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Steven C Campbell

Publications and source records attributed to Steven C Campbell.

At least 19 recordsLinked to original sources
PubMed2006

Outcomes in patients with urothelial carcinoma of the bladder with limited pelvic lymph node dissection.

OBJECTIVES: To evaluate the rates of local and systemic progression (LP and SP), recurrence-free survival and overall survival for patients with urothelial carcinoma of the bladder with limited pelvic lymph node dissection (PLND) in 1987-2000. PATIENTS AND METHODS: A consecutive series was analysed of 385 patients (median age 61.9 years, range 30.7-83.8) treated by limited bilateral PLND and radical cystectomy (RC) between 1987 and 2000, with negative surgical margins on final pathology. All patients were staged N0M0 before RC, and none received neoadjuvant radiotherapy or chemotherapy. The boundaries of the limited PLND were the pelvic side-wall between the genitofemoral and obturator nerves, and bifurcation of iliac vessels to the circumflex iliac vein. LP was defined as a radiographic soft-tissue density of > or = 2 cm below the bifurcation of the aorta. Pathological characteristics, based on the 1997 Tumour-Nodes-Metastasis system, recurrence patterns, and recurrence-free and overall survival, were determined. RESULTS The median (range) overall follow-up was 45.1 (1.1-165.6) months; the number of lymph nodes (LNs) reported per patient was 12 (2-32). Of the 385 patients, 130 (33.8%) had evidence of LP and 60 (15.6%) of SP. The 5-year recurrence-free and overall survival rates were both 71% for patients with organ-confined, N0 tumours, and 23% and 26% for unconfined, N0 tumours. Positive LNs were found in 45 (12%) patients, who had a recurrence-free and overall survival rate of 9% at 5 years. CONCLUSION: Compared with published reports of similar cohorts of patients managed with RC and extended PLND, the present study suggests that limited PLND is associated with suboptimal staging, greater rates of LP, and lower rates of recurrence-free survival, particularly for patients with unconfined or LN-positive disease.

Adult↗
PubMed2006

Renal cell carcinoma.

PURPOSE OF REVIEW: In this review we will highlight the recent novel contributions to the treatment of renal cell carcinoma in the fields of anti-angiogenesis, immunotherapeutics, and surgical management. In addition, this review will update recent advances in diagnostic and imaging modalities for renal cell carcinoma and dietary and environmental relationships to the epidemiology of this growing disease. RECENT FINDINGS: Advancements in the use of innovative treatment strategies for the management of localized renal cell carcinoma and the introduction of new targeted therapeutics with benefit in the metastatic setting has produced a major impact on the treatment of this disease. SUMMARY: The management of metastatic renal cell carcinoma has undergone a revolution in the past year with groundbreaking treatment strategies encompassing a broad range of therapeutic modalities. At the other end of the spectrum, emerging data is beginning to change our perspective about the management of small, localized renal tumors that are being discovered with increasing frequency. This review will update recent findings supporting diet and tobacco exposure as etiologic factors in the development of renal cell carcinoma, the molecular concepts that underlie the disease and the targeted therapeutics designed to inhibit specific kinase activities, and emerging use of minimally invasive therapies for localized disease.

Angiogenesis Inhibitors↗
PubMed2006

Mixed epithelial and stromal tumor of the kidney and cystic nephroma share overlapping features: reappraisal of 15 lesions.

