Percutaneous microwave ablation on management of hereditary renal cell carcinoma in Von Hippel-Lindau disease.

BACKGROUND: The effect of microwave ablation (MWA) for the renal cell carcinoma (RCC) in Von Hippel-Lindau (VHL) disease is unclear. OBJECTIVE: To assess the safety, Technique efficacy, renal function and oncological outcome of MWA for RCC in VHL patients. METHODS: Consecutive patients with RCCs in VHL disease treated by MWA were retrospectively collected from November 2009 to October 2020. The technical efficacy rate and complications were assessed. The outcomes of pre- and post-ablative eGFR were compared. The local recurrent-free survival (LRFS), renal-cancer-free survival (RCFS), cancer-specific survival (CSS), overall survival (OS) and complications were presented. RESULTS: A total of 10 patients (mean age, 39.0 years ± 10.7 [SD]; 3 women) with 28 RCCs (mean tumor size, 3.0 cm ± 0.34; mean tumor volume, 20.7 mL ± 43.3) treated with MWA were included. Th median follow-up time was 52 months(IQR:27-80). The overall technical efficacy rate was 100% with no major complications occurred. No significant statistical difference between pre-ablative and postablative creatinine level (102.0 µmol/L ± 30.4 vs 112.3 µmol/L ± 38.7, p = 0.06), but the pre-ablative eGFR level was significantly higher than the post-ablative eGFR (78.0 mL/(min*1.73m2) ± 28.6 vs 72 mL/(min*1.73m2) ± 31.4, p = 0.04), with the mean decrease of 5.86 ml/(min*1.73m2). The local recurrent-free survival(LRFS) and renal-cancer-free survival (RCFS) were 100% and 60%, respectively. The cancer specifical survival (CSS) and overall survival (OS) were 95.5% and 100%, respectively. CONCLUSION: Microwave ablation is a safe and feasible method for the treatment of RCC in VHL disease, preserving renal function and yielding satisfactory oncological outcomes.

Surgical management of endolymphatic sac tumor: classification, outcomes and strategy. A single institution's experience.

PURPOSE: To review the resections of endolymphatic sac tumor (ELST) and describe our experience in the surgical management of ELST. METHODS: Retrospective investigation of consecutive patients who underwent resection of ELSTs at our hospital between 1999 and 2019. The symptoms, diagnosis, surgical findings, and outcomes were analyzed to develop a tumor staging system and corresponding surgical strategy. RESULTS: Retrospective review revealed the surgical treatment of 22 ELSTs. Based on intraoperative findings of tumor extent and size, ELSTs were classified into two types. Type-I (n = 6) referred to the small tumors that were locally confined with limited invasion of semicircular canals and dura; type-II (n = 16) referred to the large tumors that presented extensive erosion of at least one anatomic structure apart from the semicircular canals and the dura around endolymphatic sac. In this case series, Type-I ELST is amenable to resection through a transmastoidal approach, and subtotal petrosectomy is appropriate for the resection of type-II ELST. Sensorineural hearing loss (SNHL) is the most commonly preoperative symptom in both two types of cases. Five type-II ELSTs experienced recurrence and underwent reoperation, whereas all type-I ELSTs did not. CONCLUSION: ELST usually results in SNHL (95%) at the time of diagnosis. The surgical strategy and prognosis of ELST resections are different between type-I and type-II: type-I ELST is amenable to transmastoidal approach with the preservation of facial nerve, whereas type-II ELST increase the surgical difficulty and the risk of recurrence, and subtotal petrosectomy is the basic requirement for the resection of type-II ELST.

[Stereotactic irradiation for optic nerve hemangioblastoma associated with Von Hippel-Lindau disease: a case report and literature review]. / Stereotaksicheskoe obluchenie gemangioblastomy zritel'nogo nerva, assotsiirovannogo s bolezn'yu fon Gippelya­Lindau: klinicheskii sluchai i obzor literatury.

