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Background Although grading systems have been proposed for chromophobe renal cell carcinoma (ChRCC), including a three-tiered system by Paner et al (Paner GP, Amin MB, Alvarado-Cabrero I, et al. A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade. Am J Surg Pathol 2010;34:1233–40), none have gained clinical acceptance, and the World Health Organization (WHO) currently recommends against grading ChRCC. Objective To validate a previously published grading scheme and propose a scheme that includes tumor necrosis. Design, setting, and participants A total of 266 patients who underwent nephrectomy for nonmetastatic ChRCC between 1970 and 2012 were reviewed for ChRCC grade according to the Paner system and coagulative tumor necrosis. Outcome measurements and statistical analysis Associations with cancer-specific survival (CSS) were evaluated using Cox proportional hazard regression models and summarized with hazard ratios (HRs). Results and limitations Twenty-nine patients died from RCC; the median follow-up was 11.0 (interquartile range 7.9–15.9) yr. ChRCC grade according to the Paner system was significantly associated with CSS, including the difference in outcome between grade 1 and 2 tumors. Among patients with grade 2 tumors, the presence of tumor necrosis helped delineate patients with worse CSS. As such, the Paner system was expanded to four tiers separating grade 2 into those with and without tumor necrosis. HRs for associations of the proposed grade 2, 3, and 4 tumors with CSS were 4.63 (p = 0.007), 17.8 (p Conclusions The expansion of a previously reported ChRCC grading system from three to four tiers by the inclusion of tumor necrosis helps further delineate patient outcome and can, therefore, enhance patient counseling following surgery. It also aligns the number of ChRCC grades with the WHO/International Society of Urologic Pathology four-tiered grading systems for clear cell and papillary RCC. Patient summary Chromophobe renal cell carcinoma is the third most common type of renal cancer, and unlike other renal cancers, there is no accepted prognostic grading system. In this study, we found that a grading system that included a pathologic feature of tumor necrosis could better define outcomes for patients with chromophobe renal cell carcinoma.

Five patients with unifocal, biopsy-proven prostate cancer (PCa) evident on multiparametric magnetic resonance imaging (MRI) were treated with magnetic resonance-guided focused ultrasound (MRgFUS) ablation before radical prostatectomy (RP). An endorectal probe featuring a phased-array focused ultrasound transducer was positioned for lesion ablation under MRI guidance. The tissue temperature and accumulation of thermal damage in the target zone was monitored during the procedure by MRI thermometry. Overlap between the ablation area and the devascularisation of the target lesion was evaluated by contrast-enhanced MRI performed immediately after treatment. The procedure was uneventful, and no adverse events were observed. RP was safely performed without significant surgical difficulties in relation to the previous MRgFUS treatment. The histopathology report showed extensive coagulative necrosis, with no residual tumour in the ablated area. Significant bilateral residual tumour, not evident on pretreatment MRI, was observed outside the treated area in two patients. MRgFUS ablation of focal localised PCa is feasible and, if confirmed in appropriate studies, could represent a valid option for the focal treatment of localised PCa.

Advancements in imaging and laparoscopy have led to the expansion of minimally invasive techniques in the ablation of small renal masses (SRMs). We report the results of a study aimed at assessing the efficacy of thermoablative microwave (MW) effects on SRMs and the haemostatic as well as necrotic MW effects on the parenchyma surrounding the neoplasm. From November 2008 to October 2010, 10 patients with SRMs underwent laparoscopy-guided Tru-Cut biopsy, MW tumour ablation, and enucleation. Mean age was 66 yr (range: 46–84 yr). Mean renal tumour diameter was 2.75cm (range: 1.3–4.2cm). MW antennas were applied one to three times depending on tumour volume, location, and shape. After MW thermoablation, laparoscopic enucleation was performed to evaluate the histopathologic and haemostatic effects of MW. The mean MW antenna application time was 14.1min (range: 4–30min). Enucleation did not require renal pedicle clamping in any of the cases because no significant bleeding took place. Preablation pathology revealed clear cell renal carcinoma of Fuhrman grade I–II in all cases. Postablation pathology showed extensive coagulative necrosis without skipped tumour areas. No intra- or postoperative complications were reported. Histopathologic effects on SRMs provide consistent proof of principle for future studies.