CONTEXT: Cystic nephroma is a rare cystic tumor, which only recently has been recognized as an exclusively adult lesion. Mixed epithelial and stromal tumor of the kidney is also a rare, recently recognized, biphasic tumor composed of tubular and cystic elements embedded in grossly recognizable spindle cell stroma. The histogenesis of both lesions is unclear. OBJECTIVES: To compare clinical phenotype, morphology, and immunohistochemistry in mixed epithelial and stromal tumor of the kidney and cystic nephroma in order to explore the relationship between these 2 lesions. DESIGN: Fifteen biphasic lesions (8 mixed epithelial and stromal tumors of the kidney and 7 cystic nephromas) were studied. All cases were reviewed and subjected to detailed pathologic studies, and the results were correlated with clinical findings. RESULTS: Mixed epithelial and stromal tumor of the kidney occurred exclusively in women aged 36 to 80 years (mean, 49.7 years), all of whom had a history of estrogen therapy and/or obesity. Cystic nephroma occurred in both sexes; patients were aged 22 to 71 years (mean, 50.4 years), and a history of hormonal therapy was present on occasion. All 15 lesions were benign. Lesions varied by size, the proportion of cystic component, and the amount and cellularity of stroma. However, in all lesions tested, the stroma was diffusely positive for smooth muscle actin, and smooth muscle differentiation was confirmed by electron microscopy. In mixed epithelial and stromal tumors of the kidney, the stroma was positive for estrogen and progesterone receptors in 4 of 5 lesions tested. In cystic nephroma, focal positivity for hormone receptors was seen in 2 of 7 tumors tested; both positive lesions were from women. The epithelial lining in both mixed epithelial and stromal tumor of the kidney and cystic nephroma lesions was variable with regard to shape, cytoplasmic appearance, and immunophenotype (with focal positivity for CD10, cytokeratin 7, high-molecular-weight keratin, and Ulex europaeus detectable in both lesions). This pattern suggests variable differentiation, which was confirmed by electron microscopic studies (performed in 1 case). CONCLUSIONS: While mixed epithelial and stromal tumor of the kidney has a strong association with the female sex and hormonal milieu, cystic nephroma can affect both sexes and, on occasion, may also have hormonal associations. Morphologically, there is considerable overlap between both lesions, which suggests that they may represent opposite ends of the spectrum of the same process. Our studies also suggest that the tubules may be entrapped rather than comprising an intrinsic component of the tumor. However, further studies, including molecular studies, are needed to support this hypothesis.

Adult↗
PubMed2005

Society of Urologic Oncology position statement: redefining the management of hormone-refractory prostate carcinoma.

Because patients with hormone-refractory prostate carcinoma are a very diverse group, management of these patients represents a unique challenge. Despite much research, to the authors' knowledge few studies published to date have provided definitive treatment answers. The Society of Urologic Oncology (SUO) convened a multidisciplinary panel of urologists, oncologists, and radiation oncologists to develop a treatment algorithm for patients with hormone-refractory prostate carcinoma. The resulting treatment outline was based on a review of the literature review and on the expert opinions of the panelists. The current article provided a logical progression of treatment choices that included hormonal manipulations, chemotherapeutic options, and adjunctive therapies. Future clinical trials and therapies were also discussed by the authors. Management strategies should be targeted toward the individual patient. Although significant progress has been made in understanding and treating hormone-refractory prostate carcinoma, earlier interventions would be ideal and better therapeutic approaches to prolong survival are necessary.

Algorithms↗
PubMed2005

Risk assessment for occult malignancy in the prostate before radical cystectomy.

OBJECTIVES: To assess our clinical ability to predict prostate involvement by transitional cell carcinoma (PI-TCC) or occult prostate cancer (CAP) in patients undergoing radical cystectomy (RCx). METHODS: We retrospectively analyzed 70 male patients undergoing RCx for TCC of the bladder between 1995 and 2003, focusing on preoperative factors to predict PI-TCC or CAP. RESULTS: Of 70 RCx patients, 30 (43%) had PI-TCC (14) or CAP (16). Risk factors for PI-TCC included carcinoma in situ, multifocal TCC, and bladder neck involvement (P <0.05 for all three analyses). All 14 patients with PI-TCC had one or more risk factors, and none of 40 patients without these risk factors had PI-TCC (P <0.001). Risk factors for CAP included elevated prostate-specific antigen level, abnormal results on digital rectal examination, and age more than 65 years. Of 16 patients with CAP, 14 had one or more of these risk factors (P <0.05). Sixteen of the seventy patients in this series (22.9%) had no risk factors for PI-TCC or CAP, and none of these had prostatic involvement with either malignancy (P <0.05). CONCLUSIONS: Our findings suggest that a well-defined subset of patients undergoing RCx might be at low risk for malignancy in the prostate. However, further evaluation of these risk factors in a prospective setting will be required to substantiate these findings and guide clinical decision making in this controversial field.

