Despite great improvements in the short-term patient and kidney graft survival, the long-term morbidity and mortality in kidney transplant recipients still remains a significant problem. The aim of the study was to evaluate the impact of both donor and transplant recipient factors, as well as renal function indices on the very long-term (>25 years) kidney allograft survival. MATERIAL AND METHODS: Retrospective analysis was performed on the data of 41 kidney transplant recipients (KTR), group A: follow-up = 25 years, 20 KTR, 10 male, mean age (mean [M] ± standard deviation [SD]): 34.6 ± 12.6 years, 14 living donors (LD), 6 cadaveric donors (CD); group B: follow-up > 25 years, 21 KTR, 16 male, mean age (M ± SD): 30.86 ± 12.37 years, 14 LD, 7 CD). Kidney graft origin, post-kidney transplantation diabetes mellitus, HLA compatibility, delayed graft function, and acute rejection episodes were also analyzed retrospectively. Statistical analysis with Mann-Whitney test and Kaplan-Meier survival analysis was performed (SPSS 20.0 for Windows). RESULTS: The mean age of CDs was lower than that of LDs: CD mean age (M ± SD): 23.84 ± 16.26 years vs LD mean age: 52.75 ± 12.42 years (P < .001). Cadaveric kidney graft was associated with better renal allograft function 10, 15, and 25 years post kidney transplant. None of the other factors analyzed reached statistical significance between the 2 groups. CONCLUSION: The age of the donor and the kidney graft origin are important co-factors of the very long-term kidney allograft survival.

Hepatic Artery Anatomic Variations and Reconstruction in Liver Grafts Procured in Greece: The Effect on Hepatic Artery Thrombosis.

AIMS: Variations of the anatomy of donor hepatic arteries increase the number of arterial anastomoses during liver transplantation and, possibly, the incidence of hepatic artery thrombosis (HAT). In this study, we describe the arterial anatomic variations in liver grafts procured and transplanted by a single center in Greece, the techniques of arterial anastomosis, and their effect on the incidence of early HAT. MATERIALS AND METHODS: From January 2013 to December 2017, the arterial anatomy of 116 grafts procured for liver transplantation were recorded, as well as the technique of arterial anastomosis and the incidence of early hepatic artery thrombosis (HAT <30 days). RESULTS: A single hepatic artery was recorded in 72.41% of the procured grafts, an aberrant left hepatic artery (accessory or replaced) in 18 grafts (15.52%), and an aberrant right hepatic artery (accessory or replaced) in 17 grafts (14.66%), while other variations were observed in less than 1% of the procured livers. Of the 116 primary liver transplantations, 6 patients (5.17%) developed early HAT <30 days. Two of these patients (1.72%) had 1 anastomosis of the hepatic artery and 4 (3.45%) had 2 anastomoses due to anatomic variations. CONCLUSIONS: Anatomic variations of the hepatic artery in liver grafts is a common finding and increase the incidence of early HAT but not to a degree to make these grafts unusable.

Gastric bypass for morbid obesity in a patient with situs inversus totalis.

The aim of this case report is to outline the challenge and the feasibility of laparoscopic gastric bypass in a patient with situs inversus totalis. Situs inversus totalis does not seem to be a contraindication for laparoscopic surgery.

Gastric Bypass for Morbid Obesity in a Patient with Situs Inversus Totalis.

The aim of this case report is to outline the challenge and the feasibility of laparoscopic gastric bypass in a patient with situs inversus totalis. Situs inversus totalis does not seem to be a contraindication for laparoscopic surgery.

Enhanced recovery after elective colorectal resection outside a strict fast-track protocol. A single centre experience.

INTRODUCTION: Optimising the management of hospitalised patients is a major concern. In colorectal surgery, the concept of enhanced recovery has been popularised by means of "fast-track" protocols, aiming at patient's discharge on the second postoperative day. Nevertheless, a strict fast-track protocol has several limitations. It is very demanding for the patient and therefore applicable only to a limited number of patients. AIM: In order to optimise, in every aspect, the postoperative recovery of each patient undergoing an elective colorectal resection inside our institution, we set up a "soft" enhanced recovery programme. MATERIAL-METHODS: A retrospective analysis was conducted in 92 patients evaluating the respective impact of protocol application throughout the duration of the hospital stay. RESULTS: When all the required measures of our protocol were correctly implemented, the median discharge day was postoperative day 3 (range 3-5 days). On the contrary, when deviations occurred, they resulted in longer hospital stay (p < 0.001). Patients operated by laparoscopy were discharged earlier than patients operated by laparotomy (p < 0.001). The use of nasogastric tube and postoperative drainage prolonged significantly the length of stay (p = 0.001 and p < 0.001 respectively). When the urinary catheter was not removed or oral feeding not resumed on postoperative day 1, the patients were discharged later (p < 0.001). CONCLUSIONS: There are substantial possibilities of optimising the recovery process after an elective colorectal resection, outside a strict fast-track protocol.

