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Andrew C Novick

Publications and source records attributed to Andrew C Novick.

At least 19 recordsLinked to original sources

The predictive value of helical computed tomography for collecting-system entry during nephron-sparing surgery.

OBJECTIVES: To assess the ability of helical computed tomography (CT) including multiplanar reformatting and volume rendering (3D CT) to predict collecting system entry at surgery, as helical CT can be used to delineate renal tumour and normal renal anatomy before nephron-sparing surgery (NSS). PATIENTS AND METHODS: Knowledge of the possibility of collecting system entry during surgery might either dissuade some surgeons from NSS in elective situations or influence the operative approach or ablative technology in cases where NSS is imperative, or prepare the surgeon for the possibility of collecting system repair. We reviewed all 3D CT (349 scans) obtained before NSS at our institution over three consecutive years. Tumour size, central tumour extension, and presence of calyceal involvement were prospectively recorded at the time of 3D rendering. Collecting system entry was analysed for these three CT variables, and for three clinical variables (tumour side, size and surgical approach) collected retrospectively from the medical records. Multivariate logistic regression was used to assess the sensitivity, specificity, and positive and negative predictive values. RESULTS: Of 344 patients, 170 had collecting system entry reported at surgery. There were statistically significant associations between collecting system entry and central tumour location by CT (sensitivity 58.8%, specificity 80.5%, P < 0.001), calyceal involvement at CT (sensitivity 53.5%, specificity 78.2%, P < 0.001), and tumour size on CT of > 4 cm (sensitivity 39.4%, specificity 74.7%, P = 0.005). There were no significant associations with side or type of surgery (P > 0.83). CONCLUSION: Helical CT is a reliable predictor of calyceal entry at surgery.

Adolescent↗

The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease.

Autosomal-dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently leads to renal failure. Mutations in polycystin-1 (PC1) underlie most cases of ADPKD, but the function of PC1 has remained poorly understood. No preventive treatment for this disease is available. Here, we show that the cytoplasmic tail of PC1 interacts with tuberin, and the mTOR pathway is inappropriately activated in cyst-lining epithelial cells in human ADPKD patients and mouse models. Rapamycin, an inhibitor of mTOR, is highly effective in reducing renal cystogenesis in two independent mouse models of PKD. Treatment of human ADPKD transplant-recipient patients with rapamycin results in a significant reduction in native polycystic kidney size. These results indicate that PC1 has an important function in the regulation of the mTOR pathway and that this pathway provides a target for medical therapy of ADPKD.

Animals↗

Expression of IL-8 during reperfusion of renal allografts is dependent on ischemic time.

BACKGROUND: Ischemia/reperfusion injury is an inherent consequence of solid organ transplantation that increases tissue inflammation and negatively impacts organ transplant function and survival. This study investigated the expression levels of chemokine and chemokine receptor genes in living versus cadaver donor renal allografts before and after reperfusion. METHODS: This study involved 39 renal transplant patients (19 cadaveric and 20 living donor). The ischemia biopsy was taken just before graft declamping and the reperfusion biopsy 30 min after declamping. Whole-cell RNA was isolated and chemokine (IL-8, CCL2/MCP-1, CXCL10/IP-10 and CCL5/RANTES) and chemokine receptor (CCR2 and CCR5) expression was tested by quantitative PCR. RESULTS: Just prior to declamping, ischemic cadaveric donor grafts had higher expression of CXCL10/IP-10 but not IL-8 or CCL2/MCP-1 than living donor grafts. IL-8 expression increased 50% from ischemia to reperfusion in living donor grafts but increased more than 13-fold during reperfusion of cadaver donor grafts. Increased total ischemia time induced greater IL-8 expression during reperfusion. MCP-1 expression also increased during reperfusion of living and cadaver donor grafts but differences were not observed between the two groups of grafts. RANTES, CCR2, and CCR5 expression did not change in ischemic vs. reperfusion biopsies. CONCLUSIONS: The expression of chemokines directing neutrophil and macrophage recruitment increases during reperfusion of living and cadaveric donor renal allografts. Expression levels of IL-8 correlate with the ischemic time imposed on the renal graft. Early tissue injury may be attenuated by strategies antagonizing chemokines directing the recruitment of neutrophils and macrophages into kidney grafts.

Chemokine CCL2↗

Posttransplant diabetes mellitus in kidney transplant recipients receiving calcineurin or mTOR inhibitor drugs.

