Biomedical subjects

Jonathan I Izawa

Publications and source records attributed to Jonathan I Izawa.

At least 19 recordsLinked to original sources

PubMed2006

Metallothionein expression as prognostic factor for transitional cell carcinoma of bladder.

OBJECTIVES: To determine whether metallothionein (MT) protein expression is associated with clinical outcomes in patients with transitional cell carcinoma (TCC) of the bladder. METHODS: Archival pathologic radical cystectomy and transurethrally resected specimens and medical charts were reviewed for 123 patients with TCC. Patients were divided into groups based on the TNM stage, tumor grade, and MT protein expression in the primary tumor. Survival and disease progression were correlated with MT expression. RESULTS: The mean patient age was 66 years (range 41 to 92). Of the 123 tumors, 21, 13, 18, 24, 17, and 30 were pathologically staged as pTa, pT1, pT2, pT3, pT4, and pTis, respectively; 28, 15, 14, and 66 tumors had a histologic grade of X, 1, 2, and 3, respectively. On univariate analysis, TNM stage and tumor grade predicted survival and progression outcomes. MT expression was detected in 69 (56.9%) of 123 bladder cancer specimens. Greater MT protein expression was associated with worse overall survival, disease-specific survival, disease-free survival, and disease-free progression (P = 0.0004, P = 0.05, P = 0.0008, and P = 0.0005, respectively). CONCLUSIONS: MT protein expression in the primary tumor of TCC specimens appeared to be associated with overall survival, disease-specific survival, disease-free survival, and disease-free progression. This finding requires additional validation using other data sets.

Adult↗

PubMed2006

Location of a positive biopsy as a predictor of surgical margin status and extraprostatic disease in radical prostatectomy.

OBJECTIVE: To investigate whether the location of preoperative biopsy positive cores can identify patients at higher risk of a positive surgical margin (SM) and extraprostatic extension (EPE) at radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: We retrospectively reviewed the clinical and pathological data of 371 patients who had a RRP for biopsy confirmed prostate cancer between January 2000 and October 2003. RESULTS: A positive biopsy at the apex was not predictive of a positive apical SM or EPE. However, a positive biopsy at the base was predictive of a positive basal SM and EPE. A positive SM, in turn, correlated with EPE on final pathology. Positive basal SM correlated with EPE in 75% of cases whereas positive apical SM showed EPE in only 33% (P < 0.02). CONCLUSION: A positive biopsy core at the base appears to correlate with a positive basal SM and EPE. A positive basal SM correlates with EPE at a higher rate than apical SMs.

Adult↗

PubMed2006

Malignant neoplasm of perivascular epithelioid cells of the liver.

Neoplasms of perivascular epithelioid cells (PEComas) have in common the coexpression of muscle and melanocytic immunohistochemical markers. Although this group includes entities with distinct clinical features, such as angiomyolipoma, clear cell sugar tumor of the lung, and lymphangioleiomyomatosis, similar tumors have been documented in an increasing diversity of locations. The term PEComa is now generally used in reference to these lesions that are not angiomyolipomas, clear cell sugar tumors, or lymphangioleiomyomatoses. While most reported PEComas have behaved in a benign fashion, malignant PEComas have occasionally been documented. We present a case of hepatic PEComa with benign histologic features, which nonetheless presented with metastases to multiple sites nearly 9 years later. This case represents the second documented malignant PEComa of the liver, as well as the longest follow-up of a surviving patient with a malignant PEComa, emphasizing both the need for criteria that more accurately predict the behavior of PEComas and the necessity of long-term follow-up of patients with PEComas.

Epithelioid Cells↗

PubMed2006

Treatment of radiation failure in prostate cancer.

Radiotherapy, both external beam and more recently, interstitial, have been therapeutic options for localized prostate cancer. Management of patients who have failed of local radiotherapy remains a challenge. Herein the current therapeutic options are reviewed.