An increased incidence of low-risk prostate cancer (PCa) has led investigators to develop focal therapy as a management option for PCa. We evaluated the effects of focal laser ablation (FLA) on PCa tissue and the accuracy of magnetic resonance imaging (MRI) in determining ablated lesion volume by comparing the whole-mount histology and MRI in four patients that underwent FLA followed by radical prostatectomy. Ablated areas were characterized by homogeneous coagulation necrosis. The MRI-calculated ablated volume correlated well with histopathology. We found that FLA creates confluent ablation with no evidence of viable cells in treated regions. Postablation MRI is able to determine the ablation accurately.

OBJECTIVE To evaluate the safety and efficacy of the holmium:YAG laser in the management of pelviureteric junction (PUJ) obstruction. PATIENTS AND METHODS Between November 1994 and February 1996, 8 patients with 5 primary and 3 secondary PUJ obstructions underwent retrograde ureteroscopic holmium:YAG laser endopyelotomy. A 320- to 365-micron (Slimline, Coherent) fibre was used to deliver the laser energy. A posterolateral endopyelotomy was performed under visual monitoring. All patients had a ureteral stent left in place postoperatively for 6 weeks and a renogram was performed after 3 months. The mean follow-up was 12.4 months (3-24 months). RESULTS Almost bloodless, accurate and layered division of the PUJ was easily performed. The average procedure time was 37.5 min. Our overall success rate was 87.5%. CONCLUSION The holmium:YAG laser is a safe, reliable laser with adequate coagulative properties and precise cutting abilities. This allows a 'bloodless' operative field for controlled, accurate and safe endoscopic division of the PUJ.

UNLABELLED Prostatic transurethral thermotherapy was evaluated clinically using the Prostcare microwave system of the Bruker Company, which uses a microwave radiometer to measure and control intraprostatic temperature. OBJECTIVES The aim of our study was to evaluate the immediate histological lesions induced in the prostatic tissue depending on the temperatures delivered to the prostate; the histological changes when adenectomy is carried out after thermotherapy, and the endoscopic appearance of the prostatic fossa 48 h, and 1, 2, 3 and 6 months after thermotherapy. METHODS Our study was divided into three stages: in the first stage, we conducted thermotherapy in 10 patients in whom suprapubic adenectomy was indicated. During thermotherapy, a multipoint fiber-optic receptor and two thermocouples were implanted into the prostage gland at a distance of 5-15 mm from the urethra. Adenectomy was carried out 10 min after thermotherapy; the second stage of our study concerned the changes seen over time. We heated adenomas using the same protocol and carried out adenectomy 24, 48, 72 h, and 1 week, 6 weeks and 3 months after thermotherapy, and lastly, we studied the endoscopic appearance after a single heating-session of 30 min by endoscopic controls at different times after thermotherapy (48 h, 1, 2, 3 and 6 months after thermotherapy). RESULTS Macroscopic appearance: necrotic lesions measured 30 mm in length on average. Necrosis was roughly circumferential. Immediate histological aspect: in all cases, histological examination showed coagulation necrosis with periurethral thromboses. Histological changes: at 8 days, necrosis intensity was maximal and histological structures were difficult to identify. Endoscopic appearance: 3 months after thermotherapy, the typical endoscopic appearance was a large periurethral cavity. There was a sharp demarcation between untreated areas and cicatricial tissue. CONCLUSION The efficacy of thermotherapy depends on the radiometric temperature, which should reach 47 degrees C (i.e. a temperature of 55-65 degrees C delivered to the prostate), and a rapid increase in temperature, i.e. in the power applied, which should reach the thermal radiometric level of 47 degrees C in 5 min. As soon as necrosis is obtained, the power is automatically reduced. Using this protocol, heating proves effective in 30 min.

