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Gregory T Maclennan

Publications and source records attributed to Gregory T Maclennan.

14 recordsLinked to original sources
PubMed2006

Natural history of urothelial inverted papilloma.

BACKGROUND: Inverted urothelial papilloma is an uncommon urothelial neoplasm. Although it is traditionally regarded as a benign tumor, conflicting data on multiplicity, recurrence rate, and association with urothelial carcinoma have left uncertainties concerning its biologic behavior. METHODS: The authors analyzed the clinicopathological characteristics of 75 cases of inverted papilloma in the urinary tract without prior or concurrent urothelial carcinoma to determine its biologic behavior and prognosis, and to correlate these findings with surveillance strategies. RESULTS: These patients ranged in age from 26 to 85 years (mean, 60 years). Of the 46 patients for whom tobacco use history was available, 28 gave a history of smoking. Inverted papillomas were located in the urinary bladder (67 cases), prostatic urethra (4 cases), and ureter (4 cases). The majority of vesical tumors arose from the trigone or near the bladder neck. Common presenting complaints included hematuria, dysuria, and irritative voiding symptoms. In 1 case of vesical inverted papilloma, there was a recurrence. All other patients were free of tumor recurrence or progression during a mean follow-up of 68 months (range, 2-240 months). CONCLUSIONS: Both the extremely low incidence of tumor recurrence (1%) and strikingly favorable prognosis suggest that inverted urothelial papilloma, when diagnosed according to strictly defined criteria, is a benign urothelial neoplasm not related to urothelial carcinoma. Therefore, complete transurethral resection of inverted papilloma is adequate surgical therapy, and surveillance protocols as rigorous as those employed in the management of urothelial carcinoma seem unnecessary.

Adult↗
PubMed2006

Myelolipoma.

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Humans↗
PubMed2006

Polymorphisms in polycyclic aromatic hydrocarbon metabolism and conjugation genes, interactions with smoking and prostate cancer risk.

The relationship between cigarette smoking and prostate cancer remains unclear. Any potential association may depend on the individuals' ability to metabolize and detoxify cigarette carcinogens--such as polycyclic aromatic hydrocarbons. To investigate this, we studied the association between prostate cancer and smoking, as well as the main and modifying effects of functional polymorphisms in genes that metabolize polycyclic aromatic hydrocarbons (CYP1A1 Ile(462)Val, microsomal epoxide hydrolase His(139)Arg) and detoxify reactive derivatives (GSTM1 null deletion, GSTT1 null deletion, GSTP1 Ile(105)Val and Ala(114)Val) using a family-based case-control design (439 prostate cancer cases and 479 brother controls). Within the entire study population, there were no main effects for smoking or any of the polymorphisms. However, the nondeleted GSTM1 allele was inversely associated with prostate cancer [odds ratio (OR), 0.50; 95% confidence interval (95% CI), 0.26-0.94] among men with less aggressive disease (Gleason score < 7 and clinical tumor stage < T2c) and positively associated (OR, 1.68; 95% CI, 1.01-2.79) with prostate cancer in men with more aggressive disease (Gleason score > or = 7 or clinical tumor stage > or = T2c). We also found a statistically significant negative multiplicative interaction between the GSTM1 nondeleted allele and heavy smoking (> 20 pack-years) in the total study population (P = 0.01) and in Caucasians (P = 0.01). Among Caucasians, heavy smoking increased prostate cancer risk nearly 2-fold in those with the GSTM1 null genotype (OR, 1.73; 95% CI, 0.99-3.05) but this increased risk was not observed in heavy smokers who carried the GSTM1 nondeleted allele (OR, 0.95; 95% CI, 0.53-1.71). Our results highlight the importance of considering genetic modifiers of carcinogens when evaluating smoking in prostate cancer.

Case-Control Studies↗
PubMed2005

Clonal divergence and genetic heterogeneity in clear cell renal cell carcinomas with sarcomatoid transformation.

