Hereditary Renal Tumors Research Articles

Multiple and hereditary renal tumors: a review for radiologists

80% of renal carcinomas (RC) are diagnosed incidentally by imaging. 2–4% of "sporadic" multifocality and 5–8% of hereditary syndromes are accepted, probably with underestimation. Multifocality, young age, familiar history, syndromic data, and certain histologies lead to suspicion of hereditary syndrome. Each tumor must be studied individually, with a multidisciplinary evaluation of the patient. Nephron-sparing therapeutic strategies and a radioprotective diagnostic approach are recommended.Relevant data for the radiologist in major RC hereditary syndromes are presented: von-Hippel-Lindau, Chromosome-3 translocation, BRCA-associated protein-1 mutation, RC associated with succinate dehydrogenase deficiency, PTEN, hereditary papillary RC, Papillary thyroid cancer- Papillary RC, Hereditary leiomyomatosis and RC, Birt-Hogg-Dubé, Tuberous sclerosis complex, Lynch, Xp11.2 translocation/TFE3 fusion, Sickle cell trait, DICER1 mutation, Hereditary hyperparathyroidism and jaw tumor, as well as the main syndromes of Wilms tumor predisposition.The concept of "non-hereditary" familial RC and other malignant and benign entities that can present as multiple renal lesions are discussed.

Hereditary renal cell tumors: Clinicopathologic importance

Hereditary renal cancer syndromes represent approximately 5% of renal malignancies and have distinctive clinical, histopathologic, and genetic features. Next-generation sequencing and other molecular testing methods have uncovered several hereditary renal cancer syndromes. Several autosomal dominant hereditary renal cell carcinoma (RCC) syndromes, including those related to germline pathogenic variants in VHL, BAP1, MITF, MET, FH, TSC1/TSC2, FLCN, SDH, and CDC73 have been confirmed. FH- and BAP1-related RCCs are associated with more aggressive disease. Identifying the clinical and pathological features in these hereditary RCC syndromes is important as, relative to familial cohorts, these patients require early screening and intervention and regular surveillance to improve their clinical prognosis and long-term outcomes. More importantly, identification of these syndromes plays a vital role in personalized management and systemic treatment selection in this modern era of precision medicine. Ongoing studies have demonstrated that treatment based on genetic pathway targeting is a promising approach for hereditary renal cancer management. This review describes updates in the diagnostic criteria for and management of familial kidney cancer syndromes.

Imaging evaluation of hereditary renal tumors: a pictorial review.

More than 10 hereditary renal tumor syndromes (HRTSs) and related germline mutations have been reported with HRTS-associated renal and extrarenal manifestations with benign and malignant tumors. Radiologists play an important role in detecting solitary or multiple renal masses with or without extrarenal findings on imaging and may raise the possibility of an inherited predisposition to renal cell carcinoma, providing direction for further screening, intervention and surveillance of the patients and their close family members before the development of potentially lethal renal and extrarenal tumors. Renal cell carcinomas (RCCs) associated with von Hippel-Lindau disease are typically slow growing while RCCs associated with HRTSs, such as hereditary leiomyomatosis and renal cell carcinoma syndrome, are highly aggressive. Therefore, radiologists need to be familiar with clinical and imaging findings of renal and extrarenal manifestations of HRTSs. This article reviews clinical and imaging findings for the evaluation of patients with well-established HRTSs from a radiologist's perspective to facilitate the clinical decision-making process for patient management.

18Fluorodeoxyglucose-positron emission tomography/computed tomography for differentiation of renal tumors in hereditary kidney cancer syndromes.