Hemangioblastoma is a benign tumor of the central nervous system arising sporadically or as a component of Von Hippel-Lindau disease. Von Hippel-Lindau disease is a rare autosomal dominant hereditary syndrome with various phenotypes caused by VHL gene variants. To date, only about 40 cases of optic nerve hemangioblastoma have been described in the literature. Stereotactic irradiation may be effective for supratentorial hemangioblastomas including lesions of optic nerves. The authors describe a rare case of stereotactic irradiation of intraorbital hemangioblastoma of the optic nerve in a patient with Von Hippel-Lindau disease.

Spinal hemangioblastomas: analysis of surgical outcome and prognostic factors.

The prognostic factors for surgically removed spinal hemangioblastomas, the impact of VHL disease on outcome, and the role of intraoperative neuromonitoring are still not completely clear. The aim of this study was to review our experience with spinal hemangioblastomas in order to assess potential predictors of neurological outcome after surgery. All cases of spinal hemangioblastomas removed at two Italian academic institutions from 1985 to 2020 were reviewed. Data about clinical presentation and symptom duration, diagnosis of VHL, surgical approach, use of IONM, duration of hospital stay, follow-up, and modified McCormick grade before and after surgery were extracted. Sixty-one patients (31 F, 30 M) underwent 69 surgeries to remove 74 spinal hemangioblastomas (37 cervical, 32 thoracic, 5 lumbar). Improvement was found in 32.3% of cases, neurological condition remained stable in 51.6% of cases, and deteriorated in 16.1% of patients. A worsening trend in VHL patients and an improvement trend in non-VHL patients were detected, despite the lack of statistical significance. Laminotomy and use of IONM were found to be associated with better outcome, although no association was found between surgery without IONM and worse outcome. In most cases, patients affected by spinal hemangioblastomas can expect a good long-term outcome. In our experience, laminotomy seems to be associated with better outcome compared to laminectomy. While its absence is not associated with worse outcome, IONM seems to be associated with a better neurological outcome. Our study suggests that the more impaired the preoperative neurological condition, the worse the outcome.

Symptoms and clinical features in patients affected by endolymphatic sac tumor: a systematic review and meta-analysis.

PURPOSE: Most ELST data in the literature are case studies or limited to small cohorts (< 16 patients). We evaluated the main clinical signs observed at endolymphatic sac tumor (ELST) diagnosis in patients with or without Von Hippel-Lindau disease. METHODS: We conducted a comprehensive literature search in PubMed, Scopus, and Web of Science. We included studies with at least 1 patient, of any age, affected by sporadic or VHL-related ELSTs reporting levels of hearing loss and facial nerve function and a comprehensive description of presenting symptoms at ELST diagnosis. We combined data for proportional meta-analysis. p values of 0.05 were considered statistically significant. Methodological quality was evaluated. Analyses were performed with MedCalc 14.8.1 software. RESULTS: A total of 26 studies, including 113 patients and 118 cases of ELSTs were included. Pooled proportion rates (95% CI) of overall hearing loss was 88.7%, (82.4-93.4), severe hearing loss was 21.6% (12.8-32.1) profound hearing loss was 39.8% (28.7-51.5), vertigo/imbalance was 42.0% (33.8-50.5), tinnitus was 61.8% (53.4-69.8) and facial nerve palsy was 30.6% (23.2-38.9). Generally, symptoms were homogeneous or moderately heterogeneous among included studies. CONCLUSION: This is the first systematic review of clinical presentations at ELST diagnosis. The most serious clinical events include profound hearing loss and facial impairment. Fluctuating hearing loss, tinnitus and vertigo are frequently reported and may confound correct and prompt ELST diagnosis.

Hemangioblastoma and von Hippel-Lindau disease: genetic background, spectrum of disease, and neurosurgical treatment.

