Bortezomib-containing multimodality treatment for antibody-mediated rejection with anti-HLA and anti-AT1R antibodies after kidney transplantation

For decades, the human leukocyte antigen (HLA) complex has been considered the primary target of antibody-mediated rejection (AMR), and treatment strategies have mainly focused on anti-HLA antibodies. Recently, other antibodies potentially causing organ damage and loss have been discovered. Conclusive evidence on treatment options for these subtypes of AMR is still lacking. After an experience previously reported in this journal,1 we describe a case of late-onset AMR, with mixed anti-HLA and anti-angiotensin II type 1 receptor (AT1R) antibodies, that was successfully treated with a multimodal approach, including the use of the proteasome inhibitor bortezomib

Coupled Plasma Filtration Adsorption in Patients with a History of Kidney Transplantation: Report of Two Cases

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Impact of remnant vital tissue after locoregional treatment and liver transplant in hepatocellular cancer patients. A multicentre cohort study

The role of pathological findings after locoregional treatments as predictors of hepatocellular cancer recurrence after liver transplantation has been poorly addressed. The aim of the study was to identify the role of remnant vital tissue (RVT) of the target lesion in predicting hepatocellular cancer recurrence. Two hundred and seventy-six patients firstly undergoing locoregional treatment and then transplanted between January 2010 and December 2015 in four European Transplant Centres (i.e. Rome Tor Vergata, Birmingham, Brussels and Ancona) were enrolled in the study to investigate the role of pathological response at upfront locoregional treatment. At multivariable Cox regression analysis, RVT ≥2 cm was a strong independent risk factor for post-LT recurrence (HR = 5.6; P < 0.0001). Five-year disease-free survival rates were 60.8%, 80.9% and 95.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. When only Milan Criteria-IN patients were analysed, similar results were reported, with 5-year disease-free survival rates of 58.1%, 79.0% and 94.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. RVT is an important determinant of tumour recurrence after liver transplantation performed for hepatocellular cancer. Its discriminative power looks to be evident also in a Milan-IN setting, suggesting to more liberally use locoregional treatments also in these patients

Global management of a common, underrated surgical task during the COVID-19 pandemic: Gallstone disease - An international survery

Background: Since the Coronavirus disease-19(COVID-19) pandemic, the healthcare systems are reallocating their medical resources, with consequent narrowed access to elective surgery for benign conditions such as gallstone disease(GD). This survey represents an overview of the current policies regarding the surgical management of patients with GD during the COVID-19 pandemic. Methods: A Web-based survey was conducted among 36 Hepato-Prancreato-Biliary surgeons from 14 Countries. Through a 17-item questionnaire, participants were asked about the local management of patients with GD since the start of the COVID-19 pandemic. Results: The majority (n = 26,72.2%) of surgeons reported an alarming decrease in the cholecystectomy rate for GD since the start of the pandemic, regardless of the Country: 19(52.7%) didn't operate any GD, 7(19.4%) reduced their surgical activity by 50–75%, 10(27.8%) by 25–50%, 1(2.8%) maintained regular activity. Currently, only patients with GD complications are operated. Thirty-two (88.9%) participants expect these changes to last for at least 3 months. In 15(41.6%) Centers, patients are currently being screened for SARS-CoV-2 infection before cholecystectomy [in 10(27.8%) Centers only in the presence of suspected infection, in 5(13.9%) routinely]. The majority of surgeons (n = 29,80.6%) have adopted a laparoscopic approach as standard surgery, 5(13.9%) perform open cholecystectomy in patients with known/suspected SARS-CoV-2 infection, and 2(5.6%) in all patients. Conclusion

Pharmacological advances in liver transplantation and resection

This thesis, which includes clinical and laboratory research, was meant to advance liver surgery thanks to pharmacology. Since immunosuppression, as well as rejection, is detrimental, we investigated in adult liver transplantation whether induction with depleting antibodies helps minimise immunosuppression after one year. Early histological rejection was attenuated. As organ shortage and increasing indications widen the gap between supply and demand, there is little alternative to live-donor liver transplantation. Managing a small-for-size liver in the donor or in recipient remains a challenge, where hypoxia-signalling pathways play a role. Can hypoxia gene signature be induced by means of a pharmacological stabilisation of its downstream transducers? We studied the histological and functional changes caused by roxadustat, a selective stabiliser of these transcription factors, in a model of liver resection. The drug reduced steatosis and ballooning, markers of hepatocellular injury.(MED - Sciences médicales) -- UCL, 202

Vascular tumours of the liver: a particular story.