BACKGROUND: The aim of this study was to evaluate the incidence and risk factors for posttransplant diabetes mellitus (PTDM; defined as new insulin use and/or new hyperglycemia) in 528 kidney recipients using different immunosuppressive agents. METHODS: Maintenance therapy included mycophenolate mofetil or azathioprine plus glucocorticoids in combination with Group I cyclosporine (263); Group II tacrolimus (60); or Group III sirolimus (205). RESULTS: The mean follow-up was 39.2 (range 9.0-103.8) months. Overall, the number of patients needing insulin was 7.4% (39/528). The incidences for Groups I, II, and III of 7.6%, 11.7%, and 5.9%, respectively, were not statistically different. Characteristics of patients with PTDM included older age (P=0.007); greater body weight (kg) at transplant, 6 months, and 12 months, respectively (P<0.001); greater BMI (kg/m2) at transplant, 6 months, and 12 months, respectively (P<0.001); more acute rejection episodes 28.2% vs. 13.5% (P=0.012); and increased incidence in African Americans (P=0.03). Multivariable analysis demonstrated increased risk for PTDM (defined as new insulin use) for tacrolimus, (hazard ratio [HR] 3.794, P=0.007); treated rejections (HR 2.491, P=0.0115); age (HR 1.407, P=0.0116); and BMI (HR 1.153, P<0.0001). New insulin use occurred sooner and with less total glucocorticoid dose for tacrolimus patients. If PTDM is defined as all cases of new hyperglycemia, then no immunosuppressive drug group demonstrated an increased risk. CONCLUSION.: The risk for developing PTDM is greatest among older recipients, and those obese at the time of transplant; those given steroid pulse therapy were at exceptionally high-risk. PTDM risk reduction should focus on weight loss in the obese end-stage renal disease population prior to transplant.

Adult↗

Partial nephrectomy for renal urothelial tumors: clinical update.

OBJECTIVES: To evaluate the contemporary indications and outcome after partial nephrectomy for renal urothelial cancer. Partial nephrectomy is an established treatment for renal cell cancer but its use for renal urothelial tumors has been studied less extensively. METHODS: Records were reviewed for patients undergoing partial nephrectomy for renal urothelial tumors between January 1990 and December 2001. Partial nephrectomy was selected for those with a solitary kidney, chronic renal insufficiency, or bilateral synchronous tumors. Partial nephrectomy was performed according to the principles of partial nephrectomy. Follow-up included ultrasonography, intravenous urography, computed tomography, metastatic workup, and renal function evaluation. RESULTS: This study included 12 patients (12 kidneys, 10 solitary) with a mean age of 68.5 +/- 21 years and a mean follow-up of 40.8 +/- 32 months. The pathologic T stage was Tis in 1 patient, T1 in 3, T2 in 2, and T3 in 6 patients. Of the 12 patients, 6 had negative surgical margins, and 4 of the 12 patients (30%) were tumor free after a mean follow-up of 57.7 months. Of the 6 patients with positive surgical margins (Stage T1 in 2 and T3 in 4), 1 developed recurrence and 3 developed metastasis; 4 died after a mean of 31.3 months. Overall recurrence was seen in 5 (42%) and progression (metastasis) in 6 (50%) patients. Of the 12 patients, 6 were alive, 4 of them were well (mean serum creatinine 1.83 mg/dL) at 62 months of follow-up. Two patients required dialysis. The overall long-term survival rate was 50%. CONCLUSIONS: Partial nephrectomy for renal urothelial tumors is feasible and should be considered in a select population. Dialysis or renal replacement can be delayed or avoided in most of these patients, but strict surveillance remains mandatory.

Aged↗

Open partial nephrectomy for tumor in a solitary kidney: experience with 400 cases.

PURPOSE: We present a series of 400 patients with tumor in a solitary kidney who underwent open surgical partial nephrectomy performed by a single surgeon (ACN) with a primary focus on postoperative long-term kidney function. MATERIALS AND METHODS: A total of 400 patients with sporadic nonfamilial kidney tumors in a solitary kidney underwent open partial nephrectomy between 1980 and 2002. In 323 patients (81%) the contralateral kidney had been surgically removed, while the remaining 77 (19%) had a congenital solitary kidney. Renal insufficiency was present preoperatively in 184 patients (46%). Adverse risk factors for partial nephrectomy were present in a large percent of patients. Intraoperative and postoperative parameters were evaluated at a mean followup of 44 months. RESULTS: In the overall series 5 and 10-year cancer specific survival was 89% and 82%, respectively. Surgical complications occurred in 52 patients (13%), most commonly urinary leakage. Early postoperative renal function was achieved in 398 patients (99.5%). Only 2 patients required permanent dialysis postoperatively. Satisfactory long-term renal function was achieved in 382 patients (95.5%). A total of 18 patients had progressed to renal failure a mean of 3.6 years after surgery. Patient age, the amount of renal parenchyma resected, a congenitally absent or atrophic contralateral kidney and the time of contralateral nephrectomy were noted to be significantly associated with postoperative renal function. CONCLUSIONS: Open surgical partial nephrectomy can be safely performed in patients with tumor in a solitary kidney. Long-term cancer-free survival with the preservation of renal function can be reliably expected in most of these cases.