BACKGROUND: Approximately 5% of clear cell renal cell carcinomas contain components with sarcomatoid differentiation. It has been suggested that the sarcomatoid elements arise from the clear cell tumors as a consequence of clonal expansions of neoplastic cells with progressively more genetic alterations. Analysis of the pattern of allelic loss and X-chromosome inactivation in both the clear cell and sarcomatoid components of the same tumor allows assessment of the genetic relationship of these tumor elements. METHODS: The authors of the current study examined the pattern of allelic loss in clear cell and sarcomatoid components of renal cell carcinomas from 22 patients who had tumors with both components. DNA samples were prepared from formalin-fixed, paraffin-embedded renal tissue sections using laser-capture microdissection. Five microsatellite polymorphic markers for putative tumor suppressor genes on 5 different chromosomes were analyzed. These included D3S1300 (3p14), D7S522 (7q31), D8S261 (8p21), D9S171 (9p21), and TP53 (17p13). In addition, X-chromosome inactivation analysis was performed in 14 tumors from female patients. RESULTS: The clear cell components showed loss of heterozygosity (LOH) at the D3S1300, D7S522, D8S261, D9S171, and TP53 loci in 18% (4/22), 18% (4/22), 50% (10/20), 15% (3/20), and 20% (4/20) of informative cases, respectively. LOH in the sarcomatoid components was seen at the D3S1300, D7S522, D8S261, D9S171, and TP53 loci in 18% (4/22), 41% (9/22), 70% (14/20), 35% (7/20), and 20% (4/20) of informative cases, respectively. Six cases demonstrated an LOH pattern in the clear cell component that was not seen in the sarcomatoid component. Different patterns of allelic loss were seen in the clear cell and sarcomatoid components in 15 cases. Clonality analysis showed the same pattern of nonrandom X-chromosome inactivation in both clear cell and sarcomatoid components in 13 of the 14 cases studied. One case showed a random pattern of X-chromosome inactivation. CONCLUSION: X-chromosome inactivation analysis data suggest that both clear cell and sarcomatoid components of renal cell carcinomas are derived from the same progenitor cell. Different patterns of allelic loss in multiple chromosomal regions were observed in clear cell and sarcomatoid components from the same patient. This genetic heterogeneity indicates genetic divergence during the clonal evolution of renal cell carcinoma.

Adult↗
PubMed2005

Constitutive activation of P I3 K-Akt and NF-kappaB during prostate cancer progression in autochthonous transgenic mouse model.

BACKGROUND: Cancer progression is usually facilitated by independent growth signals that may lead to increased cell survival and evasion of apoptosis. Phosphatidylinositol 3'-OH kinase (P I3 K)-Akt and transcription factor NF-kappaB are important signaling molecules and key survival factors involved in the control of cell proliferation, apoptosis, and oncogenesis. Although P I3 K-Akt and NF-kappaB have been implicated in the development and progression of prostate cancer, expression of these molecules during progression of autochthonous disease has not been elucidated. METHODS: Prostate cancer growth and progression in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and male non-transgenic littermates were observed by magnetic resonance imaging (MRI). Expression patterns of P I3 K-Akt, NF-kappaB, I kappaB, and associated signaling molecules during different stages of cancer progression in these mice were examined by Western blot analysis, electrophoretic mobility shift assay (EMSA), enzyme-linked immunoabsorbent assay (ELISA), kinase assay, and immunohistochemistry. RESULTS: Sequential MRI and gross analysis of prostate gland exhibited increasing prostate volume associated with the development and progression of prostatic adenocarcinoma in TRAMP mice, compared to male non-transgenic littermates. Differential protein expression of P I3 K, phosphorylated-Akt (Ser 473), I kappa Balpha and its phosphorylation, IKK kinase activity, NF-kappaB/p65, p50, DNA binding, and transcriptional-regulated genes, viz., Bc l2, cyclin D1, MMP-9, and VEGF were observed during prostate cancer progression in TRAMP mice, compared to male non-transgenic littermates. Expressions of these molecules were significantly increased during cancer progression observed at 24 and 32 weeks of age. CONCLUSIONS: Differential expression pattern of P I3 K-Akt, NF-kappaB and I kappaB during prostate cancer progression in TRAMP mice suggest that these molecules represent potential molecular targets for prevention and/or therapeutic intervention.

Adenocarcinoma↗
PubMed2005

Multimodal and three-dimensional imaging of prostate cancer.

Accurate characterization of prostate cancer is crucial for treatment planning and patient management. Non-invasive SPECT imaging using a radiolabeled monoclonal antibody, 111In-labeled capromab pendetide, offers advantage over existing means for prostate cancer diagnosis and staging. However, there are difficulties associated with the interpretation of these SPECT images. In this study, we developed a 3D surface-volume hybrid rendering method that utilizes multi-modality image data to facilitate diagnosis of prostate cancer. SPECT and CT or MRI (or both) images were aligned either manually or automatically. 3D hybrid rendering was implemented to blend prostate tumor distribution from SPECT in pelvis with anatomic structures from CT/MRI. Feature extraction technique was also implemented within the hybrid rendering for tumor uptake enhancement. Autoradiographic imaging and histological evaluation were performed to correlate with the in-vivo SPECT images. Warping registration of histological sections was carried out to compensate the deformation of histology slices during fixation to help the alignment between histology and in-vivo images. Overall, the rendered volumetric evaluation of prostate cancer has the potential to greatly increase the confidence in the reading of radiolabeled monoclonal antibody scans, especially in patients where there is a high suspicion of prostate tumor metastasis.

Humans↗
PubMed2005

Malakoplakia.

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Humans↗
PubMed2005

Update on fused capromab pendetide imaging of prostate cancer.

