[Endoscopic papillary abnormalities and urinary stone recognition (EPSR): How and why?] / Reconnaissance endoscopique des anomalies papillaires et des calculs urinaires (REPC) : comment et quel intérêt ?

INTRODUCTION: The purpose of this article is to present the endoscopic papillary abnormalities and stone recognition (EPSR) to state-certified nurses (IDE and IBODE) working in the operating room. METHODS: This article is based on a literature review and the author's experience concerning the endoscopic papillary abnormalities and stone recognition. RESULTS: Since the advent of minimally invasive surgery and the laser, stones are no longer sent as one piece to laboratories, but fragmented. This has made it more difficult for biologists to fully analyze the stones, because they have less morphological data than before. Therefore, endoscopic papillary abnormalities and stone recognition have positioned themselves as tools that can compensate for this loss of information. They play a pivotal role in the identification of the lithogenesis cause, and thus allow a recurrence risk reduction of stones. CONCLUSION: Endoscopic papillary abnormalities and stone recognition are recent tools that require learning. However, the benefit of their uses is proven and is necessary for a complete management of urolithiasis.

Association Between Randall's Plaque Stone Anchors and Renal Papillary Pits.

INTRODUCTION: Renal papillary pits are commonly encountered during ureteroscopy. The mechanism by which such pits arise is unclear. One hypothesis is that pits represent sites where stones overgrowing Randall's plaque (RP) were dislodged. We sought to examine this theory by using digital ureteroscopy and stone µCT. MATERIALS AND METHODS: Patients undergoing endoscopic stone removal had procedures recorded and stones analyzed by using µCT. Stones with evidence of Randall's plaque anchors (RPAs) were identified in a blinded fashion. Surgical videos were reviewed independently by two urologists. RESULTS: Twenty-eight patients had µCT-confirmed stones with RPA. Among them, 93% were recurrent stone formers and 75% had had prior stone procedures. Metabolic abnormalities were present in 87%, with 79% classified as idiopathic calcium oxalate stone formers. A mean of 7.6 stones with RPA were identified per procedure. In each case, papillary pits were visualized before any stone manipulation and in several cases the active dislodgement of an attached stone led to immediate identification of an underlying pit. Such stones routinely demonstrated an RPA on µCT. The average depth of RPA was 302 ± 172 µm, consistent with the corresponding shallow pits visualized on the papillary surface. CONCLUSIONS: Stones overgrowing RP are capable of pulling away a piece of papilla when dislodged, resulting in a visible papillary pit. This process manifests as an RPA on the undersurface of the stone and a papillary pit on the corresponding area of attachment. Identification of pits may help identify patients who form stones primarily by the RP mechanism.

Comparison of Copper Concentration Between Rejected Renal Grafts and Cancerous Kidneys.

In the body, disorders in the composition and concentration of trace elements, including copper, can lead to the development of various alterations that may result in incorrect functioning of the kidneys. Data on the concentrations of copper in human kidneys are discussed; however, little is known about the concentration of trace elements within rejected renal grafts and kidneys with tumor lesions. The aim of our study was to compare the copper concentration between cancerous kidneys and rejected renal grafts with the division on renal cortex and renal medulla. Material consisted of kidneys from patients hospitalized at the Department of Urology and General Surgery and Transplantation of the Independent Public Clinical Hospital No. 2 at the Pomeranian Medical University in Szczecin, north-western Poland. The study material consisted of kidneys with tumor lesions (n = 33), and renal grafts (n = 10), obtained from patients belongs to the north-western areas of Poland. The examination was performed using ICP-AES method. Regarding the pathological kidneys, excluding grafts, the concentration of Cu in the renal cortex was 52% higher than in medullary region and the difference between the compared concentrations was statistically confirmed (p < 0.05). Taking into account renal grafts, the concentration of Cu in the medulla was slightly lower than in the cortex (less than 3%). In summary, copper in rejected and cancerous kidneys tends to accumulate in higher amount in the renal cortex than medulla, what can be explained by the fact that renal corpuscles, where the first phase of filtration is performed, are located only in the cortical region of the kidney. Furthermore, renal grafts accumulate significantly less copper than kidneys with neoplastic changes, what could have been caused by immunosuppressive medicines used by the graft recipients. The lower copper concentration in renal grafts could be a consequence of the altered immune system, including inflammatory process or/and non-immune mechanisms. Additionally, cancerous and non-cancerous kidneys exhibit different perfusion rate in renal glomeruli, what can finally lead to disparity in chemical elements concentration, including copper.