Adolescent↗

Simultaneous vs. sequential laparoscopic bilateral native nephrectomy and renal transplantation.

We reviewed our experience with simultaneous single incision bilateral native nephrectomy and renal transplantation in 11 patients (Group 1), compared to seven recipients who underwent staged laparoscopic bilateral nephrectomy followed by kidney transplantation (Group 2). Mean age, donor source, sex, cause of ESRD, and specimen size were similar in both groups (P=0.1). All Group 2 patients and 9 of 11 Group 1 patients had autosomal-dominant polycystic kidney disease. Perioperative Group 1 complications included: bowel injury, transplant urine leak, necrotic pancreatitis, delayed bowel movement, and severe shoulder pain secondary to diaphragmatic irritation. Seven (63.6%) Group 1 patients required an additional surgical procedure: midline incisional hernia, repair ureteral fistula, and repair enterocutaneous fistula. One Group 1 patient lost his graft secondary to bowel injury and intra-abdominal sepsis. No major complications, reoperations, or graft loss occurred in Group 2. For simultaneous bilateral native nephrectomy and kidney transplantation, over 60% of patients required an additional surgical procedure. Laparoscopic bilateral nephrectomy followed by kidney transplantation is a safe and feasible alternative.

Adult↗

Absence of recipient CCR5 promotes early and increased allospecific antibody responses to cardiac allografts.

Acute rejection is mediated by T cell infiltration of allografts, but mechanisms mediating the delayed rejection of allografts in chemokine receptor-deficient recipients remain unclear. The rejection of vascularized, MHC-mismatched cardiac allografts by CCR5(-/-) recipients was investigated. Heart grafts from A/J (H-2(a)) donors were rejected by wild-type C57BL/6 (H-2(b)) recipients on day 8-10 posttransplant vs day 8-11 by CCR5(-/-) recipients. When compared with grafts from wild-type recipients, however, significant decreases in CD4(+) and CD8(+) T cells and macrophages were observed in rejecting allografts from CCR5-deficient recipients. These decreases were accompanied by significantly lower numbers of alloreactive T cells developing to IFN-gamma-, but not IL-4-producing cells in the CCR5(-/-) recipients, suggesting suboptimal priming of T cells in the knockout recipients. CCR5 was more prominently expressed on activated CD4(+) than CD8(+) T cells in the spleens of allograft wild-type recipients and on CD4(+) T cells infiltrating the cardiac allografts. Rejecting cardiac allografts from wild-type recipients had low level deposition of C3d that was restricted to the graft vessels. Rejecting allografts from CCR5(-/-) recipients had intense C3d deposition in the vessels as well as on capillaries throughout the graft parenchyma similar to that observed during rejection in donor-sensitized recipients. Titers of donor-reactive Abs in the serum of CCR5(-/-) recipients were almost 20-fold higher than those induced in wild-type recipients, and the high titers appeared as early as day 6 posttransplant. These results suggest dysregulation of alloreactive Ab responses and Ab-mediated cardiac allograft rejection in the absence of recipient CCR5.

Animals↗

The effect of 2-gram versus 1-gram concentration controlled mycophenolate mofetil on renal transplant outcomes using sirolimus-based calcineurin inhibitor drug-free immunosuppression.