INTRODUCTION: Hemangioblastomas are rare, histologically benign, highly vascularized tumors of the brain, the spinal cord, and the retina, occurring sporadically or associated with the autosomal dominant inherited von Hippel-Lindau (VHL) disease. Children or adults with VHL disease have one of > 300 known germline mutations of the VHL gene located on chromosome 3. They are prone to develop hemangioblastomas, extremely rarely starting at age 6, rarely at age 12-18, and, typically and almost all, as adults. There is a plethora of VHL-associated tumors and cysts, mainly in the kidney, pancreas, adrenals, reproductive organs, and central nervous system. Due to a lack of causal treatment, alleviation of symptoms and prevention of permanent neurological deficits as well as malignant transformation are the main task. Paucity of data and the nonlinear course of tumor progression make management of pediatric VHL patients with hemangioblastomas challenging. METHODS: The Freiburg surveillance protocol was developed by combining data from the literature and our experience of examinations of > 300 VHL patients per year at our university VHL center. RESULTS: Key recommendations are to start screening of patients at risk by funduscopy with dilated pupils for retinal tumors with admission to school and with MRI of the brain and spinal cord at age 14, then continue biannually until age 18, with emergency MRI in case of neurological symptoms. Indication for surgery remains personalized and should be approved by an experienced VHL board, but we regard neurological symptoms, rapid tumor growth, or critically large tumor/cyst sizes as the key indications to remove hemangioblastomas. Since repeated surgery on hemangioblastomas in VHL patients is not rare, modern neurosurgical techniques should encompass microsurgery, neuronavigation, intraoperative neuromonitoring, fluorescein dye-based intraoperative angiography, intraoperative ultrasound, and minimally invasive approaches, preceded in selected cases by endovascular embolization. Highly specialized neurosurgeons are able to achieve a very low risk of permanent morbidity for the removal of hemangioblastomas from the cerebellum and spinal cord. Small retinal tumors of the peripheral retina can be treated by laser coagulation, larger tumors by cryocoagulation or brachytherapy. CONCLUSION: We consider management at experienced VHL centers mandatory and careful surveillance and monitoring of asymptomatic lesions are required to prevent unnecessary operations and minimize morbidity.

Long-term outcome and prognostic factors of intramedullary spinal hemangioblastomas.

Spinal hemangioblastomas constitute 1.6-5.8% of all spinal cord tumors. Microsurgical excision of these tumors is challenging. The purpose of this study is to analyze the neurological improvement and long-term functional outcome of spinal hemangioblastomas. This retrospective study included 15 patients who underwent surgery for intramedullary spinal hemangioblastoma at the Department of Neurosurgery of Sri Chitra Tirunal Institute for Medical Sciences and Technology from January 2001 to June 2014. Eight patients (53%) were diagnosed to have von Hippel-Lindau (vHL) disease. Eight (53%) of them were females, and seven were males (47%). Mean age was 33.8 years (16-55 years). Duration of illness ranged from 2 weeks to 4 years, and average duration was 10.5 months. Most common symptom was motor weakness followed by sensory disturbances, pain, and bladder incontinence. Six (85.7%) sporadic spinal hemangioblastomas were in McCormick grade I; whereas, 7 (87.5%) of vHL spinal hemangioblastomas were in grade II or above. In the immediate postoperative period, three patients noticed improvement in their motor weakness. Six patients (40%) experienced deterioration of preoperative neurological status in the immediate postoperative period. Three of them were sporadic tumors, and others had vHL syndrome. Favorable long-term outcome was achieved in 80% of cases. Though neurological deterioration is common after surgical resection of spinal hemangioblastomas, majority of them are reversible. Long-term functional outcome is favorable with minimal postoperative morbidities. Both sporadic- and vHL-associated tumors share common clinical and radiological features, and neurological outcome is equally good in both.

Microsurgical resection of a radicular hemangioblastoma with subarachnoid hemorrhage: how I do it.

BACKGROUND: Hemangioblastomas (HBL) are benign tumors occurring sporadically or associated with Von Hippel-Lindau syndrome (VHL). METHOD: We present the pre-, per-, and postoperative course of a rare case with radicular HBL presenting with subarachnoid hemorrhage (SAH) in the frame of VHL. We describe the microsurgical approach. CONCLUSION: Complete microsurgical in bloc resection has been performed. Postoperative course was uneventful.

Combined Laparoscopic and CT Monitoring of the Ice-Ball Margin during Cryoablation for Renal Cell Carcinoma Associated with von Hippel-Lindau Disease: First Case.

We report a 47-year-old Japanese female with 10 previous treatments for multiple bilateral renal cell carcinoma (RCC) associated with von Hippel-Lindau disease. The 14-mm right lower pole renal tumor was in contact with the right ureter. Laparoscopic cryoablation was performed to protect the ureter wrapped with gauze. Computed tomography (CT) monitoring was used to confirm the precise ≥ 6 mm ice-ball margin. There was no local progression at 6-months post-surgery. The serum creatinine has been stable. This is apparently the first report of combined laparoscopic and CT monitoring of an ice-ball formation and its margin during cryoablation for RCC.

