Stephen E. Pautler

Active Surveillance of Small Renal Masses: Progression Patterns of Early Stage Kidney Cancer ☆

BACKGROUND Most early stage kidney cancers are renal cell carcinomas (RCCs), and most are diagnosed incidentally by imaging as small renal masses (SRMs). Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize. OBJECTIVE To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology. DESIGN, SETTING, AND PARTICIPANTS A multicenter prospective phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and/or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression. INTERVENTION Patients underwent serial imaging and needle core biopsies. MEASUREMENTS We measured rates of change in tumor diameter (growth measured by imaging) and progression to ≥ 4 cm, doubling of tumor volume, or metastasis with histology on biopsy. RESULTS AND LIMITATIONS Local progression occurred in 25 patients (12%), plus 2 progressed with metastases (1.1%). Of the 178 subjects with 209 SRMs, 127 with 151 SRMs had>12 mo of follow-up with two or more images, with a mean follow-up of 28 mo. Their tumor diameters increased by an average of 0.13 cm/yr. Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate. Limitations included no central review of imaging and pathology and a short follow-up. CONCLUSIONS This is the first SRM active surveillance study to correlate growth with histology prospectively. In the first 2 yr, the rate of local progression to higher stage is low, and metastases are rare. SRMs appear to grow very slowly, even if biopsy proven to be RCC. Many patients with SRMs can therefore be initially managed conservatively with serial imaging, avoiding the morbidity of surgical or ablative treatment.

Succinate Dehydrogenase Kidney Cancer: An Aggressive Example of the Warburg Effect in Cancer

PURPOSE Recently, a new renal cell cancer 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 the diagnosis, evaluation and treatment of this novel form of hereditary kidney cancer. MATERIALS AND METHODS Patients with suspected hereditary kidney cancer were enrolled on a National Cancer Institute institutional review board 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. RESULTS A total of 14 patients from 12 SDHB mutation families were evaluated. Patients presented with renal cell cancer at an early age (33 years, range 15 to 62), metastatic kidney cancer developed in 4 and some families had no manifestation other than kidney tumors. An additional family with 6 individuals found to have clear cell renal cell cancer that presented at a young average age (47 years, range 40 to 53) was identified with a germline SDHC mutation (R133X) Metastatic disease developed in 2 of these family members. A patient with a history of carotid body paragangliomas and an aggressive form of kidney cancer was evaluated from a family with a germline SDHD mutation. CONCLUSIONS SDH mutation associated renal cell carcinoma can be an aggressive type of kidney cancer, especially in younger individuals. Although detection and management of early tumors is most often associated with a good outcome, based on our initial experience with these patients and our long-term experience with hereditary leiomyomatosis and renal cell carcinoma, we recommend careful surveillance of patients at risk for SDH mutation associated renal cell carcinoma and wide surgical excision of renal tumors.

Clinically significant prostate cancer found incidentally in radical cystoprostatectomy specimens

To review the incidence, histopathological features and clinical outcomes of patients with incidental prostate cancer found in radical cystoprostatectomy (RCP) specimens excised for bladder cancer, to determine if these cancers affected the follow‐up strategy and if prostate‐sparing cystectomy would be appropriate for these patients.

PRIAPISM. FROM PRIAPUS TO THE PRESENT TIME

Advances in the pharmacotherapeutic options available to treat erectile dysfunction over the past decade have transformed the field of impotence. The initial foray into this field with intracavernous injections of papaverine rapidly expanded the number of men seeking attention for priapism, a previously rare clinical condition. The recent widespread use and acceptance of oral agents for the treatment of erectile dysfunction, with a reduced incidence of priapism has decreased the number of men at risk for injection-related prolonged erections. The use of recreational drugs (cocaine) and perineal trauma leading to presentations of priapism seem to be rising in incidence. The urologist remains the consultant-specialist ultimately responsible for these men and should be cognizant of the array of treatments described for this condition. Early determination of the state of corporal oxygenation is essential and will define the optimal management approach. A wide range of medical conditions and risk factors may be etiologic and should be elicited from the patient at the initial interview. Low-flow ischemic priapism requires a rapid resolution, often achieved through use of alpha-agonists orally or by direct injection into the penile circulation, whereas nonischemic priapism can be treated more conservatively. Research into this condition has only recently been initiated. Through greater understanding of the pathophysiology of priapism, the clinician may become armed with etiology-specific medical alternatives providing timely detumescence for men with prolonged erections.