Adult↗
PubMed2005

Renal medullary carcinoma and ABL gene amplification.

PURPOSE: We characterized the clinical course of renal medullary carcinoma (RMC) and performed an expanded analysis of BCR-ABL. MATERIALS AND METHODS: The literature was searched for all reports of RMC. New cases at Northwestern University are described and relevant clinical information was abstracted. BCR and ABL genes, and ABL protein were evaluated by fluorescence in situ hybridization and immunohistochemical analysis, respectively. RESULTS: A total of 95 cases were identified. Mean age at diagnosis was 19 years, the male-to-female ratio was 1.9:1.0, 90% of all patients were black, 98% had an abnormality in a least 1 hemoglobin gene (ie sickle cell trait, SC disease or sickle cell disease) and mean survival was 19 weeks. Two patients (3%) without metastasis were long-term survivors. The response to chemotherapy was poor. One patient treated with thalidomide survived for 52 weeks. The ABL gene was amplified a mean +/- SEM of 1.9 +/- 0.1-fold in all 3 cases evaluated, while ABL protein was increased in 2 of 3 evaluated. No evidence of BCR-ABL translocation was detected. CONCLUSIONS: RMC is typically seen in young individuals with the sickle cell trait. It is diagnosed when metastatic, is not responsive to systemic therapy and rapidly causes death. Because cure appears possible with early diagnosis, increased awareness of the disease could make an impact. The use of thalidomide or newer anti-angiogenesis agents should be considered for advanced disease. The role of ABL amplification with respect to etiology and as a therapeutic target should be investigated further.

Adolescent↗
PubMed2005

Renal neoplasms in younger adults: analysis of 112 tumors from a single institution according to the new 2004 World Health Organization classification and 2002 American Joint Committee on Cancer Staging System.

CONTEXT: Adult renal neoplasms have a predilection for older patients and are clinically and morphologically distinct from renal neoplasms found in pediatric age groups. Relatively rare tumors occur in younger adults (18-45 years of age). Whether these renal tumors are morphologically and clinically distinct from those of older adults has been the subject of controversy. Recent modification of the World Health Organization histologic classification and the American Joint Committee on Cancer staging system of adult renal tumors further highlighted the need for case analysis in this age group. OBJECTIVE: To analyze renal tumors in younger adults based on a large surgical series from a single institution. DESIGN: Of 780 renal mass nephrectomy (partial, total, or radical) specimens that were available for evaluation and had been obtained between 1986 and 2004 at Loyola University Medical Center, 112 specimens were from patients between 18 and 45 years of age. The tumors were reevaluated according to the 2004 World Health Organization classification and the 2002 American Joint Committee on Cancer staging system. RESULTS: The likelihood of clear cell renal cell carcinoma was significantly reduced from 65% in older adults to 53% in younger adults (18-45 years, P = .04). The reduction trend was more significant when comparing an even younger age group. The majority (64%) of clear cell renal cell carcinoma in younger adults was low stage, T1a. Seventeen percent of these tumors had multilocular cystic features involving more than 50% of the tumor volume (55%-85%). The number of oncocytomas was also significantly lower in younger adults than in older adults (2% vs 11%, P < .001), and this presumably age-related benign neoplasm was not identified in patients younger than 40 years in this study. In contrast, the miscellaneous tumor category showed a remarkable increase, from 4% in older adults to 26% in younger adults (P < .001). The youngest patient group (18-35 years) had a higher incidence of miscellaneous tumors, 37%. Younger female adults tended to have more benign miscellaneous neoplasms than did their male counterparts (64% vs 36%, P < .001). Clear cell and chromophobe renal cell carcinoma occurred more frequently in younger male adults than in female adults (2:1 and 8:1, respectively). CONCLUSIONS: Renal neoplasms are more heterogeneous in younger adults and have a different distribution pattern compared with that in older adults. Malignant and benign renal neoplasms tend to have a contrasting sex distribution in younger adults.

