Biomedical subjects
E A Klein
Publications and source records attributed to E A Klein.
Open pelvic lymph node dissection for prostate cancer: a reassessment.
OBJECTIVES: To provide a risk-to-benefit analysis of open staging pelvic lymph node dissection (PLND) for prostate cancer. METHODS: The medical records of all patients presenting with prostate cancer from July 1989 to April 1994 were reviewed. A total of 245 patients with clinically localized disease were selected to undergo radical retropubic prostatectomy (RRP) preceded by open PLND. Univariate and multivariate analyses were performed to evaluate the predictive value of the preoperative serum prostate-specific antigen (PSA) concentration, clinical stage, and Gleason score with regard to final nodal status. The cost and morbidity associated with PLND in the setting of RRP was also defined. RESULTS: Overall, only 16 patients (6.5%) had lymph node metastases. Lymph node involvement correlated significantly with elevated serum PSA values (P = 0.0001), high Gleason score (P = 0.0022), and advanced clinical stage (P = 0.0001). Lymph node metastases were particularly uncommon in patients with nonpalpable tumors (1 of 67 [1.5%]), PSA values less than 10 (2 of 154 [1.3%]), and Gleason score less than 6 (1 of 26 [3.8%]). Overall, 179 patients (73.1%) presented with at least one or more of these favorable characteristics, and only 4 (2.2%) had lymph node involvement. Complications related to the lymphadenectomy occurred in 10 patients (4.1%). The cost per metastasis diagnosed in patients with low-risk characteristics was approximatley $43,600. CONCLUSIONS: An open staging PLND may no longer be justified on a routine basis in patients undergoing radical retropubic prostatectomy.
Ewing's sarcoma of the mandible: a case report.
Ewing's sarcoma is an uncommon malignancy that usually occurs in childhood and is rare in the mandible. A case of Ewing's sarcoma of the mandible is presented and discussed.
Reducing length of stay after radical prostatectomy.
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Combination radiation and chemotherapy for the treatment of squamous cell carcinoma of the male and female urethra.
We report on 2 men and 2 women with locally advanced squamous cell carcinoma of the urethra who were treated with combination chemotherapy and radiation. Treatment consisted of 1,000 mg./M.2 5-fluorouracil plus 15 mg./M.2 mitomycin-C followed by 30 to 50 Gy. external beam radiation. The 2 women achieved durable complete responses, and are alive with no evidence of disease 94 and 43 months later, respectively. The men also had regional lymph node metastases, and 1 achieved complete response and has no evidence of disease 98 months posttreatment, while the other experienced partial response in the primary tumor and complete response in the involved inguinal nodes. The latter patient died of an unrelated cause with residual disease at 7 months. Only mild toxicity occurred in 3 patients. This regimen of chemotherapy and radiation is well tolerated and should be considered as primary therapy for invasive squamous cell carcinoma of the male and female urethra.
Correlation of human bladder tumor histoculture proliferation and sensitivity to mitomycin C with tumor pathobiology.
This study examined the in vitro proliferation and mitomycin C (MMC) sensitivity of patient bladder tumors as a function of the tumor pathobiology. Surgical specimens of transitional cell carcinoma of the bladder were maintained as histocultures on collagen gels. The thymidine labeling index (LI) was determined by autoradiography and the labeling for proliferating cell nuclear antigen (PCNA) by immunohistochemistry. There was a linear correlation between the thymidine LI and the PCNA LI, but the PCNA LI were quantitatively lower than the thymidine LI. The mean thymidine LI were 30.9, 32.4 and 51.5% for the grade I, II and III tumors, 33.6 and 56.3% for the superficial (Tis, Ta and T1) and invasive (T2-T4) tumors, and 28.9 and 50.9% for the diploid and aneuploid tumors. Analysis of variance indicates that these differences were statistically significant. These data indicate that the proliferation of tumor histocultures paralleled the tumor aggressiveness in vivo. The tumor sensitivity to MMC, measured by the inhibition of the thymidine LI of tumor cells, was studied in 31 tumors. At a 2 hour exposure, as is currently used in intravesical therapy, the MMC concentrations required for 50% inhibition of thymidine LI (IC50) showed a 120-fold intertumor variation (0.102 to 12.4 micrograms./ml.). The sensitivity to MMC inversely correlated with tumor aggressiveness. The IC50 increased with tumor LI (p < 0.05). The mean IC50 were 2.61 and 5.79 micrograms./ml. for superficial and invasive tumors (p < 0.05), 1.06, 3.05 and 4.49 micrograms./ml. for grade I, II and III tumors (p < 0.05), and 2.53 and 4.31 micrograms./ml. for diploid and aneuploid tumors (p = 0.14). These data indicate a large difference in sensitivity of human bladder tumors to MMC, with greater sensitivity for well-differentiated superficial tumors and lesser sensitivity for undifferentiated, invasive tumors.