Renal Cell Carcinoma, Unclassified with Medullary Phenotype and Synchronous Renal Clear Cell Carcinoma Present in a Patient with No Sickle Cell Trait/Disease: Diagnostic and Therapeutic Challenges.

Renal medullary carcinoma (RMC) is an aggressive high-grade renal cell carcinoma (RCC) associated almost exclusively with sickle cell trait or sickle cell disease. However, RCC with RMC features has rarely been reported in patients with no sickle cell trait or disease. Renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) is a newly-coined term used by an international panel of experts to describe renal cell carcinoma showing morphologic and immunohistochemical features of renal medullary carcinoma in patients without sickle cell trait/disease. So far, only one study in the English literature has described five such cases. Here, we report a case with unique clinical and pathological features in a 76-year-old male patient without sickle cell trait. The patient had a history of colon cancer with liver and lung metastases and was found to have a new renal mass in his right kidney during the follow up. A right nephrectomy was performed and showed two separate masses (tumor 1 and tumor 2). Tumor 1 had histologic features of RMC and the tumor cells were positive for CK7, Pax8, and OCT4 and showed loss of nuclear INI1 expression. Tumor 1 was diagnosed as RCCU-MP (6.3 cm, pT3aNx, WHO/ISUP nuclear grade 3). Tumor 2 showed features of clear cell type of RCC (0.6 cm, pT1aNx, WHO/ISUP grade 2) with intact nuclear INI1 expression. Three-months post-nephrectomy, the patient developed lung metastasis of RCCU-MP. To the best of our knowledge, this was the first documented case with synchronous RCCU-MP and clear cell RCC presenting in a patient without sickle cell trait. Careful histologic assessment with a panel of immunohistochemical biomarkers was helpful to render a correct diagnosis for early aggressive treatment.

Kidney stone formers have more renal parenchymal crystals than non-stone formers, particularly in the papilla region.

BACKGROUND: We investigated the renoprotective ability of healthy people against kidney stone formation. To clarify intratubular crystal kinetics and processing in human kidneys, we performed a quantitative and morphological observation of nephrectomized renal parenchyma tissues. METHODS: Clinical data and pathological samples from 60 patients who underwent radical nephrectomy for renal cancer were collected from June 2004 to June 2010. The patients were retrospectively classified as stone formers (SFs; n = 30, kidney stones detected by preoperative computed tomography) and non-stone formers (NSFs; n = 30, no kidney stone history). The morphology of parenchymal intratubular crystals and kidney stone-related gene and protein expression levels were examined in noncancerous renal sections from both groups. RESULTS: SFs had a higher smoking rate (P = 0.0097); lower red blood cell, hemoglobin, and hematocrit values; and higher urinary red blood cell, white blood cell, and bacterial counts than NSFs. Scanning electron microscopy revealed calcium-containing crystal deposits and crystal attachment to the renal tubular lumen in both groups. Both groups demonstrated crystal transmigration from the tubular lumen to the interstitium. The crystal diffusion analysis indicated a significantly higher crystal existing ratio in the medulla and papilla of SFs and a significantly higher number of papillary crystal deposits in SFs than NSFs. The expression analysis indicated relatively high osteopontin and CD68, low superoxide dismutase, and significantly lower Tamm-Horsfall protein expression levels in SFs. Multivariate logistic regression analysis involving the above factors found the presence of renal papillary crystals as a significant independent factor related to SFs (odds ratio 5.55, 95% confidence interval 1.08-37.18, P = 0.0395). CONCLUSIONS: Regardless of stone formation, intratubular crystals in the renal parenchyma seem to transmigrate to the interstitium. SFs may have reduced ability to eliminate renal parenchymal crystals, particularly those in the papilla region, than NSFs with associated gene expression profiles.

