Testicular germ cell tumor (TGCT) is the most common malignancy in young men. Familial clustering, epidemiologic evidence of increased risk with family or personal history, and the association of TGCT with genitourinary (GU) tract anomalies have suggested an underlying genetic predisposition. Linkage data have not identified a rare, highly-penetrant, single gene in familial TGCT (FTGCT) cases. Based on its association with congenital GU tract anomalies and suggestions that there is an intrauterine origin to TGCT, we hypothesized the existence of unrecognized dysmorphic features in FTGCT.
We evaluated 38 FTGCT individuals and 41 first-degree relatives from 22 multiple-case families with detailed dysmorphology examinations, physician-based medical history and physical examination, laboratory testing, and genitourinary imaging studies.
The prevalence of major abnormalities and minor variants did not significantly differ between either FTGCT individuals or their first-degree relatives when compared with normal population controls, except for tall stature, macrocephaly, flat midface, and retro-/micrognathia. However, these four traits were not manifest as a constellation of features in any one individual or family. We did detect an excess prevalence of the genitourinary anomalies cryptorchidism and congenital inguinal hernia in our population, as previously described in sporadic TGCT, but no congenital renal, retroperitoneal or mediastinal anomalies were detected.
Overall, our study did not identify a constellation of dysmorphic features in FTGCT individuals, which is consistent with results of genetic studies suggesting that multiple low-penetrance genes are likely responsible for FTGCT susceptibility.
Familial testicular cancer; Dysmorphology; Developmental anomalies
Background and Purpose
Treating patients with renal-cell carcinoma (RCC) after previous retroperitoneal surgery (renal or adrenal) is technically challenging. We present our initial experience with laparoscopic renal interventions (LRI) after previousopen retroperitoneal surgery in patients needing ipsilateral renal intervention. We report on feasibility, functional and oncologic outcomes of LRI after previous open retroperitoneal surgery.
Patients and Methods
We reviewed records of patients undergoing attempted laparoscopic or robot-assisted renal intervention after at least one previous open ipsilateral retroperitoneal surgery. We identified 34 patients who underwent 39 staged attempted LRI after 48 previous open ipsilateral renal or adrenal surgeries. The LRI included 20 minimally invasive partial nephrectomies (MIPN), 11 laparoscopic radiofrequency ablations (LRFA), and 8 laparoscopic nephrectomies (LTN). Demographic, perioperative, renal functional, and oncologic outcome data were collected. Statistical analyses were performed to identify risks for conversion to open surgery.
No attempted nephron-sparing procedure resulted in kidney loss. Overall conversion rate of the cohort was 28% and was highest in the MIPN group (40%). On univariate analysis, only multiple tumors that were treated significantly increased chances of open conversion (P<0.01). Subset analysis demonstrated similar rates of blood loss, operative times, and conversion rates in patients undergoing partial nephrectomy having previous open partial nephrectomy compared with previous open adrenal surgery only. There was no significant difference in preservation of renal function between MIPN and LRFA, with more than 85% of preoperative renal function preserved. Mean follow-up of 11.9 months (range 1–97.5 mos) metastasis-free survival and overall survival was 94.1% and 97%, respectively.
LRI after previous open ipsilateral retroperitoneal surgery is feasible. Repeated partial nephrectomy has the highest conversion risks among the laparoscopic renal interventions and appears to be independent of previous renal or adrenal procedure. Attempting repeated LRI for multiple tumors is a significant risk factor for open conversion. Renal functional and oncologic outcomes are encouraging at early follow-up.
Minimally invasive robotic assistance is being increasingly utilized to treat larger complex renal masses. We report on the technical feasibility and renal functional and oncological outcomes with minimum 1 year follow up of robot-assisted laparoscopic partial nephrectomy (RALPN) for tumors greater than 4 cm.
Methods and Materials
The urologic oncology database was queried to identify patients treated with RALPN for tumors greater than 4 cm and a minimum follow up of 12 months. We identified 19 RALPN on 17 patients treated between June 2007 and July 2009. Two patients underwent staged bilateral RALPN. Demographic, operative, and pathologic data were collected. Renal function was assessed by serum creatinine levels, estimated glomerular filtration rate and nuclear renal scans assessed at baseline, 3 and 12 months post-operatively. All tumors were assigned R.E.N.A.L. nephrometry scores (www.nephrometry.com).