Clear cell neuroendocrine tumor of the pancreas in von Hippel-Lindau disease: a case report and literature review.

Clear cell neuroendocrine tumor (NET) of the pancreas is found in von Hippel-Lindau (VHL) disease, multiple endocrine neoplasia type I (MEN I), and sporadic form. Clear cell NETs are often misdiagnosed as metastatic renal cell carcinoma. A 47-year-old woman with VHL was found to have a mass in the pancreatic tail and two masses in the right kidney with two cysts. A distal pancreatectomy and right radical nephrectomy were performed. The pancreatic lesion was a well-circumscribed, golden-yellow solid mass, which was lobulated by septal fibrosis. Microscopically, the tumor consisted of entirely of clear cells with prominent nucleoli. The tumor cell nests were separated by collagen fibrosis. Immunohistochemical studies were positive for the neuroendocrine markers and vimentin. Synchronous kidney tumors were clear cell renal cell carcinoma and cystic renal cell carcinoma. Those with syndrome are younger than those without syndrome. Sporadic tumors have larger size and higher grade than those of VHL and MEN I. Stromal sclerosis is frequently observed in VHL, compared with the other two groups. In the absence of a documented genetic profile and family history, awareness of these features should help us to diagnose clear cell pancreatic NETs resembling metastatic renal cell carcinoma.

[Optical Coherence Tomography Angiography in Diagnosis and Post-Treatment Assessment of Hemangioblastomas in Hippel-Lindau Disease]. / Möglichkeiten der optischen Kohärenztomografie-Angiografie bei Diagnostik und postoperativer Verlaufskontrolle von Hämangioblastomen bei Von-Hippel-Lindau-Syndrom.

Background Optical coherence tomography angiography (OCTA) offers the possibility to visualize, non-invasively, blood vessels of the retina. In vascular tumors, especially hemangioblastomas in Hippel-Lindau disease, new information can be obtained with OCTA concerning structure of the tumor, tumor activity and treatment success. Patients Ten eyes of 10 patients with retinal hemangioblastoma in Hippel-Lindau disease were included. The age of the patients ranged from 19 years to 65 years (median 44 years). Results A total of 10 active and one inactive hemangioblastomas were examined with OCTA. In larger tumors, only the superficial blood flow could be visualized. Four hemangioblastomas were not treated due to their location near the optic nerve head. Six hemangioblastomas in the peripheral retina were treated with laser photocoagulation. In 4 eyes, a reduced blood flow could be shown directly after the treatment. The visualization of the perfusion was partially blocked after laser treatment. Conclusion OCTA enables innovative methods of pre- and postoperative assessment of retinal hemangioblastomas. It has the potential to give new information about the morphology, activity and effects of treatment. Prospective studies with longer follow-up are needed to evaluate the therapeutic relevance of this new imaging method.

PARS PLANA VITRECTOMY IN ADVANCED CASES OF VON HIPPEL-LINDAU EYE DISEASE.