Objectives : To evaluate the efficacy of transrectal focused ultrasound on localized prostatic cancer. Methods : Fourteen patients (mean age 72.5 years) with clinical stage T1 (3) and T2 (11) prostatic cancers, who were not suitable candidates for surgery were treated. The mean PSA pretreatment level was 12 ± 10 ng/ml (Hybritech). The device used (Ablatherm, Technomed M.S.) combines a 2.25-MHz therapy transducer and a 7.5-MHz transrectal biplane ultrasound scanner probe (linked to a software enabling the operator to determine precisely the zone of the prostate to be treated. The prostate was treated in one (3 patients), two (7 patients) or three sessions (4 patients) under spinal (25 sessions) or general anesthesia (4 sessions). Results : Complications occurred in 9 of the 14 patients (64%) : early complications occurred in 6 (rectal burns 3, urinary retention 2, transient incontinence 1) and late complications in 5 (incontinence 2, bladder neck stenosis 3). The median PSA NADIR value (1.79 ± 2.35 ng/ml) was achieved at 6 months and the final PSA value was 2.94 ± 3.27 ng/ml (mean follow-up 380 days). Control biopsies demonstrated coagulative necrotic lesions of the treated prostate zones with secondary development into fibrosis. No residual cancer was observed in 7 patients after several random sextant biopsies. Residual cancer was found in 7 patients : 4 required complementary treatment (orchidectomy 2, external beam radiation therapy 2). Adjuvant therapy was deferred in 3 patients with stable PSA values under 2 ng/ml. Conclusions : A satisfactory local control with negative control biopsies was achieved in 50% of the cases in this pilot study. However, this therapy is an investigational procedure : long-term follow-up will be necessary to confirm these early results.

A system generating focused elastic ultrashort waves has been developed with the aim to destroy tumors by an extracorporeal way. Experimental studies on different targets (plastic phantoms, organ samples and normal live tissues in pigs) have been done showing the good focusing of the device and the possibility of getting a focal tissular coagulative necrosis. Studies on cultured tumor cells and implanted tumors in rats have shown a local effect on cells or tumor growth with the absence of metastatic risks. First human trials are summarized. This technique we call focused extracorporeal pyrotherapy could be useful for the treatment of cancers.

High-intensity focused ultrasound is a method of destroying tissue at a point distant from the transducer without injuring intervening tissue. A transrectal probe was developed and used to treat 26 canines in order to determine the feasibility of using this therapy in humans. Lesions of coagulative necrosis which evolved into cystic cavities were produced. Surrounding tissue was preserved without evidence of injury.

A new device made of piezoelectric ceramic placed in a semispherical dish and focussed at 320 mm was developed in order to generate heat and cavitation responsible for coagulative necrosis of deep tissues. The target to be treated is located with a central ultrasound probe of 3.5 MHz. In vitro studies with polyurethane phantoms showed that the ultrasound melted a surface of 2 x 12 mm within 1 s. The temperature recorded at the focus was 270 degrees C. In tissue samples (prostate cancer and benign prostate hyperplasia), the temperature rose to 85 degrees C in vitro and a hyperechoic zone appeared at the focus during shots. In vivo 8-mm plastic spheres, introduced surgically into the bladder of pigs, were melted by repeat shots without burning of crossed tissues. These studies were performed in the kidney and the liver. Autopsy performed on day 0 showed congestion, autopsy performed between day 6 and day 11 showed necrosis, whereas at 3 months the focussed area was fibrosed. This technique, which we called 'focussed extracorporeal pyrotherapy', combines phenomena of cavitation and high heat at the focus. Prostate tumors, bladder tumors, kidney tumors and liver metastases are potential indications for pyrotherapy.

In this comprehensive review, Ficarra et al assemble a team of expert urologic oncologists and genitourinary pathologists who succinctly lay out the current state of pathologic review of renal cell carcinoma [1]. The authors appropriately identify key issues and current controversies in the prediction of the disease based on its histologic features. Several key issues stand out and deserve emphasis. First, it is imperative that clinicians and pathologists maintain an active working relationship. Pathologists depend on clinicians for specimens that maintain structure and enable a robust histologic review of the material. Techniques such as morcellation [2] or inadequate biopsy samples make histologic interpretation more difficult and should be discouraged. In turn, clinicians depend on pathologists to perform an accurate review of the submitted material. Indeed, even in our own experience, when reviewing patients who unexpectedly progressed despite having low-risk histologic features, two thirds were found to be understaged histologically [3]. These patients were found to have an unrecognized invasion of the renal sinus, a critical highway of blood vessels and lymphatics that may facilitate metastasis from the kidney [4]. Second, accurate disease prediction is important for counseling patients regarding their risk of recurrence. But perhaps more importantly, such studies facilitate trials of adjuvant or salvage therapies by ensuring equal risk of disease progression among treatment groups. At the Mayo Clinic, we have strived to improve the outcome prediction that is obtained through routine hematoxylin and eosin staining by clarifying the role of pathologic stage, tumor size, nuclear grade, and histologic coagulative necrosis, to form the SSIGN score, a simple predictive model that has been independently validated [5]. We also support the authors’ assertion that histologic subtype in renal cell carcinoma represents a vital feature for both prognostica