The median nephrometry score for the largest tumor from each kidney was 9 (range 6–11) while the median size was 5 cm (range 4.1–15). Three of 19 cases (16%) required intraoperative conversion to open partial nephrectomy. No renal units were lost. There were no statistically significant differences between preoperative and postoperative creatinine and eGFR. A statistically significant decline of ipsilateral renal scan function (49% vs. 46.5%, p=0.006) was observed at three months and at twelve months postoperatively (49% vs. 45.5%, p=0.014). No patients had evidence of recurrence or metastatic disease at a median follow up of 22 months (range 12–36).
RALPN is feasible for renal tumors greater than 4 cm with moderate or high nephrometry scores. Although there was a modest decline in renal function of the operated unit, RALPN may afford the ability resect challenging tumors requiring complex renal reconstruction. The renal functional and oncological outcomes are promising at a median follow up of 22 months, but longer follow up is required.
Previous studies have shown that ischemia alters gene expression in normal and malignant tissues. There are no studies that evaluated effects of ischemia in renal tumors. This study examines the impact of ischemia and tissue procurement conditions on RNA integrity and gene expression in renal cell carcinoma.
Ten renal tumors were resected without renal hilar clamping from 10 patients with renal clear cell carcinoma. Immediately after tumor resection, a piece of tumor was snap frozen. Remaining tumor samples were stored at 4C, 22C and 37C and frozen at 5, 30, 60, 120, and 240 minutes. Histopathologic evaluation was performed on all tissue samples, and only those with greater than 80% tumor were selected for further analysis. RNA integrity was confirmed by electropherograms and quantitated using RIN index. Altered gene expression was assessed by paired, two-sample t-test between the zero time point and aliquots from various conditions obtained from the same tumor.
One hundred and forty microarrays were performed. Some RNA degradation was observed 240 mins after resection at 37C. The expression of over 4,000 genes was significantly altered by ischemia times or storage conditions. The greatest gene expression changes were observed with longer ischemia time and warmer tissue procurement conditions.
RNA from kidney cancer remains intact for up to 4 hours post surgical resection regardless of storage conditions. Despite excellent RNA preservation, time after resection and procurement conditions significantly influence gene expression profiles. Meticulous attention to pre-acquisition variables is of paramount importance for accurate tumor profiling.
Ischemia; gene expression microarrays; tissue procurement; renal cell carcinoma
Recently, a new renal cell cancer (RCC) syndrome has been linked to germline mutation of multiple subunits (SDHB/C/D) of the Krebs cycle enzyme, succinate dehydrogenase. We report our experience with diagnosis, evaluation and treatment of this novel form of hereditary kidney cancer.
Materials and Methods
Patients with suspected hereditary kidney cancer were enrolled on an NCI-IRB approved protocol to study inherited forms of kidney cancer. Individuals from families with germline SDHB, SDHC and SDHD mutations and kidney cancer underwent comprehensive clinical and genetic evaluation.
Fourteen patients from twelve SDHB mutation families were evaluated. Patients presented with RCC at an early age, 33 yrs (range 15–62 yrs), four developed metastatic kidney cancer and some families were found to have no manifestations other than kidney tumors. An additional family with six individuals found to have clear cell RCC that presented at a young average age, 47 yrs (range 40–53yrs), was identified with a germline SDHC mutation (R133X), two of which developed metastatic disease. A patient with a history of carotid body paragangliomas and a very aggressive form of kidney cancer was evaluated from a family with germline SDHD mutation.
SDH-RCC can be an aggressive type of kidney cancer, especially in younger individuals. Although detection and management of early tumors is most often associated with good outcome, based on our initial experience with these patients and our long term experience with HLRCC, we recommend careful surveillance of patients at risk for SDH-RCC and wide surgical excision of renal tumors.
renal cell cancer (RCC); hereditary kidney cancer; Krebs cycle; Succinate dehydrogenase
Children with von Hippel-Lindau syndrome are at an increased risk for developing bilateral pheochromocytomas. In an effort to illustrate the advantage of partial adrenalectomy (PA) over total adrenalectomy in children with VHL, we report the largest single series on PA for pediatric VHL patients, demonstrating a balance between tumor removal and preservation of adrenocortical function.
From 1994 to 2011, a prospectively maintained database was reviewed to evaluate 10 pediatric patients with hereditary pheochromocytoma for PA. Surgery was performed if there was clinical evidence of pheochromocytoma and normal adrenocortical tissue was evident on preoperative imaging and/or intraoperative ultrasonography. Perioperative data were collected and patients were followed for postoperative steroid use and tumor recurrence.
Ten pediatric patients with a diagnosis of VHL underwent 18 successful partial adrenalectomies (4 open, 14 laparoscopic). The median tumor size removed was 2.6 centimeters (range 1.2–6.5). Over a median follow up of 7.2 years (range 2.6–15.8) additional tumors in the ipsilateral adrenal gland were found in two patients. One patient underwent completion adrenalectomy and one underwent a salvage PA with resection of the ipsilateral lesion. One patient required short term steroid replacement therapy. At last follow up, 7 patients had no radiographic or laboratory evidence of pheochromocytoma.
