Current treatment strategies for primary upper extremity deep venous thrombosis; a retrospective observational multicenter case series.

Introduction: Current treatment strategies for primary upper extremity deep venous thrombosis (pUEDVT) range from conservative treatment with anticoagulation therapy to invasive treatment with thoracic outlet decompression surgery (TOD), frequently combined with catheter directed thrombolysis, percutaneous transluminal angioplasty, or stenting. Due to a lack of large prospective series with uniform data collection or a randomized trial, the optimal treatment strategy is still under debate. We conducted a multicenter observational study to assess the efficacy and safety of both the conservative and invasive treatment strategies for patients with pUEDVT. Methods: We retrospectively collected data from patients treated in five vascular referral and teaching hospitals in the Netherlands between 2008 and 2019. Patients were divided into a conservative (Group 1), an invasive treatment group (Group 2) and a cross-over group (Group 3) of patients who received surgical treatment after initial conservative therapy. Follow-up consisted of outpatient clinic visits and an electronic survey. Primary outcome was symptom free survival defined as absence of any symptom of the affected arm reported at last follow-up regardless of severity, or extent of functional disability. Secondary outcomes were incidence of bleeding complications, recurrent venous thromboembolism, surgical complications, and reinterventions. Results: A total of 115 patients were included (group 1 (N = 45), group 2 (N = 53) or group 3 (N = 27). The symptom free survival was 35.6%, 54.7% and 48.1% after a median follow-up of 36, 26 and 22 months in groups 1, 2 and 3 respectively. Incidence of bleeding complications was 8.6%, 3.8% and 18.5% and recurrent thrombosis occurred in 15.6%, 13.2% and 14.8% in groups 1-3 respectively. Conclusion: In this multicenter retrospective observational cohort analysis the conservative and direct invasive treatments for pUEDVT were deemed safe with low percentages of bleeding complications. Symptom free survival was highest in the direct surgical treatment group but still modest in all subgroups. Perioperative complications were infrequent with no related long term morbidity. Of relevance, pUEDVT patients with confirmed VTOS and recurrent symptoms after conservative treatment may still benefit from TOD surgery. However, symptom free survival of this delayed TOD seems lower than direct surgical treatment and bleeding complications seem to occur more frequently.

Renal transplant patient survives a donor-derived abdominal invasive mucormycosis (Lichtheimia ramos a).

Mucormycosis is a life-threatening invasive fungal infection, most commonly described in severely immunocompromised patients. It is characterized by rapid invasive growth of the fungus and often with fatal outcome. We report a case of a renal transplant recipient diagnosed with a donor-derived invasive mucormycosis. In this patient, we used a step-wise approach of withdrawal of immunosuppressants, antifungal induction therapy, extensive surgical debridement of all (potentially) infected tissue, abdominal irrigation of liposomal amphotericin B and interferon gamma. Due to rapid diagnosis and intensive therapy the patient survived.

Phaeochromocytomas and sympathetic paragangliomas.

BACKGROUND: About 24 per cent of phaeochromocytomas (PCCs) and sympathetic paragangliomas (sPGLs) appear in familial cancer syndromes, including multiple endocrine neoplasia type 2, von Hippel-Lindau disease, neurofibromatosis type 1 and PCC-paraganglioma syndrome. Identification of these syndromes is of prime importance for patients and their relatives. Surgical resection is the treatment of choice for both PCC and sPGL, but controversy exists about the management of patients with bilateral or multiple tumours. METHODS: Relevant medical literature from PubMed, Ovid and Embase websites until 2009 was reviewed for articles on PCC, sPGL, hereditary syndromes and their treatment. DISCUSSION: Genetic testing for these syndromes should become routine clinical practice for those with PCC or sPGL. Patients should be referred to a clinical geneticist. Patients and family members with proven mutations should be entered into a standardized screening protocol. The preferred treatment of PCC and PGL is surgical resection; to avoid the lifelong consequences of bilateral adrenalectomy, cortex-sparing adrenalectomy is the treatment of choice.

Genetic analyses of apparently sporadic pheochromocytomas: the Rotterdam experience.

Pheochromocytomas (PCCs) are neuroendocrine tumors of chromaffin tissue that produce catecholamines. They are usually located in the adrenal medulla, although in about 10% the tumors arise from extra-adrenal chromaffin tissue. The majority of PCCs arise sporadically, but PCCs occur also in the context of hereditary cancer syndromes. Familial PCC is inherited as an autosomal dominant trait alone or as a component of the multiple endocrine neoplasia Type 2 (MEN2) syndrome (RET gene), Von Hippel-Lindau (VHL) disease (VHL gene), neurofibromatosis Type 1 (NF1 gene), or familial pheochromocytoma-paraganglioma (PCC-PGL) syndrome (SDHD/B and C genes). It has been reported that 24% of apparently sporadic PCCs patients harbor germline mutations in these PCC-causing genes. We investigated the contribution of the inherited PCC-causing genes in a partly retrospectively and partly prospectively obtained series of 213 apparently sporadic PCCs. Mutation analysis was performed for RET (56 cases), VHL (136 cases), and SDHD (126 cases) and SDHB (47 cases). No germline RET mutations, six (4.4%) germline VHL mutations, two (1.5%) germline SDHD mutations, and one germline (1.6%) SDHB mutation were found. In total we found germline mutations in about 7.5% of the investigated apparently sporadic PCCs. Although 7.5% germline mutations in a series of apparently sporadic PCCs are far less than the more than 20% reported in the literature, the figure is significant enough to consider germline mutation testing for each patient with PCC.

PTEN gene loss, but not mutation, in benign and malignant phaeochromocytomas.

Mutations of the 'phosphatase and tensin homologue deleted on chromosome 10' (PTEN/MMAC1) gene have been associated with a variety of human cancers, including prostate cancer, glioblastoma, and melanoma. The gene is thought to be one of the most frequently mutated tumour suppressor genes and inactivation of PTEN is associated with disease progression and angiogenesis. High vascularization and resistance to chemo- and radio-therapy are two well-established features of phaeochromocytomas (PCCs). Furthermore, benign and malignant PCCs are found in several PTEN knockout mouse models. This study therefore evaluated whether inactivation of PTEN may be involved in the tumourigenesis of PCC in man and whether PTEN abnormalities may help to define the malignant potential of these tumours. Tumour and germline DNA was analysed from 31 patients with apparently sporadic PCC, including 14 clinically benign and 17 malignant tumours, for loss of the PTEN gene locus, mutations in the PTEN gene, and for PTEN protein expression by immunohistochemistry. Loss of heterozygosity (LOH) analysis showed loss of PTEN in four malignant tumours (40%) and in one benign tumour (14%). However, no mutations of PTEN were observed. Immunohistochemistry showed no correlation with clinical behaviour and/or LOH status. The results indicate that inactivation of the PTEN/MMAC1 gene may play a minor role in the development of malignant phaeochromocytomas.