To assess differences in FDG-PET/CT uptake among four subtypes of renal tumors: clear cell RCC (ccRCC), papillary type I and II RCC (pRCC), and oncocytoma. This retrospective study investigated 33 patients with 98 hereditary renal tumors. Lesions greater than 1cm and patients with a timeframe of less than 18months between preoperative imaging and surgery were considered. FDG-PET/CT images were independently reviewed by two nuclear medicine physicians, blinded to clinical information. Volumetric lesion SUVmean was measured and used to calculate a target-to-background ratio respective to liver (TBR). The Shrout-Fleiss intra-class correlation coefficient was used to assess reliability between readers. A linear mixed effects model, accounting for within-patient correlations, was used to compare TBR values of primary renal lesions with and without distant metastasis. The time interval between imaging and surgery for all tumors had a median of 77 (Mean: 139; Range: 1-512) days. Intra-class reliability of mean TBR resulted in a mean κ score of 0.93, indicating strong agreement between the readers. The mixed model showed a significant difference in mean TBR among the subtypes (p < 0.0001). Pairwise comparison showed significant differences between pRCC type II and ccRCC (p < 0.0001), pRCC type II and pRCC type I (p = 0.0001), and pRCC type II and oncocytoma (p = 0.0016). Furthermore, a significant difference in FDG uptake was present between primary pRCC type II renal lesions with and without distant metastasis (p = 0.023). pRCC type II lesions demonstrated significantly higher FDG activity than ccRCC, pRCC type I, or oncocytoma. These findings indicate that FDG may prove useful in studying the metabolic activity of renal neoplasms, identifying lesions of highest clinical concern, and ultimately optimizing active surveillance, and personalizing management plans.

Clinical and morphologic review of 60 hereditary renal tumors from 30 hereditary renal cell carcinoma syndrome patients: lessons from a contemporary single institution series.

Hereditary renal cell carcinoma syndromes (HRCCS) are characterized by the presence of pathogenic germline variants that predispose patients to renal cell carcinomas as well as additional extra-renal manifestations. The importance of identifying HRCCS patients cannot be overemphasized, as patients and their families can begin surveillance for syndrome-associated manifestations once identified. The present study is a retrospective clinical and morphologic review of 60 hereditary renal tumors from 30 HRCCS patients treated at our institution with either Von Hippel-Lindau disease (VHL), Birt-Hogg-Dubé syndrome (BHD), tuberous sclerosis complex (TSC), hereditary leiomyomatosis and renal cell cancer syndrome, or succinate dehydrogenase (SDH) deficiency syndrome. Hereditary renal cell carcinoma syndromes kidney tumors often demonstrate specific morphologic features, characteristic background changes in renal parenchyma, and extra-renal manifestations, which, when recognized by the pathologist, can trigger genetic testing referral for specific familial cancer syndromes. Our study demonstrates the majority of tumors were consistent with the anticipated clinicopathologic profile of renal tumors found within HRCCS patients, although we found some unique characteristics within this cohort including a case of clear cell papillary renal cell carcinoma within a VHL patient, and a unique renal tumor with tubulopapillary features present in a patient with a germline SDHD mutation. Additionally, although the literature reports the presence of epithelioid angiomyolipoma (AML) as a common occurrence in TSC patients, our cohort of 3 patients with AMLs demonstrated only classic features. The findings we describe facilitate pathologist-based recognition of HRCCS and can prompt genetic evaluation for relevant patients.

Hypoxia, angiogenesis, and metabolism in the hereditary kidney cancers.

The field of hereditary kidney cancer has begun to mature following the identification of several germline syndromes that define genetic and molecular features of this cancer. Molecular defects within these hereditary syndromes demonstrate consistent deficits in angiogenesis and metabolic signaling, largely driven by altered hypoxia signaling. The classical mutation, loss of function of the von Hippel-Lindau (VHL) tumor suppressor, provides a human pathogenesis model for critical aspects of pseudohypoxia. These features are mimicked in a less common hereditary renal tumor syndrome, known as hereditary leiomyomatosis and renal cell carcinoma. Here, we review renal tumor angiogenesis and metabolism from a HIF-centric perspective, considering alterations in the hypoxic landscape, and molecular deviations resulting from high levels of HIF family members. Mutations underlying HIF deregulation drive multifactorial aberrations in angiogenic signals and metabolism. The mechanisms by which these defects drive tumor growth are still emerging. However, the distinctive patterns of angiogenesis and glycolysis-/glutamine-dependent bioenergetics provide insight into the cellular environment of these cancers. The result is a scenario permissive for aggressive tumorigenesis especially within the proximal renal tubule. These features of tumorigenesis have been highly actionable in kidney cancer treatments, and will likely continue as central tenets of kidney cancer therapeutics.

