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Biomedical subjects

B R Konety

Publications and source records attributed to B R Konety.

35 records · Page 2Linked to original sources
PubMed1998

Prostate cancer in the post-transplant population. Urologic Society for Transplantation and Vascular Surgery.

OBJECTIVES: We conducted a multicenter retrospective study to determine the results of treatment for prostate cancer in solid organ transplant recipients. METHODS: A retrospective analysis of all patients diagnosed with prostate cancer after organ transplantation at five centers was conducted. Data were obtained by chart review and a multipoint data sheet was used to abstract the data from the patient charts. RESULTS: Eighteen cases of prostate cancer were identified from six institutions. Most (84%) of the cancers were clinically localized at the time of diagnosis. Nine (50%) of 18 patients underwent radical prostatectomy, which was the predominant mode of treatment. Overall survival at a mean follow-up of 32 months was 66%, with a cancer specific mortality of 16%. Mortality was 13% for the 15 patients with localized disease and 33% for the 3 patients with metastatic disease at the time of diagnosis. CONCLUSIONS: Most of the patients with prostate cancer being detected after solid organ transplantation were diagnosed with localized disease. Aggressive therapeutic intervention as in the general (nontransplant) population yields good results and should be pursued. Diligent surveillance for prostate cancer in this population using periodic digital rectal examination, serum prostate-specific antigen, and prostate needle biopsy as needed will ensure earlier cancer detection and allow for definitive therapeutic intervention.

Aged↗
PubMed1998

Association of vitamin D receptors with the nuclear matrix of human and rat genitourinary tissues.

Calcitrol, 1,25 dihydroxyvitamin D3 (1,25-D3) has an important role in the antiproliferative and growth regulatory effects on normal and neoplastic cells (e.g. prostate cancer cells). 1,25-D3 binds to the vitamin D receptor (VDR), a member of the steroid receptor superfamily. Steroids, via intranuclear receptors, have been demonstrated to have high affinity binding to the nuclear matrix, the tissue specific scaffolding of the nucleus that is involved in the organization of DNA, replication and transcription. We hypothesized that the VDR interacts closely with the nuclear matrix in both human and rat tissues. In the studies described here, nuclear matrix proteins (NMP) were extracted from a number of rat and human tissues and immunoblot analysis performed using a rat anti-VDR antibody. The results from these studies reveal that the anti-VDR antibody detects six forms of the VDR in the NMP preparations: human testis demonstrated a protein of 57 and 52 kDa molecular weight compared with 57 and 37 kDa in the rat testis. Human prostate demonstrated proteins of 52 kDa compared to rat ventral (57 and 37 kDa) and dorsal prostate (52 and 26 kDa). Human and rat bladder NMP demonstrated a protein binding at 55 kDa and rat seminal vesicle NMP binding at 48 kDa. This is the first report of VDRs associated with the nuclear matrix. The varying molecular weight proteins reactive with the anti-VDR antibody within these tissues may represent different isoforms, proteolytic cleavage of a larger VDR or post-translational modification. The VDR-NMP interaction may be involved in the tissue specific actions of 1,25-D3 especially growth regulatory and antiproliferative effects.

Animals↗
PubMed1998

Embryonal adenoma of the kidney associated with polycythemia and von Willebrand disease.

PURPOSE: We studied the significance, identification and management of acquired von Willebrand disease and polycythemia associated with benign renal tumors in children. MATERIALS AND METHODS: Two patients who presented with polycythemia and a renal mass were also found to have acquired von Willebrand disease. One patient was treated with radical nephrectomy and 1 was treated with partial nephrectomy. The patients have been followed for 19 and 10 months, respectively. RESULTS: Excision of the renal mass resulted in prompt resolution of polycythemia and von Willebrand disease in each patient. Perioperatively 1-deamino-(8-D-arginine)-vasopressin was given to control bleeding. Each patient had benign embryonal adenoma of the kidney. CONCLUSIONS: Polycythemia and von Willebrand disease may be associated with benign kidney neoplasms. Children and adolescents with a renal mass may benefit from preoperative screening for coagulopathy.

Adenoma↗
PubMed1998

Identification of nuclear matrix protein alterations associated with renal cell carcinoma.