Optimizing RNA Extraction of Renal Papilla Biopsy Tissue in Kidney Stone Formers: A New Methodology for Genomic Study.

INTRODUCTION: Endoscopic tools have provided versatile examination and treatment for kidney stone procedures. Despite endourologists researching urinary stone disease using endoscopes to collect tissue, this tissue collection method is limited. Endoscopically removed tissues are small in size, restricting the types of genome-based examination possible. We investigated a new method of renal papilla biopsy and RNA extraction to establish a genomic research methodology for kidney stone disease. PATIENTS AND METHODS: We conducted a prospective multi-institutional study and collected renal papilla specimens from consecutive percutaneous nephrolithotomy and ureteroscopy (URS) cases performed for removal of upper urinary tract stones. Renal papilla tissue was extracted using ureteroscopic biopsy forceps after stone removal. RNA was extracted using two different extraction kits, and their quantity and quality were examined. Additionally, the impact of biopsy on surgical complications was compared between cases performed with and without biopsy by matched case-control analysis adjusted for age, gender, body mass index, bilaterality, and stone burden. RESULTS: A total of 90 biopsies from 49 patients were performed, and the median duration between specimen collection and RNA extraction was 61 days. Both univariate and multivariate analyses showed BIGopsy® forceps usage significantly increased the total yield (p = 0.004) and quality (p = 0.001 for A260/280, p = 0.004 for A260/A230) of extracted RNA. Extraction using the RNeasy Micro Kit® also improved A260/A230, whereas reduced RNA integrity number of extracted RNA by univariate and multivariate analyses (p = 0.002 and p < 0.001, respectively). Moreover, matched case-control study demonstrated that endoscopic renal papilla biopsy caused no significant surgical complications, including bleeding, decreased stone clearance and hematocrit, and renal dysfunction. Biopsies during URS imparted an average of 20 minutes of procedure time over nonbiopsy cases. CONCLUSIONS: We demonstrate a safe methodology for optimal RNA extraction of renal papilla tissue. This technique will accelerate advanced genomic studies for kidney stone formers by facilitating larger tissue yields.

Endoscopic Evidence That Randall's Plaque is Associated with Surface Erosion of the Renal Papilla.

OBJECTIVE: This study was conducted to assess the reliability and precision of an endoscopic grading scale to identify renal papillary abnormalities across a spectrum of equipment, locations, graders, and patients. MATERIALS AND METHODS: Intra- and interobserver reliability of the papillary grading system was assessed using weighted kappa scoring among 4 graders reviewing a single renal papilla from 50 separate patients on 2 occasions. Grading was then applied to a cohort of patients undergoing endoscopic stone removal procedures at two centers. Patient factors were compared with papillary scores on the level of the papilla, kidney, and patient. RESULTS: Graders achieved substantial (kappa >0.6) intra- and inter-rater reliability in scored domains of ductal plugging, surface pitting, and loss of contour. Agreement for Randall's Plaque (RP) was moderate. Papillary scoring was then performed for 76 patients (89 kidneys, 533 papillae). A significant association was discovered between pitting and RP that held both within and across institutions. A general linear model was then created to further assess this association and it was found that RP score was a highly significant independent correlate of pitting score (F = 7.1; p < 0.001). Mean pitting scores increased smoothly and progressively with increasing RP scores. Sums of the scored domains were then calculated as a reflection of gross papillary abnormality. When analyzed in this way, a history of stone recurrence and shockwave lithotripsy were strongly predictive of higher sums. CONCLUSIONS: Renal papillary pathology can be reliably assessed between different providers using a newly described endoscopic grading scale. Application of this scale to stone-forming patients suggests that the degree of RP appreciated in the papilla is strongly associated with the presence of pitting. It also suggests that patients with a history of recurrent stones and lithotripsy have greater burdens of gross papillary disease.

Ultrasonographic Evaluation of the Kidney in 5/6 Nephrectomized Rats: Correlation with Biochemical and Histopathological Findings.