BACKGROUND: We performed a sequential study to determine the efficacy and side effects of low-dose (1 g) mycophenolate mofetil (MMF) in a CNI drug avoidance regimen including sirolimus/steroids. METHODS: A total of 260 kidney-only recipients were given basiliximab (232) or thymoglobulin (28) induction, and sirolimus/steroids. In addition, 160 recipients were begun on standard MMF 1 g twice daily (2-g group), while 100 recipients were begun on low-dose MMF 500 mg twice daily (1-g group). The 1-g recipients were concentration controlled to keep mycophenolic acid (MPA) C0 levels at 1.8-4 microg/ml. RESULTS: There were no statistically significant differences in demographics between the groups. At 6 months there were no significant differences between the 2-g and 1-g MMF groups in patient survival (96.8% vs. 96%), graft survival (92.5% vs. 95%), biopsy-confirmed and treated acute rejection (8.8% vs. 13%), or mean creatinine mg/dL (1.41+/-0.52 vs. 1.47+/-0.67), respectively. Mean MPA C0 levels microg/ml were (4.7 vs. 2.3) at 1 month, (4.1 vs. 3.1) at 3 months, and (3.9 vs. 2.4) at 6 months. There were no significant differences at 1, 3, or 6 months in mean WBC, HgB, or platelets, or wound complications. There were significant reductions in the number of patients reporting nausea-vomiting-dyspepsia (20.6% vs. 8%, P=0.007), diarrhea (34.3% vs. 20%, P=0.01), and abdominal pains (10.6% vs. 4%, P=0.05), between the 2-g and 1-g MMF groups, respectively. CONCLUSIONS: The use of concentration-controlled 1-g MMF results in comparable transplant outcomes with less GI toxicity during the first 6 months posttransplant in a CNI drug-free sirolimus based immunosuppressive regimen.

Adolescent↗

Laparoscopic live donor nephrectomy has equivalent early and late renal function outcomes compared with open donor nephrectomy.

OBJECTIVES: To assess the patterns of early functional recovery and long-term function in laparoscopic and open procured live donor nephrectomy (LDN) kidneys, highlighting the radionuclide scan as an additional tool for assessment, because of concerns regarding renal functional recovery after laparoscopic LDN. METHODS: We reviewed the donor and recipient records of 101 laparoscopic and 35 open LDNs performed between August 1997 and September 2001. Data were collected on demographic, immunologic, and intraoperative variables and ureteral/vascular complications. Delayed renal function recovery in recipients was evaluated by serum creatinine greater than 2.5 mg/dL on postoperative day 5, dialysis in first postoperative week, and two renographic criteria--the time to peak activity and the time to one-half peak activity on postoperative day 5. Long-term outcomes were evaluated by serum creatinine at 1, 3, 6, and 12 months and 2 and 3 years, creatinine clearance at 1 year, and patient and allograft survival. RESULTS: Donor and recipient age, sex, body mass index, and number of HLA mismatches did not differ between the two groups. The mean operating room time and blood loss were comparable. No differences were found in the early functional parameters (renography, creatinine at postoperative day 1 and 5, or dialysis in week 1) or long-term outcome (patient and graft survival, creatinine, and rejection at 1 year and patient and graft survival at 1, 2, and 3 years). CONCLUSIONS: Early recovery of graft function, longer term renal function, and 3-year patient and allograft survival are similar for live donor kidneys obtained by either a laparoscopic or an open surgical technique.

Adult↗

Ureteropelvic junction obstruction after partial nephrectomy.

BACKGROUND AND PURPOSE: As the experience with partial nephrectomy continues to grow and the procedure increasingly becomes the standard of care for properly selected patients, it is critical to understand the potential complications and how these complications are best managed. Presented herein is the presentation, work-up, and treatment of ureteropelvic junction (UPJ) obstruction after partial nephrectomy. PATIENTS AND METHODS: From 1993 to 2004, 1154 partial nephrectomies have been performed at our institution by one surgeon. From the database of these patients, four (0.35%) were identified with postoperative UPJ obstruction. The charts of these patients were reviewed to identify preoperative and intraoperative characteristics as they relate to the development and risk of UPJ obstruction. Additionally, the presentation of UPJ obstruction, its management, and long-term follow-up are reported. RESULTS: Tumor location in the lower pole appears to be a risk factor for the development of UPJ obstruction, which is likely a result of ischemic or mechanical injury. This complication was managed successfully by endoscopic approaches in three of four cases. At a mean follow-up of 43 months, all patients remain free of obstruction according to both the absence of symptoms and radiographic evidence. CONCLUSION: Obstruction of the UPJ is an uncommon complication of partial nephrectomy. Endoscopic treatment of this complication yields a durable outcome, as all patients with a mean follow-up of more than 3 years show resolution of their obstruction.

Adult↗

Complications of laparoscopic partial nephrectomy in 200 cases.

