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Biomedical subjects

R G Uzzo

Publications and source records attributed to R G Uzzo.

At least 19 recordsLinked to original sources

Inhibition of NFkappaB induces caspase-independent cell death in human T lymphocytes.

Nuclear factor kappaB (NFkappaB) regulates the expression of various genes essential for cell survival. Here we demonstrate that suppression of NFkappaB nuclear import with SN50 peptide carrying the nuclear localization sequence (NLS) of the NFkappaB p50 subunit induces apoptosis in human peripheral blood T lymphocytes (T-PBL), which can be blocked with the pan-caspase inhibitor Z-VAD.fmk. However, even when caspase function is blocked, the addition of SN50 induces irreversible cell loss due to the reduction in the mitochondrial transmembrane potential (DeltaPsim) followed by disruption of the cell membrane, hallmarks of necrosis. These observations demonstrate that although inhibition of NFkappaB nuclear translocation by SN50 peptide can induce caspase-dependent apoptosis in T-PBL, cell death may still proceed in the absence of functional caspase activity. The availability of downstream caspases appears to determine the mode of cell death in NFkappaB defective cells.

Active Transport, Cell Nucleus↗

Quality of life and psychological adaptation after surgical treatment for localized renal cell carcinoma: impact of the amount of remaining renal tissue.

OBJECTIVES: To analyze the quality of life and psychological adjustment after surgical therapy for localized renal cell carcinoma. METHODS: Postal questionnaires including measures of quality of life (SF-36) and the impact of the stress of cancer (Impact of Events Scale) were completed by 97 patients who had undergone radical or partial nephrectomy for localized renal cell carcinoma. Data were analyzed for the group as a whole and comparing the partial nephrectomy and radical nephrectomy groups. The variables examined included the impact of the type of partial nephrectomy (elective versus mandatory) and the amount of self-reported renal tissue remaining. RESULTS: The quality of life for the group as a whole was good, with no significant differences between the sample and U.S. norms for an age and sex-matched community sample on both the mental and physical health composite scores. Having undergone a partial versus a radical nephrectomy did not influence the patients' overall quality of life. Multiple linear regression modeling demonstrated that having more remaining renal parenchyma was an independent predictor of better self-reported physical health on the SF-36 (P <0.001). The entire sample had low mean scores on both avoidance and intrusion on the Impact of Events Scale, suggesting a lack of daily anxiety about cancer. Multiple linear regression modeling showed that patients who reported having more remaining renal parenchyma had lower intrusion and avoidance scores (P = 0.002 and 0.01, respectively). Multiple logistic regression modeling also demonstrated that the patients' perception of their remaining renal parenchyma was associated with less concern about cancer recurrence (P = 0.018) and less impact of cancer on patients' overall health (P <0.001). CONCLUSIONS: Most survivors of localized kidney cancer have normal physical and mental health regardless of the type of nephrectomy performed. The quality of life is better for patients with more renal parenchyma remaining after surgery for localized renal cell carcinoma.

Adaptation, Psychological↗

Strategies for transplantation of cadaveric kidneys with congenital fusion anomalies.

PURPOSE: The dire shortage of cadaveric kidneys has led to a gradual expansion of donor criteria in the transplant community. The use of kidneys with anatomical fusion anomalies is uncommon and has not been well defined in the literature. We evaluated the surgical strategies and postoperative outcomes of transplanting cadaveric kidneys with congenital fusion anomalies. MATERIALS AND METHODS: Three cadaveric kidneys with congenital fusion anomalies were procured and transplanted between May 1994 and November 1999. None of the 3 donors had any significant urological history. All fusion anomalies were identified during the organ procurement process. RESULTS: Anomalies included 1 L-shaped cross-fused ectopic and 2 horseshoe kidneys. All 3 kidneys were procured en bloc. One horseshoe kidney with a narrow isthmus was split and the 2 kidneys were transplanted into separate recipients, while the other horseshoe kidney was transplanted en bloc into a single recipient. The L-shaped kidney was transplanted en bloc into 1 patient. All transplants were successful with a serum creatinine of 1.1 to 1.9 mg/dl. CONCLUSIONS: To our knowledge we present the initial case of transplantation of an L-shaped kidney. Cadaveric kidneys with congenital fusion anomalies may be transplanted successfully using various individual technical strategies based on the specific renal anatomy. As such, these kidneys may be used to maximize the increasingly inadequate donor pool.