PURPOSE: Neoplastic transformation, including renal cell carcinoma (RCC), is always accompanied by changes in nuclear morphology. Nuclear grading of RCC is based on characteristic alterations in nuclear shape, size, area and other morphologic parameters. The nuclear matrix, which forms the skeleton of the nucleus, determines nuclear morphology. Alterations in nuclear matrix protein (NMP) composition specific to tissue and cancer type have been described in a variety of human cancers. We conducted a study to analyze the nuclear matrix protein composition of renal cell carcinoma and compare it to that of normal renal tissue and renal cell carcinoma cells grown in culture. MATERIALS AND METHODS: We analyzed the nuclear matrix protein composition of RCC tumor tissue and that of normal kidney tissue obtained from seventeen patients undergoing radical nephrectomy for RCC. We also analyzed the NMP composition of two renal cancer cell lines (A-498 and 769-P). RESULTS: We were able to identify five different and unique NMPs which were present only in the human RCC tumor samples and were absent in all normal kidney tissue. One NMP was found specifically in the normal kidney tissue. All five RCC specific NMPs were also identified in the nuclear matrix of the two cell lines analyzed. CONCLUSIONS: Five nuclear matrix proteins specific and unique to RCC were identified. These NMPs are different from those previously identified in other tissues and neoplasms. The RCC specific NMPs identified in this study can potentially be used as diagnostic markers for renal cell carcinoma and for therapeutic tumor targeting.

Aged↗
PubMed1997

Perineural invasion in transitional cell carcinoma and the effect on prognosis following radical cystectomy.

OBJECTIVES: The relationship between perineural invasion and prognosis has been demonstrated to be poor in a number of malignancies. This has not been evaluated in the bladder. We performed a study to determine the occurrence of nodal metastases, extranodal metastases, and disease-free survival in patients with perineural invasion (PNI) and/or angiolymphatic invasion (ALI) in transitional cell carcinoma of the bladder (TCCB) from radical cystectomy specimens. METHODS: A retrospective review of 27 patients treated with radical cystectomy for TCCB was conducted. Comparisons were performed between three groups: PNI with or without ALI (PNI +/- ALI, 12 patients), ALI alone (8 patients), and a control group (no PNI or ALI) (7 patients). RESULTS: The mean patient age was 70 years (range 49 to 83). The overall median follow-up period was 11 months (range 1 to 32). PNI +/- ALI was predominantly found in Stage T3b disease (14 of 20 [70%] cases). The overall 1-year disease-free survival was 48%, 67%, and 83% for the PNI +/- ALI, ALI alone, and control groups, respectively. Nodal metastases (for all stages combined) were found in 6 of 12 (50%), 3 of 8 (38%), and 1 of 7 (14%) patients in the PNI +/- ALI, ALI alone, and control groups, respectively. Similarly, extranodal metastatic disease was found in 5 of 12 (42%), 4 of 8 (50%), and 1 of 7 (14%) patients in the PNI +/- ALI, ALI alone, and control groups, respectively. The percentage of deaths for the PNI +/- ALI, ALI only, and control groups were 33%, 50%, and 14%, respectively. CONCLUSIONS: In TCCB, perineural invasion with or without angiolymphatic invasion and angiolymphatic invasion alone are associated with a higher incidence of nodal and extranodal metastases and death.

Aged↗
PubMed1997

Vitamin D inhibition of prostate adenocarcinoma growth and metastasis in the Dunning rat prostate model system.

OBJECTIVES: Risk factors for prostate cancer (PCa)-related mortality include old age, black race, and residence in northern latitudes. The objectives of this study are to examine the in vitro and in vivo effects of 1,25-dihydroxycholecalciferol (1,25-D3) and less-hypercalcemic analogues on the Dunning rat prostate adenocarcinoma model. METHODS: To evaluate the effect of 1,25-D3 on PCa in vitro, we used the highly metastatic Mat-lylu (MLL) and moderately metastatic R3327-AT-2 (AT-2) Dunning prostate cell lines, and examined effects on growth, clonogenicity, differentiation, and cell cycle. In vivo analysis included examination of the effects of these compounds on tumor growth and metastasis. RESULTS: Using both the 3-day MTT and 7-day clonogenic assay, 1,25-D3 demonstrated a growth inhibitory effect with a concentration for 50% inhibition (IC50) of approximately 20 microM for both MLL and AT-2. Cell cycle analysis of treated MLL cells (10 microM 1,25-D3 for 48 hours) had 25% more cells in the G0/G1 phase than did control cells. To examine the in vivo effect of 1,25-D3 and the less hypercalcemic vitamin D analogue, Ro25-6760 (or 6760), on MLL PCa growth and metastasis, tumors (5 x 10(5) cells) were implanted subcutaneously into the flank of Copenhagen rats on the same day that treatment was initiated with 1,25-D3 (1 microgram) or 6760 (1 or 5 micrograms); rats received treatment three times a week. After 3 weeks, 1,25-D3 and 6760 (5 micrograms dosing) resulted in an inhibition of tumor volume and a reduction in the number and size of lung metastases. CONCLUSIONS: These preclinical studies demonstrate the profound in vitro, or in vivo, or both antiproliferative and differentiating effects of 1,25-D3 and 6760 on PCa and suggest that these drugs may have potential beneficial effects in the treatment of advanced PCa.

