Management recommendations for pancreatic manifestations of von Hippel-Lindau disease.

Von Hippel-Lindau disease (VHL) is a multineoplasm inherited disease manifesting with hemangioblastoma of the central nervous system and retina, adrenal pheochromocytoma, renal cell carcinoma, pancreatic neuroendocrine tumors and cysts, and neoplasms/cysts of the ear, broad ligament, and testicles. During 2018-2020, the VHL Alliance gathered several committees of experts in the various clinical manifestations of VHL to review the literature, gather the available evidence on VHL, and develop recommendations for patient management. The current report details the results of the discussion of a group of experts in the pancreatic manifestations of VHL along with their proposed recommendations for the clinical surveillance and management of patients with VHL. The recommendations subcommittee performed a comprehensive systematic review of the literature and conducted panel discussions to reach the current recommendations. The level of evidence was defined according to the Shekelle variation of the Grading of Recommendations, Assessment, Development, and Evaluation grading system. The National Comprehensive Cancer Network Categories of Evidence and Consensus defined the committee members' interpretation of the evidence and degree of consensus. The recommendations encompass the main aspects of VHL-related pancreatic manifestations and their clinical management. They are presented in a clinical orientation, including general planning of screening and surveillance for pancreatic neuroendocrine tumors, utility of biochemical biomarkers, the optimal choice for imaging modality, indirect risk stratification, indications for tissue sampling of VHL-related pancreatic neuroendocrine tumors, and interventions. These recommendations are designed to serve as the reference for all aspects of the screening, surveillance, and management of VHL-related pancreatic manifestations.

Endolymphatic sac tumor: single-institution series of seven cases with updated review of literature.

BACKGROUND: Endolymphatic sac tumour (ELST) is a rare low-grade locally aggressive neoplasm arising from the endolymphatic duct or sac. It presents mostly with vestibulo-cochlear symptoms either sporadically or as part of von Hippel-Lindau (VHL) syndrome. Micro-neurosurgical excision remains the cornerstone of therapy with the role of radiotherapy (RT) being controversial. This is a clinico-pathological analysis of consecutive ELST patients presenting to a single-institution in India. METHODS: Neuropathology database of a tertiary-care comprehensive cancer centre was searched electronically to identify consecutive patients with histopathological diagnosis of ELST registered at the institute over last one decade. Data regarding demographic profile, clinical presentation, histopathological features, treatment details and outcomes were retrieved from electronic medical records for this retrospective analysis. RESULTS: Electronic search identified seven unique patients with biopsy-proven ELST registered at the institute between 2009 and 2020. Median age of the study cohort was 39 years (range 24-65 years) with strong male predilection (5:2 ratio) and left-sided preponderance (71%). Most common presenting symptoms were hearing loss (86%) and earache (71%) on affected side followed by headache (43%). All patients underwent maximal safe resection at initial diagnosis and were followed-up closely with periodic surveillance imaging. Two patients underwent salvage RT using high-precision conformal techniques at recurrence/progression. CONCLUSION: ELST is a rare low-grade locally aggressive neoplasm that arises generally as part of VHL syndrome or sometimes sporadically. Gross total resection provides the best chance of cure with RT being reserved for unresectable disease, large residue, medical inoperability, or as salvage therapy for recurrent/progressive tumor.

Through the looking glass: an exploratory study of the lived experiences and unmet needs of families affected by Von Hippel-Lindau disease.

Despite well-established protocols for the medical management of Von Hippel-Lindau disease (VHL), families affected by this rare tumour syndrome continue to face numerous psychological, social, and practical challenges. To our knowledge, this is one of the first qualitative studies to explore the psychosocial difficulties experienced by families affected by VHL. A semi-structured interview was developed to explore patients' and carers' experiences of VHL along several life domains, including: self-identity and self-esteem, interpersonal relationships, education and career opportunities, family communication, physical health and emotional well-being, and supportive care needs. Quantitative measures were also used to examine the prevalence of anxiety, depression, and disease-specific distress in this sample. Participants were recruited via the Hereditary Cancer Clinic at the Prince of Wales Hospital in Sydney, Australia. A total of 23 individual telephone interviews were conducted (15 patients, 8 carers), yielding a response rate of 75%. A diverse range of experiences were reported, including: sustained uncertainty about future tumour development, frustration regarding the need for lifelong medical screening, strained family relationships, difficulties communicating with others about VHL, perceived social isolation and limited career opportunities, financial and care-giving burdens, complex decisions in relation to childbearing, and difficulties accessing expert medical and psychosocial care. Participants also provided examples of psychological growth and resilience, and voiced support for continued efforts to improve supportive care services. More sophisticated systems for connecting VHL patients and their families with holistic, empathic, and person-centred medical and psychosocial care are urgently needed.

[Neuroendocrine tumors of the gastrointestinal tract]. / Neuroendokrine Tumoren des Gastrointestinaltraktes.