At our institution, partial adrenalectomy is the preferred form of management for pheochromocytoma in the (VHL) pediatric population. This surgical approach allows for removal of tumor while preserving adrenocortical function and minimizing the side effects of long term steroid replacement on puberty and quality of life.
adrenalectomy; partial adrenalectomy; pediatric VHL; pheochromocytoma
Despite the high morbidity of reoperative renal surgery (RRS) in patients with multifocal recurrent renal carcinoma, most patients are able to preserve adequate renal function to obviate the need for dialysis. The economic burden of RRS has not been evaluated. We aim to provide a cost-effectiveness analysis for patients requiring RRS on a solitary kidney.
Materials and Methods
We reviewed the charts of patients treated at the National Cancer Institute (NCI) requiring RRS from 1989 to 2010. Functional, oncological and surgical outcomes were evaluated, and the costs of RRS were calculated. We then compared the costs of a 33 patients cohort who underwent RRS on a solitary kidney and a hypothetical cohort of patients that would undergo uncomplicated nephrectomy, fistula placement and dialysis. All costs were calculated based on Medicare reimbursement rates derived from Current Procedural Terminology (CPT) codes. A cost-effectiveness analysis was applied.
Despite a high complication rate (45%), 87% of patients maintained adequate renal function to avoid dialysis and 96% remained metastasis free at an average follow up of 3.12 years (range 0.3-16.4). When compared to hypothetical dialysis cohort, the financial benefit of RRS was reached at 0.68 years.
RRS is a viable alternative for patients with multifocal renal cell carcinoma requiring multiple surgical interventions, especially when left with a solitary kidney. Despite the high complication rate, most patients are able to preserve renal function and have excellent oncological outcomes. The financial benefit of RRS is reached at less than 1 year.
Reoperative renal surgery; repeat partial nephrectomy; cost effectiveness; nephron sparing surgery
While nephron-sparing surgery has been advocated for patients with bilateral renal masses, the long-term functional and oncological outcomes are lacking.
To determine the outcomes of patients with bilateral renal masses (BRM) and a minimum of 10 years of follow-up.
Design, Setting, and Participants
Patients with BRM evaluated at the National Cancer Institute who underwent their initial surgical intervention at least 10 years ago and had interventions on both renal units were included in our analysis. The data collected included demographics, hereditary diagnosis, number of renal interventions, renal function, and mortality status.
Bilateral renal surgery.
Outcome Measurements and Statistical Analysis
Overal and RCC specific survival was assessed. Comparisons of renal function and overall survival between groups containing both renal units and solitary kidneys were performed using the student T-test and Kaplan-Meier analysis.
Results and Limitations
128 patients met our inclusion criteria. The median follow-up of our cohort was 16 years (10-49), mean 17 years. The median number of surgical interventions was 3 (2-10). Eighty-seven patients (68%) required repeat interventions on their ipsilateral renal unit at last follow-up, with a median time between interventions of 6.2 years (0.7-21). Overall and RCC-specific survival of the cohort was 88% and 97%, respectively. Six patients (4.7%) ultimately underwent bilateral nephrectomies.
Although renal function was better preserved in patients with both kidneys (70 vs. 53 mL/min/1.73m2, P=0.0002) there was no difference in overall survival between those with bilateral or solitary kidneys (mean 21.5 vs. 20.8 years, respectively). Limitations of the study are in its retrospective design and inclusion of closely surveilled patients.
At a minimum of 10 years follow-up after initial surgery, nephron-sparing surgery allows for excellent oncologic and functional outcomes. Despite the need for repeat surgical interventions, employing NSS allows for avoidance of dialysis in over 95% of patients.
Familial renal cancer (FRC); bilateral renal masses (BRM); nephron-sparing surgery (NSS); partial nephrectomy; outcomes
We evaluate presentation and outcome of patients with metastatic RCC to the gallbladder from our institution and published literature.
Patients with a history of gallbladder metastasis from RCC were selected from our institution’s prospective database. A systematic PubMed search was performed to identify articles describing patients with metastatic RCC to the gallbladder. The final cohort included 33 patients: 4 from our institution and 29 from 28 previously published cases. Survival analysis was conducted using LogRank Kaplan-Meier analysis.
