Biomedical subjects
Publications and source records attributed to A C Novick.
Retroperitoneal surgery during pregnancy is rarely indicated. Major considerations are the optimal timing of surgery and the consequences of nonoperative management on mother and fetus. We report on the first partial nephrectomy performed during pregnancy and one nephroadrenalectomy. When indicated, the second trimester is the ideal time to perform nonobstetric surgery during gestation.
OBJECTIVES: Angiomyolipoma (AML) is a benign renal tumor that may require treatment because of associated local complications. The present study was undertaken to evaluate the efficacy of nephron-sparing surgery (NSS) in the management of renal AML, with respect to the long-term preservation of renal function and absence of tumor recurrence. METHODS: From 1980 to 1997, 27 patients underwent NSS for treatment of renal AML. The clinical presentation, surgical approach, and outcome in these patients were analyzed. Surgical treatment for renal AML was indicated because of associated symptoms, size of 4.5 cm or greater, and/or suspicion of renal malignancy. RESULTS: In symptomatic patients (52%) the most common presenting signs or symptoms were pain (50%), retroperitoneal hemorrhage or shock (43%), hematuria (36%), hypertension (7%), palpable mass (7%), and anemia (7%). Two patients had tuberous sclerosis. Fifteen patients had a solitary functioning kidney (group I), 6 patients had an impaired contralateral kidney (group II), and 6 patients had a normal contralateral kidney (group III). All operations were performed in situ. There were no operative deaths. All operated kidneys functioned postoperatively, and no patient required dialysis. The mean postoperative serum creatinine level in groups I, II, and III was 1.81, 0.98, and 0.97 mg/dL, respectively. No patients have developed recurrent AML, related symptoms, or required dialysis with follow-up to 177 months (median 39). CONCLUSIONS: When surgical treatment for renal AML is indicated, NSS can be performed with a high success rate even in patients with a very large tumor involving a solitary kidney.
OBJECTIVES: To present the technique and short-term results of retroperitoneal laparoscopic renal cryoablation. METHODS: Ten patients underwent laparoscopic renal cryoablation of 11 exophytic renal tumors ranging in size from 1.5 to 3 cm identified on computed tomography. Tumors were located at the upper (3), middle (5), or lower (3) pole of the kidney. Three patients had a solitary kidney. A 3-port retroperitoneal laparoscopic approach was used to create renal cryolesions. Puncture cryoablation was performed with a 4.8-mm cryoprobe. Real-time, endoscopic, steerable, color Doppler ultrasound was used to monitor the evolving cryolesion. All patients have completed a minimum follow-up of 3 months (mean 5.5, range 3 to 9). RESULTS: Cryoablation was technically successful in all 10 patients (11 tumors). Under ultrasound guidance, the ice ball was intentionally created up to 1 cm beyond the tumor edge with the aim of achieving negative margins. Mean surgical time was 2.4 hours, cryoablation (double freeze-thaw) time 12.9 minutes, cryoprobe tip temperature -186 degrees C, and blood loss 75 mL. Systemic temperature remained unaltered. Hospital stay was less than 23 hours in 9 of 10 patients. Follow-up magnetic resonance imaging at 1 day and 1, 2, and 3 months identified the punched-out, nonenhancing, spontaneously resorbing, renal cryolesion. Follow-up biopsies of the cryoablated tumor site were negative for cancer in the 3 patients who have undergone the biopsy. CONCLUSIONS: The initial series of laparoscopic renal cryoablation is presented. The retroperitoneoscopic approach, by avoiding the peritoneal cavity, minimizes the chances of the bowel coming in contact with the evolving cryolesion, and the potential sequelae thereof. Laparoscopic renal cryoablation is currently developmental and long-term data are awaited. Nevertheless, it is potentially an attractive addition to available nephron-sparing surgical techniques.
In summary, NSS is the indicated treatment for patients with localized RCC and an intercurrent urological or medical condition that poses a threat to overall renal function. Recent studies have clarified the role of NSS in patients with localized unilateral RCC and a normal contralateral kidney. Recent results indicate that radical nephrectomy and NSS provide equally effective curative treatment for patients who present with a single, small (< 4 cm), and clearly localized RCC. The long-term renal functional advantage of NSS with a normal opposite kidney requires further study.