Algorithms↗

Nephron sparing surgery for renal tumors: indications, techniques and outcomes.

PURPOSE: A contemporary review of the indications, techniques and outcomes is presented for nephron sparing approaches to solid renal masses, emphasizing their role for the treatment of renal cell carcinoma. We also reviewed the evolving role of minimally invasive forms of parenchymal sparing renal surgery. MATERIALS AND METHODS: MEDLINE and CANCERLIT computerized literature searches, and manual bibliographic reviews were performed to identify published peer reviewed articles pertaining to nephron sparing surgery or partial nephrectomy from 1980 to 2000. Pertinent articles were collated and reviewed. RESULTS: Nephron sparing surgery is increasingly being used to treat patients with solid renal lesions. The technical success rate of nephron sparing surgery is excellent, and operative morbidity and mortality are low. For renal cell carcinoma long-term cancer-free survival is comparable to that after radical nephrectomy, particularly for low stage disease. The overall incidence of local recurrence is low at 0% to 10%. For tumors 4 cm. or less local recurrence rates are even less at 0% to 3%. The risk of local recurrence depends primarily on the initial local pathological tumor stage. The reported incidence of multifocal renal cell carcinoma is approximately 15% and it also depends on tumor size, histology and stage. The risk of multifocal disease is low at less than 5% when the maximal diameter of the primary tumor is 4 cm. or less. Recent advances in renal imaging limit the radiographic evaluation necessary when planning complex nephron sparing approaches. Three-dimensional, volume rendered computerized tomography integrates all of the necessary information previously obtained by conventional computerized tomography, angiography, venography and pyelography into a single preoperative test, allowing better operative planning with maximal preservation of unaffected parenchyma in the remnant kidney. Minimally invasive modalities of tumor resection or destruction should be reserved for highly select patients and await improvements in technology, standardization of technique and long-term outcomes data before they may be completely integrated options. CONCLUSIONS: Nephron sparing surgery provides effective therapy for patients in whom preservation of renal function is a relevant clinical consideration. The importance of meticulous operative technique for achieving acceptable oncological and functional outcomes is emphasized. Accumulating data in appropriately select patients suggest a long-term functional advantage gained by the maximal preservation of unaffected renal parenchyma without sacrificing cancer control.

Carcinoma↗

Caspase-dependent and -independent death pathways in cancer therapy.

The majority of current anticancer therapies induce tumor cell death through the induction of apoptosis. Alterations in the apoptotic pathways may determine tumor resistance to these therapies. Activation of the proteolytic cascade involving caspase family members is a critical component of the execution of cell death in apoptotic cells. However, recent studies suggest that cell death can proceed in the absence of caspases. In this review we describe the role of caspase-dependent and -independent pathways as targets for anticancer treatment. A better understanding of diverse modes of tumor cell death will help to avoid ineffective treatment and provide a molecular basis for the new strategies targeting caspase-independent death pathways in apoptosis-resistant forms of cancer.

Antineoplastic Agents↗

Tumor-induced dysfunction in interleukin-2 production and interleukin-2 receptor signaling: a mechanism of immune escape.

