Chronic granulomatous disease (CGD) is a rare hereditary disease in which phagocytes have difficulty forming the superoxide radical required to kill certain pathogens. Individuals with CGD are susceptible to a specific set of infections and granulomatous lesions. We present the case of a 15 year old male with X-linked CGD who presented with unremitting cough and fevers. He had a left sided pneumonia which persisted despite home IV antibiotics. He was admitted to an outside facility for bronchoalveolar lavage to obtain cultures and polymerase chain reaction (PCR). Computed Tomography (CT) of chest, abdomen and pelvis was done for baseline evaluation of extent of disease. CT revealed a fluid collection in the prostatic fossa, later determined to be a prostatic abscess. To our knowledge, this is the first reported case of a prostatic abscess in a pediatric patient with CGD.

This work characterizes the uptake of 11C-Acetate in prostate cancer (PCa), benign prostate hyperplasia (BPH) and normal prostate tissue in comparison with multi-parametric MRI, whole mount histopathology and clinical markers, to evaluate its potential utility for delineating intra-prostatic tumors in a population of patients with localized PCa.

METHODS

39 men with presumed localized PCa underwent dynamic/static abdomen-pelvic 11C-Acetate PET/CT for 30-minutes and 3T multi-parametric (MP) MRI prior to prostatectomy. PET/CT images were registered to MRI using pelvic bones for initial rotation-translation, followed by manual adjustments to account for prostate motion and deformation from the MRI endorectal coil. Whole-mount pathology specimens were sectioned using an MRI-based patient specific mold resulting in improved registration between the MRI, PET and pathology. 11C-Acetate PET standardized uptake values were compared with MP-MRI and pathology.

RESULTS

11C-Acetate uptake was rapid but reversible, peaking at 3–5 minutes post-injection and reaching a relative plateau at ~10 minutes. The average SUVmax(10–12min) of tumors was significantly higher than that of normal prostate tissue (4.4±2.05, range 1.8–9.2 vs. 2.1±0.94, range 0.7–3.4; p<0.001); however it was not significantly different from benign prostatic hyperplasia (4.8±2.01; range 1.8–8.8). A sector-based comparison with histopathology, including all tumors > 0.5 cm, revealed a sensitivity and specificity of 61.6 % and 80.0 % for 11C-Acetate PET/CT, and 82.3% and 95.1% for MRI, respectively. Considering only tumors >0.9 cm the 11C-Acetate accuracy was comparable to that of MRI. In a small cohort (n=9), 11C-Acetate uptake was independent of fatty acid synthase expression based on immunohistochemistry.

CONCLUSION

11C-Acetate PET/CT demonstrates higher uptake in tumor foci than normal prostate tissue; however 11C-Acetate uptake in tumors is similar to BPH nodules. While 11C-Acetate PET/CT is not likely to have utility as an independent modality for evaluation of localized PCa, the high uptake in tumors may make it useful for monitoring focal therapy, where tissue damage after therapy may limit anatomic imaging methods.

The multifocal nature of prostate cancer has necessitated whole-gland therapy in the past; however, since the widespread use of PSA screening, patients frequently present with less-advanced disease. Many men with localized disease wish to avoid the adverse effects of whole-gland therapy; therefore, focal therapy for prostate cancer is being considered as a treatment option. For focal treatment to be viable, accurate imaging is required for diagnosis, staging, and monitoring of treatment. Developments in MRI and PET have brought more attention to prostate imaging and the possibility of improving the accuracy of focal therapy. In this Review, we discuss the advantages and disadvantages of conventional methods for imaging the prostate, new developments for targeted imaging, and the possible role of image-guided biopsy and therapy for localized prostate cancer.