Safety of transurethral surgery in the early postoperative period following an open cardiac procedure.
A retrospective investigation was performed to determine whether patients undergoing transurethral surgery soon after cardiac surgery experienced increased morbidity or mortality rates. From 1986 to 1990, 24 patients first underwent open heart surgery and then either transurethral prostatectomy, bladder tumor resection or bladder cup biopsy during the same hospital stay. Postoperative complications included significant hematuria in 2 patients (8%), mild stress incontinence in 1 (4%) and bladder perforation in 1. One patient died of a spontaneous pneumothorax 17 days after the urological operation. None of these patients had had a previous myocardial infarction. The outcome of these patients was compared to that of 115 men who underwent transurethral prostatectomy for presumed benign disease during 1990. Complications of transurethral prostatectomy in this group included significant gross hematuria in 5 men, while 6 experienced urinary retention (1), atrial fibrillation (1), delirium (1), myocardial infarction (1), seizure (1) and intraoperative urethral injury (1). There was 1 death from multiple postoperative complications. Morbidity and mortality rates did not differ significantly between the 2 groups. Transurethral surgery performed after cardiac surgery during the same hospital stay appears to be safe, provided the patient is stable.
Intercellular adhesion molecule-1 expression by bladder cancer cells: functional effects.
The role of intercellular adhesion molecule-1 (ICAM-1) and its ligand, leukocyte function-associated antigen-1 (LFA-1), in the interaction between bladder cancer cells and lymphokine activated killer (LAK) cells was investigated. Expression and modulation of ICAM-1 by cytokine treatment was assessed by immunocytometry and Northern blot analysis. Four of five human bladder cancer cell lines expressed ICAM-1 constitutively and responded to cytokine stimulation. Expression of ICAM-1 was upregulated most consistently by treatment with interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha), cytokines that are released into the urine after intravesical BCG treatment. In contrast, interleukin-1 and phorbol myristate acetate exhibited variable effects on ICAM-1 expression, and interferon-alpha had no effect. The adherence of LAK cells to bladder cancer cell monolayers and LAK cell-mediated cytolysis were then studied. Monoclonal antibodies to ICAM-1 and LFA-1 significantly decreased the binding of LAK cells to the cell lines that express ICAM-1 (37 to 75% reduction, p < 0.05), and cytokine treatment (IFN gamma, TNF alpha) of these cells enhanced ICAM-1 dependent adherence (18 to 39% increase, p < 0.05). In contrast, these manipulations had no effect on the binding of LAK cells to the UMUC3 cell line, which does not express ICAM-1. Monoclonal antibodies to LFA-1 decreased LAK cell mediated cytolysis of the bladder cancer cells from 27 to 65% (p < 0.05), but anti-ICAM-1 antibodies were much less effective (0 to 25% decrease in cytolysis). Cytokine treatment (IFN gamma, TNF alpha) of the tumor cells did not significantly increase LAK cell-mediated cytolysis, despite upregulation of ICAM-1. These data demonstrate that ICAM-1 plays a role in the binding of LAK cells to bladder cancer cells but is only marginally involved in the process of LAK cell-mediated cytolysis. These findings suggest that adhesion molecules may be important mediators of the immune response to bladder cancer after intravesical BCG therapy.
Impact of bladder neck preservation during radical prostatectomy on continence and cancer control.
OBJECTIVES: To assess the effect of preservation of the bladder neck and other factors on the rate of postoperative urinary continence and cancer control after radical prostatectomy. METHODS: Prospective analysis of clinical and pathologic findings in 206 consecutive patients undergoing radical prostatectomy with a surgical technique that emphasizes preservation of periurethral supporting tissue, urethral length, incorporation of the posterior periurethral fascia into the vesicourethral anastomosis, and preservation of the bladder neck. RESULTS: Uni- and multivariate statistical analysis demonstrated that patient age (p = 0.033) and vesical neck contracture (p = 0.047) were predictive of incomplete return of urinary control. Preservation of the vesical neck had no impact on return of continence, but was associated with a trend to a lower incidence of vesical neck contractures. A positive bladder neck margin occurred in 6.8% of surgical specimens and was associated with a higher grade, more advanced local stage, and other positive margins in all cases. The rate of local recurrence or prostate-specific antigen (PSA)-only failure was similarly independent of whether the vesical neck was preserved or resected and reconstructed. CONCLUSIONS: Age greater than 65 and occurrence of a vesical neck contracture are adverse predictors for return of urinary continence after radical prostatectomy. Preservation of the bladder neck does not have an impact on return of urinary control but may be associated with a lower risk of vesical neck contracture. Preservation of the bladder neck does not compromise cancer control as assessed by local or PSA-only failure rates.