PURPOSE: The development of an effective antitumor immune response is compromised in patients with renal cell carcinoma. Despite significant infiltration by T lymphocytes into renal tumors, no detectable induction of gene expression is associated with the generation of an antitumor immune response. Tumor-induced down-regulation of interleukin (IL)-2 expression may contribute to the impaired development of the T cell-mediated antitumor immune response. Within renal tumors, there is no detectable expression of IL-2 or the IL-2 receptor alpha chain, and only low levels of interferon gamma (IFN-gamma) mRNA are detected. Products in the tumor environment may suppress the expression of these genes, thus inhibiting production of type 1 helper T cell cytokines. METHODS: Peripheral blood lymphocytes obtained from healthy volunteers were exposed to supernatants from renal cell carcinoma explants, and the immunologic consequences of this were assessed using a variety of molecular assays. RESULTS: Soluble products from renal tumor explants can inhibit the production of IL-2 and IFN-gamma by peripheral blood lymphocytes and can suppress T-cell proliferation. Soluble products from renal cell carcinoma explants appear to block the nuclear translocation of nuclear factor kappa B (NFkappaB) proteins p50 and RelA without affecting cytoplasmic levels of these proteins. In some experiments, a reduction in the nuclear translocation of other transcription factors involved in IL-2 gene expression, including nuclear factor of activated T cells and accessory protein-1, was observed. Gangliosides isolated from tumor supernatants blocked the production of IL-2 and IFN-gamma in response to ionomycin plus phorbol myristate acetate stimulation. These gangliosides also inhibited stimulus-dependent activation and nuclear accumulation of NFkappaB. Coculture experiments demonstrated that renal cell carcinoma lines known to express gangliosides could inhibit the activation of NFkappaB in normal T cells and the Jurkat T-cell line. Supernatants from renal cell carcinoma explants and renal cell carcinoma cell lines can also suppress the proliferation of normal T cells, thus reproducing another defect observed in tumor-infiltrating lymphocytes. Supernatants from renal cell carcinoma tumors also appear to inhibit signaling through the IL-2 receptor. Although tumor supernatants had little effect on IL-2 receptor (alpha, beta or gamma) expression, they did block expression of JAK3, a key kinase involved in signaling through the IL-2 receptor pathway. Moreover, downstream events in IL-2 receptor signaling linked to JAK3 were impaired in T cells treated with tumor supernatants. CONCLUSION: These findings suggest that soluble products from renal tumors may suppress T-cell responses by blocking both IL-2 production and normal IL-2 receptor signaling.

Carcinoma, Renal Cell↗

Laparoscopic retroperitoneal live donor right nephrectomy for purposes of allotransplantation and autotransplantation.

PURPOSE: We report the technique of and initial experience with retroperitoneal laparoscopic live donor right nephrectomy for purposes of renal allotransplantation and autotransplantation. MATERIALS AND METHODS: A total of 5 patients underwent retroperitoneoscopic live donor nephrectomy of the right kidney for autotransplantation in 4 and living related renal donation in 1. Indications for autotransplantation included a large proximal ureteral tumor, a long distal ureteral stricture and 2 cases of the loin pain hematuria syndrome. In all cases a 3-port retroperitoneal laparoscopic approach and a pelvic muscle splitting Gibson incision for kidney extraction were used. In patients undergoing autotransplantation the same incision was used for subsequent transplantation. RESULTS: All procedures were successfully accomplished without technical or surgical complications. Total mean operating time was 5.8 hours and average laparoscopic donor nephrectomy time was 3.1 hours. Mean renal warm ischemia time, including endoscopic cross clamping of the renal artery to ex vivo cold perfusion, was 4 minutes. Average blood loss for the entire procedure was 400 cc. Radionuclide scan on postoperative day 1 confirmed good blood flow and function in all transplanted kidneys. Mean analgesic requirement was 58 mg. fentanyl. Mean hospital stay was 4 days (range 2 to 8), and convalescence was completed in 3 to 4 weeks. CONCLUSIONS: In the occasional patient requiring renal autotransplantation live donor nephrectomy can be performed laparoscopically with renal extraction and subsequent transplantation through a single standard extraperitoneal Gibson incision, thus, minimizing the overall operative morbidity. Furthermore, these data demonstrate that live donor nephrectomy of the right kidney can be performed safely using a retroperitoneal approach with an adequate length of the right renal vein obtained for allotransplantation or autotransplantation.

Adult↗

Dead or dying: necrosis versus apoptosis in caspase-deficient human renal cell carcinoma.