Median patient age was 63 years and the majority of patients were male. Most patients were asymptomatic and diagnosed with gallbladder metastasis on imaging performed for surveillance or staging. The median time to gallbladder metastasis following nephrectomy was 4 years. Metastasis to the gallbladder occurred both synchronously (33%) and metachronously (67%). Of the patients with available histology, all had clear cell RCC (n=28). Of all patients, 13 (39%) only had metastasis to the gallbladder, while 20 (61%) had additional sites of metastasis. The most common sites of additional metastasis were contralateral kidney (30%), pancreas (21%), lung (18%), adrenal (18%), and lymph nodes (9%). All patients underwent cholecystectomy. At a median follow up time of 1.5 years after cholecystectomy, 54% of patients had no evidence of disease, 14% were alive with metastasis, 23% had died from metastatic RCC, and 9% died from causes unrelated to their cancer.
Gallbladder metastasis from RCC is a rare event that may occur synchronously or metachronously with most patients being asymptomatic. Clear cell carcinoma appears to be the primary pathology associated with gallbladder metastasis. High rates of bilateral RCC and pancreatic metastasis suggest novel associations in patients with RCC and gallbladder metastasis.
renal cell carcinoma; bilateral RCC; metastatic kidney cancer; gallbladder metastases; pancreatic metastases
The role of energy deregulation and altered/adapted metabolism in tumor cells is an increasing important issue in understanding cancer. Hereditary leiomyomatosis renal cell carcinoma (HLRCC) is an aggressive form of RCC characterized by germline mutation of fumarate hydratase (FH) followed by somatic loss of the remaining wild type allele, and known to be a highly metastatic and lethal malignancy compared to other RCCs. The intrinsic loss of normal tricarboxylic acid (TCA) cycle presumably aids tumorigenesis due to the necessary metabolic alterations required and the enforced dependence on glycolysis derived energy, mimicking the Warburg effect. Thus, there is considerable utility in establishing a preclinical cell model from these tumors to study energy metabolism deregulation, as well as, developing new targeted therapeutic approaches for TCA cycle enzyme-deficient cancers.
Here we describe a new immortalized cell line, UOK268, derived from a patient’s primary HLRCC-associated kidney cancer. This represents the first primary renal cell line to model TCA cycle gene loss and provides a perfect partner cell line to our previously described metastasis derived HLRCC-associated cell line, UOK262. We identified a novel germline FH missense mutation, p.His192Asp, and the subsequent loss of heterozygosity in UOK268. The UOK268 cell line expressed mutant FH protein, which localized to the mitochondria, but with loss of almost all catalytic activity. The UOK268 cells had severely compromised oxidative phosphorylation and increased glycolytic flux. Ingenuity® pathways analysis of hMitChip3 gene chip data confirmed the altered mRNA expression patterns of genes involved in several important pathways, such as lipid metabolism, apoptosis and energy production/glycolysis. UOK268 provides a unique model of a primary cell line demonstrating an enforced, irreversible Warburg effect and, combined with UOK262, provides a unique in vitro preclinical model for studying the bioenergetics of the Warburg effect in human cancer.
Hereditary Leiomyomatosis Renal Cell Carcinoma (HLRCC); FH (Fumarate hydratase) gene; Warburg Effect; Human mitochondrial focused cDNA microarray (hMitChip3)
Phaeochromocytomas and paragangliomas (PPGLs) are highly heterogeneous tumours with variable catecholamine biochemical phenotypes and diverse hereditary backgrounds. This analysis of 18 catecholamine-related plasma and urinary biomarkers in 365 patients with and 846 subjects without PPGLs examined how catecholamine metabolomic profiles are impacted by hereditary background and relate to variable hormone secretion. Catecholamine secretion was assessed in a subgroup of 156 patients from whom tumour tissue was available for measurements of catecholamine contents. Among all analytes, the free catecholamine O-methylated metabolites measured in plasma showed the largest tumour-related increases relative to the reference group. Patients with tumours due to multiple endocrine neoplasia type 2 and neurofibromatosis type 1 (NF1) showed similar catecholamine metabolite and secretory profiles to patients with adrenaline-producing tumours and no evident hereditary background. Tumours from these three groups of patients contained higher contents of catecholamines, but secreted the hormones at lower rates compared to tumours that did not produce appreciable adrenaline, the latter including PPGLs due to von Hippel-Lindau and succinate dehydrogenase gene mutations. Large increases of plasma dopamine and its metabolites additionally characterized patients with PPGLs due to the latter mutations, whereas patients with NF1 were characterized by large increases in plasma dihydroxyphenylglycol and dihydroxyphenylacetic acid, the deaminated metabolites of noradrenaline and dopamine. This analysis establishes the utility of comprehensive catecholamine metabolite profiling for characterizing the distinct and highly diverse catecholamine metabolomic and secretory signatures among different groups of patients with PPGLs. The data further suggest developmental origins of PPGLs from different populations of chromaffin cell progenitors.
phaeochromocytoma; paraganglioma; noradrenaline; adrenaline; dopamine; normetanephrine; metanephrine; methoxytyramine; von Hippel-Lindau syndrome; neurofibromatosis type 1; multiple endocrine neoplasia type 2; succinate dehydrogenase
The historic background, histologic features, molecular characterization, diagnosis, prognosis, treatment strategies, and active clinical trials of the sarcomatoid variant of renal cell carcinoma are described.