Humans↗

PubMed2006

Timing cystectomy and perioperative chemotherapy in the treatment of muscle invasive bladder cancer.

INTRODUCTION: The ability of cystectomy to cure patients with muscle-invasive transitional carcinoma of the bladder (TCC) is diminished by the presence of occult micrometatases. Chemotherapy contributes to cure to the extent that it may eradicate these micrometastases. In the absence of methods to preoperatively stage TCC precisely or assess tumor biology, we review the current literature regarding the timing of cystectomy and use of perioperative chemotherapy. Based on this data, we suggest optimal and feasible strategies for treating TCC in a resource-constrained environment. MATERIALS AND METHODS: Systematic reviews of TCC were sought using electronic databases to obtain optimal information about: 1) the relationship between TNM stage and survival, 2) the effect of surgical waiting times on tumor stage and survival outcomes, 3) the benefits of neoadjuvant and adjuvant chemotherapy, and 4) the patients who benefit most from perioperative chemotherapy. RESULTS: Prospective data from the largest contemporary series of patients treated with cystectomy confirmed long-term survival in patients with extravesical and/or lymph node disease of 25%-47% at 5 years and 17%-27% at 10 years. Lymph node involvement was more common in patients with extravesical tumors. Retrospective studies of the effect of delay to cystectomy on outcomes showed higher tumor stage and reduced survival with delay of cystectomy beyond 12 weeks. Two individual patient data meta-analyses, including all currently available randomized controlled trials (RCTs), comparing neoadjuvant and adjuvant chemotherapy to local therapy alone confirmed that overall survival is modestly improved by cisplatin-based combination neoadjuvant chemotherapy. None of these RCTs showed a detrimental effect of delaying cystectomy for this treatment. Tumor status at cystectomy appears to correlate with overall survival. CONCLUSIONS: We propose immediate use of neoadjuvant chemotherapy in patients suspected of having extravesical TCC. As most have micrometatastases, immediate surgery is less critical. For patients suspected of having organ-confined TCC, immediate cystectomy is recommended with adjuvant chemotherapy recommendations based on pathological staging. If surgery within 12 weeks is not possible for these patients, neoadjuvant chemotherapy with monitoring of response can be used. Improved preoperative staging and understanding of tumor biology are required to optimize the multimodality treatment of TCC.

Carcinoma, Transitional Cell↗

PubMed2005

A new three-dimensional ultrasound microimaging technology for preclinical studies using a transgenic prostate cancer mouse model.

Prostate cancer is the most common cancer in adult men in North America. Preclinical studies of prostate cancer employ genetically engineered mouse models, because prostate cancer does not occur naturally in rodents. Widespread application of these models has been limited because autopsy was the only reliable method to evaluate treatment efficacy in longitudinal studies. This article reports the first use of three-dimensional ultrasound microimaging for measuring tumor progression in a genetically engineered mouse model, the 94-amino acid prostate secretory protein gene-directed transgenic prostate cancer model. Qualitative comparisons of three-dimensional ultrasound images with serial histology sections of prostate tumors show the ability of ultrasound to accurately depict the size and shape of malignant masses in live mice. Ultrasound imaging identified tumors ranging from 2.4 to 14 mm maximum diameter. The correlation coefficient of tumor diameter measurements done in vivo with three-dimensional ultrasound and at autopsy was 0.998. Prospective tumor detection sensitivity and specificity were both >90% when diagnoses were based on repeated ultrasound examinations done on separate days. Representative exponential growth curves constructed via longitudinal ultrasound imaging indicated volume doubling times of 5 and 13 days for two prostate tumors. Compared with other microimaging and molecular imaging modalities, the application of three-dimensional ultrasound imaging to prostate cancer in mice showed advantages, such as high spatial resolution and contrast in soft tissue, fast and uncomplicated protocols, and portable and economical equipment that will likely enable ultrasound to become a new microimaging modality for mouse preclinical trial studies.