The antitumor effect of immuno- and chemotherapeutic agents is executed through stimulation of apoptotic programs in susceptible cells. Apoptosis induced in tumor cells requires activation of members of the caspase family of proteases. Deficient expression or activation of caspases may account in part for the failure of many current anticancer therapies. However, recent studies suggest that cell death can proceed in the absence of caspases. We investigated the susceptibility of human renal cell carcinoma (RCC) lines to two distinct modes of cell death, apoptosis and necrosis. RCC lines displayed almost complete resistance to apoptosis in response to the intracellular zinc chelator, N,N,N'N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), which instead induced dramatic accumulation of nonapoptotic necrotic cells. Conversely, TPEN was a potent inducer of apoptosis in caspase-competent normal kidney cells (NK-72) and Jurkat T lymphocytes. Resistance to apoptosis in RCC lines correlated with almost complete loss of caspase-3 expression and variable down-regulation of caspase-7, caspase-8, and caspase-10. These data may explain the resistance of RCC to drugs inducing apoptosis and have important consequences for further attempts to manipulate tumor cell death.

Apoptosis↗

Comparison of direct hospital costs and length of stay for radical nephrectomy versus nephron-sparing surgery in the management of localized renal cell carcinoma.

OBJECTIVES: Recent work has demonstrated comparable surgical results and 5-year cancer-specific survival rates between radical nephrectomy and nephron-sparing surgery (NSS) in the treatment of patients with small (4 cm or smaller) solitary renal cell carcinomas (RCCs). However, differences exist in the intraoperative management and postoperative care of patients undergoing NSS versus radical nephrectomy, and we sought to compare direct hospital costs and length of stay (LOS) between these two groups to determine whether either treatment imparts a specific cost advantage. METHODS: Data were retrieved from medical records and administrative data sets containing billing encounters for all costs incurred during hospitalization at the Cleveland Clinic Foundation. Individual costs were grouped together using nine cost center categories encompassing every aspect of direct hospital care, including anesthesiology, laboratory, radiology, nursing, pharmaceutical, and emergency services, and medical care, surgical care, and miscellaneous costs. Each cost center was further subdivided, and a total of 52 cost subcategories were assessed. The total direct costs of hospitalization were compared using a multivariate regression model in which patient demographics and tumor characteristics, type and year of surgery, LOS, and cost center categories were assessed as single and interactive factors. Postoperative complication and cancer-specific survival rates were also compared to identify any potential therapeutic differences between the two groups. RESULTS: Between 1991 and 1995, 80 patients underwent surgery at the Cleveland Clinic Foundation for solitary RCCs 4 cm or smaller, including 52 partial and 28 radical nephrectomies. We found no difference in the postoperative complication rate or cancer-specific survival rate between the two surgical groups. Total direct hospital costs and LOS were not statistically different between the NSS and radical nephrectomy groups (P >0.05). This was further supported by our multivariate model, which accounted for 61% of the observed variance in the total costs (F = 12.11, P = 0.0001). The type of surgery was not associated with total cost when controlling for all other factors, including age, sex, year of surgery, tumor size, grade, and stage, and postoperative complications (P = 0.7). There was no significant interaction between the type of surgery and the LOS (P = 0.5). CONCLUSIONS: This study demonstrated that elective NSS can be performed with equivalent direct hospital costs and LOS when compared with patients undergoing radical nephrectomy for small solitary RCCs. These data have significant economic implications for the comparison of competing surgical treatment strategies for localized RCC.

Aged↗

Renal cell carcinoma-derived gangliosides suppress nuclear factor-kappaB activation in T cells.

Activation of the transcription factor nuclear factor-kappaB (NFkappaB) is impaired in T cells from patients with renal cell carcinomas (RCCs). In circulating T cells from a subset of patients with RCCs, the suppression of NFkappaB binding activity is downstream from the stimulus-induced degradation of the cytoplasmic factor IkappaBalpha. Tumor-derived soluble products from cultured RCC explants inhibit NFkappaB activity in T cells from healthy volunteers, despite a normal level of stimulus-induced IkappaBalpha degradation in these cells. The inhibitory agent has several features characteristic of a ganglioside, including sensitivity to neuraminidase but not protease treatment; hydrophobicity; and molecular weight less than 3 kDa. Indeed, we detected gangliosides in supernatants from RCC explants and not from adjacent normal kidney tissue. Gangliosides prepared from RCC supernatants, as well as the purified bovine gangliosides G(m1) and G(d1a), suppressed NFkappaB binding activity in T cells and reduced expression of the cytokines IL-2 and IFN-gamma. Taken together, our findings suggest that tumor-derived gangliosides may blunt antitumor immune responses in patients with RCCs.