Safety Considerations and Local Tumor Control Following Percutaneous Image-Guided Cryoablation of T1b Renal Tumors.

To retrospectively assess the safety and oncological efficacy of percutaneous image-guided cryoablation (CA) of T1b (>4cm/<7cm) renal tumors. Institutional electronic records were retrospectively reviewed to identify the patients who had undergone percutaneous CA of T1b renal tumors between 2008 and 2016. CA was proposed by a multidisciplinary tumor board for cases with poor renal function or a single kidney; unsuitable for surgical resection; or genetic syndromes predisposing to multiple hereditary renal tumors. Patients' demographics, procedural and follow-up data were accurately collected and analyzed. Twenty-seven consecutive patients (12 females, 15 males; mean age 72.3±14.3years) were included. Mean tumor diameter was 47.9±6.3mm. MRI guidance was used in 6/27 cases (22.2%) and CT guidance in the remaining 21/27 (77.8%) cases. Hydro- and/or carbo-dissections were necessary in 21/27 cases (77.8%). Complications graded≥II were reported in three (11.1%) patients. Technical success and technical efficacy were 100 and 87.5%, respectively. Local tumor control (LTC) evaluated at imaging follow-up≥6months was 82.6, 72.3 and 60.3% at 12-, 24- and 36-month follow-up, respectively. One patient passed away 3months after CA due to the metastatic evolution of the primary kidney cancer. Percutaneous CA of T1b renal tumors is safe and satisfactory rates of LTC are expected at the early follow-ups. Further studies are needed to confirm the long-term efficacy of this procedure.

Hereditary Renal Tumor Syndromes: Update on Diagnosis and Management

Hereditary renal cancers account for approximately 5%-8% of all renal tumors. Over the past 2 decades, a number of syndromes have been identified that predispose patients to early renal cancer development, representing all the major histologic types of tumor pathology. In this article, we describe the current knowledge concerning the cell type, known mechanism of tumor development, other manifestations of the syndrome, imaging findings, genetic screening, and imaging surveillance recommendations for each of the major syndromes associated with hereditary renal cancers.

Nephron-sparing surgery for multifocal and hereditary renal tumors.

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. 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. 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.

Application of retroperitoneal laparoscopic partial nephrectomy in the treatment of unilateral multifocal renal tumors

Objective To discuss the safety and efficacy of retroperitoneal laparoscopic partial nephrectomy in the treatment of unilateral multifocal renal tumors.Methods The data of 12 patients with unilateral multifocal renal tumors managed with retroperitoneal laparoscopic partial nephrectomy between 2009 and 2012 were reviewed retrospectively.The 12 patients had a mean age of 42 years (28 to 62) and body mass index of 23.5 kg/m2 (18.6 to 29.3),including 4 males and 8 females.Four cases were in the left side,7 cases were in the right side,and 1 case had bilateral renal tumors.The diameter of renal tumors ranged from 0.5 cm to 4.7 cm,and all tumors were projected on the surface of kidney.Nine cases were diagnosed as renal cell carcinoma,and 3 cases were diagnosed as angiomyolipoma before operation.All patients underwent retroperitoneal laparoscopic partial nephrectomy under general anesthesia,while 1 patient with bilateral renal tumors experienced radical nephrectomy of the contralateral renal tumor 3 months after the first operation.Results All the oprations were successful without conversion to open surgery.The mean renal artery cut off time,operative time,estimated blood loss and hospital stay were 36 min (26-60),126 min (75-184),142 ml (50-300) and 5 d (3-9),respectively.No complication occurred and 1-week postoperative serum creatinine was (78.1 ±8.1)μmol/L.Histopathological study revealed 9 cases of renal cell carcinomaand 3 cases of angiomyolipoma.During the follow-up for 33 months (13-51),1 patient with yon Hippel-Lindau syndrome was operated with ipsilateral radical nephrectomy for a local recurrence while the remains had no local recurrence or metastasis.Conclusions For localized and exogenous unilateral multifocal renal tumors,retroperitoneal laparoscopic partial nephrectomy is feasible and safe.Those who have hereditary and/or malignant renal tumors should be monitored closely. Key words: Kidney neoplasms; Multifocal; Multicentricity; Laparoscopes