Neuroendocrine tumors (NET) of the gastrointestinal tract are rare and constitute 0.5-1% of all human malignancies. Based on their endocrine secretion, they are functional active or inactive. They are further classified into fore-, mid-, or hindgut tumors. The recently published WHO-classification grouped the tumors according to their tumor size, angioinvasion and Ki-67 index. NET are mainly diagnosed in an advanced tumor stadium because of the paucity of symptoms or when symptoms occur due to endocrine hypersecretion. NET are diagnosed serologically by their hormone secretion and by measuring Chromogranin A levels. They are further detected by CT, MRI or endoscopy including endoscopic ultrasound. Many NET have somatostatin receptors on their surface and can be diagnosed by somatostatin receptor scintigrafy with high sensitivity and specificity. Only by surgery NET can be cured. Because many tumors are diagnosed late, medical options are of utmost importance. Symptom control can be established by somatostatin analogues and interferon-ot. Diazoxid can further inhibit insulin secretion, proton pump inhibitors are the therapy of choice for acid hypersecretion in Zollinger-Ellison syndrome. Advanced neuroendocrine cancers can be treated with chemotherapy. Recently, radio receptor therapy with 90Y-DOTA Octreotid and 177Lu-DOTA Octreotate was established in advanced neuroendocrine cancers and is further evaluated in studies. Net of the gastrointestinal tract should be treated in a multidisciplinary approach with gastroenterologists, surgeons and experts in nuclear medicine. An overview about epidemiology, clinical features, diagnostic methods and therapy of NET of the gastrointestinal tract will is provided in this article.

[Retinal angiomatosis- an ophthalmological challenge]. / Angiomatosis retinae- Eine ophthalmologische Herausforderung.

BACKGROUND: In this report we provide a description of new findings in retinal angiomatosis (RA) and, in particular, of treatment procedures. METHOD: A review of relevant publications in the literature has been carried out and remarks on differential diagnosis are provided. RESULTS: Haemangioblastomas of the retina and the central nervous system are the dominant manifestations in von Hippel-Lindau syndrome (VHL). As in patients with VHL syndrome the danger of new tumours is great, lifelong follow-up examinations are necessary. A genetic counselling with a DNA-based test of index patients and first degree relatives is recommended. The most frequently occurring retinal peripheral small tumours should be treated with the laser, large tumours, however, with kryo. or brachytherapy. Photodynamic therapy was successfully carried out in some patients as described in the literature. Treatment of tumours in the retinal middle periphery may result in central exudates with visual deterioration. Up to now, no sufficient experience exists concerning treatment with VEGF inhibitors, proton therapy, or transpupillary thermotherapy. Large tumours with retinal complications such as retinal detachment should be treated with combined procedures, mainly with vitrectomy. CONCLUSIONS: An early diagnosis and treatment of retinal haemangioblastomas including examination of first-degree family members with a DNA-based test are necessary.

[Retinal angiomatosis]. / Angiomatosis retinae.

BACKGROUND: Retinal capillary hemangioblastomas occur sporadically or as one of the manifestations of VHL (von Hippel-Lindau syndrome). In the assessment of retinal hemangioblastomas it is necessary to know about VHL, an autosomal dominant disease, a multisystem familial tumour syndrome. METHODS: An overview of the diagnosis and therapy of VHL is presented. RESULTS: Minimal criteria of the syndrome are tumours in one index patient and one of the typical lesions in another first-degree relative. Retinal hemangioblastomas were already found in children. Only 5 % of patients with VHL present retinal capillary hemangioma before the age of 10 years, and most patients present between the ages of 10 and 40 years. Data suggest that retinal capillary hemangioma is usually manifested by the age of 30 years. The VHL gene functions as a tumour suppressor gene and is mapped to the short arm of chromosome 3p25. The mapping of a locus for VHL has offered the prospect of presymptomatic diagnosis of the disease using DNA markers. Small retinal tumours are treated by photocoagulation, big hemangioblastomas by cryotherapy. Modern options in treatment of retinal tumours are proton therapy, plaque radiotherapy, pars-plana vitrectomy, photodynamic therapy, transpupillary thermotherapy and systemic treatment with the vascular endothelial growth factor (VEGF) receptor inhibitor, in addition. CONCLUSIONS: The interdisciplinary Freiburg VHL study which has been in existence for more than 20 years, has shown that an extensive family screening for early detection of the disease is necessary. The assessment of the diagnosis in a VHL carrier requires close follow-up for multiple and recurrent tumours.

Early experience with percutaneous radiofrequency ablation of small solid renal masses.

OBJECTIVE: Incidental small renal-cell masses are often seen in elderly patients with significant comorbidity who are unfit to undergo major surgery. This study was conducted to determine the safety and efficacy of percutaneous imaging-guided radiofrequency ablation in the management of small solid renal masses, almost all of which are renal cell cancers. CONCLUSION: Early experience suggests that radiofrequency ablation is a safe, well-tolerated, and minimally invasive therapy for patients with solid renal masses. In the era of nephron-sparing surgery, radiofrequency ablation may have a role in the management of small problematic renal masses.

Transpupillary thermotherapy for retinal capillary hemangioma in von Hippel-Lindau disease.

Retinal capillary hemangiomas are a common manifestation of von Hippel-Lindau disease. We report the treatment of a peripapillary retinal capillary hemangioma in the left eye of a 30-year-old woman with this condition, using infrared diode laser transpupillary thermotherapy (TTT). The hemangioma was evaluated before and after treatment by ophthalmoscopy, fundus fluorescein angiography, and Doppler ultrasonography. Infrared diode laser TTT was delivered over 3 sessions during a period of 22 weeks, resulting in an improvement in visual acuity from counting fingers to 6/24 and a marked decrease in exudates surrounding the hemangioma. Doppler ultrasonography demonstrated a decrease in intralesional blood flow from 7 cm per second to less than 3 cm per second, together with a decrease in the size of the lesion. Infrared diode laser TTT provides a useful modality in the treatment of retinal capillary hemangiomas, and may be particularly favorable for peripapillary lesions because of its relatively nondestructive characteristics.