PURPOSE: To investigate spectrum of patients with Von Hippel-Lindau disease (VHL) that required pars plana vitrectomy and evaluate anatomical and functional outcomes of surgery. METHODS: Twenty-three patients who underwent surgery for advanced VHL eye disease were assessed by genetic tests, diagnostic tests for systemic lesions, and clinical eye examination. The vitrectomized eyes were divided into two groups: with or without retinotomy (group R vs. NR). Functional and anatomical outcome was analyzed and compared between the groups. RESULTS: All patients had central nervous system hemangioblastomas and 57% had other systemic tumors. Point germline mutations, large partial deletions, and complete vhl gene deletions were found in 64%, 27%, and 9% of patients, accordingly. Destruction of hemangioblastomas by retinotomy, laser, or cryotherapy and anatomical attachment of the retina were achieved in all eyes. Preoperative mean distance best-corrected visual acuity was logarithm of the minimum angle of resolution 2.66 (20/9,140) in group R and 1.76 (20/1,150) in group NR (P < 0.05). At 6 months postoperatively, distance best-corrected visual acuity improved in 20 eyes (83%). After over 24 months postoperatively, distance best-corrected visual acuity remained better than preoperatively in 36% in the R group and in 70% in the NR group of eyes. During 24 months postoperatively in 17 eyes, new retinal capillary hemangiomas developed. The mean number of new retinal capillary hemangiomas per eye was higher in group R than in group NR (3.14 vs. 0.70; P < 0.01). In group R, number of new retinal capillary hemangioblastoma was higher in retinal segments where retinotomy was performed (n = 29) than in other areas (n = 13) (P < 0.01). CONCLUSION: Advanced VHL eye disease correlates with occurrence of central nervous system and systemic lesions. Spectrum of vhl gene mutation in the patients corresponds to that of the general VHL population. Pars plana vitrectomy in advanced VHL eye disease can improve or preserve visual function, but postoperative progression of ocular VHL disease can be accelerated in cases where retinotomy is performed.

Hemangioblastomas with leptomeningeal dissemination: case series and review of the literature.

BACKGROUND: Leptomeningeal dissemination of hemangioblastomas (HB) of the central nervous system (CNS) is extremely rare. Few studies have reported leptomeningeal involvement in sporadic HB or in HB associated with von Hippel-Lindau syndrome. The clinical and radiological features of leptomeningeal involvement in HB after surgery have not been described in detail. MATERIALS AND METHODS: This retrospective case review involved patients from three different tertiary referral centers with leptomeningeal dissemination of HB after surgery for the primary mass. A literature review was also performed to describe the clinical and radiological characteristics and long-term outcomes of patients who developed leptomeningeal dissemination after initial surgical resection. RESULTS: This study included seven patients, five males and two females, ranging in age from 36 to 54 years. Incidence of leptomeningeal dissemination in patients with HB was about 4.3 % (3/69). It appeared at a mean 94.9 months (range, 39-204 months) after gross total resection of CNS HBs. Three of the seven patients died 5, 38, and 79 months, respectively, after diagnosis of leptomeningeal dissemination. Review of the literature identified 21 patients with characteristics of leptomeningeal dissemination similar to those in our series. CONCLUSIONS: Leptomeningeal dissemination of HB is a rare pattern of long-term recurrence. Long-term outcomes may be fatal. The long developmental period suggests that early detection and aggressive management may improve prognosis in patients with CNS leptomeningeal dissemination of HB.

A rare case of peripheral nerve hemangioblastoma­case report and literature review.

Hemangioblastoma is a rare benign tumor that consists of neoplastic vacuolated stromal cells and highly developed capillary blood vessels. These tumors are almost exclusively found in the central nervous system, but in extremely rare cases, it can arise in peripheral nerves. In the majority of cases, it occurs sporadically (60 to 75%), but in about 25% of cases, it is associated with von Hippel-Lindau disease. We present the first case of ulnar nerve hemangioblastoma in a 70-year-old male. The patient presented with a slow-growing palpable mass on the front side of the right upper arm. Macroscopically, the tumor was round shaped, encapsulated, reddish-orange in color, very well vascularized, and about 3 cm in diameter; one nerve fascicle was entering the tumor tissue, so it was resected with the tumor. The rest of the nerve fascicles were intact. Postoperative course was uneventful. Histopathological analysis with immunohistochemical analysis confirmed that the tumor was a peripheral nerve hemangioblastoma WHO grade I. Physical treatment was conducted, and there was no motor neurological deficit on follow-up after 3 months, only hypoesthesia of the fourth and fifth finger. These lesions are so rarely found arising from peripheral nerves that only four published cases exist in literature today. There is very little data about these tumors in world literature, so we consider our paper a valuable contribution to global knowledge on these tumors.

Metastatic pancreatic neuroendocrine tumor to the central nervous system in a patient with von Hippel-Lindau disease: A case report and literature review.

Pancreatic neuroendocrine tumor (NET) is frequently encountered in patients with von Hippel-Lindau disease (VHL) and uncommonly metastasizes to the central nervous system. Here, we present the case of a VHL patient with symptomatic pancreatic NET metastases to both the cervical spinal cord and a preexisting brainstem hemangioblastoma (e.g., tumor- to-tumor metastasis).