During transrectal ultrasound (TRUS)-guided prostate biopsies, the actual location of the biopsy site is rarely documented. Here, we demonstrate the capability of TRUS-magnetic resonance imaging (MRI) image fusion to document the biopsy site and correlate biopsy results with multi-parametric MRI findings. Fifty consecutive patients (median age 61 years) with a median prostate-specific antigen (PSA) level of 5.8 ng/ml underwent 12-core TRUS-guided biopsy of the prostate. Pre-procedural T2-weighted magnetic resonance images were fused to TRUS. A disposable needle guide with miniature tracking sensors was attached to the TRUS probe to enable fusion with MRI. Real-time TRUS images during biopsy and the corresponding tracking information were recorded. Each biopsy site was superimposed onto the MRI. Each biopsy site was classified as positive or negative for cancer based on the results of each MRI sequence. Sensitivity, specificity, and receiver operating curve (ROC) area under the curve (AUC) values were calculated for multi-parametric MRI. Gleason scores for each multi-parametric MRI pattern were also evaluated. Six hundred and 5 systemic biopsy cores were analyzed in 50 patients, of whom 20 patients had 56 positive cores. MRI identified 34 of 56 positive cores. Overall, sensitivity, specificity, and ROC area values for multi-parametric MRI were 0.607, 0.727, 0.667, respectively. TRUS-MRI fusion after biopsy can be used to document the location of each biopsy site, which can then be correlated with MRI findings. Based on correlation with tracked biopsies, T2-weighted MRI and apparent diffusion coefficient maps derived from diffusion-weighted MRI are the most sensitive sequences, whereas the addition of delayed contrast enhancement MRI and three-dimensional magnetic resonance spectroscopy demonstrated higher specificity consistent with results obtained using radical prostatectomy specimens.

Objectives

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).

Results

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).

Conclusions

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.

Purpose

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.

Results

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.

Conclusions

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.

Background

Partial adrenalectomy has recently been advocated to preserve unaffected adrenal tissue during resection of pheochromocytoma.

Objective

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).

Surgical procedure

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.

Measurements

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.

Conclusions

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.

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.

Methods

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.

Results

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.

Conclusions

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.

Prostate T2 mapping was performed in 34 consecutive patients using an accelerated multi-echo spin-echo sequence with four-fold k-space undersampling leading to a net acceleration factor of 3.3 on a 3T scanner. The mean T2 values from the accelerated and conventional, unaccelerated sequences demonstrated a very high correlation (r = 0.99). Different prostate segments demonstrated similarly good interscan reproducibility (p = NS) with slightly larger difference at base: 2.0 ± 1.6 % for left base and 2.1 ± 1.1 % for right base. In patients with subsequent targeted biopsy, T2 values of histologically proven malignant tumor areas were significantly lower than the suspicious looking but non-malignant lesions (p<0.05) and normal areas (p<0.001): 100 ± 10 ms for malignant tumors, 114 ± 23 ms for suspicious lesions and 149 ± 32 ms for normal tissues. The proposed method can provide an effective approach for accelerated T2 quantification for prostate patients.

Objectives

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.

Methods

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.

Results

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).

Conclusions

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.

This paper reports the development, evaluation, and first clinical trials of the access to the prostate tissue (APT) II system—a scanner independent system for magnetic resonance imaging (MRI)-guided transrectal prostate interventions. The system utilizes novel manipulator mechanics employing a steerable needle channel and a novel six degree-of-freedom hybrid tracking method, comprising passive fiducial tracking for initial registration and subsequent incremental motion measurements. Targeting accuracy of the system in prostate phantom experiments and two clinical human-subject procedures is shown to compare favorably with existing systems using passive and active tracking methods. The portable design of the APT II system, using only standard MRI image sequences and minimal custom scanner interfacing, allows the system to be easily used on different MRI scanners.

Objective

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.

Methods

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.

Results

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)

Conclusion

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.

OBJECTIVE

To develop a system that documents the location of transrectal ultrasonography (TRUS)-guided prostate biopsies by fusing them to MRI scans obtained prior to biopsy, as the actual location of prostate biopsies is rarely known.

PATIENTS AND METHODS

Fifty patients (median age 61) with a median prostate-specific antigen (PSA) of 5.8 ng/ml underwent 3T endorectal coil MRI prior to biopsy. 3D TRUS images were obtained just prior to standard TRUS-guided 12-core sextant biopsies wherein an electromagnetic positioning device was attached to the needle guide and TRUS probe in order to track the position of each needle pass. The 3D-TRUS image documenting the location of each biopsy was fused electronically to the T2-weighted MRI. Each biopsy needle track was marked on the TRUS images and these were then transposed onto the MRI. Each biopsy site was classified pathologically as positive or negative for cancer and the Gleason score was determined.