Adenocarcinoma↗
PubMed1997

Expression of SSEA-1 (Lewis(x)) on transitional cell carcinoma of the bladder.

The expression of stage-specific embryonic antigen 1 (SSEA-1) in transitional cell carcinomas of the bladder (TCCB) has been reported to correlate with tumor grade and the likelihood of lymphatic metastases. We examined the expression of this antigen in TCCBs to evaluate if staining correlated with grade, stage, recurrence, progression and response to intravesical chemotherapy. We studied the expression of SSEA-1 in TCCBs from 74 patients by staining with two different monoclonal antibodies (Mabs), P-12 and anti-SSEA-1, to evaluate if staining correlated with grade, stage and tumor recurrence. Staining was considered as positive or negative irrespective of the intensity of staining. Extent of tumor staining was measured in quartiles of 100% (25, 50, 75 and 100). Follow-up was available in 47/74 (63%) patients and ranged from 6 months to 13 years (median 2 years). Staining with one or both Mabs was observed in 57/75 (76%) tumors. None of the grade I tumors showed > 50% staining while 26% of grade II and only 33% of grade III tumors showed staining of > 50% of cells. 21% of patients whose tumors showed staining with both Mabs were free of recurrence after resection of the primary tumor; 41% of patients with tumors staining negative with both Mabs showed no recurrence. Expression of SSEA-1 does correlate with tumor recurrence especially in grade II tumors, but the correlation is not very strong (0.05 < p < 0.1). Expression of this antigen is a weak indicator of recurrence in superficial TCCBs.

Aged↗
PubMed1997

Novel therapies for advanced prostate cancer.

Approximately a third of the patients diagnosed with prostate cancer will present with advanced disease. Metastasis commonly occurs to the regional lymph nodes and/or the bony skeleton. Total androgen ablation by means of castration, antiandrogens or luteinizing hormone-releasing hormone analogs remains the standard of care for patients. However, responses are short-lived in most patients with progression of hormone refractory disease being inevitable over the course of 2 to 3 years. Advances in molecular and cellular biology have led to an improved understanding of prostate biology and the characteristics of prostate cancer. Based on this improved understanding, several new approaches are being developed for the treatment of metastatic prostate cancer. These range from traditional dietary modifications to altering the microcellular environment of the prostate cancer cell and gene therapy. This article provides an overview of some of the more promising novel therapeutic approaches being investigated in prostate cancer. While many of these treatments are still experimental, some are undergoing preliminary clinical trials and will hopefully result in new management choices for these patients in the near future.

Animals↗
PubMed1996

Bladder cancer-associated nuclear matrix proteins.

The early diagnosis of bladder cancer is central to the effective treatment of the disease. Presently, there are no methods available to easily and specifically identify the presence of bladder cancer cells. The prevailing method for the detection of bladder cancer is the identification of bladder cancer cells by morphological examination of exfoliated cells or biopsy material by a pathologist. A hallmark of the malignant or transformed phenotype is an abnormal nuclear shape, the presence of multiple nucleoli, and altered patterns of chromatin organization. Nuclear structural alterations are so prevalent in cancer cells that they are commonly used as markers of transformation for many types of cancer. Nuclear shape is determined by the nuclear matrix, the dynamic skeleton of the nucleus. The nuclear matrix is the structural component of the nucleus that determines nuclear morphology, organizes the DNA in a three-dimensional fashion that is tissue specific, and has a central role in the regulation of a number of nuclear processes, including the regulation of DNA replication and gene expression. Previous investigations into prostate and breast cancer have revealed that nuclear matrix protein (NMP) composition undergoes alterations with transformation and that the nuclear matrix can serve as a marker for the malignant phenotype. In this study, we have identified NMPs with which it is possible to differentiate human bladder tumors from normal bladder epithelial cells. We examined the NMP composition of 17 matched tumor and normal samples from patients undergoing surgery for bladder cancer. We have identified six proteins present in all tumor samples that are not present in the corresponding normal samples and three proteins that are unique to the normal bladder tissues in comparison with the tumor samples. Five of the six bladder cancer-associated proteins were also identified in three human bladder cancer cells lines examined (253j, UMUC-2, and T24). Therefore, we have demonstrated that nuclear matrix composition is able to differentiate bladder cancer from normal bladder tissue and may provide useful tools for early detection and recurrence of the disease. Importantly, these markers may provide valuable tools for cytopathological screening for bladder carcinoma.

Antigens, Nuclear↗
PubMed1996

Simultaneous radical nephrectomy and repair of abdominal aortic aneurysm.