Adenocarcinoma↗

PubMed2005

Increased intratumoral expression of prostate secretory protein of 94 amino acids predicts for worse disease recurrence and progression after radical prostatectomy in patients with prostate cancer.

OBJECTIVES: To examine the impact of prostate secretory protein of 94 amino acids (PSP94) expression within the primary tumor on disease recurrence and progression using radical prostatectomy specimens from patients with adenocarcinoma of the prostate. METHODS: PSP94 immunohistochemistry was performed on 59 radical prostatectomy specimens. The degree of PSP94 expression was reported as either present (group 1) or absent (group 2). Clinical data, including survival outcome measures, were correlated with PSP94 expression. RESULTS: The time to disease progression for group 1 was shorter compared with that for group 2 (P = 0.042). Disease-free survival was also less in group 1 than in group 2 (P = 0.033). Multivariate analyses demonstrated that PSP94 expression was an independent prognostic factor for a shorter interval to disease progression (P = 0.046) and disease-free survival (P = 0.049). CONCLUSIONS: PSP94 expression in radical prostatectomy tumor specimens appears to be associated with worsened survival outcomes and may provide additional prognostic information.

Adenocarcinoma↗

PubMed2005

A novel knock-in prostate cancer model demonstrates biology similar to that of human prostate cancer and suitable for preclinical studies.

Preclinical studies of prostate cancer (CaP) have employed a genetically engineered mouse model, since there is no naturally occurring CaP in rodents. We have previously reported a new knock-in mouse adenocarcinoma prostate (KIMAP) model. In this study, we demonstrate that the new model possesses a tumor architecture of heterogeneity and multifocality similar to that of human CaP, by utilizing a new compound scoring system to compare with the PSP94 (approved gene symbol Msmb) gene-directed transgenic mouse CaP model (TGMAP). KIMAP mice showed a balanced distribution of tumor extent, which penetrated the prostate gland. Comparative studies on cDNA microarrays demonstrated that KIMAP tumors were upregulated with higher contents of immunoresponse genes, whereas PSP-TGMAP tumors had neuroendocrine (NE) differentiation. The majority of KIMAP mice did not progress to NE CaP, which was observed only at a very late stage and a low frequency. Several tumor marker genes characteristic of human CaP were uniquely identified in KIMAP tumors, including hepsin, maspin, Nkx3.1, CD10 and PSP94 (similar to PSA), etc. The differences between these two CaP models are attributed to the introduction of a single endogenous knock-in mutation. Due to the similarities between human CaP tumors and the PSP-KIMAP tumors, this preclinical model may supplement the current transgenic models to study CaP more accurately.

Adenocarcinoma↗

PubMed2005

Current status of local salvage therapies following radiation failure for prostate cancer.

PURPOSE: We reviewed the curative options available to patients with local failure after radical radiotherapy for prostate cancer and identified the patients best suited for such salvage therapies. MATERIALS AND METHODS: A literature search of English language publications was done using the key terms salvage, prostatectomy, cryosurgery, brachytherapy and radiation failure. RESULTS: Salvage radical prostatectomy offers 5-year biochemical relapse-free rates between 55 and 69%. Higher complication rates are reported with salvage compared to primary radical prostatectomy, including rectal injuries, bladder neck contracture and urinary incontinence. Cryosurgery biochemical response rates vary according to the definition of failure but they are generally lower than those of salvage radical prostatectomy. The local control rates of cryosurgery are acceptable. Major complications related to cryotherapy are urinary incontinence, impotence, pelvic pain and urinary retention. Experience with salvage brachytherapy has been limited but some success has been reported in terms of biochemical control. CONCLUSIONS: Salvage prostatectomy for localized radiation failure is a good option in the patient with a life expectancy of at least 10 years, preradiation and preoperative prostate specific antigen less than 10 ng/ml, and localized preoperative stage with the understanding that complication risks are higher. Salvage cryotherapy is a valid option in patients with preoperative prostate specific antigen less than 10 ng/ml and Gleason score less than 8, clinical stage less than T3 who are hormonally naive. Salvage cryotherapy is especially suited for older patients with some comorbidities who are still considered to be at reasonable anesthetic risk. The study of brachytherapy remains in its infancy and the efficacy of this modality remains to be determined.

