Zohar Dotan

Renal Angiomyolipoma: Long-term Results Following Selective Arterial Embolization

BACKGROUNDnThe treatment for and long-term outcome of renal angiomyolipoma (AML) at high-risk for bleeding has not been determined.nnnOBJECTIVEnTo evaluate the complication rates and the long-term outcomes among patients treated by selective arterial embolization (SAE) for a large or symptomatic renal AML.nnnDESIGN, SETTING, AND PARTICIPANTSnForty-one patients with 48 kidneys containing AML were treated by SAE at a single tertiary academic center.nnnINTERVENTIONnAll patients were treated by SAE and followed in a single center.nnnMEASUREMENTSnSAE was performed with a mixture of 96% ethanol and polyvinyl alcohol particles. The variables used for the analysis included age, gender, presence of tuberous sclerosis (TS), and maximal tumor size prior to SAE. The study end points were recurrence of symptoms or bleeding, the need for re-embolization or surgery, and disease-specific survival. The mean follow-up period for the entire group was 4.8 yr.nnnRESULTS AND LIMITATIONSnMean patient age was 51 yr (range: 24-82), and the mean initial tumor size was 10.3 cm. Successful SAE was achieved in 40 patients (91%) with a minor complication rate of 11%. Avoidance of surgery was achieved in 96% of the kidneys. No retroperitoneal hemorrhage was noted during follow-up, and 98% of the kidneys were preserved during the follow-up period. No significant changes in creatinine levels were noted following SAE (P=0.27). The freedom from surgical treatment at 5 yr following SAE was 94% (95% CI, 89-99%). Disease-specific survival of the entire cohort was 100%. The study is a retrospective, and treatment was not given according to prospective protocol, and therefore sample bias may be present.nnnCONCLUSIONSnSAE of renal AML has long-term efficacy in preventing hemorrhagic complications of renal AML, and preservation of the involved kidneys is amenable in both TS and sporadic cases.

The Efficacy and Safety of Perioperative Low Molecular Weight Heparin Substitution in Patients on Chronic Oral Anticoagulant Therapy Undergoing Transurethral Prostatectomy for Bladder Outlet Obstruction

PURPOSEnCandidates for prostatectomy who require chronic anticoagulant therapy present a major perioperative management problem due to the threat of significant hemorrhage associated with surgery and the risk of thromboembolism associated with discontinuation of the anticoagulants. We evaluated prospectively a perioperative routine using low molecular weight heparin substitution to allow safe discontinuation of prophylactic oral anticoagulants in patients undergoing transurethral resection of the prostate.nnnMATERIALS AND METHODSnWe treated 20 patients on chronic oral anticoagulant therapy who required prostatectomy for bladder outlet obstruction according to a prospective protocol based on exchange of the oral anticoagulants with perioperative injections of low molecular weight heparin and resumption of oral anticoagulants early postoperatively. The safety and efficacy of this regimen were assessed in comparison to a control group comprised of 20 randomly selected nonwarfarin treated patients who underwent prostatectomy during the same period.nnnRESULTSnThe need for blood transfusions and mean number of units transfused did not significantly differ between the 2 groups. Due to persistent hematuria routine removal of the catheter was possible only in 9 of 20 patients (45%) in the heparin group compared to 18 of 20 (90%) in the control group. Average catheterization and hospitalization period in the heparin group was 3.2 days and 4.2 days respectively, compared to 2.1 and 2.1 days in the control group, respectively (p <0.01). No long-term hemorrhagic or thromboembolic complications were noted at 3 months postoperatively.nnnCONCLUSIONSnDespite longer hospitalization in the heparin treated group, our substitution protocol is safe and effective.

Laparoscopic Partial Nephrectomy for Central Tumors: Analysis of Perioperative Outcomes and Complications

PURPOSEnWe report our experience with laparoscopic partial nephrectomy for central tumors compared to peripheral tumors to analyze the feasibility and safety of the laparoscopic approach to these complex cases.nnnMATERIALS AND METHODSnBetween October 2002 and July 2007, 212 patients underwent laparoscopic partial nephrectomy. In 53 patients the tumor was central and in 159 it was peripheral. The preoperative, intraoperative and postoperative data, the type and incidence of complications, and the quality of excision in terms of surgical margin status were compared between the 2 groups.nnnRESULTSnMean estimated blood loss (320 and 360 ml, respectively, p >0.05) and mean operative time (126 and 118 minutes, respectively, p >0.05) were similar in the central and peripheral tumor groups. Mean warm ischemia time in the central tumor group was longer (37 and 28 minutes, respectively, p <0.05) but median time was similar (30 and 29 minutes, respectively, p >0.05). The open conversion rate was significantly lower in the study group (1% vs 5.6%, p <0.05). The urological complication rate was similar in the 2 groups (9.4% vs 8.4%, p >0.05). However, different types of complications developed in each group. Four patients (7.5%) with central tumors had late hematuria (arterial pseudoaneurysm) and only 1 (1.9%) had a urine leak. Central tumors were larger (3.2 vs 2.5 cm) and more frequently malignant (94% vs 82%, p >0.05). Positive surgical margins were diagnosed in 0% vs 5% of cases (p <0.05).nnnCONCLUSIONSnProvided that there is adequate laparoscopic expertise the outcome of laparoscopic partial nephrectomy for central tumors is comparable to that of peripheral tumors. The main major complication in this group was late onset hematuria, which necessitated angiographic embolization. This facility should be available at centers where these advanced procedures are performed.