Adult↗
PubMed2004

Alpha1-antitrypsin inhibits angiogenesis and tumor growth.

Disturbances of the ratio between angiogenic inducers and inhibitors in tumor microenvironment are the driving force behind angiogenic switch critical for tumor progression. Angiogenic inhibitors may vary depending on organismal age and the tissue of origin. We showed that alpha(1)-antitrypsin (AAT), a serine protease inhibitor (serpin) is an inhibitor of angiogenesis, which induced apoptosis and inhibited chemotaxis of endothelial cells. S- and Z-type mutations that cause abnormal folding and defective serpin activity abrogated AAT antiangiogenic activity. Removal of the C-terminal reactive site loop had no effect on its angiostatic activity. Both native AAT and AAT truncated on C-terminus (AATDelta) inhibited neovascularization in the rat cornea and delayed the growth of subcutaneous tumors in mice. Treatment with native AAT and truncated AATDelta, but not control vehicle reduced tumor microvessel density, while increasing apoptosis within tumor endothelium. Comparative analysis of the human tumors and normal tissues of origin showed correlation between reduced local alpha(1)-antitrypsin expression and more aggressive tumor growth.

Angiogenesis Inhibitors↗
PubMed2004

Cytogenetic analysis of a series of 13 renal oncocytomas.

PURPOSE: Only about 50 renal oncocytomas have been studied cytogenetically. They fall into 3 categories, namely 1-normal karyotype, 2-monosomy 1, often with Y chromosome loss, and 3-structural abnormalities of 11q13. Additional abnormalities may occur with transformation to chromophobe renal cell carcinoma, although exactly which one is unclear. We expanded the oncocytoma data base to shed light on changes that characterize transformation. MATERIALS AND METHODS: A total of 14 oncocytomas from 12 patients were collected in 2(1/2) years. One tumor failed to grow but 13 were successfully karyotyped. RESULTS: Seven tumors (53.8%), including 2 from 1 kidney, had normal karyotypes or abnormalities characteristic of normal kidney tissue. A total of 6 tumors from 5 individuals (46.2%) had chromosome 1 abnormalities. Monosomy 1 was detected in 2 single tumors and in both tumors in a bilateral case. Structural anomalies resulting in loss of the short arm of chromosome 1 were found in an additional 2 patients. Other abnormalities, including Y chromosome loss and monosomy 14, were observed but no abnormalities of 11q13 were seen. CONCLUSIONS: Our series confirms that 1p loss is the most common anomaly in oncocytoma. Additional studies are required to understand the transformation potential of this usually benign tumor, identify the putative 1p tumor suppressor gene and determine whether karyotypically normal tumors have molecular abnormalities of 1p.

Adenoma, Oxyphilic↗
PubMed2004

Renal tumor with overlapping distal nephron morphology and karyotype.