Hereditary Renal Tumor Syndromes: Imaging Findings and Management Strategies

It is not rare for the radiologist to identify multiple renal masses and be the first to raise the possibility of a hereditary renal tumor syndrome. Characteristic renal and extrarenal imaging findings aid in making the correct diagnosis. The imaging findings, screening guidelines, and management techniques for the most common hereditary renal tumor syndromes are reviewed. Hereditary renal tumor syndromes have specific screening guidelines and unique management techniques in which imaging plays a central role.

Radiofrequency-Assisted Laparoscopic Partial Nephrectomy: Clinical and Histologic Results

To evaluate a surface conductive radiofrequency (RF) coagulation instrument (Tissuelink FB3.0) in laparoscopic and open partial nephrectomy (PN) in hereditary kidney cancer. The lesion depth and viability in the pathologic specimens from a surgical series and an acute porcine model were characterized under conditions of vascular perfusion and occlusion. A total of 19 patients underwent 20 laparoscopic and open procedures with the device. Data were acquired on tumor number, size, operative time, blood loss, length of stay, renal function, complications, pathologic diagnosis, and surgical-margin status. Renal lesions were created in pigs with the device, ultrasonic shears, and a standard electrocautery for specified time intervals and operative energy settings. These lesions were analyzed for depth, diameter, and tissue viability. In 20 separate (14 laparoscopic; 6 open) procedures in 19 patients, a total of 112 tumors were removed (range 1-31 tumors per procedure). The median operative time, blood loss, and length of stay were 310 minutes, 250 mL, and 4 days, respectively. There were no positive surgical margins. Median preoperative and postoperative creatinine concentrations were similar (1.0 v 1.0 mg/dL). The average treatment margin depth was 3 mm. In the porcine experiments, the treatment depth in the unclamped vascular model was significantly less in than the clamped model (4.0 +/- 1.7 mm v 7.0 +/- 1.6 mm; P < 0.05). Lesion depth and diameter increased with treatment time. Viability depth correlated well with the depth of the visible thermal lesions (Pearson correlation 0.989). This RF energy device can provided adequate and uniform hemostatic control without hilar clamping during laparoscopic and open PN for hereditary renal tumors. Gross measures of renal function after surgery appeared clinically unchanged. Coagulation depth is dependent on both tissue perfusion and time in the porcine model.

Hereditary Leiomyomatosis and Renal Cell Cancer: A Syndrome Associated With an Aggressive Form of Inherited Renal Cancer

Hereditary leiomyomatosis and renal cell cancer is a recently described hereditary cancer syndrome in which affected individuals are at risk for cutaneous and uterine leiomyomas, and kidney cancer. Our initial experience revealed the aggressive behavior of these renal tumors, often with early metastasis, despite small primary tumor size. We report the clinical characteristics and urological treatment of patients with hereditary leiomyomatosis and renal cell cancer associated renal tumors. A total of 19 patients with hereditary leiomyomatosis and renal cell cancer associated renal tumors were evaluated. The 11 women and 8 men had a median age at diagnosis of 39 years (range 22 to 67), and a median clinical and radiological followup of 34 months (range 6 to 141). Hereditary leiomyomatosis and renal cell cancer manifestations in patients with renal tumors included cutaneous leiomyomas in 11 of 17 evaluable patients (65%) and uterine leiomyomas in 7 of 7 evaluable females (100%). Median pathological tumor size was 7.8 cm (range 1.5 to 20). Histological subtypes were consistent with hereditary leiomyomatosis and renal cell cancer renal carcinoma. Four of 7 patients with 2.0 to 6.7 cm T1 tumors had spread to regional lymph nodes or metastases at nephrectomy. Overall 9 of 19 patients (47%) presented with nodal or distant metastases. Renal tumors in patients with hereditary leiomyomatosis and renal cell cancer syndrome are significantly more aggressive than those in patients with other hereditary renal tumor syndromes. In contrast to other familial renal cancer syndromes, the observation of 3 cm or less renal tumors associated with hereditary leiomyomatosis and renal cell cancer is not recommended. Careful followup of affected and at risk individuals in families is necessary.