Reactivation of NCAM1 Defines a Subpopulation of Human Adult Kidney Epithelial Cells with Clonogenic and Stem/Progenitor Properties

The nephron is composed of a monolayer of epithelial cells that make up its various compartments. In development, these cells begin as mesenchyme. NCAM1, abundant in the mesenchyme and early nephron lineage, ceases to express in mature kidney epithelia. We show that, once placed in culture and released from quiescence, adult human kidney epithelial cells (hKEpCs), uniformly positive for CD24/CD133, re-express NCAM1 in a specific cell subset that attains a stem/progenitor state. Immunosorted NCAM1(+) cells overexpressed early nephron progenitor markers (PAX2, SALL1, SIX2, WT1) and acquired a mesenchymal fate, indicated by high vimentim and reduced E-cadherin levels. Gene expression and microarray analysis disclosed both a proximal tubular origin of these cells and molecules regulating epithelial-mesenchymal transition. NCAM1(+) cells generated clonal progeny when cultured in the presence of fetal kidney conditioned medium, differentiated along mesenchymal lineages but retained the unique propensity to generate epithelial kidney spheres and produce epithelial renal tissue on single-cell grafting in chick CAM and mouse. Depletion of NCAM1(+) cells from hKEpCs abrogated stemness traits in vitro. Eliminating these cells during the regenerative response that follows glycerol-induced acute tubular necrosis worsened peak renal injury in vivo. Thus, higher clone-forming and developmental capacities characterize a distinct subset of adult kidney-derived cells. The ability to influence an endogenous regenerative response via NCAM1 targeting may lead to novel therapeutics for renal diseases.

DNA based therapy with diphtheria toxin-A BC-819: a phase 2b marker lesion trial in patients with intermediate risk nonmuscle invasive bladder cancer.

PURPOSEnH19 is a paternally imprinted oncofetal gene expressed in various embryonic tissues and in 85% of bladder tumors but suppressed in the adult healthy bladder. BC-819 is a DNA plasmid that carries the gene for diphtheria toxin-A under regulation of the H19 promoter sequence. We assessed the efficacy and toxicity of intravesical BC-819 instillations to prevent tumor recurrence and ablate a marker lesion in a phase 2b trial.nnnMATERIALS AND METHODSnA total of 47 patients with recurrent, multiple nonmuscle invasive bladder tumors in whom prior intravesical therapy had failed underwent transurethral resection of all except 1 marker tumor. Patients expressing H19 received a 6-week induction course of intravesical BC-819. Patients who achieved a complete response (absent new tumors at 3 months) were given 3 maintenance courses of 3-weekly instillations every 3 months.nnnRESULTSnAll patients were evaluable for adverse effects and 39 were evaluable forxa0efficacy. Complete tumor ablation was achieved in 33% of patients and in 64%xa0there were no new tumors at 3 months. Median time to recurrence was 11.3xa0months in all cases but significantly longer (22.1 months) when analyzed byxa0response status at 3 months. Adverse events were mild. The study was limited by the small number of patients.nnnCONCLUSIONSnBC-819 prevented new tumor growth in two-thirds of the patients and ablated a third of the marker lesions. Prolonged time to recurrence was observed in responding patients. These results along with the good safety profile make BC-819 a potential medication for bladder cancer.

Traumatic testicular dislocation: a case report and review of published reports

Testicular dislocation after blunt scrotal trauma is a rare event. Its diagnosis depends on the awareness of the physician of its possible occurrence. It is usually a late finding during treatment of a motorcyclist brought to the emergency room because of multitrauma injury and is sometimes demonstrated in an abdominal computed tomography scan. We describe a typical case and discuss the chain of events leading toward the correct diagnosis and treatment based on a review of published reports.

Bone imaging in prostate cancer

Bone metastases of solid tumors are common, and about 80% of them occur in patients with breast, lung or prostate cancer. Bone metastases can be suspected clinically and by laboratory tests; however, a final diagnosis relies on radiographic evidence. Bone metastases of prostate cancer usually have osteoblastic characteristics, manifested by pathological bone resorption and formation. Conventional bone scans (e.g. with 99mTc-labeled methylene diphosphonate) are preferred to plain-film radiography for surveillance of the entire skeleton. Radiologic diagnosis of bone metastases, particularly in patients with low burden of disease, is difficult because noncancerous bone lesions that mimic cancer are common. Conventional bone scans are limited by their low sensitivity and high false-negative rate (up to 40%) compared with advanced bone-imaging modalities such as PET, PET–CT and MRI, which might assist or replace conventional scanning methods. The correct diagnosis of bone involvement in prostate cancer is crucial to assess the effects of therapy on the primary tumor, the patients prognosis, and the efficacy of bone-specific treatments that can reduce future bone-associated morbidity. In addition, predictive tools such as nomograms enable the identification of patients at risk of bone involvement during the course of their disease. Such tools may limit treatment costs by avoidance of unnecessary tests and might reduce both short-term and long-term complication rates.

