Biomedical subjects

Jonathan I Izawa

Publications and source records attributed to Jonathan I Izawa.

At least 19 recordsLinked to original sources

PubMed2006

Clinically significant prostate cancer found incidentally in radical cystoprostatectomy specimens.

OBJECTIVE: To review the incidence, histopathological features and clinical outcomes of patients with incidental prostate cancer found in radical cystoprostatectomy (RCP) specimens excised for bladder cancer, to determine if these cancers affected the follow-up strategy and if prostate-sparing cystectomy would be appropriate for these patients. PATIENTS AND METHODS: We retrospectively reviewed the charts of men who had a RCP for transitional cell carcinoma (TCC) of the bladder, at our institution between 1987 and 2003. Patients with a preoperative diagnosis or clinical suspicion of prostate cancer were excluded from further analysis. We identified those men with incidental prostate cancer in the RCP specimens. The patients' demographic, histopathological and clinical outcome data were collected. RESULTS: In all, 217 men had RCP for TCC between 1987 and 2003; 13 were excluded from the study due to a preoperative diagnosis or clinical suspicion of prostate cancer, and 58 (28%) were found to have incidental prostate cancer. The mean (range) follow-up was 47 (6-157) months. Of these prostate cancers, 20% were of Gleason score > or = 7 and two patients developed local and metastatic prostate cancer recurrences. CONCLUSION: Incidental prostate cancer is a relatively common finding in RCP specimens, with a significant proportion having the characteristics of clinically relevant prostate cancer. The follow-up for prostate cancer should be incorporated with that for TCC and adapted according to the grade and stage of the prostate cancer. Preserving the prostate in an attempt to decrease the morbidity after RCP carries a high risk of significant prostate cancer in the residual prostatic tissue, suggesting that prostate-sparing cystectomy should only be reserved for a highly selected group of patients.

Aged↗

PubMed2006

Primary PEComa of the bladder treated with primary excision and adjuvant interferon-alpha immunotherapy: a case report.

BACKGROUND: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms of uncertain malignant potential, which have in common the co-expression of muscle and melanocytic immunohistochemical markers. CASE PRESENTATION: A 48-year-old man presented with dysuria, passage of urinary sediment and lower abdominal discomfort. A three centimeter mass was identified by cystoscopy in the posterior midline of the bladder. Computerized tomography suggested an enterovesical fistula. The patient underwent laparotomy, partial cystectomy and partial small bowel resection. Pathological examination revealed PEComa of the bladder. The patient underwent adjuvant interferon-alpha immunotherapy. Subsequent follow-up procedures, including cystoscopy and imaging, have not revealed evidence of recurrence. The patient is clinically free of disease 48 months after surgery. CONCLUSION: This case represents the second documented PEComa of bladder and demonstrates that adjuvant therapies, including anti-angiogenic and immunotherapy, may be considered for patients with locally advanced or metastatic genitourinary PEComa.

Chemotherapy, Adjuvant↗

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

Intraoperative laparoscopic renal ultrasonography: use in advanced laparoscopic renal surgery.

OBJECTIVES: To highlight the use of intraoperative laparoscopic ultrasonography (ILUS) in complex renal surgery, as well its impact on management. ILUS has been used to facilitate advanced laparoscopic surgery, but only limited descriptions of the indications for its use have been published. METHODS: All patients undergoing laparoscopic renal procedures requiring ILUS from October 2001 to March 2005 were reviewed. A total of 50 cases, including 35 partial nephrectomies, cryoablation of 6 renal tumors, 6 radical nephrectomies, 2 perinephric explorations, and 1 resection of a renal artery aneurysm were assessed by ILUS. RESULTS: The average tumor size in the patients undergoing laparoscopic partial nephrectomy was 3.1 cm (range 1.4 to 8.0), and all margins were negative. Also, a previously unidentified satellite lesion was found in 1 patient. ILUS was essential in assessing iceball formation during laparoscopic renal cryotherapy. ILUS also proved useful in defining the anatomy during laparoscopic perinephric exploration, assessing renal vein thrombi during laparoscopic nephrectomy, and evaluating renal perfusion during laparoscopic renal artery aneurysm repair. CONCLUSIONS: ILUS can be extremely useful in advanced laparoscopic renal surgery. In a number of situations, it is an essential surgical tool. With expanding indications for laparoscopic surgery, the indications for ILUS continue to grow.

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

Histological changes in prostate biopsies after salvage cryotherapy: effect of chronology and the method of biopsy.

OBJECTIVES: To examine changes in prostate biopsies at different intervals after salvage cryotherapy and the effect of biopsy type (transrectal ultrasonography-guided vs transurethral resection, TUR), as the sequence and extent of histological changes occurring in the prostate after salvage cryotherapy for local failure of prostate cancer treatment are unknown. PATIENTS AND METHODS: In all, 158 prostate biopsies from 150 patients were examined histologically after salvage cryotherapy for prostate cancer after radiotherapy had failed. Specimens were grouped by time from cryotherapy and biopsy technique. RESULTS: Biopsies showed hyalinization, necrosis, inflammation and residual cancer. Hyalinization became predominant over time, most notably in biopsies with no residual cancer. Core biopsies showed more hyalinization and regenerating glands, while TUR biopsies showed more necrosis and inflammation. CONCLUSIONS: Tissue cryo-injury and reactive changes last for >1 year; more extensive cryo-injury suggests more effective cancer ablation. A long-term follow-up is necessary, as prostate cancer might remain indolent for >1 year.

Analysis of Variance↗

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↗