Expression of Hypoxia Inducible Factor-1α and 2α in Genetically Distinct Early Renal Cortical Tumors

The role of the HIF class of transcription factors has been implicated to be a critical step in clear cell kidney tumorigenesis. To assess if HIF over expression is a prominent feature of other renal cell carcinoma histological subtypes we characterized the expression of HIF-1alpha and HIF-2alpha in genetically distinct early renal cortical tumors. Nascent renal tumors of distinct histology from patients with a hereditary renal tumor syndrome were characterized for HIF expression using high amplification immunohistochemistry. In addition, indirect immunofluorescence and confocal microscopy were used for subcellular localization of HIF-1alpha and 2alpha in clear cell renal carcinoma cells. Clear cell RCC tumors from patients with von Hippel-Lindau disease strongly expressed HIF-1alpha and HIF-2alpha (10 of 12 and 12 of 12 tumors, respectively). Chromophobe tumors from patients with Birt-Hogg-Dubé syndrome expressed predominantly HIF-2alpha with weaker HIF-1alpha expression (12 of 12 and 6 of 12 tumors, respectively). Consistent HIF-1alpha expression was not seen in type I papillary tumors from patients with hereditary papillary renal carcinoma (3 of 12 tumors). However, half of the type I papillary tumors (6 of 12) expressed HIF-2alpha. Differential patterns of HIF-1alpha and HIF-2alpha protein over expression were found among the 3 human kidney tumor types associated with multifocal hereditary kidney tumor syndromes. Consistent, simultaneous over expression of HIF-1alpha and HIF-2alpha appears to be specific to VHL negative clear cell renal cell carcinoma. Consistent HIF-2alpha expression was found in all 3 renal cortical tumor subtypes, suggesting a pivotal role in renal cortical tumorigenesis. Differential function of HIF-1alpha vs HIF-2alpha is suggested by the distinct subcellular localization pattern of HIF-1alpha and HIF-2alpha in clear cell renal carcinoma cells.

P.382 Trends in mortality from liver cancer in the USA, 1993–2002

With evolving radio frequency technology, the clinical application of radio frequency ablation (RFA) has been actively investigated in the treatment for small renal tumors. We present our intermediate patient outcomes after RFA.Since January 2001, 17 patients with a total of 24 hereditary renal tumors ranging from 1.2 to 2.85 cm were treated with RFA using the 200 W Cool-tip RF System (Radionics, Burlington, Massachusetts) under laparoscopic (9) or percutaneous (8) guidance and had a minimum 1-year followup. A percutaneous approach was considered unsuitable if kidney tumors were contiguous to bowel, ureter or large vessels. Treatment eligibility criteria included an average tumor diameter of less than 3.0 cm, tumor growth during 1 year and solid appearance with contrast enhancement (HU change greater than 20) on computerized tomography (CT). Postoperative followup consisted of CT with and without intravenous contrast, and renal function assessment at regular intervals.Median patient age was 38 years (range 20 to 51). At a median followup of 385 days (range 342 to 691), median tumor or thermal lesion diameter decreased from 2.26 to 1.62 cm (p = 0.0013), and only 1 lesion (4%), which was located centrally near the hilum, exhibited contrast enhancement (HU change greater than 10) on CT at 12 months. Of the 15 renal tumors ablated laparoscopically, 13 were in direct contact with the bowel and 2 were abutting the ureter, necessitating mobilization before RFA. Laparoscopic ultrasound was used to guide radio frequency electrode placement and monitor the ablation process in these cases. Operative time and intraoperative blood loss (mean ± standard mean of error) were 243 ± 29 minutes and 67 ± 9 cc, respectively. In 1 patient whose ureter was adherent to the tumor a ureteropelvic junction obstruction developed after laparoscopic RFA, requiring open repair.At the minimum 1-year followup 23 of 24 ablated tumors lacked contrast uptake on CT, meeting our radiographic criteria of successful RFA treatment. RFA treatment of small renal tumors using the Radionics system appears to result in superior treatment outcomes compared to those of earlier series with lower radio frequency power generators. A high wattage generator might attain more consistent energy deposition with subsequent cell death in the targeted tissue due to less convective heat loss.

