Search Results

You are looking at 1 - 3 of 3 items for

  • Author: Radu Mihai x
  • All content x
Clear All Modify Search
Open access

Radu Mihai and Rajesh V Thakker

Background.

Permanent post-surgical hypoparathyroidism (POSH) is a major complication of anterior neck surgery in general and of thyroid surgery in particular. Depending of diagnostic criteria, up to 10% of patients undergoing bilateral thyroid surgery develop POSH. This leads to a multitude of symptoms that decrease the quality of life and burden the healthcare provision through complex needs for medication and treatment of specific complications, such as seizures and laryngospasm.

Methods.

Narrative review of current medical treatments for POSH and of the experience accumulated with parathyroid allotransplantation.

Results.

In most patients, POSH is controlled with regular use of calcium supplements and active vitamin D analogues but a significant proportion of patients continue to experience severe symptoms requiring repeated emergency admissions. Replacement therapy with synthetic PTH compounds (PTH1-34, Natpara® and PTH1-84, teriparatide, Forsteo®) has been assessed in multicentre trials, but the use of this medication is restricted by costs and concerns related to the risk of development of osteosarcoma.

Based on recent case reports of successful allotransplantation of parathyroid tissue between siblings, there is renewed interest in this technique. Data on selection of donors, parathyroid cell preparation before allotransplantation, site and timing of transplantation, need for immunosuppression and long-term outcomes are reviewed.

Conclusion.

A prospective trial to assess the efficacy of parathyroid allotransplantation in patients with severely symptomatic protracted post-surgical hypoparathyroidism is warranted.

Free access

Martin Fassnacht, Olaf M Dekkers, Tobias Else, Eric Baudin, Alfredo Berruti, Ronald R de Krijger, Harm R Haak, Radu Mihai, Guillaume Assie, and Massimo Terzolo

Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone-producing tumor with variable prognosis. The purpose of these guidelines is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with ACC based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions, which we judged as particularly important for the management of ACC patients and performed systematic literature searches: (A) What is needed to diagnose an ACC by histopathology? (B) Which are the best prognostic markers in ACC? (C) Is adjuvant therapy able to prevent recurrent disease or reduce mortality after radical resection? (D) What is the best treatment option for macroscopically incompletely resected, recurrent or metastatic disease? Other relevant questions were discussed within the group. Selected Recommendations: (i) We recommend that all patients with suspected and proven ACC are discussed in a multidisciplinary expert team meeting. (ii) We recommend that every patient with (suspected) ACC should undergo careful clinical assessment, detailed endocrine work-up to identify autonomous hormone excess and adrenal-focused imaging. (iii) We recommend that adrenal surgery for (suspected) ACC should be performed only by surgeons experienced in adrenal and oncological surgery aiming at a complete en bloc resection (including resection of oligo-metastatic disease). (iv) We suggest that all suspected ACC should be reviewed by an expert adrenal pathologist using the Weiss score and providing Ki67 index. (v) We suggest adjuvant mitotane treatment in patients after radical surgery that have a perceived high risk of recurrence (ENSAT stage III, or R1 resection, or Ki67 >10%). (vi) For advanced ACC not amenable to complete surgical resection, local therapeutic measures (e.g. radiation therapy, radiofrequency ablation, chemoembolization) are of particular value. However, we suggest against the routine use of adrenal surgery in case of widespread metastatic disease. In these patients, we recommend either mitotane monotherapy or mitotane, etoposide, doxorubicin and cisplatin depending on prognostic parameters. In selected patients with a good response, surgery may be subsequently considered. (vii) In patients with recurrent disease and a disease-free interval of at least 12 months, in whom a complete resection/ablation seems feasible, we recommend surgery or alternatively other local therapies. Furthermore, we offer detailed recommendations about the management of mitotane treatment and other supportive therapies. Finally, we suggest directions for future research.

Free access

Joakim Crona, Eric Baudin, Massimo Terzolo, Alexandra Chrisoulidou, Anna Angelousi, Cristina L Ronchi, Cristina Lamas Oliveira, Els J M Nieveen van Dijkum, Filippo Ceccato, Françoise Borson-Chazot, Giuseppe Reimondo, Guido A M Tiberi, Hester Ettaieb, Andreas Kiriakopoulos, Letizia Canu, Darko Kastelan, Esthr Osher, Eugenia Yiannakopoulou, Giorgio Arnaldi, Guillaume Assié, Isabel Paiva, Isabelle Bourdeau, John Newell-Price, Karolina M Nowak, M Tous Romero, Maria Cristina De Martino, Maria João Bugalho, Mark Sherlock, Marie-Christine Vantyghem, Michael Conall Dennedy, Paula Loli, Patrice Rodien, Richard Feelders, Ronald de Krijger, Sam Van Slycke, Simon Aylwin, Valentina Morelli, Laurent Vroonen, Zulfiya Shafigullina, Irina Bancos, Małgorzata Trofimiuk-Müldner, Marcus Quinkler, Michaela Luconi, Matthias Kroiss, Mitsuhide Naruse, Peter Igaz, Radu Mihai, Silvia Della Casa, Alfredo Berruti, Martin Fassnacht, and Felix Beuschlein

Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.