Intraoperative ultrasound aids in dissection during laparoscopic partial adrenalectomy

PURPOSE Adrenal cortical sparing surgery is a relatively new approach to adrenal tumors. Laparoscopic partial nephrectomy is a technically feasible but challenging operation. We describe the use of intraoperative ultrasound to facilitate laparoscopic partial nephrectomy in a population with a hereditary predisposition to multifocal pheochromocytoma. MATERIALS AND METHODS All patients underwent a history, physical examination, serum and urine catecholamine determinations, abdominal computerized tomography-magnetic resonance imaging and metaiodobenzylguanidine scan. The adrenal gland was exposed using a standard 3 or 4 port approach. Intraoperative ultrasound was performed using a 7.5 MHz. 10 mm. transducer placed through a 12 mm. port. After imaging the whole gland and adjacent structures partial adrenalectomy was performed based on intraoperative ultrasound images using a harmonic scalpel or alternatively using a cut and sew technique that provided a 5 mm. margin. Tumors were removed intact and sent for pathological examination. RESULTS Since 1998, 11 patients have undergone laparoscopic partial adrenalectomy. Intraoperative ultrasound was performed in 7 patients with suspected multiple adrenal masses, including 4 and 3 who underwent unilateral and bilateral laparoscopic partial nephrectomy, respectively. Six of the 7 patients had germline defects in the von Hippel-Lindau disease gene and 1 had no identifiable alteration in the von Hippel-Lindau disease or RET gene. A solitary tumor was identified in 3 cases and multiple lesions were noted in 4. In 1 case intraoperative ultrasound localized a tumor not identified on preoperative imaging that was not readily visible via laparoscopy. Intraoperative ultrasound guided surgical dissection in all cases and identified an extra-adrenal mass in 1 patient with bilateral adrenal masses. There were no complications due to intraoperative ultrasound and no conversions to open surgery. Mean operative time was 335 minutes and mean estimated blood loss was 179 ml. Histological study demonstrated pheochromocytoma in 14 lesions and the extra-adrenal mass proved to be a splenic rest. At short-term followup no recurrences have been noted. All patients retained sufficient adrenal cortical function to avoid steroid replacement therapy. CONCLUSIONS Laparoscopic ultrasound differentiates normal adrenal parenchyma from adrenal tumors and facilitates laparoscopic partial adrenalectomy.

Fused video and ultrasound images for minimally invasive partial nephrectomy: a phantom study

The shift to minimally invasive abdominal surgery has increased reliance on image guidance during surgical procedures. However, these images are most often presented independently, increasing the cognitive workload for the surgeon and potentially increasing procedure time. When warm ischemia of an organ is involved, time is an important factor to consider. To address these limitations, we present a more intuitive visualization that combines images in a common augmented reality environment. In this paper, we assess surgeon performance under the guidance of the conventional visualization system and our fusion system using a phantom study that mimics the tumour resection of partial nephrectomy. The RMS error between the fused images was 2.43mm, which is sufficient for our purposes. A faster planning time for the resection was achieved using our fusion visualization system. This result is a positive step towards decreasing risks associated with long procedure times in minimally invasive abdominal interventions.

Growth kinetics of small renal masses: A prospective analysis from the Renal Cell Carcinoma Consortium of Canada

INTRODUCTION Most small renal masses (SRMs) are diagnosed incidentally and have a low malignant potential. As more elderly patients and infirm patients are diagnosed with SRMs, there is an increased interest in active surveillance (AS) with delayed intervention. Patient and tumour characteristics relating to aggressive disease have not been well-studied. The objective was to determine predictors of growth of SRMs treated with AS. METHODS A multicentre prospective phase 2 clinical trial was conducted on 207 SRMs in 169 patients in 8 institutions in Canada from 2004 to 2009; in these patients treatment was delayed until disease progression. Patient and tumour characteristics were evaluated to determine predictors of growth of SRMs by measuring rates of change in growth (on imaging) over time. All patients underwent AS for presumed renal cell carcinoma (RCC) based on diagnostic imaging. We used the following factors to develop a predictive model of tumour growth with binary recursive partitioning analysis: patient characteristics (age, symptoms at diagnosis) and tumour characteristics (consistency [solid vs. cystic] and maximum diameter at diagnosis. RESULTS With a median follow-up of 603 days, 169 patients (with 207 SRMs) were followed prospectively. Age, symptoms at diagnosis, tumour consistency and maximum diameter of the renal mass were not predictors of growth. This cohort was limited by lack of availability of patient and tumour characteristics, such as sex, degree of endophytic component and tumour location. CONCLUSION Slow growth rates and the low malignant potential of SRMs have led to AS as a treatment option in the elderly and infirm population. In a large prospective cohort, we have shown that age, symptoms, tumour consistency and maximum diameter of the mass at diagnosis are not predictors of growth of T1a lesions. More knowledge on predictors of growth of SRMs is needed.