Cryosurgery↗

PubMed2005

Do all patients with high-grade prostatic intraepithelial neoplasia on initial prostatic biopsy eventually progress to clinical prostate cancer?

OBJECTIVE: To assess the clinical outcome of patients with a diagnosis of high-grade prostatic intraepithelial neoplasia (PIN) on initial prostatic biopsy, with a minimum of 5 years of follow-up, as such patients are at greater risk of having prostate cancer on subsequent biopsy. PATIENTS AND METHODS: Between November 1992 and October 1998, 21 patients were identified as having PIN on their initial transrectal ultrasonography-guided prostate biopsy. None of these patients had a focus of cancer on the initial biopsy. Their medical data were reviewed retrospectively to determine the natural history of PIN in these patients. Patients who were not identified as having cancer were followed every 6-12 months with prostate-specific antigen (PSA) testing and digital rectal examinations (DRE). RESULTS: A mean (range) of 7 (2-8) cores were taken at initial biopsy; the mean age of the patients was 63 (53-77) years and mean PSA level 9.1 (4.9-17.6) ng/mL. Six patients had an abnormal DRE at presentation. A mean of 8 (7-10) cores were obtained on the second biopsy; six patients were diagnosed with cancer, with a mean Gleason score of 6 (5-7), while three were diagnosed with persistent PIN. These three patients had a third prostate biopsy which showed cancer of Gleason score 6 in one and benign prostatic hyperplasia in two. After a mean follow-up of 72.2 (60-84) months, none of the remaining 12 patients was diagnosed with clinically significant cancer. Five of these patients went on to a third prostate biopsy, with no evidence of cancer. One patient died from unrelated causes during this period. CONCLUSION: This study affirms our current practice of following patients with PIN conservatively if a second or third subsequent prostate biopsy is negative. Whether PIN is a premalignant lesion or merely a lesion associated with cancer needs to be addressed in multicentre studies with a follow-up of > 10 years.

Aged↗

PubMed2005

Plasma osteopontin levels are predictive of disease stage in patients with transitional cell carcinoma of the bladder.

OBJECTIVE: To measure plasma levels of osteopontin in patients with transitional cell carcinoma (TCC) of the bladder, and to determine if osteopontin levels relate to disease stage. PATIENTS AND METHODS: Blood samples were collected from 72 consecutive patients with TCC. Clinical data were obtained from medical record reviews. Patients were divided into subgroups based on disease status (active vs inactive) and clinical and pathological stage of TCC (tumour, nodes and metastases staging system). Osteopontin levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Plasma osteopontin levels were higher in patients with active TCC than in controls (P = 0.035). Plasma osteopontin levels were not significantly different between patients with active and inactive TCC, but were higher in patients with metastases than in patients with active, clinically organ-confined TCC (P = 0.021). CONCLUSIONS: Plasma osteopontin levels increase with tumour stage in TCC of the bladder. These findings suggest that larger, more extended studies on plasma osteopontin levels in patients with TCC are warranted.

Aged↗

PubMed2004

Metastatic Merkel cell tumor to the prostate and bladder.

Merkel cell carcinoma is an uncommon cutaneous neoplasm of neuroendocrine origin. We report the case of a 71-year-old man with Merkel cell carcinoma metastases to the prostate and bladder presenting with lower urinary tract obstruction. Efforts should be made to optimize the patient's quality of life with the finding of metastatic Merkel cell carcinoma to the bladder or prostate until better adjuvant therapies are identified.

Aged↗

PubMed2004

Laparoscopic versus open partial nephrectomy.