Although most renal epithelial tumors are derived from the proximal nephron, approximately 10% are believed to originate in the distal nephron. This latter group encompasses oncocytoma, chromophobe renal cell carcinoma, and several rare types, including collecting duct carcinoma and renal medullary carcinoma. Despite progress in the classification of renal tumors, a small subset of renal carcinomas remains unclassified (ie, renal cell carcinoma, not otherwise specified). We describe a metastatic tumor consisting of cells with overlapping distal nephron morphologies, including foci of oncocytoma, chromophobe renal cell carcinoma, and collecting duct carcinoma, as well as sarcomatoid dedifferentiation. Special stains were inconclusive, and ultrastructural study demonstrated abundant mitochondria and no microvesicles. The karyotype was hypodiploid with 41 chromosomes and abnormalities reported in all 3 phenotypes present. Rearrangements of 1p and of 11q13 previously seen in divergent subsets of oncocytomas were concomitantly present in the current tumor. Thus, this malignancy has features consistent with distal nephron derivation and demonstrates the convergence of the varied tumor morphologies arising within this site. Furthermore, this case exemplifies the value of cytogenetic analysis in the characterization of renal cell carcinoma, not otherwise specified. In view of recent advances in treatment approach, especially for collecting duct carcinoma, further categorization of this nondescript and heterogeneous group of renal cell carcinomas, not otherwise specified, at least by its derivation in relationship to the renal nephron (distal vs proximal), may be of value in the choice of treatment modality.

Bone Neoplasms↗
PubMed2004

Peroxisome proliferator-activated receptor gamma ligands improve the antitumor efficacy of thrombospondin peptide ABT510.

An expanding capillary network is critical for several pathologic conditions. In cancer, the decrease of antiangiogenic thrombospondin-1 (TSP1) often enables an angiogenic switch, which can be reversed with exogenous TSP1 or its peptide derivative ABT510. TSP1 acts by inducing endothelial cell apoptosis via signaling cascade initiated at CD36, a TSP1 antiangiogenic receptor. Here, we show that the ligands of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma), 15-deoxy-delta(12,14)-prostaglandin J2, troglitazone, and rosiglitazone increased PPARgamma and CD36 expression in endothelial cells and improved the efficacy of TSP1 and ABT510 in a CD36-dependent manner. The ABT510 and PPARgamma ligands cooperatively blocked angiogenic endothelial functions in vitro and neovascularization in vivo. In tumor xenografts, 15-deoxy-delta(12,14)-prostaglandin J2 and troglitazone synergistically improved antiangiogenic and antitumor effects of ABT510. Our data provide one mechanism for the in vivo angioinhibitory effect of PPARgamma ligands and show fine-tuning of the antiangiogenic efficacy via targeted up-regulation of the endothelial receptor.

Angiogenesis Inhibitors↗
PubMed2003

Nephrectomy in metastatic renal cell carcinoma.

Patients presenting with metastatic renal cell carcinoma (RCC) face a dismal prognosis, with a median survival time of only 6 to 12 months and a 2-year survival rate of 10% to 20%. RCC is notoriously chemorefractory, and immunotherapy is associated with total response rates of less than 20% and complete response rates of less than 5%. Therefore, surgery has continued to play a prominent role in the management of patients with metastatic RCC. Recent randomized prospective trials suggest a survival advantage for cytoreductive nephrectomy, and some patients with advanced RCC may also achieve palliation. Patients with limited and resectable metastases should be considered for combined nephrectomy and metastasectomy. The other main option for patients with advanced RCC is systemic immunotherapy followed by assessment for surgical consolidation, but responses in the primary tumor are uncommon and results with this pathway have not been encouraging. Tumor embolization can be a valuable palliative adjunct for some patients with metastatic RCC. Cytoreductive nephrectomy represents the most aggressive pathway for patients with metastatic RCC. Although cytoreductive nephrectomy can extend survival by approximately 50% for many patients, it can be associated with morbidity and delay in administration of systemic therapy. Therefore, patient selection, taking into account performance status and sites and burden of disease, which are well-established prognostic factors for patients with metastatic RCC, is of paramount importance in managing this challenging group of patients.

Adult↗
PubMed2003

Metastatic renal cell carcinoma.