The objective of interstitial laser coagulation (ILC) of benign prostatic enlargement is to achieve a marked volume reduction and to decrease bladder outlet obstruction and lower urinary tract symptoms with minimal morbidity. Coagulation necrosis is generated well inside the adenoma by means of specifically designed laser applicators combined with either a Nd:YAG laser or a diode laser. Because the laser applicators can be inserted as deeply and as often as necessary, it is possible to coagulate any amount of tissue at any desired location while preserving adjacent structures such as the urethra. Postprocedural, the intraprostatic lesions result in secondary atrophy and regression of the prostate lobes, rather than sloughing of necrotic tissue. Several single-armed and randomized studies indicated the effectiveness of interstitial laser coagulation of BPH-syndrome. Marked improvements in AUA score, peak flow rate, residual urine volume and prostate volume were reported. Pressure-flow studies demonstrated a sufficient decrease of the intravesical/detrusor pressure, urethral opening pressure and urethral resistance. Long-term results demonstrating sustained success for up to 3 years were reported on a series of 394 patients. ILC is suitable to debulk even large prostates and to treat highly obstructive patients. Therefore, ILC can be seen as a true alternative to TURP with certain advantages, such as almost no serious morbidity and with certain disadvantages, such as the need for postoperative catheterization. However, ILC can be done under local anesthesia and does not require hospitalization.

The effect of high-intensity focused ultrasound (HIFU) ablation on the morphology of prostatic, renal and testicular tissue was studied by light and electron microscopy. Specimens were obtained in 21 patients 1 h to 10 weeks after lesioning. Histological findings showed consistent coagulative necrosis with precisely defined, sharp margins to normal tissue. Lesion size and position correlated well with the assumed target zones, suggesting that HIFU permits therapeutic tissue ablation.

Many attempts have been made to develop a method for treating benign prostatic hyperplasia (BPH) that is minimally invasive, efficacious, and low cost. The transurethral needle ablation (TUNA) device has recently been developed to treat BPH by selectively ablating hyperplastic prostatic tissue. A special catheter incorporates needles that deliver low-level radiofrequency power directly to a very localized area of the prostate. The needles have adjustable shields to protect the urethra if desired or necessary. It is positioned via transrectal ultrasound or direct vision. A pilot study was performed in patients to evaluate TUNA feasibility via histopathological measurement of thermal lesion size and TUNA safety by: (1) monitoring urethral and rectal temperatures; (2) assessing the ability to localize lesions, and (3) determining patient tolerance of the procedure without anesthesia. Twenty patients were treated using TUNA prior to scheduled retropubic prostatectomy. The surgical prostatic specimens were recovered from 1 day to 1 month after TUNA, were step-sectioned, and examined histologically. Patients were 68 years old on average with prostate weight varying from 14 to 88 g. The TUNA procedure averaged 27 min, 4 lesion treatments per prostate, and 4-15 W of power applied for 3 min. Proximal lesion temperature was about 40-50 degrees C with central lesion temperatures of about 80-100 degrees C. Urethral temperature averaged 37-42 degrees C and rectal temperature remained unchanged. Macroscopic examination of the specimens demonstrated localized lesions averaging 12 x 7 mm. Microscopic examination showed larger lesions of extensive coagulative necrosis averaging 30 x 15 mm. Specific immunohistochemical staining showed destruction of all tissue components.(ABSTRACT TRUNCATED AT 250 WORDS)