OBJECTIVES: To compare, retrospectively, the results of laparoscopic partial nephrectomy (LPN) to open partial nephrectomy (OPN) using a tumor size-matched cohort of patients. Limited data are available comparing LPN to OPN in the treatment of small renal tumors. METHODS: Between September 2000 and September 2003, 27 LPNs and 22 OPNs were performed to treat renal masses less than 4 cm. Patient demographics and tumor location and size (2.4 +/- 1.0 cm versus 2.9 +/- 0.9 cm, respectively; P = not statistically significant) were similar between the LPN and OPN groups. RESULTS: Although the mean operative time was longer in the LPN than in the OPN group (210 +/- 76 minutes versus 144 +/- 24 minutes; P <0.001), the blood loss was comparable between the two groups (250 +/- 250 mL versus 334 +/- 343 mL; P = not statistically significant). No blood transfusions were performed in either group. The hospital stay was significantly reduced after LPN compared with after OPN (2.9 +/- 1.5 days versus 6.4 +/- 1.8 days; P <0.0002), and the postoperative parenteral narcotic requirements were lower in the LPN group (mean morphine equivalent 43 +/- 62 mg versus 187 +/- 71 mg; P <0.02). Three complications occurred in each group. With LPN, no patient had positive margins or tumor recurrence. Also, direct financial analysis demonstrated lower total hospital costs after LPN (4839 dollars+/- 1551 dollars versus 6297 dollars+/- 2972 dollars; P <0.05). CONCLUSIONS: LPN confers several benefits over OPN concerning patient convalescence and costs, despite prolonged resection times at our current phase of the learning curve. Long-term results on cancer control in patients treated with LPN continue to be assessed.

Adult↗

PubMed2004

Management of endosalpingiosis of urinary bladder.

We report on a 48-year-old woman who presented with abnormal uterine bleeding secondary to uterine fibroids and who was found to have incidental endosalpingiosis of the urinary bladder. Follow-up is necessary for bladder endosalpingiosis because of its tendency to recur. Follow-up should include cystoscopy and renal, and possibly pelvic, ultrasonography.

Cystoscopy↗

PubMed2004

Characterization of initiation of angiogenesis in early stages of prostate adenocarcinoma development and progression in a transgenic murine model.

OBJECTIVES: A novel prostate-specific protein of 94 amino acids (PSP94) promoter/enhancer-directed transgenic murine model of prostate cancer (CaP) was examined to determine the temporal relationship of angiogenesis with the development and progression of CaP. METHODS: Immunohistochemistry and in situ hybridization were performed to determine the protein and mRNA expression of basic fibroblast growth factor, vascular endothelial growth factor, and microvessel formation at different stages of CaP development and progression. RESULTS: Differential expression of basic fibroblast growth factor and vascular endothelial growth factor protein was found with the development and progression of CaP (P <0.0001 and P <0.0001, respectively). Angiogenesis was identified in CaP. mRNA expression of basic fibroblast growth factor and vascular endothelial growth factor was present from high-grade prostatic intraepithelial neoplasia to poorly differentiated CaP. CONCLUSIONS: The PSP94 gene is conserved in humans and rodents; therefore, the PSP94 transgenic murine model of CaP provides a preclinical model to test such antiangiogenic or other chemopreventive therapies that may be predictive of human CaP.

Adenocarcinoma↗

PubMed2003

Incomplete glandular ablation after salvage cryotherapy for recurrent prostate cancer after radiotherapy.