[Multidisciplinary management of hepatocellular carcinoma in cirrhotic patients]. / Traitement du carcinome hépato-cellulaire chez le patient cirrhotique: la nécessité d'une approche pluridisciplinaire.

The treatment of hepatocellular carcinoma (HCC) in cirrhotic patients is challenging: the incidence is increasing, the cirrhosis dramatically limits the tolerance to treatment possibilities, there are many therapeutic modalities but resources are limited, namely in the context of organ shortage for transplantation. Liver transplantation (LT) is the optimal treatment as it combines the largest tumor resection possible and the correction of the underlying liver disease. Due to organ shortage however, LT is reserved for early-stages HCC. Surgical resection and radiofrequency destruction represent potentially curative options in highly selected patients. Arterial embolizations, chemo- or radio-embolizations, allow local tumor control but are not curative. These techniques could be performed before surgical resection or LT, to downstage the tumor and/or to control tumor progression while waiting for a graft. Finally, sorafenib is the only systemic treatment which has shown a survival benefit in advanced HCC. The benefit of combination of sorafenib and surgical treatments remains undetermined. The challenge in the management of HCC in cirrhotic patients is to integrate both individual (age, comorbidities, cirrhosis stage, tumor stage, specific contraindications to LT, etc.) and collective variables (expected waiting time before LT) to determine the best therapeutic option for each patient. In this process, multidisciplinarity is a key for success.

Efforts to counteract locally the effects of systemic immunosupression: a review on the use of imiquimod, a topical immunostimulator in organ transplant recipients.

The potent systemic immunosuppression therapy necessary to sustain a life-saving solid organ transplant is associated with an increased incidence of various infections including human papillomavirus infection and skin cancers in organ transplant recipients. Imiquimod, a topical agent that functions through local induction of a specific anti-viral or anti-tumor immune response, appears to be a promising therapeutic option that could potentially counteract in situ the effects of systemic immunosupression in this vulnerable group. Up-to-date studies using this local immune-response modifier in transplanted patients have yielded reassuring and encouraging results regarding its safety and efficacy in this population. However, in order to establish the use of imiquimod as a standard treatment option for organ transplant recipients, additional research and clinical trials are required.

Mast cells and chemokines.

Chemokines are small proteins (8-12 kD polypeptides) secreted by the cells of innate and adaptive immunity that mediate many of the functions of these cells, including recruitment of other cells. They are classified into families: CC, CXC and CX3C. CXC chemoattract mainly on neutrophils and CC act mainly on monocytes, eosinophils and mast cells. Mast cells are important cells in the modulation of allergic and inflammatory diseases. Activation of mast cells with specific IgE antibody and antigens or other active compounds such as Substance P and corticotrophin releasing hormone causes transcription and translation of several different cytokines/chemokines such as tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1 (MIP-1) and GM-CSF, RANTES, MCP-1, CXCL8, along with other proinflammatory compounds, proteases (chymase and tryptase), histamine, leukotrienes and prostaglandin D2. Neutralization of chemokines may reduce inflammatory cell accumulation and may protect against allergy, toxic shock syndrome and inflammatory diseases.

Impact of substance P on cellular immunity.

Much evidence suggests a cross-talking between nerve fibers and the immunity system. The immunomodulation by substance P includes cell activation and proliferation of human cells, with cytokine and chemokine generation and release. Substance P was first isolated by Leeman et al. as an undecapeptide with important neurotransmitter-neuromodulator effects. In addition, substance P was shown to induce and mediate inflammation, angiogenesis, infections, intestinal mucosal immunity and stress. Substance P is able to activate several immune cells, such as CD4+ and CD8+ T lymphocytes, mast cells, NK cells and macrophages. In recent studies we have shown that substance P can activate interleukin-8, a CXC chemokine, demonstrating its involvement in immune cell chemoattraction. We believe that substance P is important in understanding the pathophysiology of inflammation.

Biology of neurotensin: revisited study.

The tridecapeptide neurotensin (NT) acts in the mammalian brain as a primary neurotransmitter or neuromodulator of classical neurotransmitters. Morphological and functional in vitro and in vivo studies have demonstrated the existence of close interactions between NT and dopamine both in limbic and in striatal brain regions. Additionally, biochemical and neurochemical evidence indicates that in these brain regions NT also plays a crucial role in the regulation of the aminoacidergic signalling. Immune cells, such as lymphocytes, macrophages and mast cells are reported to be activated by neuropeptides, such as neurotensin; this activation leads to cytokine and immunoglobulin production. In addition, neurotensin increases calcium level and the production of nitric oxide. Therefore neurotensin is deeply involved in immunity and inflammation but its real function still remains to be elucidated.