53: Outcome in Sporadic and Hereditary Renal Tumors Treated by Nephron Sparing Surgery (NSS)

53: Outcome in Sporadic and Hereditary Renal Tumors Treated by Nephron Sparing Surgery (NSS)

Radio Frequency Ablation of Small Renal Tumors: Intermediate Results

With evolving radio frequency technology, the clinical application of radio frequency ablation (RFA) has been actively investigated in the treatment for small renal tumors. We present our intermediate patient outcomes after RFA. Since January 2001, 17 patients with a total of 24 hereditary renal tumors ranging from 1.2 to 2.85 cm were treated with RFA using the 200 W Cool-tip RF System (Radionics, Burlington, Massachusetts) under laparoscopic (9) or percutaneous (8) guidance and had a minimum 1-year followup. A percutaneous approach was considered unsuitable if kidney tumors were contiguous to bowel, ureter or large vessels. Treatment eligibility criteria included an average tumor diameter of less than 3.0 cm, tumor growth during 1 year and solid appearance with contrast enhancement (HU change greater than 20) on computerized tomography (CT). Postoperative followup consisted of CT with and without intravenous contrast, and renal function assessment at regular intervals. Median patient age was 38 years (range 20 to 51). At a median followup of 385 days (range 342 to 691), median tumor or thermal lesion diameter decreased from 2.26 to 1.62 cm (p = 0.0013), and only 1 lesion (4%), which was located centrally near the hilum, exhibited contrast enhancement (HU change greater than 10) on CT at 12 months. Of the 15 renal tumors ablated laparoscopically, 13 were in direct contact with the bowel and 2 were abutting the ureter, necessitating mobilization before RFA. Laparoscopic ultrasound was used to guide radio frequency electrode placement and monitor the ablation process in these cases. Operative time and intraoperative blood loss (mean +/- standard mean of error) were 243 +/- 29 minutes and 67 +/- 9 cc, respectively. In 1 patient whose ureter was adherent to the tumor a ureteropelvic junction obstruction developed after laparoscopic RFA, requiring open repair. At the minimum 1-year followup 23 of 24 ablated tumors lacked contrast uptake on CT, meeting our radiographic criteria of successful RFA treatment. RFA treatment of small renal tumors using the Radionics system appears to result in superior treatment outcomes compared to those of earlier series with lower radio frequency power generators. A high wattage generator might attain more consistent energy deposition with subsequent cell death in the targeted tissue due to less convective heat loss.

Chromophobe Renal Cell Carcinoma In A Patient With The Birt-Hogg-dube Syndrome

A 42-year-old pregnant white female was treated for spontaneous pneumothorax at 6 weeks of gestation. During hospitalization signs and symptoms of an acute urinary tract infection with left flank pain developed. A 20 cm. left renal mass was found on abdominal ultrasonography, which prompted a urological consultation. In an effort to limit radiation exposure in the first trimester of pregnancy local tumor staging was completed with magnetic resonance imaging. The scan revealed a large lower pole lesion without obvious perirenal, vascular or lymphatic extension (fig. 1, A). Left radical nephrectomy was performed through a supracostal 12th rib incision at the beginning of the second trimester. Histopathological examination demonstrated an eosinophilic variant of chromophobe renal cell carcinoma with oncocytic features and no capsular penetration (fig. 1, B). Postoperative course was uneventful and the patient delivered a healthy baby girl at term. During a departmental discussion held in the interim, the association of spontaneous pneumothoraces and renal tumors in the Birt-Hogg-Dube syndrome was raised. This syndrome is associated with characteristic cutaneous features and has been described in the dermatological literature but to our knowledge it has been mentioned only once in a urological article regarding hereditary renal tumors.1–3 At the time of our patient’s followup examination she was noted to have facial eruptions consisting of small skin-colored, dome-shaped papules over the malar area and nose, which are characteristic of this syndrome (fig. 2). Skin biopsy showed characteristic perifollicular fibrosis. The patient has been constitutionally well since nephrectomy and has recently been invited to the National Institutes of Health along with her family to undergo further study of this syndrome. Accepted for publication May 24, 2002. * Financial interest and/or other relationship with Ilex Pharmaceuticals and PhotoCure. FIG. 1. A, T2-weighted axial magnetic resonance imaging demonstrates 20 cm. heterogeneous mass arising from left kidney and displacing it across midline. B, chromophobe renal cell carcinoma (solid nests of cell in organoid pattern at center) with eosinophilic variance (left). H & E, reduced from 100.