After completing this course, the reader will be able to:
Describe histologic features associated with sarcomatoid renal cell carcinoma.Outline current surgical approaches to treating sarcomatoid renal cell carcinoma.
This article is available for continuing medical education credit at CME.TheOncologist.com
Recent advancements in the molecular characterization of renal cell carcinoma altered the classification system and now kidney cancer is divided into several distinct histologic subtypes. Although once a separate histologic category, sarcomatoid renal cell carcinoma is no longer considered a separate tumor type because it can occur with all histologic subtypes. Limited research on tumors with sarcomatoid change has led to minimal progress in the understanding and treatment of these tumors. Because the sarcomatoid variant of renal cell carcinoma can account for approximately one in six cases of advanced kidney cancer, we hope to familiarize clinicians with these tumors by describing the historic background, histologic features, molecular characterization, diagnosis, prognosis, treatment strategies, and active clinical trials of this aggressive type of tumor.
Sarcomatoid; Renal cell carcinoma; Kidney cancer
Inactivation of the TCA cycle enzyme, fumarate hydratase (FH), drives a metabolic shift to aerobic glycolysis in FH-deficient kidney tumors and cell lines from patients with hereditary leiomyomatosis renal cell cancer (HLRCC), resulting in decreased levels of AMP-activated kinase (AMPK) and p53 tumor suppressor, and activation of the anabolic factors, acetyl-CoA carboxylase and ribosomal protein S6. Reduced AMPK levels leads to diminished expression of the DMT1 iron transporter, and the resulting cytosolic iron deficiency activates the iron regulatory proteins, IRP1 and IRP2, and increases expression of the hypoxia inducible factor HIF-1α, but not HIF-2α. Silencing of HIF-1α or activation of AMPK diminishes invasive activities, indicating that alterations of HIF-1α and AMPK contribute to the oncogenic growth of FH-deficient cells.
Purpose of Review
The greater utilization of partial nephrectomy and ablative procedures has increased the incidence of patients presenting with local renal recurrence. The choice to either perform a partial or radical nephrectomy in these situations can be a challenging decision.
Repeat and salvage partial nephrectomy, while challenging and potentially associated with increased complications, offers patients the ability to maintain excellent renal functional outcomes and promising oncologic outcomes at intermediate follow up.
Surgeons should be familiar with the surgical complications and the functional and oncologic outcomes of re-operative nephron-sparing surgery. Recent data and outcome analysis support utilization of these procedures in patients presenting with either local recurrence or de novo lesions in the ipsilateral kidney.
Salvage renal surgery; re-operative Surgery; RCC; nephron-sparing surgery; post-ablation partial nephrectomy
Prevention of bladder cancer recurrence is a central challenge in the management of this highly prevalent disease. The histone deacetylase inhibitor valproic acid (sodium valproate) has anti-angiogenic properties and has been shown to decrease bladder cancer growth in model systems. We have previously shown reduced expression of thrombospondin-1 in a mouse model and in human bladder cancer relative to normal urothelium. We speculated that inhibition of angiogenesis by valproate might be mediated by this anti-angiogenic protein.
Bladder cancer cell lines UMUC3 and T24 were treated with valproate or another histone deacetylase inhibitor, vorinostat, in culture for a period of three days. Proliferation was assessed by alamar blue reduction. Gene expression was evaluated by reverse transcription of RNA and quantitative PCR.
Proliferation assays showed treatment with valproate or vorinostat decreased proliferation in both cell lines. Histone deacetylase inhibition also increased relative expression of thrombospondin-1 up to 8 fold at 5 mM valproate.
Histone deacetylase inhibitors warrant further study for the prevention or treatment of bladder cancer.
Bladder cancer; Valproic acid; Thrombospondin-1, Urothelial carcinoma; Gene expression
Development of new renal tumors or recurrence after radio frequency ablation not amendable for repeat ablation presents a difficult therapeutic dilemma. We report on the outcomes of partial nephrectomy on kidneys previously treated with radio frequency ablation.