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PURPOSE: Recent studies have suggested that nephron sparing surgery and radical nephrectomy provide equally effective therapy for patients with small (less than 4 cm.), solitary, unilateral renal cell carcinoma and a normal contralateral kidney. We evaluate whether central versus peripheral tumor location in the involved kidney is a significant factor affecting treatment outcome in these patients. MATERIALS AND METHODS: Patients with a single, small (less than 4 cm.), localized, unilateral, sporadic renal cell carcinoma were identified from our institutional registry. From 1972 to 1995, 145 patients fulfilling these criteria were treated with either nephron sparing surgery (86) or radical nephrectomy (59). Mean postoperative followup was 51.4 months. Tumor characteristics and outcome measures were analyzed in 35 patients with central versus 110 with peripheral renal cell carcinomas according to the type of treatment. RESULTS: We detected 27 central (77%) and 75 peripheral renal cell carcinomas (68%) incidentally. Nephron sparing surgery was used to treat 19 central (54%) and 67 peripheral (61%) carcinomas. Pathological tumor stage was T1 to 2 in 33 central (94%) and 91 peripheral (82%) cases. Grade 1 to 2 renal cell carcinoma was present in 28 central (80%) and 85 peripheral (77%) tumors. Postoperatively, when comparing patients with central versus peripheral renal cell carcinomas there was no difference in 5-year cancer specific survival (100 versus 97%), tumor recurrence (5.7 versus 4.5%) or renal function (mean serum creatinine 1.43 mg./dl. in both groups). These parameters were also equivalent in patients treated with nephron sparing surgery versus radical nephrectomy overall and within the central versus peripheral renal cell carcinoma subgroups. Nephron sparing surgery was technically more complicated in central renal cell carcinomas with a longer renal ischemia time (55 versus 34 minutes, p <0.05) and more frequent entry of the collecting system (74 versus 47%, p <0.05) compared to peripheral carcinomas. Two patients (2.3%, 1 central, 1 peripheral) had local tumor recurrence after nephron sparing surgery. CONCLUSIONS: There were no significant biological differences between centrally versus peripherally located small solitary unilateral renal cell carcinomas. Nephron sparing surgery is technically more demanding in patients with central tumors. However, treatment with nephron sparing surgery or radical nephrectomy is equally effective regardless of tumor location.
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BACKGROUND: Patients with von Hippel-Lindau (VHL) disease are at risk for the development of end-stage renal failure from the treatment of localized renal cell carcinoma. Transplantation with its attendant immunosuppression may predispose patients to tumor recurrence; however, there is little information regarding the outcome with this approach. In this article, we review the North American and European experience with renal transplantation in this patient population. METHODS: The study group comprises 32 patients who have VHL rendered anephric secondary to localized renal cell carcinoma and who have undergone renal transplantation. Patients were identified from North American (n=18) and European (n=14) registries. The outcome of the study group is compared with a cohort of 32 renal transplant recipients without VHL from the Cleveland Clinic Unified Transplant Data Base, who were matched for donor source, gender, age, transplant status (primary vs. regraft), and date of transplantation. RESULTS: The 23 men and 9 women in the study group received transplants between 1974 and 1996. The average age at transplantation was 36 years, and the average duration of dialysis before transplantation was 26 months. Patients have been followed for 48+/-35 months. There was no statistically significant difference in graft survival, patient survival, or renal function between the study and control groups. There were five deaths in both the study and control groups. In the study group, three patients died with metastatic disease. There was no difference in the duration of dialysis before transplantation between patients who developed metastatic disease and those who did not. CONCLUSION: These data support the utility of renal transplantation as an effective form of renal replacement therapy in this unique population, with a limited risk of recurrent cancer.