AIM: To characterize the kidney alterations associated with renal mass reduction by two-dimensional ultrasound and assess the correlation of the ultrasonographic parameters with the histological and biochemical findings. MATERIALS AND METHODS: Rats were divided into two groups: sham-operated animals (n=13), and animals which underwent renal mass reduction (RMR) through 5/6 nephrectomy (n=14). Renal length, renal thickness, cortical thickness, medullary length and echogenicity of the kidneys were evaluated by ultrasonography at 3 and 6 months after the RMR. RESULTS: Except for the renal length, the renal dimensions at 3 and 6 months were significantly higher in the RMR group when compared to the sham-operated group (p<0.05). Furthermore, the cortical and medullary echogenicity was significantly higher in the RMR group when compared to the sham-operated group (p<0.05). A significant correlation was observed between the plasma creatinine level and the renal length 3 months after RMR (r=-0.612, p=0.045). CONCLUSION: These data support future application of ultrasonography for monitoring the progression of renal damage in chronic studies with the 5/6 nephrectomy model.

Effects of Thermal Preconditioning on Tissue Susceptibility to Histotripsy.

Histotripsy is a non-invasive ablation method that mechanically fractionates tissue by controlling acoustic cavitation. Previous work has revealed that tissue mechanical properties play a significant role in the histotripsy process, with stiffer tissues being more resistant to histotripsy-induced tissue damage. In this study, we propose a thermal pretreatment strategy to precondition tissues before histotripsy. We hypothesize that a thermal pretreatment can be used to alter tissue stiffness by modulating collagen composition, thus changing tissue susceptibility to histotripsy. More specifically, we hypothesize that tissues will soften and become more susceptible to histotripsy when preheated at ∼60°C because of collagen denaturation, but that tissues will rapidly stiffen and become less susceptible to histotripsy when preheated at ∼90°C because of collagen contraction. To test this hypothesis, a controlled temperature water bath was used to heat various ex vivo bovine tissues (tongue, artery, liver, kidney medulla, tendon and urethra). After heating, the Young's modulus of each tissue sample was measured using a tissue elastometer, and changes in tissue composition (i.e., collagen structure/density) were analyzed histologically. The susceptibility of tissues to histotripsy was investigated by treating the samples using a 750-kHz histotripsy transducer. Results revealed a decrease in stiffness and an increase in susceptibility to histotripsy for tissues (except urethra) preheated to 58°C. In contrast, preheating to 90°C increased tissue stiffness and reduced susceptibility to histotripsy for all tissues except tendon, which was significantly softened due to collagen hydrolysis into gelatin. On the basis of these results, a final set of experiments were conducted to determine the feasibility of using high-intensity focused ultrasound to provide the thermal pretreatment. Overall, the results of this study indicate the initial feasibility of a thermal pretreatment strategy to precondition tissue mechanical properties and alter tissue susceptibility to histotripsy. Future work will aim to optimize this thermal pretreatment strategy to determine if this approach is practical for specific clinical applications in vivo without causing unwanted damage to surrounding or overlying tissue.

Functional characterization of isolated, perfused outermedullary descending human vasa recta.

AIM: The renal medulla plays an important role in the control of water and salt balance by the kidney. Outer medullary descending vasa recta (OMDVR) are microscopic vessels providing blood flow to the renal medulla. Data on the physiology of human vasa recta are scarce. Therefore, we established an experimental model of human single isolated, perfused OMDVR and characterized their vasoactivity in response to angiotensin II and to pressure changes. METHODS: Human non-malignant renal tissue was obtained from patients undergoing nephrectomy due to renal cell carcinoma. OMDVR were dissected under magnification and perfused using concentric microscopic pipettes. The response of OMDVR to angiotensin II and pressure changes was quantified in serial pictures. All patients signed a consent form prior to surgery. RESULTS: Outer medullary descending vasa recta constricted significantly after bolus applications of angiotensin II. OMDVR constriction to angiotensin II was also concentration dependent. Response to luminal pressure changes was different according to the diameter of vessels, with larger OMDVR constricting after pressure increase, while smaller ones did not. CONCLUSION: Outer medullary descending vasa recta constrict in response to angiotensin II and pressure increases. Our results show that OMDVR may take part in the regulation of medullary blood flow in humans. Our model may be suitable for investigating disturbances of renal medullary circulation in human subjects.