PURPOSE: To determine the clinical variables associated with inadequate salvage cryotherapy and to correlate the disease-free survival rates associated with biopsy results in prostate cancer (CaP). METHODS AND MATERIALS: Between July 1992 and January 1995, 150 patients underwent salvage cryotherapy for locally recurrent CaP. Biopsy specimens were examined for the presence of cancer cells and normal or atypical glands, all of which were considered evidence of inadequate cryotherapy. Clinical variables, as predictors of biopsy results, were evaluated with univariate and multivariate analyses. The impact of the biopsy results on disease-free survival was also determined. RESULTS: The number of cryoprobes and freeze-thaw cycles correlated with inadequate cryotherapy (p = 0.037 and p = 0.0022, respectively). The number of freeze-thaw cycles was an independent predictor of inadequate cryotherapy (p = 0.003). The finding of cancer cells in the biopsy specimens was the only histopathologic variable that affected disease-free survival (p = 0.016). CONCLUSION: Complete ablation of the prostate gland and tumor is difficult to achieve with salvage cryotherapy. To optimize for complete ablation, salvage cryotherapy should include at least two freeze-thaw cycles and a minimum of five cryoprobes. The finding of atypical or normal epithelial tissue in biopsy specimens after salvage cryotherapy is not predictive of biochemical failure.

Analysis of Variance↗

PubMed2003

Clinical presentation and outcome of high-grade urinary bladder leiomyosarcoma in adults.

OBJECTIVES: To determine the clinical presentation and outcome of patients with high-grade bladder leiomyosarcoma. METHODS: Between July 1986 and April 1998, 36 adult patients (mean follow-up 56 months) with a diagnosis of urinary bladder leiomyosarcoma were evaluated at the University of Texas M. D. Anderson Cancer Center. We retrospectively reviewed the records of these patients for information on clinical features, treatment, and outcome. RESULTS: The mean age of the patients was 63 years. Twenty-six patients were white men in their seventh decade. The most common symptom at presentation was gross hematuria (81% of patients), followed by increased urinary frequency (28%), and dysuria (19%). Thirty-five patients were treated surgically for bladder leiomyosarcoma; of these, 12 (34%) developed recurrent disease (5 with local recurrence and 7 with distant metastasis), with a median time to diagnosis of recurrent disease of 8.3 months. The most common site of distant failure was the retroperitoneum. The disease-specific survival rate at 1, 3, and 5 years was 88.6%, 62.0%, and 62.0%, respectively. Multivariate analyses demonstrated that only the Memorial Sloan-Kettering Cancer Center disease stage system was a significant predictor of survival of patients with bladder leiomyosarcoma (P = 0.018). CONCLUSIONS: In patients with high-grade leiomyosarcoma of the bladder, radical cystectomy in the face of localized disease, whether at the initial presentation or after neoadjuvant chemotherapy, can result in a 5-year, disease-specific survival rate of 62.0%.

Adult↗

PubMed2003

The prognostic significance of metastatic perivesical lymph nodes identified in radical cystectomy specimens for transitional cell carcinoma of the bladder.

PURPOSE: We determined the prognostic significance of metastatic perivesical lymph nodes (PVLN) in transitional cell carcinoma of the bladder (TCC). MATERIALS AND METHODS: A retrospective review of 198 consecutive patients who underwent radical cystectomy for clinically organ confined TCC identified 32 patients with PVLN in pathology specimens. Patient characteristics were compared. Overall survival, disease-specific survival (DSS) and disease-free survival were estimated using Kaplan-Meier actuarial methodology. The log-rank test was used to compare the differences between patients with and without metastatic TCC to PVLN. Cox multivariate regression analysis was used to determine whether the effect of metastatic PVLN on survival was independent of pathological stage. RESULTS: Metastatic TCC was found in the PVLN of 14 patients. Median followup and age were 13.5 months and 66.5 years, respectively. Patients with and without metastatic PVLN had similar characteristics and pathological disease staging. The overall survival, DSS and disease-free survival were significantly less for patients with metastatic TCC in PVLN (p = 0.002, p = 0.013 and p <0.001, respectively), and involvement of PVLN and pelvic nodes (p = 0.001, p = 0.010 and p = 0.041, respectively). Metastatic PVLN was an independent predictor of OS and DSS (p = 0.016 and p = 0.025, respectively). CONCLUSIONS: Metastases to PVLN appear to confer a significantly worse prognosis for patients undergoing radical cystectomy. Patients with identifiable metastatic PVLN may benefit from early adjuvant therapies.

Aged↗