High intensity-focused ultrasound (HIFU) has been used transrectally to induce an intraprostatic coagulation necrosis lesion in human prostatic adenoma. The device to produce HIFU combines a firing system (power amplifier and therapy transducer) and an imaging system (ultrasound scanner). Nine patients have been treated on epidural anaesthesia with an ultrasound intensity similar to or higher than the acoustic intensity used in previous experiments on canine prostates. Intraprostatic lesions were obtained without any damage to the rectal wall. These lesions were also histologically determined to be coagulation necrosis with a complete destruction of the glandular tissue. These studies confirm the possibility of creating irreversible lesions in the prostatic tissue through the rectal wall. The destruction of localised prostatic cancer would seem to be possible in the near future by using HIFU delivered by the transrectal route.

The safety and effectiveness of tissue ablation by coagulative necrosis with high-intensity focused ultrasound (HIFU) applied through a rectal probe to 36 patients with symptomatic benign prostatic hyperplasia (BPH) was investigated in a phase II clinical trial. Overall, HIFU treatment was well tolerated, the mean hospital stay being 1.1 days. Negative side effects were transient urinary retention in 32/36 patients, hematuria in 2 patients and hematospermia resolving after 3-4 weeks (n = 15). After 3 months the maximum flow rate/s (Qmax) increased from 9.0 +/- 3.9 to 14.4 +/- 7.0 ml/s, the median flow rate/s (QM90) from 4.9 +/- 2.4 to 7.6 +/- 4.17 ml/s; the postvoid residual volume decreased from 128 +/- 88 to 57 +/- 35 ml and the AUA symptom score from 25.5 +/- 5 to 13.2 +/- 4.4. In conclusion, it was shown that tissue ablation in patients with symptomatic BPH using HIFU is safe and dramatically reduces both obstructive and irritative symptoms and leads to a significant increase in uroflow and a decrease in postvoid residual volume.

The indications, risks and benefits of surgical treatment of benign prostatic hyperplasia (BPH) have recently been scrutinized, and interest in the development of less invasive alternative nonsurgical approaches has emerged. Among the nonsurgical alternatives, thermal treatments have been clinically introduced for a few years but are still under evaluation. Microwaves and radiofrequency waves are generated by various devices applied by the transrectal or transurethral approach, with different treatment and temperature schedules. Results achieved with the various devices did not show large significant differences. Improvement is mainly observed by a decrease in irritative symptoms rather than by modifications of obstructive parameters. The placebo effect must not be underestimated in all these new alternative methods. Fifty percent of patients in retention and unfit for anesthesia voided satisfactorily after thermal treatment. Pathological studies of operative specimens after transurethral thermotherapy showed coagulative necrosis with destruction of smooth muscle and glandular components. The destruction of alpha-receptors or sensory nerves in the prostate stroma is a possible explanation for the reduction of irritative symptoms. No significant histological lesions were found however after transrectal hyperthermia. Various factors such as differences in tissue thermosensitivity, tissular architecture and thermoregulation related to variation in the prostate blood supply may all play a part in the final heating effect and determine the clinical response for a given patient. Better understanding of these various factors may improve patient selection. Although thermal treatment of BPH cannot be seen as a substitution for surgery, it may represent an alternative option in selected patients essentially to alleviate irritative symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo tissue destruction was performed on 124 rat and 16 canine kidneys by focusing high-intensity ultrasound with a 1- and 2.25-MHz transducer. A precise tissue lesion was obtained in both models which varied in size according to the number of firings and the acoustic intensity. In the rat experiments, which were used to define the constants necessary to produce a localized tissue lesion at the focus of the transducer, the lesions obtained were either coagulating necrosis or a ‘punched out’ cavity which represented the threshold of tissue ablation. In the canine experiments, a kidney lesion was achieved in 10 animals (63%) extracorporally. These lesions were also histologically determined to be coagulation necrosis. These lesions are created by highly focused ultrasound and are caused most likely by a combination of cavitation and thermal effects, depending on the duration and frequency of the ultrasound bursts. Exact mechanism of this effect is explored as well as potential clinical applications in treating kidney, liver, and prostate tumors in humans.