Multi-institutional assessment of ureteroscopic laser papillotomy for chronic flank pain associated with papillary calcifications.

PURPOSE: We evaluated the long-term safety, efficacy and durability of ureteroscopic laser papillotomy for chronic flank pain associated with renal papillary calcifications. MATERIALS AND METHODS: We reviewed the medical records of all patients who underwent ureteroscopic laser papillotomy in the absence of free urinary calculi at our institutions from 1998 through 2008. Success was defined as patient report of significant pain relief. The duration of response was considered the time from papillotomy to repeat papillotomy in the same renal unit, patient report of recurrent pain or final followup. RESULTS: Ureteroscopic Ho:YAG laser papillotomy was done a total of 176 times in 65 patients, including 147 unilateral and 29 bilateral procedures. Of the patients 39 underwent multiple procedures (2 to 12). Symptomatic followup was available in 50 patients (146 procedures) during a mean of 38 months. Significantly less pain was reported after 121 procedures (83%). The mean duration of response per procedure was 26 months and 30 patients (60%) had a mean remission duration of greater than 1 year. Postoperatively hospital admission was required after 14 procedures (8%). There was no significant change in the mean estimated glomerular filtration rate during a mean 41.3-month followup. Seven of the 65 patients (11%) had hypertension before papillotomy. In 3 of the 49 patients (6.1%) with adequate followup new hypertension developed during a mean of 38 months. CONCLUSIONS: Ureteroscopic laser papillotomy is safe and effective. In patients with papillary calcifications and characteristic chronic, noncolicky pain this procedure provides significant, moderately durable symptom relief.

Intramedullary cavity as implantation site for bioartifical pancreas: preliminary in vivo study.

BACKGROUND: The intramedullary cavity is a widely distributed well-vascularized microenvironment capable of sustaining grafts, and is a potential site for islet transplantation. The bone marrow offers sufficient space that may also be suitable for bioartificial pancreas (BAP) implantation. OBJECTIVE: To evaluate the feasibility of bone marrow as an implantation site for BAPs. MATERIALS AND METHODS: A calcium phosphate cement chamber satisfies the criteria for immunoisolation. Mouse insulinoma cells were suspended with agarose gel and enclosed in a calcium phosphate cement chamber to create a BAP, which was implanted in the intramuscular space in diabetic swine or the intramedullary cavity in diabetic dogs. Blood glucose and C-peptide concentrations were determined perioperatively. RESULTS: In the swine, the mean ± SD blood glucose concentration decreased from 413 ± 24 mg/dL to 285 ± 47 mg/dL, and was maintained in the range of 285 to 336 mg/dL for 15 days. It increased to 368 to 450 mg/dL after the BAPs were implanted in the intramuscular space. In the dogs, the blood glucose concentration decreased from 422 ± 32 mg/dL to 247 ± 52 mg/dL, and was maintained in the range of 247 to 347 mg/dL after the BAPs were implanted in the intramedullary cavity. The C-peptide concentration increased from 6.1 ± 2.8 pmol/L to 104.7 ± 16.4 pmol/L when the BAPs were implanted in the intramedullary cavity. CONCLUSION: This study indicates superior effectiveness of BAPs implanted in the intramedullary cavity compared with the intramuscular space. This observation may be attributed to the greater oxygen tension in the bone marrow. The BAPs in direct contact with the circulatory system receive sufficient blood flow for function and survival. This preliminary study demonstrates that the intramedullary cavity may be an implantation site for BAP transplantation.

Cold renal ischemia: comparison of efficacy between two techniques of cooling, in a swine model.