Carcinoma, Renal Cell↗

3-dimensional volume rendered computerized tomography for preoperative evaluation and intraoperative treatment of patients undergoing nephron sparing surgery.

PURPOSE: Computerized tomography (CT) is the diagnostic and staging modality of choice for renal neoplasms. Existing imaging modalities are limited by a 2-dimensional (D) format. Recent advances in computer technology now allow the production of high quality 3-D images from helical CT. Nephron sparing surgery requires a detailed understanding of renal anatomy. Preoperative evaluation must delineate the relationship of the tumor to adjacent normal structures and demonstrate the vascular supply to the tumor for the surgeon to conserve as much normal parenchyma as possible. We propose that helical CT combined with 3-D volume rendering provides all of the information required for preoperative evaluation and intraoperative management of nephron sparing surgery cases. We prospectively evaluated the role of 3-D volume rendering CT in 60 patients undergoing nephron sparing surgery for renal cell carcinoma at the Cleveland Clinic Foundation. MATERIALS AND METHODS: Triphasic spiral CT was performed preoperatively in 60 consecutive patients undergoing nephron sparing surgery for renal neoplasms. A 3 to 5-minute videotape was prepared using volume rendering software which demonstrated the position of the kidney, location and depth of extension of the tumor(s), renal artery(ies) and vein(s), and relationship of the tumor to the collecting system. These videotapes were viewed by a radiologist and urologist in the operating room at surgery, and immediately correlated with surgical findings. Corresponding renal arteriograms of 19 patients were retrospectively compared to 3-D volume rendering CT and operative findings. RESULTS: A total of 97 renal masses were identified in 60 cases evaluated with 3-D volume rendering CT before nephron sparing surgery. There were no complications related to the 3-D protocol and 3-D rendering was successful in all patients. The number and location of lesions identified by 3-D volume rendering CT were accurate in all cases, while enhancement and diagnostic characteristics were consistent with pathological findings in 95 of 97 tumors (98%). Of 77 renal arteries identified at surgery 74 were detected by 3-D volume rendering CT (96%). Helical CT missed 3 small accessory arteries, including 1 in a cross fused ectopic kidney. All major venous branches and anomalies were identified, including 3 circumaortic left renal veins. Of 69 renal veins identified at surgery 64 were detected by 3-D volume rendering CT (93%). All 5 renal veins missed by CT were small, short, duplicated right branches of the main renal vein. Renal fusion and malrotation anomalies were correctly identified in all 4 patients. CONCLUSIONS: The 3-D volume rendering CT accurately depicts the renal parenchymal and vascular anatomy in a format familiar to most surgeons. The data integrate essential information from angiography, venography, excretory urography and conventional 2-D CT into a single imaging modality, and can obviate the need for more invasive imaging. Additionally, the use of videotape in an intraoperative setting provides concise, accurate and immediate 3-D information to the surgeon, and it has become the preferred means of data display for these procedures at our center.

Adult↗

The effects of mesh bioprosthesis on the spermatic cord structures: a preliminary report in a canine model.