RESULTS

The location of all (n = 605) needle biopsy tracks was successfully documented on the T2-weighted (T2W) MRI. Among 50 patients, 20 had 56 positive cores. At the sites of biopsy, T2W signal was considered ‘positive’ for cancer (i.e. low in signal intensity) in 34 of 56 sites.

CONCLUSION

It is feasible to document the location of TRUS-guided prostate biopsies on pre-procedure MRI by fusing the pre-procedure TRUS to an endorectal coil MRI using electromagnetic needle tracking. This procedure may be useful in documenting the location of prior biopsies, improving quality control and thereby avoiding under-sampling of the prostate as well as directing subsequent biopsies to regions of the prostate not previously sampled.

Summary

Objective

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.

Results

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).

Conclusions

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.

Purpose

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.

Results

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).

Conclusions

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.

Purpose

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.

Methods

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.

Results

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%).

Conclusion

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.

Purpose

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.

Results

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).

Conclusions

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.

Purpose

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.

Results

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.

Conclusions

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.

Background

In patients with primary hyperaldosteronism, distinguishing between unilateral and bilateral adrenal hypersecretion is critical in assessing treatment options. Adrenal venous sampling (AVS) has been advocated by some to be the gold standard for localization of the responsible lesion however there remains a lack of consensus for the criteria and the standardization of technique.

Study Design

A retrospective study of 114 patients with a biochemical diagnosis of primary hyperaldosteronism who all underwent CT scan and AVS before and after ACTH stimulation. Univariate and multivariate analyses were performed to determine what factors were associated with AVS lateralization, and which AVS values were the most accurate criteria for lateralization.

Results

Eighty-five patients underwent surgery at our institution for unilateral hyperaldosteronism. Of the 57 patients that demonstrated unilateral abnormalities on CT, AVS localized to the contralateral side in 5 patients and revealed bilateral hyperplasia in 6 patients. Of the 52 patients who showed bilateral disease on CT scan, 43 lateralized with AVS. The most accurate criterion on AVS for lateralization was the post-ACTH stimulation values. Factors associated with AVS lateralization included a low renin value, high plasma aldosterone-to plasma-renin ratio, and adrenal mass ≥ 3cm on CT scan.

Conclusions

Because 50% of patients would have been inappropriately managed based on CT scan findings, patients with biochemical evidence of primary hyperaldosteronism and considering adrenalectomy should have AVS. The most accurate measurement for AVS lateralization was the post-ACTH stimulation values. Although several factors predict successful AVS lateralization, none are accurate enough to perform AVS selectively.

Purpose

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.

Results

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.

Conclusions

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.

Purpose

To examine the outcomes of patients with recurrent or de novo renal lesions treated with repeat partial nephrectomy on a solitary kidney.

Methods

We reviewed the records of patients who underwent nephron-sparing surgeries at the NCI from 1989 to 2008. Patients were included in the analysis if they underwent a repeat partial nephrectomy on a solitary kidney. Perioperative, functional, and oncologic outcomes were assessed. Functional outcomes were evaluated using the MDRD equation for eGFR. Oncologic efficacy was examined by the need for subsequent repeat renal surgery and development of metastatic disease.

Results

Twenty-five patients were included in the analysis. The median number of tumors resected was 4; with median EBL of 2,400ml, and median operative time of 8.5 hours. Perioperative complications occurred in 52% of the cases and included one mortality, and the loss of 3 renal units. There was a decline in eGFR (p<0.01) on the first follow up visit within 3 months after surgery, but at the 1 year follow up, the difference was not significant (p=0.12). Surgical interventions were recommended to eight patients (38%) for recurrent or de-novo tumors at a median time of 36 months, while metastasis-free survival of the cohort at an average of 57 months (range 3–196, median 50 months) was 95%.

Conclusions

Repeat partial nephrectomy for patients with a solitary kidney is a high risk alternative. Although the complication rates are high and there is a modest decline in renal function, most patients remain free from dialysis with acceptable oncologic outcomes at intermediate follow up.