Factors that impact the outcome of minimally invasive pyeloplasty: Results of the multi-institutional laparoscopic and robotic pyeloplasty collaborative group

PURPOSE We compared laparoscopic and robotic pyeloplasty to identify factors associated with procedural efficacy. MATERIALS AND METHODS We conducted a retrospective multicenter trial incorporating 865 cases from 15 centers. We collected perioperative data including anatomical and procedural factors. Failure was defined subjectively as pain that was unchanged or worse per medical records after surgery. Radiographic failure was defined as unchanged or worsening drainage on renal scans or worsening hydronephrosis on computerized tomography. Bivariate analyses were performed on all outcomes and multivariate analysis was used to assess factors associated with decreased freedom from secondary procedures. RESULTS Of the cases 759 (274 laparoscopic pyeloplasties with a mean followup of 15 months and 465 robotic pyeloplasties with a mean followup of 11 months, p <0.001) had sufficient data. Laparoscopic pyeloplasty, previous endopyelotomy and intraoperative crossing vessels were associated with decreased freedom from secondary procedures on bivariate analysis, with a 2-year freedom from secondary procedures of 87% for laparoscopic pyeloplasty vs 95% for robotic pyeloplasty, 81% vs 93% for patients with vs without previous endopyelotomy and 88% vs 95% for patients with vs without intraoperative crossing vessels, respectively. However, on multivariate analysis only previous endopyelotomy (HR 4.35) and intraoperative crossing vessels (HR 2.73) significantly impacted freedom from secondary procedures. CONCLUSIONS Laparoscopic and robotic pyeloplasty are highly effective in treating ureteropelvic junction obstruction. There was no difference in their abilities to render the patient free from secondary procedures on multivariate analysis. Previous endopyelotomy and intraoperative crossing vessels reduced freedom from secondary procedures.

INTENTIONAL RESECTION OF THE DIAPHRAGM DURING CYTOREDUCTIVE LAPAROSCOPIC RADICAL NEPHRECTOMY

PURPOSE Laparoscopic radical nephrectomy is being performed more commonly. To our knowledge intentional resection of the diaphragm during laparoscopic radical nephrectomy for large renal tumors has not yet been described. We detail the laparoscopic management of diaphragmatic resection. MATERIALS AND METHODS From March 1996 to February 2001, 36 patients underwent cytoreductive laparoscopic radical nephrectomy at our institution in preparation for systemic immunotherapy. Charts and operative tapes were reviewed and cases were identified in which diaphragmatic resection was performed for locally invasive tumors. RESULTS In 3 patients a portion of the diaphragm was dissected via laparoscopy during debulking nephrectomy. All patients had renal cell carcinoma with documented metastatic disease. The diaphragm was repaired laparoscopically using intracorporeal suturing techniques in 2 of the 3 patients and a chest tube was placed in all 3. Transient systolic hypotension and hypercarbia in 1 case resolved with manual ventilation. The chest tube was removed on postoperative days 2 to 4. There were no complications and no ipsilateral pleural metastasis was identified at an average of 6 weeks (range 2 to 23) of followup. CONCLUSIONS A portion of the diaphragm may be intentionally resected during laparoscopic radical nephrectomy. This maneuver may be successfully managed without conversion to an open procedure. In cases of a large diaphragmatic defect or the potential for coagulopathy postoperatively a chest tube should be inserted. Potential invasion of the diaphragm by large tumors should not be considered a contraindication to cytoreductive laparoscopic radical nephrectomy.

Cumulative summation graphs are a useful tool for monitoring positive surgical margin rates in robot-assisted radical prostatectomy

Study Type – Therapy (case series) 
Level of Evidence 4