Materials and Methods
We performed a chart review of 13 patients who underwent 16 attempted partial nephrectomies following radio frequency ablation. Hospital records and operative reports were reviewed for demographic data, perioperative data and outcomes. The outcomes of the present series were compared to historical controls of published studies in similar patient populations.
No cases were converted to radical nephrectomy. Median time from radio frequency ablation to surgery was 2.75 years (range 1 to 7.1). A median of 7 tumors (range 2 to 40) were removed with a median estimated blood loss of 1,500 ml (range 500 to 3,500) and a median operative time of 7.8 hours (range 5 to 10.7). Operative notes commented on the presence of severe fibrosis in the operative field in 12 of 16 cases (75%). There was a modest but statistically significant decrease in renal function. Partial nephrectomy after radio frequency ablation had a higher reoperation rate compared to other series of primary or repeat partial nephrectomies but had the lowest rate of vascular or visceral injuries.
Partial nephrectomy on kidneys previously treated with radio frequency ablation is a technically challenging but feasible procedure. Residual or metachronous disease after radio frequency ablation may be salvaged with partial nephrectomy with a modest decrease in renal function. A trend toward a higher chance of reoperation and urine leak after partial nephrectomy after radio frequency ablation may be useful information for the planning and discussion of treatment decisions.
nephrectomy; catheter ablation; treatment outcome
Partial adrenalectomy has recently been advocated to preserve unaffected adrenal tissue during resection of pheochromocytoma.
To describe a robot-assisted laparoscopic partial adrenalectomy (RALPA) technique and to report on early functional and oncologic outcomes.
Design, setting, and participants
From 2007 to 2010, 15 RALPA were performed on 12 consecutive patients with pheochromocytoma. Follow-up data of >1 yr are available on 11 procedures. Median follow-up for the entire cohort was 17.3 mo (range: 6–45).
Positioning and port placement is designed for adequate reach and visualization of the upper retroperitoneum. The plane between the adrenal cortex and pheochromocytoma pseudocapsule is identified visually and with laparoscopic ultrasound. The tumor is dissected away from normal adrenal cortex, preserving normal adrenal tissue.
Preoperative, perioperative, pathologic, and functional outcomes data were analyzed.
Results and limitations
Fourteen of 15 cases were completed robotically. Among 15 procedures, 4 were performed on a solitary adrenal gland. Four cases required resection of multiple tumors (up to six) with two performed in a solitary gland. The mean age of the patients was 30 yr, and the mean body mass index was 27. The mean operative time was 163 min, the median estimated blood loss was 161 ml, and the median tumor size was 2.7 cm (range: 1.3–5.5). There was one conversion to an open procedure in a patient requiring reoperation on a solitary adrenal gland. One patient who underwent RALPA on a solitary adrenal gland required postoperative steroid supplementation at last follow-up. At a median follow-up of 17.3 mo (range: 6–45), there were no recurrences or metastatic events. Study limitations include small sample size and short follow-up.
RALPA for the treatment of pheochromocytoma is feasible and safe and provides encouraging functional and oncologic outcomes, even in patients with a solitary adrenal lesion or multiple ipsilateral lesions.
Adrenalectomy; Laparoscopy; Partial adrenalectomy; Pheochromocytoma; Robotic surgery
Introduction and Objective
Managing patients presenting with oncocytoma in the setting of bilateral renal masses is a challenging scenario. Nevertheless, pathologic concordance of oncocytic neoplasm in one kidney with tumors in the contralateral kidney is not known. We aim to evaluate the influence of germline Birt-Hogg-Dubé (BHD) mutation on concordance rates to assist in management of these patients.
We reviewed records of the NIH patients between 1983 and 2009 having bilateral renal masses, known pathology bilaterally, and presence of oncocytoma or oncocytic neoplasm in at least one kidney. The presence of oncocytoma or oncocytic neoplasm in two renal units was considered concordant. Demographic, pathological and clinical data were collected.
The patient population consisted of 40 patients: 23 with BHD and 17 patients without diagnosis of BHD. Patients with BHD were younger (p<0.01) but there were no other differences between two groups. However, patients with BHD had a statistically lower histologic concordance between bilateral masses when compared to patients without the diagnosis of BHD (Fisher's exact test, p<0.01). Additionally, the subgroup of patients (n=8) without BHD who had multifocal renal masses demonstrated 100% oncocytoma concordance between renal units.