Vascular tumours of the liver represent an underrated chapter of medical and surgical hepatology. These tumours cover a wide spectrum ranging from the frequent and most benign hepatic haemangioma (HH), via the rare and intermediately aggressive hepatic epithelioid haemangioendothelioma (HEHE) to the rare and most malignant hepatic haemangiosarcoma (HHS). In contrast to the treatment algorithms for hepatocellular and cholangiocellular cancer, the diagnostic and therapeutic approaches to HEHE and HHS are not well developed. The related uncertainty is explained by their rare occurrence and their protean clinical, morphological (imaging) and histopathological presentation and behaviour. This article gives an update about these particular tumours based on the analysis of the recent literature and of the studies on vascular tumours published by the European Liver Intestine Transplantation Association (ELITA)-European Liver Transplant Registry (ELTR). It focuses also on the place of liver transplantation (LT) in the respective therapeutic algorithms. The differential diagnosis between these vascular and other tumour types may be very difficult. Correct diagnosis is of utmost importance and is based on a high index of clinical suspicion and on the integration of clinical, radiological, histological [including immunohistochemistry (IHC) and molecular biology findings]. Surgery, be it partial or total hepatectomy (LT), should be proposed whenever possible, because it is the therapeutic mainstay. In HEHE, LT provides excellent results, with long-term disease-free survivals (DFS) reaching 75%. Good results can be obtained even in case of (frequent) extrahepatic spread. Based on the extensive ELITA-ELTR study a HEHE-LT prognostic score has been proposed in order to estimate the risk of recurrence after LT. In contrast, results of surgery and LT are extremely poor for HHS, for the almost invariably rapid recurrence (within 6 months) and related death within 2 years. LT remains a contraindication for HHS. Due to the still important recurrence rate after surgical resection (25% in HEHE and almost 100% in HHS), there is an urgent need to develop pharmacological treatments targeting angiogenic and non-VEGF angiogenic pathways. To date, some prospective pilot studies and case reports have shown some short-term stabilisation of the disease in small groups of patients. In order to make progress, combination of surgery, anti-angiogenic and immunotherapy seems worthwhile. To complete the panel of vascular liver tumours, infantile haemangioendothelioma, haemangiopericytoma, nodular regenerative hyperplasia (NRH) and hepatic small vessel neoplasms (HSVN) are also discussed

Immunosuppression and Liver Transplantation

Perfect surgical techniques and adequate immunosuppression are key to ensuring optimal graft and patient survival. The availability of different drugs has led to several, often industry-driven, heterogeneous clinical trials to discover an ideal immunosuppressive regimen. However, the considerable and conceptually diverse study designs have failed to afford a clear definition of the optimal immunosuppression regimen. The triple-drug immunosuppressive regimen, based on the calcineurin inhibitor tacrolimus, antimetabolites mofetil mycophenolate or azathioprine, and short-term steroids—beyond possible induction—remains the currently accepted standard immunosuppression in liver transplantation. However, this regimen needs to be challenged in light of the changing definitions of rejection, customization of the immunosuppressive load, and long-term side effects due to chronic immunosuppression. Future trials should preferably include more than a single endpoint rather than acute T-cell-mediated acute rejection (a-TCMR) or kidney failure. Conversely, a comprehensive endpoint that covers patient and graft survival rates and the incidence of both acute and chronic rejection is warranted. These immune phenomena should be examined in light of serial long-term biological and histological follow-up. The diagnosis and treatment of clinically relevant a-TCMR should be based on integrated biological, immunological, and histopathological findings. Both elements are critical to progress toward more prudent immunosuppression handling and favor clinical operational tolerance

Liver transplantation for hepatocellular carcinoma: role of immunosuppression and rejection treatment in cancer recurrence - results of a multicenter study

Liver transplantation for hepatocellular carcinoma : role of immunosuppression and rejection treatment in cancer recurrence - results of a multicenter study. FOGUENNE Maxime Promotor : Pr J. LERUT Co-promotor : Dr S. IESARI INTRODUCTION Liver transplantation (LT) was initially dedicated to the treatment of cirrhosis. Nowadays, it is playing an increasingly important role in the treatment of hepatocellular carcinoma (HCC). Surgery, in the form of partial or total (i.e., transplantation) liver resection, represents the only curative treatment of HCC. It is important to keep in mind that a patient affected by HCC has in fact two diseases: the cancer itself and the underlying cirrhosis. LT thus represents a very interesting approach that treats both of them, but is really challenging. Due to liver allograft shortage, graft allocations must be cautiously selected. HCC recurrence must indeed be considered as a failure of the selection process. In the 1980s, LT for HCC was not popular due to poor long-term results, but the situation changed in 1996, when Mazzaferro introduced the Milan criteria. When following these criteria, LT for HCC was associated to an almost similar overall and disease-free survival compared to LT for benign diseases. However, these morphologic criteria rapidly appeared to be too restrictive, which led to the development of numerous prediction scores in order to widen the eligibility criteria for LT in HCC. These scores currently include morphological as well as biological parameters, both of static and dynamic nature. Notwithstanding, the role of immunosuppression (IS) remains unclear and has not been thoroughly investigated. This is surprising, since it is well known that the immune system plays a key role in the defence against cancer. MATERIAL AND METHODS This retrospective observational study sought to fill this gap of knowledge by analyzing the impact of acute cellular rejection (ACR) treatment on HCC recurrence in a large cohort of 781 European patients transplanted for HCC between February 1985 and June 2016. After propensity score matching (PSM), 116 patients treated with corticosteroid boluses for ACR were compared to 115 patients who were not treated for (histologically proven) ACR or did not present ACR at all. RESULTS The treated group presented an 18-fold higher risk of HCC recurrence (16.4% vs. 0.9%; p<0.0001), all recurrences having occurred after treatment. Following multivariate Cox regression analysis, corticosteroid use as ACR treatment appeared to be an independent risk factor for HCC recurrence (HR = 14.2; p = 0.01). Continuation of corticosteroid therapy for more than 12 months after rejection as well as high IS load were also associated with a higher recurrence rate (57.6% vs. 32.0% [p = 0.04] and 68.4% vs. 37.1% [p = 0.02], respectively). CONCLUSION ACR treatment using corticosteroids appears to be a risk factor for HCC recurrence. The intensification of immunosuppressive treatment after ACR also tends to be associated with a higher risk of cancer recurrence. More studies – especially prospective ones – are however needed to confirm these results and analyze the phenomenon more deeply