PURPOSE: The use of mesh bioprosthesis during inguinal herniorrhaphy is now considered routine. To our knowledge, no studies have examined the effects of mesh induced fibrosis on the structure and function of the adjacent spermatic cord. We present our experience in a canine model. MATERIALS AND METHODS: Unilateral inguinal hernia defects were created in 12 male beagle dogs. Half were repaired using Marlex mesh and half using a classic Shouldice technique. The inguinal anatomy was then re-examined at 6 and 12 months. Testicular temperature and volume, peripheral and testicular vein testosterone levels, testicular blood flow, vasography, testicular and cord histology, and sperm motility/morphology were recorded. Groups were compared with each other as well as to the non-operated (control) side. RESULTS: Although post-operative testicular volumes from both the mesh and Shouldice groups were similar to controls (p >0.05), there was a downward trend after mesh repair (17.8 cc pre versus 12.6 cc post) but this did not reach statistical significance (p = 0.17). Testicular temperatures and blood flow did not differ between experimental groups and controls. While testicular vein testosterone levels were significantly higher than peripheral venous levels after Shouldice repair, this difference was lost after mesh repair. Contralateral (control) testicular vein testosterone levels were higher in animals repaired with mesh than by an anatomic Shouldice repair (p <0.05). There was a significant decrease in cross sectional vasal luminal diameter in both the anatomic and mesh repair groups versus their respective contralateral controls (p <0.05). This was correlated with a marked foreign body reaction to the mesh in the soft tissues surrounding the vas in spermatic cords exposed to Marlex. All vasograms demonstrated patency. Gross pathology was abnormal in 3/6 dogs with mesh repair (2 hydroceles and 1 ischemic testis) and 0/6 animals after Shouldice repair. A traumatic neuroma was identified in the mesh group. Sperm morphology and motility did not differ between the two groups. CONCLUSIONS: Half of the testicles had gross abnormalities after mesh repair versus none in the control and Shouldice dogs. Although all vasograms were patent, vasal luminal size was significantly decreased with a marked soft tissue foreign body reaction identified after mesh repair. A traumatic neuroma was identified suggesting nerve entrapment in the fibrotic mesh reaction, which may account for post-operative pain seen in some patients. Marlex mesh may adversely affect spermatic cord structure and function and further work is required to fully elucidate its effects.

Animals↗

Mechanisms of apoptosis in T cells from patients with renal cell carcinoma.

Tumors may escape immune recognition and destruction through the induction of apoptosis in activated T lymphocytes. Results from several laboratories suggest that FasL (L/CD95L) expression in tumors may be responsible for this process. In this study of patients with renal cell carcinoma (RCC), we provide evidence for two mechanisms of T-cell apoptosis. One mechanism involves the induction of apoptosis via FasL expression in tumor cells. This is supported by several observations, including the fact that tumor cells in situ as well as cultured cell lines expressed FasL mRNA and protein by a variety of techniques. The FasL in RCC is functional because in coculture experiments, FasL+ tumors induced apoptosis in Fas-sensitive Jurkat T cells and in activated peripheral blood T cells but not in resting peripheral blood T cells. Most importantly, antibody to FasL partially blocked apoptosis of the activated T cells. Moreover, Fas was expressed by T cells derived from the peripheral blood (53% median) and tumor (44.3% median) of RCC patients. Finally, in situ staining for DNA breaks demonstrated apoptosis in a subset of T cells infiltrating renal tumors. These studies also identified a second mechanism of apoptosis in RCC patient peripheral T cells. Whereas these cells did not display DNA breaks when freshly isolated or after culture for 24 h in medium, peripheral blood T cells from RCC patients underwent activation-induced cell death after stimulation with either phorbol 12-myristate 13-acetate/ionomycin or anti-CD3/CD28 antibodies. Apoptosis mediated by exposure to FasL in tumor cells or through T-cell activation may contribute to the failure of RCC patients to develop an effective T-cell-mediated antitumor response.

Apoptosis↗

Use of a free bladder mucosal graft for simple repair of vesicovaginal fistulae.

The aim of this paper is to describe a simple, fast, and effective method for repair of difficult vesicovaginal fistulae by means of a free bladder mucosal graft. Six patients with high, large, multiple, or recurrent vesicovaginal fistulae were treated using a free bladder mucosal graft. Three patients underwent "early" repair (less than 3 months from time of injury) and 3 "late" repair (more than 6 months from time of injury). Via a suprapubic cystotomy, the mucosa of the fistulous tract was debrided without any attempt to excise the tract or close the bladder or vaginal defects. A free bladder mucosal graft was harvested from an unaffected portion of the bladder and placed over the fistulous tract, and mucosal approximation was made using interrupted 5-0 chromic stay sutures. The donor urothelial defect was allowed to re-epithelialize. A Foley catheter, suprapubic tube, and vaginal packing were left in place. Five patients noted an immediate result, with no evidence of leakage, and the suprapubic tube was removed by week 3. One patient required prolonged catheter drainage, and the tube was successfully removed by week 6. This patient had undergone irradiation. All patients remain dry at follow-up, which ranges from 2 to 6 years. We describe a simple and effective method for transabdominal vesicovaginal fistula repair, involving minimal mobilization, decreased dissection, and no need for rotational or interposition flaps, obviating the need to open the peritoneum. A free bladder mucosal graft can be used regardless of the individual anatomy or proximity to the ureteral orifices, because it can easily be tailored. This technique represents an important repair of difficult, recurrent, or multiple vesicovaginal fistulae.