Early hospital discharge after radical retropubic prostatectomy: impact on cost and complication rate.
OBJECTIVES: To assess the impact of shortened hospital stay after radical retropubic prostatectomy for localized prostate cancer on complication rates and hospital costs. METHODS: A comparison of results between 171 consecutive patients undergoing radical retropubic prostatectomy between July 1989 and January 1993 (group 1) and 101 consecutive patients operated on since February 1993 (group 2) during a prospective effort to reduce hospital length of stay by home-based preoperative bowel preparation, direct admission to the operating room on the day of surgery, earlier and more extensive postoperative ambulation, earlier initiation of postoperative oral intake, earlier use of oral analgesics, and routine pelvic drain removal at 72 to 96 hours after surgery independent of volume of drainage. RESULTS: Median length of stay was reduced from 8 to 5 days (p < 0.0001, group 1 versus group 2), with 10% of patients in group 2 having hospital stays of 4 days or less. The overall nature and rate of complications (13.5% versus 11.9%, p = NS) were similar in both groups. Reduced length of stay was associated with a 32% decrease in hospital-associated cost per case in group 2 versus group 1 for patients in diagnosis-related group (DRG) 334 (radical prostatectomy with comorbidity) and a 26% decrease for DRG 335 (radical prostatectomy without comorbidity). CONCLUSIONS: Reduced hospital length of stay after radical retropubic prostatectomy results in significant cost savings without increasing morbidity.
Metastatic meningioma: hemangiopericytoma or angioblastic meningioma?
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Modified apical dissection for early continence after radical prostatectomy.
A prospective evaluation of urinary continence in 83 consecutive patients undergoing radical prostatectomy using a modified apical urethral dissection is described. Using this technique, complete continence has been achieved in 88%, with stress incontinence in 11% and total incontinence in 1%. Continence was achieved in less than 1 week to a maximum of 16 weeks, with 17% dry during the first week, 53% dry by 6 weeks, and 81% by 3 months. Median time to continence was 5 weeks. Median age of the continent patients was significantly lower than that of incontinent patients. Neither the number of neurovascular bundles resected, the need to reconstruct the vesical neck, nor the number of anastomotic sutures used affected the rate of continence. The described technique, which incorporates the fascia posterior to the urethra into the vesicourethral anastomosis, results in earlier continence after radical prostatectomy, and thereby lessens the morbidity of this procedure.
Management of renal cell carcinoma with coexistent renal artery disease.
Coexistence of renal cell carcinoma and renal artery disease is an unusual and challenging problem. From 1969 to 1991, 34 patients presented with localized renal cell carcinoma and renal artery disease affecting all of the functioning renal parenchyma. These patients represented 4 categories: 1) a solitary kidney with renal cell carcinoma and renal artery disease (5), 2) bilateral renal cell carcinoma and coexistent renal artery disease (5), 3) unilateral renal cell carcinoma and contralateral renal artery disease (13), and 4) unilateral renal cell carcinoma and bilateral renal artery disease (11). Atherosclerosis was the most common cause of renal artery disease (30), followed by medial fibroplasia (2), renal artery aneurysm (1) and arteriovenous malformation (1). A total of 23 patients (68%) presented with azotemia (serum creatinine 1.5 mg./dl. or more) and 11 (32%) presented with hypertension. All patients underwent complete surgical excision of renal cell carcinoma. A nephron sparing operation was performed preferentially (30 patients) and bilateral renal cancer operations were staged. Eight patients underwent simultaneous partial (6) or radical (2) nephrectomy and surgical renal revascularization. There were no operative deaths. Postoperatively, preservation of renal function was achieved in 33 patients and 1 required chronic dialysis. At mean followup of 47 months 23 patients (68%) were alive with no evidence of malignancy and 2 were alive with recurrent renal cell carcinoma. Three patients died of metastatic renal cell carcinoma, while 6 died of unrelated causes. All of the latter 6 patients were free of renal cell carcinoma at death. Nephron sparing surgery combined occasionally with renal arterial reconstruction can yield gratifying results in this complex patient population.
Renal oncocytoma: clinical and biological correlates.
