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
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.
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
Background: Metastatic renal cell carcinoma (RCC) to the liver portrays a poor prognosis and liver directed therapy remains controversial. We aimed to determine potential selection criteria for patients who might benefit from this strategy.
Materials and Methods: We evaluated 247 consecutive patients with RCC metastatic to the liver from a prospectively maintained database.
Results: Eighteen patients received liver directed therapy (18/247, 7%). Ten patients underwent liver resection (10/247, 4%) and eight patients underwent radiofrequency ablation (RFA, 8/247, 3%). All were rendered free of disease in the liver. Five had synchronous liver disease and underwent synchronous resections with their primary. Mortality was 0%. Fourteen had single (surgery 7, RFA 7) and four (surgery 3, RFA 1) had multiple liver lesions, respectively. Median size of lesions was 5cm (0.5 - 10cm) and 2.5cm (1 - 6cm) in the surgery and RFA groups, respectively. Median DFI was 10 months, and no difference was observed in those with a longer vs. shorter than median DFI (p = 0.95); liver specific progression free survival for the surgery and RFA groups were 4 and 6 months, respectively (p= 0.93). 1, 3 and 5-year actuarial survivals for the whole group were 89%, 40%, 27%. Median survival for the surgery group was 24 (3 to 254+) months, and for the RFA group 15.6 (7-56+) months (p = 0.56). Metachronous liver disease was associated with prolonged survival (p = 0.02).
Conclusions: Liver directed therapy for RCC is safe. For highly selected patients with metachronous liver RCC metastases, liver directed therapy should be considered in a multidisciplinary manner.
liver resection; metastatic renal cell carcinoma; liver metastases; radiofrequency ablation.
Multifocal renal cell carcinoma (RCC) has been reported in 5–25% of cases worldwide. Although management of patients with multifocal RCC has not been clearly defined, presence of multifocal renal masses in one kidney and a normal contralateral kidney has often been considered a reason for performing radical nephrectomy. This study reviews the world literature to provide an accurate estimate of the prevalence of multifocal RCC and evaluates the oncologic outcomes of multifocal RCC after exclusion of patients with known hereditary and familial renal syndromes. A PubMed search of the literature was performed for articles in the English language using the following terms for the query: “multifocal RCC,” “multifocality and RCC,” “multicentric RCC,” or “bilateral RCC.” The references of the published articles were also reviewed for additional publications. Articles that did not specifically exclude patients with familial RCC or known hereditary RCC syndromes were excluded for estimation of multifocality prevalence and oncologic outcomes. After applying our exclusion criteria, nine articles were selected and form the basis of the current analysis. Weighted averages were used to calculate the prevalence of multifocality. Multifocal RCC was found in 6.8% of cases (373 of 5433 patients). Ipsilateral multifocality was found in 6.8% of cases. Bilateral multifocality was found in 11.7% of cases. Of all cases reported in this study, only 10% underwent partial nephrectomy. The rest of the study cohort underwent radical nephrectomy. The review of the literature showed that the use of nephron-sparing techniques in patients with multifocal disease did not compromise oncologic outcomes, despite the need for reoperation in certain cases. In conclusion, multifocal RCC remains a prevalent entity. Most clinicians still prefer to perform radical nephrectomies in these patients despite proven equivalent oncologic outcomes compared to nephron-sparing techniques. Urologists should be aware of these data when proposing treatment options to patients with multifocal RCC.
multifocality; multifocal RCC; bilateral RCC; nephron-sparing surgery; partial nephrectomy; outcomes
Although the safety and feasibility of partial adrenalectomy in VHL patients has been established, long-term outcomes have not been examined. In this study we evaluate the recurrence and functional outcomes of a VHL cohort treated for pheochromocytoma with partial adrenalectomy with a follow up of at least 5 years.
We reviewed records of VHL patients treated with partial adrenalectomy for pheochromocytoma at the National Cancer Institute. Demographic, germline mutation status, surgical indication, oncologic and functional outcome data were collected. Local recurrence was defined as radiographic evidence of recurrent tumor on the ipsilateral side of partial adrenalectomy. Patients were considered steroid-dependent if they required steroids at most recent follow up.
Thirty-six partial adrenalectomies for pheochromocytoma were performed in 26 VHL patients between September 1995 and December 2003. Twenty-three cases were performed open and 13 using laparoscopic techniques. Prior surgical history was obtained for all patients. At a median follow up of 9.25 years (5–46 years), no patient has developed metastatic pheochromocytoma. Three patients (11%) developed 5 local recurrences, treated with surgical extirpation or active surveillance. All recurrences were asymptomatic and detected by radiographic imaging on follow up. Additionally, 3 of 26 patients (11%) subsequently required partial adrenalectomy for pheochromocytoma on the contralateral adrenal gland. In the entire cohort, only three patients became steroid dependent (11%).
Outcomes for partial adrenalectomy in VHL patients with pheochromocytoma are encouraging at long-term follow up and should be recommended as a primary surgical approach whenever possible. Adrenal-sparing surgery can obviate the need for steroid replacement in the majority of patients. Local recurrence rates appear to be infrequent and can be managed successfully with subsequent observation or intervention.
Pheochromocytoma; VHL; partial adrenalectomy; adrenal sparing surgery; hereditary syndromes
Despite aggressive screening, patients with hereditary renal cancers can present with large, multifocal tumors. We present oncologic outcomes in hereditary renal cell carcinoma patients treated with partial nephrectomy for multifocal solid tumors with the largest lesion greater than 4 cm.