Female↗

Microsurgical repair of the adolescent varicocele.

PURPOSE: Since clinically apparent varicoceles may affect testicular volume and sperm production, early repair has been advocated. However, repair of the pediatric varicocele with conventional nonmagnified techniques may result in persistence of the varicocele after up to 16% of these procedures. Also testicular artery injury and postoperative hydrocele formation can occur after nonmagnified repair. The microsurgical technique has been successfully completed in a large series of adults with a dramatic reduction in complication and recurrence rates. We report our experience with the microsurgical technique in boys. MATERIALS AND METHODS: A total of 30 boys (average age 15.9 years) underwent 42 microsurgical varicocelectomies (12 bilateral). All patients had a large left varicocele. Indications for repair included testicular atrophy (size difference between testicles of greater than 2 ml.) in 20 boys, pain in 5 and a large varicocele without pain or testicular atrophy in 5. Six boys were referred following failure of conventional nonmicrosurgical techniques. All boys were examined no sooner than 1 month postoperatively (mean followup 12). RESULTS: Preoperative volume of the affected testis averaged 13.0 ml., and an average size discrepancy between testicles of 2.8 ml. was noted before unilateral varicocelectomy. No cases of persistent or recurrent varicoceles were detected, and 1 postoperative hydrocele resolved spontaneously. After unilateral varicocelectomy the treated testes grew an average of 50.1%, while the contralateral testes grew only 23%. Overall, 89% of patients with testicular atrophy demonstrated reversal of testicular growth retardation after unilateral varicocelectomy. In contrast, both testes showed similar growth rates after bilateral varicocelectomy (45% left testis, 39% right testis). CONCLUSIONS: The meticulous dissection necessary to preserve arterial and lymphatic supply, and to ligate all spermatic veins in the pediatric patient is readily accomplished using a microsurgical approach, and results in low recurrence and complication rates. Rapid catch-up growth of the affected testis after microsurgical varicocelectomy suggests that intervention during adolescence is effective and warranted.

Adolescent↗

Laparoscopic surgery in children with ventriculoperitoneal shunts: effect of pneumoperitoneum on intracranial pressure--preliminary experience.

OBJECTIVES: We monitored changes in intracranial pressure (ICP) in 2 children with myelodysplasia undergoing laparoscopic bladder autoaugmentation. Both children had ventriculoperitoneal shunts (VPS) secondary to Arnold-Chiari malformations (type II). METHODS: ICP was monitored through a 23-gauge needle placed into the shunt reservoir and connected to a pressure transducer and drainage system. Intraoperative mean arterial pressure, end-tidal CO2 (ETCO2), ICP, abdominal pressure, and cerebral perfusion pressures were all monitored. RESULTS: Both children demonstrated rapid onset and sustained increases in ICP of greater than 12 mm Hg above baseline to a maximum pressure of 25 mm Hg. The average cerebrospinal fluid removed from each patient was 30 cc, thereby lowering ICP with no adverse neurologic sequela. The pCO2 remained constant throughout the procedures, as measured by ETCO2. CONCLUSIONS: We believe that intracranial hypertension (IH) results from a "Valsalva-like" phenomenon, which causes cerebral vascular engorgement. In addition, the pneumoperitoneum may increase the resistance to outflow through the distal peritoneal catheter, causing a partial or complete shunt obstruction. Untreated IH may result in adverse neurologic sequelae from brain herniation in these children with hindbrain anomalies and potentially altered brain compliance. We believe it is prudent to perform intraoperative ICP monitoring in this subgroup of patients undergoing laparoscopic surgery and that IH should be treated by ventricular drainage.

Child↗