Energy deregulation and abnormalities of tumor cell metabolism are critical issues in our understanding of cancer. Hereditary leiomyomatosis renal cell carcinoma (HLRCC) is an aggressive form of RCC characterized by germline mutation of the Krebs cycle enzyme, fumarate hydratase (FH), and is known to be highly metastatic and unusually lethal. There is significant utility in establishing preclinical cell and xenograft models for study of disorder of energy metabolism as well as development of new therapeutic approaches targeting of tricarboxylic acid (TCA) cycle deficient human cancers. Here we report the first immortal cell line derived from a patient having aggressive HLRCC-associated recurring kidney cancer, designated as UOK 262. We investigated gene expression, chromosome profiles, efflux bioenergetic analysis, mitochondrial ultrastructure, FH catabolic activity, invasiveness, and optimal glucose requirements for in vitro growth. UOK 262 cells have isochromosome 1q [i(1)(q10)] as recurring chromosome abnormality; demonstrate compromised oxidative phosphorylation and in vitro dependence on anaerobic glycolysis consistent with the clinical manifestation of HLRCC. Furthermore the cells display glucose-dependent growth, an elevated rate of lactate efflux, over-expression of the glucose transporter Glut 1 and lactate dehydrogenase (LDH) 5. Mutant FH protein was primarily present in edematous mitochondria, but its catalytic activity was nearly undetectable. UOK 262 xenografts retain the characteristics of HLRCC histopathology. Our findings indicate that the severe compromise of oxidative phosphorylation and rapid glycolytic flux in UOK 262 are an essential feature of this TCA cycle enzyme deficient form of kidney cancer. This tumor model is the embodiment of the “Warburg effect”. UOK 262 provides a unique in vitro and in vivo preclinical mode to study the bioenergetics of the Warburg effect in human cancer.

Kidney cancer is not a single disease; it is made up of a number of cancers that occur in the kidney, each with a different histology, having a different clinical course, responding differently to therapy and caused by a different gene. Understanding the genetic basis of cancer of the kidney has significant implications for diagnosis and management of this disease. The VHL gene is the gene for clear cell kidney cancer. The VHL protein forms a complex that targets the hypoxia inducible factors for ubiquitin-mediated degradation. Knowledge of this pathway has provided the foundation for the development of a number of novel therapeutic approaches that have been approved by the FDA for treatment of this disease. The MET gene is the gene for the hereditary form of type 1 papillary renal carcinoma and has been found to be mutated in a subset of sporadic type 1 papillary kidney cancers. Clinical trials are currently ongoing with agents targeting the tyrosine kinase domain of MET in sporadic and hereditary forms of papillary kidney cancer. The BHD gene is the gene for the hereditary type of chromophobe kidney cancer. The BHD gene is thought to be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. Hereditary Leiomyomatosis Renal Cell Carcinoma, a hereditary form of type 2 papillary renal carcinoma, is caused by inactivation of the Krebs cycle enzyme, fumarate hydratase (fumarase, FH). Loss of FH activity has been shown to alter the degradation of hypoxia inducible factor (HIF) in a VHL-independent fashion. Knowledge of these kidney cancer gene pathways has enabled new approaches for the management of this disease and has provided the foundations for the development of targeted therapeutics for this disease.

The tumor microenvironment is comprised of multiple cell types arranged in a three-dimensional structure. Interactions amongst the various cell components play an important role in neoplasia, including the inflammatory reaction that occurs as part of the host response. In this study, the regional lymphocyte subpopulations and cytokine profiles associated with prostate cancer were examined using a quantitative imaging approach and expression microarray analysis. Lymphocytes were measured in four different epithelial phenotypes in prostate cancer specimens: carcinoma; prostatic intraepithelial neoplasia (PIN); benign prostate hyperplasia (BPH); and normal epithelium. The data indicate that CD8 positive, cytotoxic T lymphocytes are significantly decreased in regions adjacent to hyperplasia and carcinoma as compared to normal epithelium and PIN. In contrast the relative number of CD4 positive and CD20 positive lymphocytes did not change markedly. Parallel mRNA expression array analysis of the normal and tumor microenvironments identified a distinct cytokine profile in cancer, with 24 dysregulated genes in tumor epithelium and nine altered in tumor-associated stroma. Overall, these data indicate that the spatial distribution of CD8 positive, cytotoxic T lymphocytes is dysregulated in human prostate glands that contain cancer, and cytokine profiles are altered at the mRNA level.