In patients with bilateral renal masses BHD patients have significantly lower histologic concordance rates compared to patients without BHD. Patients with BHD should be monitored and managed differently than patients without detected genetic mutations, especially those with multifocal oncocytomas. Genetic testing for BHD should be considered in the algorithm for management of patients with bilateral renal masses and known oncocytoma.
oncocytoma; oncocytic tumor; Birt-Hogg-Dube; concordance; bilateral renal tumors
We evaluated the feasibility of performing robot assisted laparoscopic partial adrenalectomy (RALPA) in patients seen at the National Cancer Institute and report the results of our initial experience.
We reviewed the records of patients with adrenal masses who underwent attempted RALPA from July of 2008 until January of 2010. Demographic, perioperative, and pathologic data were collected. The functional and early oncologic outcomes were examined by the need for steroid replacement and development of recurrent disease, respectively.
Ten patients underwent a total of 13 attempted RALPA for removal of 19 adrenal tumors. There was one open conversion with successful completion of partial adrenalectomy. Of the patients, 80% had a known hereditary syndrome predisposing them to adrenal tumors. One patient had bilateral multifocal adrenal masses with unknown germ line genetic alteration and one patient had a sporadic adrenal mass. Of the 19 tumors removed, 17 were pheochromocytoma and 2 were adrenal-cortical hyperplasia. Two patients underwent partial adrenalectomy on a solitary adrenal gland with one subsequently requiring steroid replacement post-operatively. On postoperative imaging all but one operated adrenal gland demonstrated contrast enhancement. No patient developed local recurrence at a median follow-up of 16.2 months (range 2- 29).
RALPA appears safe and feasible in our early experience. Only one patient in our series required steroid replacement. Local recurrence rates are low but will require longer follow up.
Robotic; partial adrenalectomy; adrenal sparing surgery; pheochromocytoma; hereditary syndromes
We sought to determine if there is a correlation between D'Amico risk stratification and degree of suspicion of prostate cancer on multi-parametric MRI, based on targeted biopsies obtained with our electromagnetically (EM) tracked MRI/ultrasound (US) fusion platform.
101 patients underwent 3 Tesla multi-parametric MR imaging of the prostate which consisted of T2, DCE, DWI, and spectroscopy images in patients with a suspicion for, or diagnosis of prostate cancer. All prostate MRI lesions were then identified and graded by the number of modalities positive: low (≤2), moderate (3) and high (4) suspicion. Patients and lesions were stratified by D'Amico risk stratification. The biopsy protocol included a standard 12 core biopsy followed by real-time MRI/US fusion-targeted biopsies of the suspicious MR lesions.
90.1% of men were clinical T1c with a mean age of 62.7 ± 8.3 years and the median PSA was 5.8 ng/ml. 54.5% of the patients were positive for cancer on the protocol biopsy. A Chi-squared analysis resulted in a statistically significant correlation between the MR suspicion and D'Amico risk stratification for patients (p<0.0001). Within-cluster re-sampling technique determined that there was a statistically significant correlation between MR suspicion and D'Amico risk stratification for MR ‘targeted’ core biopsies and MR lesions (p<0.01)
Our data supports that with multi-parametric MR prostate imaging, one may be able to quantitatively assess the degree of risk associated with MR visible lesions within the prostate.
Prostate Cancer; Fusion Imaging; Biopsy; Magnetic Resonance Imaging; Transrectal Ultrasound
Pheochromocytomas are rare catecholamine–producing tumors derived in at least 30% of cases from mutations in 9 tumor-susceptibility genes identified to date. Testing of multiple genes at considerable expense is often undertaken before a mutation is detected. This study assessed whether measurements of plasma metanephrine, normetanephrine and methoxytyramine, the O-methylated metabolites of catecholamines, might help distinguish different hereditary forms of the tumor.
Plasma concentrations of O-methylated metabolites were measured by liquid chromatography with electrochemical detection in 173 patients with pheochromocytoma, including 38 with multiple endocrine neoplasia type 2 (MEN 2), 10 with neurofibromatosis type 1 (NF1), 66 with von Hippel-Lindau (VHL) syndrome and 59 with mutations of succinate dehydrogenase (SDH) type B or D genes.
In contrast to patients with VHL and SDH mutations, all patients with MEN 2 and NF1 presented with tumors characterized by increased plasma concentrations of metanephrine (indicating epinephrine production). VHL patients usually showed solitary increases in normetanephrine (indicating norepinephrine production), whereas additional or solitary increases in methoxytyramine (indicating dopamine production) characterized 70% of patients with SDH mutations. Patients with NF1 and MEN 2 could be discriminated from those with VHL and SDH mutations in 99% of cases by the combination of normetanephrine and metanephrine. Measurements of plasma methoxytyramine discriminated patients with SDH mutations from those with VHL mutations in a further 78% of cases.