Materials and Methods
Between 1995 and 2008, we identified 58 patients with hereditary RCC treated at our institution with partial nephrectomy for solid tumors greater than 4cm. The data collected included demographic parameters, tumor size, tumor pathology, and laterality. Overall survival and metastasis-free survival were calculated based on the information from the most recent follow up evaluation and imaging.
The cohort included 58 patients consisting of 41 (71%) patients with VHL, 10 (17%) patients with BHD, and 7 (11%) with HPRC. The mean age was 43.7 (range 18–63) and the mean largest tumor size was 5.3 cm (range 4–13). The mean number of resected kidney tumors was 6.4 (range 1–44). There was a predominance of nuclear grade 2 tumors 51 (85%) and a predominance of clear cell histology 44 (73%), followed by papillary type I histology 7 (11.7%). Overall survival of the cohort was 93% and metastasis-free survival was 96.5% at the median follow up of 45 months (range 2–163).
The metastasis-free and overall survival of our patients is similar to those reported in the literature series for patients undergoing partial nephrectomy for T1B tumors in the sporadic population. The presence of multifocality does not affect oncologic outcomes at an intermediate follow up. Partial nephrectomy can be offered to hereditary patients presenting with multifocal tumors greater than 4 cm.
partial nephrectomy; multifocality; renal cell carcinoma; clinical stage T1B; outcomes
A novel platform was developed that fuses pre-biopsy magnetic resonance imaging with real-time transrectal ultrasound imaging to identify and biopsy lesions suspicious for prostate cancer. The cancer detection rates for the first 101 patients are reported.
Materials and Methods
This prospective, single institution study was approved by the institutional review board. Patients underwent 3.0 T multiparametric magnetic resonance imaging with endorectal coil, which included T2-weighted, spectroscopic, dynamic contrast enhanced and diffusion weighted magnetic resonance imaging sequences. Lesions suspicious for cancer were graded according to the number of sequences suspicious for cancer as low (2 or less), moderate (3) and high (4) suspicion. Patients underwent standard 12-core transrectal ultrasound biopsy and magnetic resonance imaging/ultrasound fusion guided biopsy with electromagnetic tracking of magnetic resonance imaging lesions. Chi-square and within cluster resampling analyses were used to correlate suspicion on magnetic resonance imaging and the incidence of cancer detected on biopsy.
Mean patient age was 63 years old. Median prostate specific antigen at biopsy was 5.8 ng/ml and 90.1% of patients had a negative digital rectal examination. Of patients with low, moderate and high suspicion on magnetic resonance imaging 27.9%, 66.7% and 89.5% were diagnosed with cancer, respectively (p <0.0001). Magnetic resonance imaging/ultrasound fusion guided biopsy detected more cancer per core than standard 12-core transrectal ultrasound biopsy for all levels of suspicion on magnetic resonance imaging.
Prostate cancer localized on magnetic resonance imaging may be targeted using this novel magnetic resonance imaging/ultrasound fusion guided biopsy platform. Further research is needed to determine the role of this platform in cancer detection, active surveillance and focal therapy, and to determine which patients may benefit.
prostatic neoplasms; biopsy; magnetic resonance imaging; ultrasonography; early detection of cancer
Many patients with small adrenal masses undergo total adrenalectomy. We evaluate the outcomes of partial adrenalectomy by performing a comprehensive literature review.
Materials and Methods
We performed a Pubmed search of literature published in the English language using the following queries: “partial adrenalectomy” and “adrenal sparing surgery”, and identified 317 and 155 articles, respectively. We excluded case reports or series containing less than 5 patients, articles not focused on surgical management, and those that did not indicate perioperative outcomes. The remaining articles were cross-referenced by author and institution in order to eliminate studies with redundant cases. Demographics, diagnosis, tumor characteristics, perioperative and functional outcomes, as well as recurrence data was collected when available.
Twenty-two articles from 22 first authors met our inclusion criteria describing outcomes of 417 patients. There is an increasing trend towards utilization of partial adrenalectomy worldwide over the past 20 years. Partial adrenalectomy is most commonly performed for Conn's Syndrome, followed by pheochromocytoma. Most of the procedures are performed laparoscopically with minimal morbidity. The recurrence rate is only at 3% and over 90% of patients remain steroid independent.
Surgical outcomes and perioperative complications of partial adrenalectomy are similar to those reported for total adrenalectomy. When partial adrenalectomy is performed for small adrenal lesions, the rate of malignancy is negligible, the recurrence rate is low, and the vast majority of patients remain steroid independent at long-term follow up. These data strongly support acceptance of partial adrenalectomy as a first line treatment for small adrenal masses.
adrenalectomy; outcomes; review
Patients with bilateral multifocal renal cell carcinoma (RCC) are at increased risk for development of locally recurrent or de novo tumors after nephron sparing procedures. When dealing with recurrent renal masses the options are limited to observation, total nephrectomy, ablation, or repeat surgical intervention. We review the literature for association of bilaterality and multifocality, and multifocality as a main factor for development of locally recurrent renal tumors. The importance of maximal renal preservation and morbidity of renal replacement therapy is discussed. The outcome data of repeat renal interventions are presented and demonstrates reasonable functional and oncologic outcomes despite higher perioperative complications. Our results support use of reoperative renal surgery over total nephrectomy and renal replacement therapy.