OBJECTIVES: In a swine model of renal ischemia, we compared the effectiveness of the transurethral retrograde cold saline perfusion technique to the traditional method of renal cooling with ice slush, in achieving adequate parenchymal temperatures for functional preservation of the organ. Physiological and histological effects were also assessed. METHODS: Twenty-four domestic male pigs were sampled into four groups to be submitted to a 60-minute ischemia of the left kidney without cooling, with either one of the two cooling techniques (cold saline retrograde perfusion or ice slush), or sham surgery. All of them had also a concomitant right nephrectomy. Renal cortical and medullary temperatures were recorded throughout the experiment. Urinary output was measured, and serum renal function tests were carried on, pre- and postoperatively. After 5 days, the animals were euthanized and their kidneys were submitted to histological analysis. RESULTS: Mean renal temperature fell in both groups submitted to kidney cooling. With ice slush, a faster drop was observed and a lower minimum temperature was achieved (5.0 degrees C in the cortex and 6.3 degrees C in the medulla, vs. 25.4 degrees C and 24.9 degrees C with retrograde cooling). In the other groups, temperature was unchanged. Urinary output and serum creatinine worsened after the experiment, but without significant differences among groups. The histological analysis showed no differences among the four groups, for the studied ischemia time. CONCLUSIONS: Ice slush and retrograde perfusion of cold saline are both effective for cooling the kidney during ischemia. Ice slush is faster in doing so, and it allows much lower temperatures to be achieved in the renal parenchyma. With ischemia time of 60 minutes, no significant differences on the occurrence of functional and histological alterations were detected, even for the group without a cooling procedure.

Renal histopathology of stone-forming patients with distal renal tubular acidosis.

To define the renal tissue changes in stone-forming patients with distal renal tubular acidosis (dRTA), we performed intra-operative papillary and cortical biopsies in five patients. The main abnormalities were plugging of inner medullary collecting ducts (IMCD) and Bellini ducts (BD) with deposits of calcium phosphate in the form of apatite; epithelial cell injury and loss was marked. Plugged ducts were surrounded by interstitial fibrosis, but the fibrosis was generalized, as well, and was a main feature of the histopathology even when plugging was not present. In contrast, common idiopathic calcium oxalate stone formers (SF) never manifest intra-tubule crystals or interstitial fibrosis. Patients with brushite (calcium monohydrogen phosphate) stones and those with cystine stones have many fewer IMCD and BD plugged with apatite (or cystine, in cystinuria), and interstitial fibrosis is limited to the regions around plugged ducts. Patients with dRTA often present a radiographic picture of nephrocalcinosis. Our direct surgical observations reveal that these may be surgically removable stones, especially in patients with well preserved renal function. In all, dRTA SF have a more diffuse papillary renal disease than other SF thus studied, and are also unusual for the degree of interstitial fibrosis.

Primary ureteroscopic treatment for obstructive ureteral stone-causing fornix rupture.

BACKGROUND: Management of fornix rupture (FR) by obstructive stone is comprised of extravasation control and the elimination of the obstruction. For all patients, management initially remains conservative under close follow up. Endoscopic management of FR involved with an obstructive stone of the ureter or the pelvi-ureteric junction (UPJ) consists mainly of stenting the ureter. Our endoscopic approach to this pathological entity comprises of the sole stenting of the ureter, as well as primary ureteroscopic lithotripsy followed by ureter stenting. PATIENTS AND METHODS: In the Department of Urology at the General Hospital of Rhodos Island, Rhodos, Greece, over the last 15 years, 51 of 86 patients with FR due to an obstructive stone, were treated endoscopically. Twenty-two patients underwent sole stenting of the ureter (option A) and 29 patients underwent primary ureteroscopic lithotripsy and stenting (option B). RESULTS: The overall primary 'successful outcome' was achieved in nine of the 22 patients (40.9%) in the group treated with sole stenting, while the remaining 59.1% required secondary interventions. However, 27 of the 29 patients (93.1%) treated with primary ureteroscopic lithotripsy and stenting required no auxiliary treatment. The primary successful outcome results for obstructive middle and lower ureteral stones with FR were eight out of 12 (66.6%) and 26 out of 27 (96.3%) for therapeutic options A and B, respectively. Upper obstructive ureteral stones with FR required secondary intervention in most cases, regardless of the therapeutic option chosen. (In nine out of 10 and one out of two cases for options A and B, respectively). The mean duration of hospitalization for options A and B were 7.6 and 5.3 days, respectively. The mean duration that the ureter stent remained in situ for A and B treatment options was 30.9 and 10.2 days, respectively. CONCLUSIONS: Sole stenting of the ureter is reserved for infected FR or for stones of the upper ureter or the UPJ. Ureteroscopic lithotripsy followed by double-J stenting of the ureter may offer a quick and safe therapeutic alternative for distal and middle obstructive ureteral stones with FR.