BACKGROUND: The results of renal transplantation in obese recipients have been controversial, with some reports finding increased morbidity prohibitive and others finding increased morbidity acceptable. We attempted to determine whether obese patients in extreme excess of their ideal body weight should undergo transplantation. METHODS: The study population included 127 obese (body mass index >30 kg/m2) patients who were compared with a matched nonobese control group (body mass index <27 kg/m2) of 127 recipients with similar demographics. There were no significant differences between the groups according to donor source, recipient race or sex, retransplants, transplant percent reactive antibodies, cause of renal failure, or hypertension. However, significantly more obese patients had a pretransplant history of angina (11.2% vs. 3.2%, P=0.02) or a previous myocardial infarction (5.6% vs. 0.8%, P=0.04). RESULTS: The mean follow-up was 58.9+/-40 (range 3-170) months. Nonobese patients enjoyed a significantly (P=0.0002) greater patient survival (89% vs. 67%) at 5 years and suffered only about half the number of deaths (25 vs. 46) during the period of observation. Cardiac disease was the leading cause of death (39.1%) in the obese group. Patient death had a major impact on graft survival because there were no differences between the groups when death with graft function was censored from the analysis. There were no significant differences between the groups in delayed graft function, acute rejection, chronic rejection, length of hospital stay, operative blood loss, or mean serum creatinine up to 5 years. However, obese patients experienced significantly (P=0.0001) more complications per patient (3.3 vs. 2.2) and a greater incidence (P=0.0003) of posttransplant diabetes (12% vs. 2%). Similar cyclosporine blood levels were observed in obese recipients even though they were receiving 0.75-2 mg/kg/day less cyclosporine than the nonobese recipients. CONCLUSIONS: Outcome differences in obese renal transplant patients were primarily due to a higher mortality resulting from cardiac events. Obesity seems to have little effect on immunologic events, long-term graft function, or cyclosporine delivery. Aggressive pretransplant screening for ischemic heart disease is essential to identify an especially high-risk subgroup of obese patients. Although it would seem prudent to recommend weight reduction <30 kg/m2 to all patients before transplant, these data suggest that obese patients with a history of cardiac disease should not be transplanted until weight reduction has been accomplished.
Chemoattractant cytokines, chemokines, are likely to play a critical role in directing leukocytes to graft sites and in amplifying intragraft inflammation during rejection. Since second-set graft rejection occurs at an accelerated rate, we hypothesized that chemokine genes would be expressed earlier during secondary allograft rejection than during rejection of primary allografts. We have tested this hypothesis by using Northern blot analysis to compare intragraft expression levels of genes encoding interleukin (IL) 1beta and six chemokines during rejection of C57BL/6 skin grafts on naive and C57BL/6-sensitized BALB/c recipients. Expression levels of IL-1beta, interferon-gamma inducible protein, macrophage inflammatory protein-1 (MIP-1) alpha, and MIP-1beta genes were 10- to 17-fold higher on day 5 after transplantation in C57BL/6 grafts on C57BL/6-presensitized recipients than in C57BL/6 grafts on unprimed recipients. Intragraft expression of the chemokines regulated upon activation, normal T cell expressed and secreted (RANTES), during primary C57BL/6 graft rejection was virtually undetectable at day 7 after primary transplantation, but was expressed at high levels by day 5 after secondary transplantation. In third-party CBA/Ca allografts on unsensitized and C57BL/6-presensitized BALB/c mice, similar levels of IL-1beta, MIP-1alpha, and MIP-1beta expression were observed. High levels of RANTES and interferon-gamma inducible protein expression, however, were observed at day 5 after transplantation in CBA/Ca grafts on C57BL/6-presensitized recipients and correlated with accelerated rejection of the third-party grafts. Although T cells from C57BL/6-presensitized recipients did not express increased reactivity to CBA/Ca stimulator cells in vitro, serum antibodies from these recipients demonstrated reactivity to cells from CBA/Ca and A/J mice. When compared with transfer of unprimed cells, transfer of C57BL/6-primed lymphoid cells to sublethally irradiated BALB/c mice engrafted with C57BL/6 grafts resulted in increased intragraft proinflammatory cytokine gene expression. Deletion of T cells before transfer abrogated the increased intragraft expression of proinflammatory cytokine genes. Collectively, these results indicate that the accelerated expression of chemokine genes during second-set rejection of allogeneic skin grafts is mediated by immune T cells.