Cord compression due to extradural thoracic nerve root hemangioblastoma.

Hemangioblastomas (HGBs) are benign tumors that occur sporadically or as part of von Hippel-Lindau (VHL) disease. 6-8% of spinal HGBs are extramedullary in location, and basically referred to as HGB of the spinal nerve root. Purely extradural (ED) location is the rarest form of these tumors. We report a case of a non-VHL patient with large thoracic ED HGB, who presented with myelopathy due to cord compression. We emphasize the importance of correct pre-operative diagnosis as well as pre-operative embolization in order to reach the goal of complete tumor resection with minimal complications. We also review the relevant literature and summarize the few case reports of this unique tumor.

Nephron-sparing surgery for multifocal and hereditary renal tumors.

PURPOSE OF REVIEW: Despite the controversy surrounding the benefits of nephron-sparing surgery, multiple absolute indications for nephron-sparing surgery still exist, including the classic indications of hereditary and bilateral kidney tumors. RECENT FINDINGS: Multiple genetic mutations have been identified which lead to hereditary kidney cancer conditions. These are briefly reviewed because the surgical management of hereditary kidney tumors depends on the genetic and histologic subtypes involved. Clear understanding of these hereditary conditions is crucial for proper surgical management of these tumors. SUMMARY: Complex partial nephrectomy for multiple renal tumors, or multiplex partial nephrectomy, requires not only exceptional surgical skills but expertise of numerous nonsurgical methodologies, such as hands-on intraoperative ultrasonography and interpretation of multiple imaging modalities. In addition, multidisciplinary management is crucial for optimal outcomes in patient care. This review evaluates the most advanced surgical techniques and perioperative management required to successfully care for these challenging cases.

Paraplegia in a patient with Von Hippel Lindau syndrome: surgical and reconstructive treatment of Marjolin's ulcer. A case report.

STUDY DESIGN: Marjolin's ulcer is a squamous cell carcinoma that develops in posttraumatic scars and chronic wounds. Suspicion of such lesions should be raised in chronic wounds demonstrating characteristic changes. We have reported the peculiar phenomenon of malignant transformation of chronic pressure sores that occurred in a paraplegic patient. OBJECTIVES: The aim of this study was to cover the extensive defects by a last resort reconstructive option. SETTING: Department of Plastic and Reconstructive Surgery, Università Politecnica delle Marche, Ancona, Italy. METHODS AND RESULTS: A 40-year-old paraplegic man, with multiple hemangioblastomas of the brain and spinal cord due to Von Hippel Lindau syndrome developed pressure ulcers with unstable healing over the sacral, trochanteric, bilateral, and ischiatic areas after 15 years from neurosurgery. The biopsy result showed an invasive squamous carcinoma. Carcinomas in pressure sores are highly aggressive, and they need to be treated more radically. In our case we opted for a demolitive surgical treatment including musculocutaneous rotational flap harvested from total left thigh to cover the extensive defects. The limb was previously disarticulated. CONCLUSION: In Marjolin's ulcer, multiple biopsies are the first-line modality for the early diagnosis as they are a safe method with high rate of accuracy. First-line treatment is surgery consisting of radical excision with lymph node dissection, if they are involved. Adjuvant radiation therapy may be used in selected patients. Management of massive pelvic defects can be a challenging problem. The pedicled lower limb flap offers a technique that can be considered as a last resort procedure for extensive defects where other options are insufficient or not available anymore. In our case the patient is disease-free after 2 years of follow-up.

Superior mediastinal paraganglioma associated with von Hippel-Lindau syndrome: report of a case.

Extra-adrenal pheochromocytomas are termed paragangliomas. Paragangliomas in the mediastinum, especially the superior mediastinum, are extremely rare. It is known that paragangliomas or pheochromocytomas occur in combination with von Hippel-Lindau syndrome. We present the case of a non-functional superior mediastinal paraganglioma in a patient with von Hippel-Lindau syndrome, without a familial history suggestive of the condition. This case highlights that we should be aware of possible sporadic von Hippel-Lindau syndrome in patients with a mediastinal paraganglioma.