OBJECTIVES: The combination of abdominal aortic aneurysm repair with other intra-abdominal surgery is controversial. Most studies have shown that a variety of procedures can be performed at the same time as an aneurysm repair with little change in mortality or complication rates. We conducted a retrospective study to determine if aneurysm repair could be safely and effectively combined with radical nephrectomy. METHODS: We studied 10 patients who underwent combined abdominal aortic aneurysm repair and radical nephrectomy during a 4-year period. Results from this group were compared to a separate control group of 10 patients who underwent radical nephrectomy alone and another of 12 patients underwent abdominal aortic aneurysm repair alone, during the same time period. RESULTS: The overall mortality was 10% and significant complications occurred in an additional 10% of patients. Minor, self-limiting complications occurred in 30% of patients. There were no aortic graft infections that occurred in the entire series of patients at 18 months of mean follow-up. There were no remarkable differences in the entire series of patients and the combined values in a separate group of control patients who had undergone either procedure alone. CONCLUSIONS: Simultaneous radical nephrectomy for presumed renal cell carcinoma can be safely combined with repair of abdominal aortic aneurysm in selected patients.

Aged↗
PubMed1996

Ureteral entrapment in the sacroiliac joint in pelvic trauma.

We describe a case of unilateral entrapment of the ureter in the sacroiliac joint of a patient who sustained blunt abdominal trauma resulting in fractures of the public rami and sacroiliac joint and multiple bladder perforations. The entrapment was discovered intraoperatively and released by external traction and reduction of the pelvic fractures. No ureteric damage was observed, and reimplantation was not necessary. The importance of evaluating the upper tracts for potential injury in patients with fractures of the bony pelvis and concomitant bladder rupture is emphasized.

Abdominal Injuries↗
PubMed1996

Scrotal elephantiasis associated with hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic relapsing infection of the apocrine sweat glands. Its association with penoscrotal lymphedema is not well recognized. A case of massive scrotal elephantiasis associated with chronic hidradenitis of the perineum and scrotum is described. A wide resection of the scrotal mass and perineum was performed, with reconstruction of the perineum and penis carried out using local skin flaps and split-thickness skin grafts. This one-stage treatment yielded an excellent cosmetic and functional outcome.

Elephantiasis↗
PubMed1996

Leiomyosarcoma with osteoclast-like giant cells of the spermatic cord. A case report and review of the literature.

We describe a case of leiomyosarcoma with osteoclast-like giant cells arising form the spermatic cord and involving the testis. This is a rare tumor which is histologically similar to the giant cell variant of malignant fibrous histiocytoma. No such cases have been reported arising from the external genitalia. The patient was initially treated with local excision. He had a local recurrence 7 years later which was treated with radical excision and adjuvant radiation. The indolent nature of the tumor, with a long survival of 7 years after initial diagnosis followed subsequently by a more aggressive clinical course, is emphasized.

Aged↗
PubMed1996

Management of stage T1b (A2) and stage T1c adenocarcinoma of the prostate.

The management of stage T1b (A2) and T1c adenocarcinoma of the prostate is somewhat controversial. With the widespread use of serum prostate-specific antigen (PSA) determinations, an increasing number of these cancers are likely to be diagnosed. Hence, it is important to formulate a cogent management strategy for these patients, because a large percentage of them can be expected to have clinically and pathologically localized disease. Expectant observation with deferred treatment, radical prostatectomy, radiation therapy (external beam or brachytherapy), and cryosurgical ablation are all primary therapeutic options that have individual merit. In this review, we attempt to analyze the results of the various treatment options for these patients and evolve a practical approach towards their management.

Adenocarcinoma↗
PubMed1996

The role of vitamin D in normal prostate growth and differentiation.

Although increasing data indicate a role for vitamin D in prostate cancer, little is known about the role of this hormone in the noncancerous prostate. We examined the effect of 1,25-dihydroxyvitamin D3 (1,25 D) on the growth of noncancerous rat prostates in vivo. Rats were castrated and treated with vehicle (controls), 1,25 D, testosterone, or a combination of both hormones for 2 weeks. Histological examination of the harvested prostates revealed that 1,25 D had a selective regressive effect on epithelial cells in treated rats compared to untreated castrated rats and to normal uncastrated rats. However, 1,25 D stimulated stromal growth in the prostate. The mean prostatic weight of the vitamin D-treated rats was twice that of the untreated rats (0.13 +/- SEM 0.005 g versus 0.06 +/- SEM 0.006 g). The histological differences were less marked in the testosterone-supplemented animals. A greater degree of cellular differentiation was observed in the rats treated with testosterone and vitamin D compared to rats that received testosterone supplementation alone. Studies of the nuclear matrix composition revealed differences between the testosterone-supplemented and the testosterone and 1,25 D-treated rat prostates. We conclude that in the absence of testosterone, 1,25 D may exert a growth-promoting effect on the prostatic stroma in vivo. In concert with testosterone, it may play an important role in the growth and differentiation of the normal rat prostate.

Animals↗