The distinct patterns of plasma catecholamine O-methylated metabolites in patients with hereditary pheochromocytoma provide an easily utilized tool to guide cost-effective genotyping of underlying disease-causing mutations.
pheochromocytoma; paraganglioma; norepinephrine; epinephrine; dopamine; normetanephrine; metanephrine; methoxytyramine; von Hippel-Lindau syndrome; neurofibromatosis type 1; multiple endocrine neoplasia type 2; succinate dehydrogenase
Kidney cancer is a heterogeneous disease comprised of a number of histologic subtypes, each associated with unique genetic mutations, clinical features, and sensitivity to treatment. By examining families affected with the hereditary kidney cancer syndromes von Hippel-Lindau, hereditary papillary renal cell carcinoma, hereditary leiomyomatosis and renal cell carcinoma, and Birt-Hogg-Dube', researchers have been able to identify the genes responsible for these syndromes. This work has revealed that kidney cancer is fundamentally a metabolic disorder, and as such, novel targeted therapies specific to their molecular biology have been developed and employed in both the hereditary and sporadic forms of renal cell carcinoma.
Kidney cancer; Genetics; VHL; HPRC; HLRCC; BHD; Clear cell; Papillary; Chromophobe
To evaluate the outcomes and timing of intervention for adrenal sparing surgery in patients left with a solitary adrenal remnant after bilateral adrenal surgeries.
Subjects/Patients and Methods
Patients were included in the study if they had undergone bilateral adrenal surgery as a treatment for pheochromocytoma and were left with a solitary adrenal remnant. Perioperative, functional, and oncologic outcomes were evaluated on 21 patients that met the inclusion criteria.
There was minimal perioperative morbidity and no perioperative mortality. After a median follow up of 21 months (range 3–143) there were two cases of persistent disease. Ten patients (48%) required steroid supplementation upon discharge with 4 subsequently discontinuing steroid supplementation. Patients were more likely to require steroid supplementation postoperatively if they underwent simultaneous adrenalectomy and contralateral partial adrenalectomy, rather than staged procedures (86% versus 40%, p=0.02). Additionally, patients who underwent surgery for tumors greater than 4 cm were more likely to require long-term steroids than patients who underwent surgery for lesions less than 4 cm (75% versus 18%, p=0.05).
Patients left with a solitary adrenal remnant after bilateral adrenal surgery have low surgical morbidity, reasonable functional outcomes and low rates of recurrence at an intermediate follow-up period. A staged approach may decrease the immediate postoperative need for steroids, and intervention before the largest tumor reaches 4 cm may decrease the rate of long-term steroid dependence.
Adrenal sparing surgery; complications; partial adrenalectomy; treatment outcome
Three recent genome-wide association studies of testicular germ cell tumors have uncovered predisposition alleles in or near several genes, including KITLG, BAK1, SPRY4, TERT, ATF7IP, and DMRT1. The calculated per-allele odds ratio for variants in the region of KITLG is the highest reported for any malignancy so far. These findings are in agreement with epidemiological data indicating that testicular cancer has a higher heritability than most other cancers. Here, we discuss the question of whether the newly identified risk polymorphisms can be used to guide patient care.
Patients with hereditary renal cancer are at increased risk for formation of recurrent, bilateral, multifocal tumors and may require aggressive nephron sparing surgery to prevent renal replacement therapy. Here, we evaluate the feasibility and outcomes of patients who underwent partial nephrectomy with removal of at least 20 tumors from a single renal unit in one setting.
Materials and Methods
We retrospectively reviewed the records of 30 patients who underwent 34 partial nephrectomies with removal of at least 20 tumors at our institution from 1993 to 2008. Operative reports and hospital records were reviewed for perioperative data, renal function and oncologic outcomes. Comparison of preoperative and postoperative renal function was performed using the 2-tailed T test.
There were no mortalities and only one renal unit was lost. The median number of tumors removed was 26.5. The median EBL was 3,500ml, and the median operative time was 9 hours. Perioperative complications occurred in greater than 50% the of cases. There was a statistically significant decrease in postoperative eGFR (67 vs 59 ml/min/1.73m2, p <0.001) at 3 months. Only one patient developed metastatic disease, and 8 of the 34 operated kidneys required subsequent intervention during the median follow up of 52 months (4-187).
Aggressive partial nephrectomy for resection of multiple tumors is technically feasible. Although there was a significant decrease in postoperative renal function, more than 80% of the starting renal function was preserved in this cohort, except for one patient. In addition, oncologic outcomes are encouraging at intermediate term follow up.
hereditary RCC; partial nephrectomy; outcomes; complications; multifocal RCC