Patients with renal cell cancer (RCC) develop metastatic spread in approximately 33% of cases. The clinical management of patients with metastatic RCC is complicated by the lack of significant efficacy from available therapies. Common sites of metastases include the lung, liver, bone, brain, and adrenal gland, with case reports detailing the capacity of RCC to appear almost anywhere in the body. More than one organ system is often involved in the metastatic process. Metastases may be found at diagnosis or at some interval after nephrectomy. Approximately 20% to 50% of patients will eventually develop metastatic disease after nephrectomy. A shorter interval between nephrectomy and the development of metastases is associated with a poorer prognosis. Patients with metastatic RCC face a dismal prognosis, with a median survival time of only 6 to 12 months and a 2-year survival rate of 10% to 20%. Recent advances in biologic response modifier therapy have brought new hope to a small percentage of patients who respond to this therapy and rekindled interest in cytoreductive nephrectomy as an integral part of the management of these patients.

Adult↗
PubMed2003

Prognostic factors in renal cell carcinoma.

Several well-established prognostic factors are now available for RCC and have proven utility for patient counseling and management. Consideration of these factors allows for a rational stratification of patients into clinical trials and facilitates the comparison of reports from diverse institutions. Tumor stage remains the most important prognostic factor for RCC, but compelling data have also been accumulated in support of various clinical signs and symptoms, tumor grade, size, histologic subtype, and DNA content and nuclear morphometry. Novel efforts to integrate these factors show great promise and are likely to incorporate molecular factors in the near future.

Carcinoma, Renal Cell↗
PubMed2003

Laparoscopic renal cryosurgery: the Northwestern experience.

PURPOSE: Laparoscopic renal cryosurgery provides a minimally invasive alternative for the treatment of small renal lesions of undefined malignant potential. We report on our series of patients treated with laparoscopic renal cryosurgery. MATERIALS AND METHODS: Fifteen patients underwent laparoscopic renal cryoablation of peripheral, exophytic unifocal renal lesions. Patients were managed with a 4-port transperitoneal approach for anteromedial tumors and 3 to 4-port retroperitoneal approach for posterolateral tumors. All lesions were biopsied and sent to pathology for permanent section. A 4.8 mm cryoprobe (CMS cryoprobe, 4.8 mm x 2 cm x 40 cm, Cryomedical Sciences Inc., Ewing, New Jersey) was placed into the tumor using visual and ultrasonographic guidance, and a double freeze-passive thaw cycle was performed. The iceball was extended at least 1 cm beyond the tumor margin under ultrasound guidance. Followup biopsies were performed on all consenting patients with renal cell carcinoma at least 3 months after cryosurgery was performed. RESULTS: Laparoscopic renal cryosurgery was successfully performed on all 15 patients (6 male and 9 female). Of the 15 patients 10 had renal cell carcinoma. Mean age was 68.5 years (range 49 to 86). Mean tumor size was 2.15 cm (range 1.2 to 3.2) and mean estimated blood loss was 67 cc (range 15 to 125). There were 2 perioperative complications. Mean hospital stay was 3.5 days (range 1 to 11). Patients returned to work after 16.5 days (range 7 to 28). Radiographic followup revealed stable cryoablative lesions in all patients. Mean radiographic followup was 453 days (range 147 to 816). Mean preoperative creatinine was 1.25 mg/dl (range 0.8 to 4.3) and mean postoperative creatinine obtained 1 month postoperatively was 1.36 (range 0.8 to 4.8). There was 1 treatment failure, although another patient had a positive biopsy outside the ablated area. The failure occurred in the largest tumor treated (3.2 cm) and was due to incomplete treatment of the periphery of the lesion. The other patient had a successfully treated tumor but a positive followup biopsy due to multifocal papillary renal cell carcinoma and required nephrectomy. CONCLUSIONS: Laparoscopic renal cryosurgery appears to be a safe and effective minimally invasive alternative for the treatment of small renal masses. Careful selection of patients with lesions that are less than 3.0 cm and close monitoring of the iceball is necessary to treat these patients successfully.

Aged↗