Intercellular adhesion molecule-1 (ICAM-1) mediates two important functional aspects of tumor biology, namely enhancement of tumor metastasis and mediation of host defense mechanisms such as lymphocyte-mediated tumor cytotoxicity. Since ICAM-1 is expressed by most renal cell carcinomas (RCC), the regulation of ICAM-1 expression is important in understanding the biological behavior of RCC. We report an investigation on ICAM-1 expression and molecular regulation by cytokines and protein kinase C activator on RCC cell lines. Of the various cytokines, tumor necrosis factor alpha (TNF alpha), interferon-gamma (IFN gamma), and phorbol myristate acetate (PMA) strongly upregulated ICAM-1 protein expression on RCC. The kinetics of ICAM-1 message induction was studied by Northern analysis of total RNA extracted from RCC and normal kidney proximal tubular (NKPT) cells. Time course studies showed that ICAM-1 mRNA was upregulated by INF gamma, TNF alpha, and PMA, plateaued after 2 h, and remained increased for up to 24 h. Although ICAM-1 mRNA in NKPT cells was upregulated by these cytokines, their messages returned to basal levels after 24 h. ICAM-1 mRNA stability assays showed that both unstimulated and stimulated RCC cells had very stable ICAM-1 mRNA up to 24 h. In order to investigate whether increased gene transcription contributes to ICAM-1 upregulation, RCC cells were treated with TNF alpha, IFN gamma, or PMA with or without simultaneous addition of actinomycin D. ICAM-1 message induction-blocking studies suggested that primary upregulation of ICAM-1 mRNA may be caused by transcriptional upregulation. These results suggest that long-lasting ICAM-1 message upregulation in response to cytokines or PMA may be due to transcriptional upregulation in the early phase and stabilization of ICAM-1 message in the later phase (after 4 h). These observations suggest that RCC may lack the normal downregulatory mechanisms which control ICAM-1 expression and may explain the high frequency of ICAM-1 expression observed on primary human RCC.
An intercellular adhesion molecule-1 (ICAM-1)-negative RT4 transitional cell carcinoma (TCC) cell line was transduced with full-length ICAM-1 cDNA via a retroviral vector. Flow cytometry showed that a sense-oriented clone (S20) highly expressed ICAM-1 while an anti-sense clone (AS6) did not. Both S20 and AS6 bound with equal frequency (30 +/- 8.7% vs 30 +/- 9.4%) to unstimulated human umbilical vein endothelial cells (HUVECs) in cell attachment assays. However, when phorbol myristate acetate (PMA)-activated T lymphocytes, which express lymphocyte function-associated antigen-1 (LFA-1), were cocultured with tumor cells, attachment of S20 increased twofold (60 +/- 11.9%) but AS6 showed no change (32 +/- 11%). Blocking studies with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies caused an inhibition of the attachment to baseline levels, demonstrating that the enhancement of S20 attachment was dependent upon the LFA-1/ICAM-1 interaction. Enhanced attachment of S20 was not inhibited by the addition of isotypic immunoglobulin G. These results suggest that LFA-1-expressing leukocytes may act as a bridge between the endothelium and tumor cells which express ICAM-1 and, thereby, enhance the potential for hematogenous metastasis.
PURPOSE: We conducted a psychosocial followup of living kidney donors from 1983 to 1995. MATERIALS AND METHODS: A new questionnaire about donor satisfaction and the Medical Outcomes Study Short-Form Health Survey, a standardized measure of health related quality of life, were completed by 167 donors (67% response rate). RESULTS: Of respondents 90% would make the same choice again and 83% would strongly encourage others to donate. However, 15% of respondents believed that donating had impacted negatively on their health and 23% reported negative financial consequences. Respondent health related quality of life was not impaired. The strongest correlates of donor dissatisfaction included a conflicted initial relationship with the recipient, believing that information given preoperatively had been inadequate and perceived damage to health or finances. CONCLUSIONS: Only a minority of living kidney donors suffer psychosocial morbidity. Better psychological preparation for surgery and more consistent followup could decrease negative outcomes further.