PARENCHYMAL SPARING SURGERY IN PATIENTS WITH HEREDITARY RENAL CELL CARCINOMA: 10-YEAR EXPERIENCE

von Hippel-Lindau disease, hereditary papillary renal cell carcinoma, the Birt-Hogg-Dubé syndrome and familial renal oncocytoma are familial renal tumor syndromes. These hereditary disorders are noteworthy for the development of multiple bilateral renal tumors and the risk of new tumors throughout life. One management strategy is observation of solid renal tumors until reaching 3 cm, then performing parenchymal sparing surgery. We present a 5-year update on our experience. From May 1988 to October 1998, 49 patients with hereditary renal cell carcinoma, including von Hippel-Lindau disease in 44, hereditary papillary renal cell carcinoma in 4 and the Birt-Hogg-Dubé syndrome in 1, and 1 with familial renal oncocytoma underwent exploration to attempt renal parenchymal sparing surgery. Patients were followed prospectively with periodic screening for recurrence, metastasis and loss of renal function. Median followup was 79.5 months (range 0.7 to 205). A total of 50 patients underwent 71 operations resulting in unilateral nephrectomy in 6, bilateral nephrectomy in 1 and partial nephrectomy in 65, with 1 to 51 tumors removed from each kidney (mean 14.7). Mean patient age was 39.5 years (range 18 to 70). Of the 65 (40%) partial nephrectomies 26 were performed with cold renal ischemia. Mean blood loss was 2.9 +/- 0.5 l (range 0.15 to 23). Postoperative complications included renal atrophy in 3 patients. Mean preoperative serum creatinine was 1.05 +/- 0.03 mg/dl (range 0.6 to 1.8), and postoperative creatinine was 1.06 +/- 0.04 mg/dl (range 0.6 to 2.0). No patient who underwent renal parenchymal sparing surgery required renal replacement therapy. Metastatic disease developed in 1 patient with a 4.5 cm renal tumor. Parenchymal sparing surgery with a 3 cm threshold in patients with hereditary renal cancer appears to be an effective therapeutic option to maximize renal function while minimizing the risk of metastatic disease.

ADAMTS9, a Novel Member of the ADAM-TS/ Metallospondin Gene Family

ADAM-TS/metallospondin genes encode a new family of proteins with structural homology to the ADAM metalloprotease-disintegrin family. However, unlike other ADAMs, these proteins contain thrombospondin type 1 (TSP1) repeats at the carboxy-terminal end and are secreted proteins instead of being membrane bound. Members of the ADAM-TS family have been implicated in the cleavage of proteoglycans, the control of organ shape during development, and the inhibition of angiogenesis. We have cloned a new member of the ADAM-TS/metallospondin family designated here as ADAMTS9. This protein has a metalloprotease domain, a disintegrin-like domain, one internal TSP1 motif, and three carboxy-terminal TSP1-like submotifs. In contrast to other ADAM-TS family members, ADAMTS9 is expressed in all fetal tissues examined as well as some adult tissues. Using FISH and radiation hybrid analysis, we have localized ADAMTS9 to chromosome 3p14.2–p14.3, an area known to be lost in hereditary renal tumors.