PURPOSE: We analyzed complications of the initial 200 cases treated with laparoscopic partial nephrectomy for a suspected renal tumor. MATERIALS AND METHODS: Since August 1999, 200 consecutive patients have undergone laparoscopic partial nephrectomy. Mean patient age was 61.6 years, mean body mass index was 29.9 and mean tumor size was 2.9 cm (range 1 to 10). There were 51 central tumors (25%) and 15 solitary kidneys (7.5%). A central tumor was defined as any tumor infiltrating up to the collecting system or renal sinus, during the excision of which entry into and repair of the collecting system was necessary. Mean estimated blood loss was 247 cc and mean operative time was 3.3 hours. Data on complications were obtained from a prospectively maintained computerized database and via telephone calls to patients and/or local referring physicians. RESULTS: A total of 66 patients (33%) had 1 or more complications, which were intraoperative in 11 (5.5%), postoperative in 24 (12%) and delayed in 31 (15.5%). Overall 30 patients (15%) had a non-urological complication and 36 (18%) had a urological complication, including hemorrhage in 19 (9.5%) and urine leakage in 9 (4.5%). Hemorrhage occurred intraoperatively in 7 cases (3.5%) and postoperatively in 4 (2%), while it was delayed in 8 (4%). Of patients with urine leakage none required reoperation, 6 (3%) required a Double-J stent (Medical Engineering Corp., New York, New York) only, 2 (1%) required a Double-J stent with computerized tomography guided drainage and 1 required no treatment. Open conversion was necessary in 2 patients (1%), reoperation was done in 4 (2%) and elective laparoscopic radical nephrectomy was performed in 1 (0.5%). CONCLUSIONS: Laparoscopic partial nephrectomy is an advanced procedure with potential for complications. It requires considerable experience with reconstructive laparoscopy.

Adolescent↗

Renal cryoablation: outcome at 3 years.

PURPOSE: We report intermediate term oncological followup data on 56 patients undergoing laparoscopic renal cryoablation, of whom each completed a 3-year followup. MATERIALS AND METHODS: Since September 1997, 56 patients undergoing laparoscopic renal cryoablation have completed a followup of 3 years each. The postoperative followup protocol comprised serial magnetic resonance imaging (MRI) at 1 day, months 1, 3, 6, 12, 18 and 24, and yearly thereafter for 5 years. Computerized tomography guided needle biopsy of the cryolesion was performed 6 months postoperatively and repeated if MRI findings were abnormal. Followup data were obtained prospectively. RESULTS: For a mean renal tumor size of 2.3 cm mean intraoperative size of the created cryolesion was 3.6 cm. Sequential mean cryolesion size on MRI on postoperative 1 day, and at 3 and 6 months, and 1, 2 and 3 years was 3.7, 2.8, 2.3, 1.7, 1.2 and 0.9 cm, representing a 26%, 39%, 56%, 69% and 75% percent reduction in cryolesion size at 3 and 6 months, and 1, 2 and 3 years, respectively. At 3 years 17 cryolesions (38%) had completely disappeared on MRI. Postoperative needle biopsy identified locally persistent/recurrent renal tumor in 2 patients. In the 51 patients undergoing cryotherapy for a unilateral, sporadic renal tumor 3-year cancer specific survival was 98%. There was no open conversion, kidney loss, urinary fistula, dialysis requirement, or perirenal or port site recurrence in any patients. CONCLUSIONS: Three-year outcomes following renal cryoablation are encouraging. Longer term (5-year) data are necessary to determine the proper place of renal cryotherapy among minimally invasive, nephron sparing options.

Adult↗

National urology resident preceptorship program in female pelvic medicine and reconstructive surgery.

PURPOSE: There is a shortage of urologists specializing in female pelvic medicine and reconstructive surgery (FPMRS). We assessed the effects of an educational preceptorship program on the resident perception and desire to pursue careers in FPMRS. MATERIALS AND METHODS: Between 2002 and 2004, 113 mid level residents from approximately 120 urology residency programs who were nominated by their respective program directors attended a 4-day course in FPMRS. The preceptorship course included live surgical FPMRS cases, didactic lectures, and discussions of research opportunities and career options. Participants in 2002 and 2003 evaluated the program content. Participants in 2004 completed a questionnaire to determine the effect of the course on their perception of FPMRS, and research and career opportunities in FPMRS. RESULTS: In 2002 to 2004, 113 residents participated in the program. An informal survey of residency program directors showed that 10 of 36 participants in 2002 had applied and enrolled in fellowship programs in FPMRS. Of the 32 of 40 participants in 2004 who completed the program evaluation 71% stated that greater than 50% of the material on female urology research was new to them and 90% of participants stated that their interest in female urology was "much higher to somewhat higher" as a result of the program. CONCLUSIONS: A preceptorship program in FPMRS incorporating in-depth review of the subject and demonstration of surgical cases has been successful in promoting and encouraging career selection in FPMRS. This approach may also encourage interest in other underrepresented subspecialties in urology or other medical specialties.

Adult↗