PURPOSE: Cushing's syndrome due to adrenal adenoma or adrenocortical carcinoma is rare. To understand better the clinical and biochemical presentation of this disorder, as well as therapy efficacy and patient survival, we conducted a retrospective review. MATERIALS AND METHODS: Between August 1971 and April 1994, 40 patients presented to our institution with adrenal Cushing's syndrome (27 adenomas and 13 carcinomas). These groups were analyzed with respect to clinical signs and symptoms preoperatively and postoperatively, biochemical analysis, length of postoperative steroid replacement therapy, disease recurrence and patient survival. Followup was obtained by chart review and telephone interviews and averaged 59.6 +/- 66.4 and 47.6 +/- 56.2 months for adenoma and carcinoma patients, respectively. RESULTS: Women predominated in both groups (26 of 27 adenomas, 11 of 13 carcinomas), and tumors affected the left adrenal gland more frequently (19 of 27 adenomas, 9 of 13 carcinomas). Adenoma patients were younger than carcinoma patients (39.6 +/- 14.4 versus 51.5 +/- 16.6 years, p = 0.026) and presented with smaller tumors (3.3 +/- 1.0 versus 8.6 +/- 4.5 cm., p = 0.001). There was a trend toward increased incidence of glucose intolerance among carcinoma patients but no significant differences in clinical signs or symptoms between adenoma and carcinoma patients could be made. Similarly, while there was no significant difference in biochemical evaluation of adenoma versus carcinoma patients, 24-hour urinary free cortisol and serum lactate dehydrogenase levels tended to be higher among carcinoma patients. In addition 17-ketosteroid and dehydroepiandrosterone sulfate levels were more elevated in carcinoma than in adenoma patients, and several adenoma patients actually had subnormal levels. Among adenoma patients mean length of steroid replacement therapy was 16.8 +/- 9.1 months. However, 7 adenoma patients (25.9%) required greater than 24 months of exogenous steroids, and only 1 of these patients was subsequently weaned off steroid replacement. There were no recurrences among adenoma patients, although there was 1 perioperative death due to hypoglycemia. Ten (76.9%) carcinoma patients had recurrences at a mean followup of 33 months. The 3 and 5-year survival rates were 41.5 and 31.2%, respectively. CONCLUSIONS: While presenting signs and symptoms and hormonal analysis may suggest benign or malignant disease, only tumor size and patient age are reliable preoperative indicators of adrenal adenoma versus adrenocortical carcinoma among patients with adrenal Cushing's syndrome. Surgery is curative for adenoma patients, but lifelong steroid replacement may be required. Survival remains poor among carcinoma patients.
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OBJECTIVES: Renal cell carcinoma extends into the inferior vena cava (IVC) in 4% to 10% of patients. The purpose of this study was to evaluate the diagnostic accuracy of preoperative transesophageal echocardiography (TEE) in determining the presence and level of IVC involvement in such cases. METHODS: From June 1992 to December 1995, 13 patients with suspected IVC tumor thrombi were studied with preoperative TEE. These patients were also evaluated with either magnetic resonance imaging (MRI; n = 10), contrast venacavography (CVC; n = 8), or both of the latter (n = 5). All patients subsequently underwent surgical removal of the primary tumor and IVC thrombus. The presence and level of IVC thrombus at surgery was correlated with that predicted by the various preoperative imaging modalities. RESULTS: Preoperative TEE accurately delineated the presence and extent of IVC tumor thrombus involvement in 11 of 13 patients (85%); the level of IVC involvement was overstaged in 1 patient and understaged in 1 patient. Accurate diagnostic information was provided by MRI in 9 of 10 patients (90%) and by CVC in 6 of 8 patients (75%). CONCLUSIONS: In patients with IVC tumor thrombi, preoperative TEE can provide accurate information regarding the presence and extent of IVC involvement. However, TEE is an invasive and costly procedure with no diagnostic advantage over MRI in the preoperative evaluation of these patients.
OBJECTIVES: To determine the accuracy and clinical utility of fine needle aspiration (FNA) of small, solid renal masses. METHODS: A total of 25 patients with small (less than 5.0 cm), solid, clinically localized renal masses were prospectively identified and evaluated with computed tomography guided FNA with analysis for presence of malignant cells and determination of nuclear grade. The final pathologic findings were used for comparison in each case. All patients had renal cell carcinoma and were managed with radical or partial nephrectomy; 3 had low-grade lesions (Fuhrman's grade 1/4), 2 had high-grade lesions (Fuhrman's grade 4/4), and all other patients had intermediate-grade lesions (Fuhrman's grade 2/4 or 3/4) on final histopathologic assessment. RESULTS: Overall, 10 aspirations yielded diagnostic malignant cells, and 9 were read as rare as rare atypical cells suspicious for malignancy. The remainder were negative (n = 6). Correlation with final nuclear grade was observed in eight instances and discordance in two instances. Subcapsular hematomas were observed at the time of surgery in 10 patients, but in no instance was the operation adversely affected. CONCLUSIONS: The diagnostic yield of FNA of small, solid renal masses appears to be too low to justify the potential morbidity of the procedure.
A 48-year-old woman underwent renal transplantation of an organ from a living related donor in 1978. She experienced excellent graft function for 18 years. Recent evaluation for hypertension revealed two large solid masses involving the allograft. Nephron-sparing excision of two renal cell carcinomas was performed with preservation of renal function. Genitourinary malignancies in transplant recipients and partial nephrectomy in renal allografts are reviewed.