Blunted tubuloglomerular feedback by absence of angiotensin type 1A receptor involves neuronal NOS.

To define the role of angiotensin type 1A (AT1A) receptor in modulating tubuloglomerular feedback signals and to determine its relationship to neuronal NO synthase (nNOS), the diameter of the afferent arterioles of wild-type and AT1A receptor-deficient mice was measured by the blood-perfused juxtamedullary nephron technique. The afferent arteriolar diameter of wild-type and AT1A receptor-deficient mice averaged 16.7+/-0.6 (n=9) and 16.8+/-0.7 micro m (n=9), respectively. In the wild-type mice, addition of 10 micro mol/L acetazolamide to the blood perfusate exerted a biphasic afferent arteriolar constriction, with the initial response and sustained response averaging 47.2+/-3.8% and 33.9+/-3.3%, respectively. In AT1A receptor-deficient mice, the initial response and sustained response averaged 51.6+/-3.6% and 9.5+/-1.3%, respectively, and the sustained response was significantly attenuated compared with that of wild-type mice. Inhibition of nNOS with 10 micro mol/L S-methyl-L-thiocitrulline significantly decreased the afferent arteriolar diameter of AT1A receptor-deficient mice, from 15.1+/-1.2 to 5.0+/-0.3 micro m (n=7), and the decrease was significantly greater than that observed in wild-type mice (from 15.9+/-1.2 to 10.6+/-1.3 micro m; n=8). During nNOS inhibition, the initial and sustained afferent arteriolar constrictor responses to acetazolamide in wild-type mice averaged 54.4+/-6.4% and 44.8+/-11.3%; respectively, and were similar to those in AT1A receptor-deficient mice (53.2+/-6.4% and 59.5+/-4.4%, respectively). These results suggest that AT1A receptors enhance tubuloglomerular feedback-mediated afferent arteriolar constriction, at least in part, through reducing the counteracting modulation by nNOS.

Evaluation of superficial papillary ablation by endoscopic lasers in an ex vivo kidney model.

BACKGROUND AND PURPOSE: Endoscopic examinations of stone-forming kidneys show a coincidence of plaques and microliths on the surface of and within papillary epithelial tissue. These calcifications are thought to be precursors of calcium oxalate urolithiasis. We hypothesized that minimally invasive endoscopic laser ablation of microliths and necrotic cell layers enables epithelial regeneration and prevents recurrent urolithiasis. The aim of this study was to determine the most suitable laser type and dose intensity for selective superficial cell ablation. MATERIALS AND METHODS: Conventional Nd:YAG (1-40 W) or Ho:YAG (0.5-3 J/single impulse) lasers were used endoscopically on an ex vivo blood-perfused porcine kidney model. Defined doses were applied to the papillary surface in the contact and noncontact modes for 10 to 30 seconds. Papillae were excised after treatment and histopathologically analyzed in continuous sections. Lesions were microscopically assessed with the aid of a Leica Quantimed computer program. RESULTS: Depending on the time and dose, vaporization by the Nd:YAG laser caused large tissue defects and coagulation necrosis at energy levels over 5 W (contact and noncontact mode). Lower energy levels with tissue contact produced only superficial cell defects (<20 cell layers) but more extensive coagulation necrosis, whereas no histologic effects were observed at the same energy level without contact. In contrast, independent of delivered energy but dependent on time, Ho:YAG laser application caused pure tissue loss without relevant coagulation necrosis. The generation of small lesions (6-10 cell layers) without tissue contact was possible at energy levels under 2 J. CONCLUSIONS: Selective superficial papillary cell ablation is possible. Low-energy Nd:YAG treatment in the contact mode and Ho:YAG treatment in the noncontact mode led to superficial vaporization with no (Ho:YAG) or minimum (Nd:YAG) coagulation defects.

