The management of VHL syndrome is multidisciplinary. The urologist's challenge is to preserve renal and adrenal function in a multifocal, bilateral disease with a high propensity to recur . The diagnosis is clinical and is aided by genetic analysis (3p25 germ-line mutation).
VHLS is detected commonly in the third decade. The median age at presentation shown in the literature varies from 30 to 40 years [3, 9, 10]. In the current series, the median age at presentation was 39 years (23–45). Family history is an essential factor in the clinical criteria for diagnosis and was positive in 60% of patients in this series, similar to previously reported reviews [9, 11].
The presentation of VHLS is varied. The spectrum ranges from incidentally or screen-detected to patients who present with features of cerebellar tumors, pheochromocytomas, or hematuria. If the patients were diagnosed with pheochromocytomas, adrenalectomy gets priority, followed by NSS and then excision of cerebellar tumors. In the present series, 41% of patients presented with hematuria, and a diagnosis of multifocal RCC was made.
The majority of the data on VHLS are from retrospective reviews [10, 11] and a few prospective cohorts . Mutational analysis was performed in 7 of the patients in the present study, which were confirmatory of a germ-line mutation in the short arm of chromosome 3. Neumann et al. and Baghai et al. also performed the above-mentioned mutational analysis (184 and 12 patients) [9, 11].
The prognosis and management of VHLS have significantly improved. Nephron sparing surgery is the current gold standard in managing multifocal RCC in patients with VHLS. We had 13 patients who underwent nephron sparing surgeries (open partial nephrectomy). The immediate postoperative renal recovery was good except in one patient who required postoperative hemodialysis for a week. Her renal functions gradually improved, and at five years follow up, it normalized. In the earlier case series published in 1992 by Novick and Streem , the author reported NSS in 12 patients. Two required to be on maintenance hemodialysis, and one patient underwent a renal transplant. However, no patients required renal replacement therapy in the subsequent case reports and series by Shinohara and Jilg et al. [10, 12]. As the operative techniques of NSS and perioperative care have improved over time, the preservation of renal function can be achieved consistently, though multiple surgeries are required.
In the present series, the median follow-up was 6.5 years [2,3,4,5,6,7,8,9,10,11,12]. Patients with VHL who undergo NSS have a high chance of recurrence. In the current series, there were seven patients who developed local recurrence (53%). Of these, three patients (17%) required two nephron sparing surgeries. The median time of recurrence was ten years. Local recurrence has also been reported after ten years [13, 14]. Metastasis is rare [3, 9]. In this series, one patient with multifocal RCC developed a local recurrence and metastasis to the pancreas at a follow-up of 10 years. There was no mortality in the present case series. However, there was a 5–10% mortality in the earlier studies [3, 9].
Management of pheochromocytomas in patients with VHLS is also a challenge because of their bilateral occurrence. In the present series, seven patients underwent total adrenalectomies, and 3 with bilateral tumors underwent cortical sparing adrenalectomy. None of the patients developed adrenal insufficiency or crisis in the immediate postoperative period, and none required long-term steroid replacement at a median follow-up of 10 years. In a prospective cohort study by Neumann et al. , 184 patients with VHLS underwent adrenalectomy (30%—cortical sparing). 30% of patients developed adrenal crisis, while 13% of the patients developed iatrogenic Cushings and needed to be on steroid replacement at a median follow-up of 8 years. However, retrospective reviews [11, 15] showed no incidence of adrenal insufficiency.
The study's limitations were that it was a retrospective review with its inherent bias and that the diagnosis in the earlier cases was based on clinical criteria only. Due to the rarity of the disease, the number of patients was few. However, the study's strengths include an excellent follow-up and only a few studies about VHLS from India.
It seems clear that oncological clearance can be optimally achieved by nephron sparing surgery. Though there is a high incidence of recurrence, a second NSS can salvage them without affecting the overall survival. Cortical sparing adrenalectomy in bilateral pheochromocytoma preserves adrenal function and avoids steroid supplementation.