We treated 31 patients with renal oncocytoma. Renal cell carcinoma was found existing separately within the same or contralateral kidney in 10 patients (32%). Followup of 29 patients revealed 24 alive with no evidence of disease and 1 alive with recurrent oncocytoma, while 1 with coexistent tumors died of progressive renal cell carcinoma and 3 tumor-free patients died of unrelated diseases. Quantitative deoxyribonucleic acid analysis was performed on cell suspensions of fresh tumor by flow cytometry or by image cytometry on touch preparations from frozen tissue in 16 patients with renal oncocytoma. Ploidy analysis revealed all oncocytomas to be diploid. Frozen tissue immunohistology was performed using murine monoclonal antibody against human HLA-A, B and C (class I) antigens with the avidin-biotin peroxidase technique in 11 patients with renal oncocytoma. Ten oncocytomas did not express these self-recognition antigens and 1 was only weakly positive for antigen expression. In contrast, renal cell carcinomas strongly expressed HLA class I antigens. The high incidence of coexistence of renal oncocytoma and renal cell carcinoma has important clinical implications. Loss of HLA class I antigen expression by renal oncocytomas may provide an additional method for differentiating this lesion from renal cell carcinoma.
Tumor markers in testis cancer.
Human chorionic gonadotropin and alpha-fetoprotein are well established as serum markers for germ-cell tumors of the testis. Other protein markers of this disease are lactic acid dehydrogenase and placental alkaline phosphatase. There also are cytogenetic or chromosomal markers, particularly i(12p), and molecular markers in the form of oncogenes and tumor suppressor genes. Markers are valuable in diagnosis, staging, predicting tumor behavior, and monitoring therapy and disease recurrence.
Combined radical retropubic prostatectomy and proctosigmoidectomy for en bloc removal of locally invasive carcinoma of the rectum.
A novel technique of combined radical retropubic prostatectomy and restorative proctosigmoidectomy is described, and indications and expected complications are discussed. It is offered as an alternative to total pelvic exenteration for patients with carcinoma of the rectum exhibiting isolated extension to the prostate gland or seminal vesicles. This procedure obviates the need for urinary and fecal diversion and provides excellent exposure for optimal rectal dissection. Thus, it offers the opportunity for improved functional results without compromising the principles important for local tumor control.
Sinonasal primitive neuroectodermal tumor arising in a long-term survivor of heritable unilateral retinoblastoma.
BACKGROUND: Patients who survive retinoblastoma (RB) are at risk for having second nonocular tumors, usually osteosarcomas, which often are fatal. Such patients almost always have bilateral RB. METHODS: This article reports a woman who, at the age of 1 year had been cured of a unilateral RB by radiation therapy and enucleation. Eighteen years later, she had a sinonasal small cell tumor that rapidly recurred and proved fatal 2 months after surgical debulking. The tumor was studied by immunohistochemistry and electron microscopic (EM) examination. RESULTS: It showed diffuse neuron-specific enolase staining, focal weak staining for chromogranin, synaptophysin, and Leu-7 monoclonal antibodies in paraffin-embedded, B5-fixed tissue (Great Lakes Diagnostics, Troy, MI). EM study showed an undifferentiated primitive neuroectodermal tumor with many polyribosomes, simple cell junctions, few microtubules, and rare dense core granules. CONCLUSIONS: The combined immunohistochemical, ultrastructural, and clinical features of the tumor were interpreted as a sinonasal primitive neuroectodermal tumor with early neuronal differentiation. The tumor was pathologically indistinguishable from poorly differentiated olfactory neuroblastoma (ONB) and Ewing sarcoma.
Viruses in idiopathic inflammatory myopathies: absence of candidate viral genomes in muscle.
There is indirect evidence that various viruses have aetiological roles in the idiopathic inflammatory myopathies. By means of a sensitive and specific method based on the polymerase chain reaction (PCR), we sought direct evidence for the presence in affected muscle of nucleic acid sequences from Coxsackie virus, mumps virus, encephalomyocarditis virus, adenovirus, human T-lymphotropic virus types I and II, and human immunodeficiency virus. RNA was extracted from muscle biopsy samples obtained from 44 patients with idiopathic inflammatory myopathies a mean of 45 (range 0-216) months after disease onset. All the subjects were older than 16 years at disease onset. The integrity of the mRNA extracted was confirmed by the successful PCR amplification of insulin receptor mRNA in all samples. The PCR method was able to detect between 1 and 20 molecules of added viral nucleic acid for the picornaviruses sought. No detectable virus sequences were found, however, in any of the patients' muscle samples or in samples from 13 controls. We tested for retroviral DNA in 22 samples (17 patients, 5 controls) that met our criterion for adequate DNA extraction (detectable beta-actin DNA by PCR); again no virus sequences were found. Persistence in muscle of these or closely related viruses is unlikely to be a continuing stimulus for disease in the idiopathic inflammatory myopathies.