Optease vena cava filter optimal indwelling time and retrievability.

The purpose of this study was to assess the indwelling time and retrievability of the Optease IVC filter. Between 2002 and 2009, a total of 811 Optease filters were inserted: 382 for prophylaxis in multitrauma patients and 429 for patients with venous thromboembolic (VTE) disease. In 139 patients [97 men and 42 women; mean age, 36 (range, 17–82) years], filter retrieval was attempted. They were divided into two groups to compare change in retrieval policy during the years: group A, 60 patients with filter retrievals performed before December 31 2006; and group B, 79 patients with filter retrievals from January 2007 to October 2009. A total of 128 filters were successfully removed (57 in group A, and 71 in group B). The mean filter indwelling time in the study group was 25 (range, 3–122)xa0days. In group A the mean indwelling time was 18 (range, 7–55)xa0days and in group B 31xa0days (range, 8–122). There were 11 retrieval failures: 4 for inability to engage the filter hook and 7 for inability to sheathe the filter due to intimal overgrowth. The mean indwelling time of group A retrieval failures was 16 (range, 15–18)xa0days and in group B 54 (range, 17–122)xa0days. Mean fluoroscopy time for successful retrieval was 3.5 (range, 1–16.6)xa0min and for retrieval failures 25.2 (range, 7.2–62)xa0min. Attempts to retrieve the Optease filter can be performed up to 60xa0days, but more failures will be encountered with this approach.

Isolated testicular polyarteritis nodosa mimicking testicular neoplasm-long-term follow-up.

Polyarteritis nodosa is a systemic vasculitis characterized by segmental necrotizing lesions of medium and small-size arteries. Rarely, the inflammatory process is isolated and involves a single organ without systemic manifestations. We describe a patient with isolated polyarteritis nodosa of the testis who presented with a testicular mass mimicking primary testicular tumor. The postoperative laboratory evaluation was negative. Long-term follow-up, without systemic treatment, showed no evidence of recurrence in the remainder of the testis or development of systemic vasculitis.

SOLITARY FIBROUS TUMOR PRESENTING AS PERIRENAL MASS ASSOCIATED WITH HYPOGLYCEMIA

Solitary fibrous tumor is an uncommon mesenchymal lesion, seldom associated with hypoglycemia and rarely presents as a perirenal mass. We describe a perirenal solitary fibrous tumor presenting as a renal mass associated with recurrent hypoglycemic events that resolved after nephrectomy. We discuss the diagnosis, endocrine evaluation and mechanism of the associated hypoglycemia of the solitary fibrous tumor. CASE REPORT An 82-year-old patient presented with episodes of severe symptomatic hypoglycemia without other symptoms or any relevant medical history. Physical examination revealed a left upper quadrant abdominal mass. Computerized tomography of the abdomen showed a localized solid left renal mass 13 cm. in diameter. Endocrine evaluation during a hypoglycemic episode revealed undetected levels of serum insulin and C peptide. Somatostatin scan did not support the preliminary diagnosis of an insulinoma. A 72-hour fasting test was associated with a decrease in blood glucose level to a nadir of 30 mg./dl. (normal 70 to 115) associated with severe confusion. Blood samples taken concomitantly disclosed suppressed levels of insulin, C peptide, growth hormone and insulin-like growth factor without ketonemia. Cortisol levels were high. These findings raised the possibility of a nonislet cell tumor hypoglycemia. The patient underwent radical nephrectomy. During exploration the mass was identified as a perirenal tumor adherent to the renal capsule. Convalescence was uneventful with no further episodes of hypoglycemia after 24 months. Repeat 12-hour fasting test at 3 weeks postoperatively did not indicate hypoglycemia (serum blood glucose was 104 mg./dl.). Plasma insulin, C peptide, growth hormone and insulin-like growth factor-1 increased to normal levels. Pathological examination revealed a large 8 3 13.5 3 14.5 cm. encapsulated mass in the perirenal adipose tissue (fig. 1). The mass had no connection to the renal capsule. On light microscopy the tumor was composed of uniform spindle cells forming a solid pattern with some areas showing abundant deposition of collagen and only a few mitoses (fig. 2). Immunohistochemical studies revealed immunoreactivity for CD 34 and vimentin. Stains for S-100 protein, keratin, MNF 116, desmin, a-1 muscle, CD 68 and factor VIII were negative. These features are consistent with the diagnosis of perirenal benign solitary fibrous tumor.