[Intramedullary spinal cord metastasis: is there a place for surgery? Case report and review of literature]. / Métastases intramédullaires de cancers viscéraux: quelle place pour la chirurgie? Revue de la littérature à propos d'un cas.

BACKGROUND AND PURPOSE: The usual onset of intramedullary spinal cord metastases at an advanced stage of cancer disease explains that surgical removal of such lesions is rarely performed. We tried to define the place for surgery in the management of such lesions. METHODS: We report the observation of a 52-year-old male patient presenting with a metastasis of the conus medullaris revealing a lung cancer. Surgical excision of the lesion led to pain relief and improvement of bladder dysfunction. We present a review of pertinent literature. RESULTS: Surgery allows histological diagnosis in case of isolated, revealing tumor. In other selected cases, radical removal of intramedullary metastases could improve the quality and comfort of life although it does not seem to affect the duration of survival.

Functional effects of unilateral laser papillectomy in the pig.

OBJECTIVES: To evaluate the use of endoscopic laser papillectomy in a multi-papillary animal model to unilaterally impair concentrating ability and increase the urinary flow rate. METHODS: Domestic pigs underwent unilateral retrograde flexible nephroscopy. With a holmium:yttrium-aluminum-garnet laser, varying numbers of papillae were ablated. Four weeks after the procedure, renal function studies were performed during hydropenia and after hydration, the animals were killed, and the kidneys were examined histologically. RESULTS: The urine flow rate per 100 mL creatinine clearance was significantly increased in the papillectomized kidney compared with the control kidney during hydropenia (1.50 versus 0.94, P <0.01). The papillectomized kidneys were unable to concentrate the urine as well as the control kidneys during both hydropenia (urine osmolarity 430 versus 534 mOsm/L, P <0.01) and after hydration (329 versus 362 mOsm/L, P = 0.02). The free water reabsorption per 100 mL creatinine clearance was impaired in the papillectomized kidneys compared with the control kidneys (0.48 versus 1.00, P = 0.02) after hydration. A significant correlation existed between the percentage of papillae ablated and the difference in osmolarity between the operated and control kidneys (r(2) = 0.50, P = 0.015). Histologic examination demonstrated transitional re-epithelialization with moderate collecting duct dilation and medullary fibrosis underlying the ablated papillae early in the series; however, the histologic features normalized and the creatinine clearance was less impaired with a more proficient technique later in the series. CONCLUSIONS: Endoscopic laser papillectomy results in increased urine flow and impaired urinary concentrating ability. This surgical technique should be investigated further for its role in the prevention of nephrolithiasis.

Unilateral renal papillectomy via laser or incisional techniques: chronic functional effects in the dog.

OBJECTIVE: To determine if selective renal papillectomy would impair urinary concentrating ability, thereby decreasing urinary calcium concentration. METHODS: Left papillectomy was performed in dogs using either incisional (n = 6) or Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (n = 5) techniques. Split renal function studies were then performed four months postoperatively to determine the effect on multiple parameters including inulin and para-aminohippurate (PAH) clearance, free water reabsorption, and calcium concentrations. Partially infarcted kidneys (n = 6) were evaluated in a similar fashion to determine the role of impaired glomerular filtration rate (GFR) in the observed concentrating defect occurring after papillectomy. RESULTS: Papillectomized kidneys demonstrated impaired free water reabsorption, resulting in a decreased urinary osmolality and an increased fractional excretion of water. Osmolar clearance [Na+] and Na+ excretion were unaffected by papillectomy, whereas [Ca++] was significantly reduced. While a slight defect in free water reabsorption existed following partial infarction, urinary osmolality was only minimally decreased, fractional excretion of water was unchanged, and Na+ excretion was decreased. CONCLUSIONS: The concentrating defect induced by papillectomy via either sharp excision or laser ablation is due to loss of medullary tissue and is greater than the defect resulting from impaired GFR, which is presumably due to decreased medullary solute delivery and increased flow of water in remaining nephrons. Since the physiologic consequences of papillectomy (formation of less concentrated urine with decreased [Ca++]) have potential clinical applicability, further study of this concept is warranted.