The primary objective of this overview is to apprise clinical urologists and oncologists of the current state of fused multimodality imaging of prostate cancer, which can be applied to optimize treatment by ensuring that a patient's disease is characterized as well as current imaging technology permits. The focus of this study is the monoclonal antibody capromab pendetide, which targets prostate specific membrane antigen (PSMA), a type II membrane glycoprotein strongly associated with prostate cancer. Identifying where capromab pendetide uptake occurs can be done accurately if this functional imaging modality is combined with a modality that provides anatomic detail, such as computed tomography (CT) or magnetic resonance imaging (MRI). Image fusion, or coregistration, which is overlaying the functional images of capromab pendetide uptake on the anatomic CT or MRI images, provides a detailed map of cancer localization inside and outside the prostate gland. This same principle of fusing functional images on anatomic images is the basis for enormous growth of positron emission tomography with CT during the past 2 years. Positron emission tomography imaging has a different functionality base than does capromab pendetide, and thus the 2 modalities should be complementary. However, the key to both functional imaging modalities is accurate fusion with anatomic images, which is illustrated in our case reports. The cases cited demonstrate the need to optimize every phase of imaging from patient preparation to reading and reporting increased PSMA concentration seen on the fused images. Reference is also made to applying capromab pendetide/CT fused imaging to radiation therapy planning.

Aged↗
PubMed2002

Does the size of the surgical margin in partial nephrectomy for renal cell cancer really matter?

PURPOSE: Although many groups recommend a surgical margin of 1 to 2 cm., to our knowledge the amount of normal renal parenchyma that must be excised during partial nephrectomy for stages T1-2N0M0 renal cell carcinoma to ensure a safe margin has never been critically evaluated. We investigated whether the size of the surgical margin has any effect on recurrence. MATERIALS AND METHODS: All partial nephrectomies performed for localized renal cell carcinoma at our institution from 1988 to 1999 were retrospectively analyzed via a review of hospital records, pathology reports and histological slides. Parenchymal margin status was assessed and quantified by microscopy. Followup data were obtained via patient chart review and telephone interview. Average negative margin size and postoperative followup were determined, and renal cell carcinoma recurrence was assessed. RESULTS: A total of 44 partial nephrectomies were performed with a mean followup of 49 months (range 8 to 153). Mean tumor size was 3.22 cm. (range 1.3 to 10). Surgical margins were negative for malignancy in 41 cases and positive in 3. All patients with negative margins were without local recurrence at followup except 1 with a recurrent mass adjacent to the kidney at a site distant from the original lesion. Mean and median size of the negative margins was 0.25 and 0.2 cm., respectively (range 0.05 to 0.7). In the 3 cases with positive margins there was no evidence of disease at 39 and 62 months of followup in 2, while multiple local and metastatic recurrences developed in 1. CONCLUSIONS: No patient with negative parenchymal margins after nephron sparing surgery for stages T1-2N0M0 renal cell carcinoma had local recurrence at the resection site at a mean followup of 49 months. Margin size was irrelevant. Only a minimal margin of normal renal parenchyma of less than 5 mm. must be removed during partial nephrectomy for localized renal cell carcinoma.

Adult↗
PubMedDate not supplied

P53 expression in small cell carcinoma of the urinary bladder: biological and prognostic implications.

Small cell carcinoma of the urinary bladder is a rare and highly aggressive tumor. P53 expression has been shown to be associated with poor prognosis in a variety of tumors. This study was undertaken to investigate p53 expression in a large series of small cell carcinomas of the urinary bladder and to correlate the findings with clinicopathologic parameters and clinical outcome. Pathologic findings were reviewed and were correlated with clinical findings and follow-up information. Immunohistochemical staining for p53 was performed on paraffin-embedded tissue sections using the avidin-biotin-peroxidase method. Results were recorded as positive expression (> or =10% of cells with nuclear staining) or negative expression (<10% of cells with nuclear staining). The series included 40 males and 10 females. All 50 patients except one had advanced disease (T2 or above) at presentation. Pathologic stages were as follows: T1 in 1, T2 in 25, T3 in 21, and T4 in 3 patients. During a median follow-up of 12 months (range: 1 month to 122 months), 38 patients died of cancer. Two-year and 5-year cancer-specific survival rates were 45% and 16%, respectively. P53 overexpression was present in 27 out of 50 (54%) cases (7 with 10-25% staining, 4 with 25-50% staining, 11 with 50-75% staining and 5 with 75-100% staining); conversely, negative staining for p53 was observed in 23 out of 50 (46%) cases (19 with no staining and 4 with <10% staining). No correlation was demonstrated between the level of p53 expression and survival (p =0. 16). The 5-year cancer-specific survival was 16.6% for patients with tumors expressing p53 in greater than or equal to 10% of cells and was 14.7% for patients with tumors expressing p53 in less than 10% of tumor cells. There was no correlation between p53 expression and other clinicopathologic characteristics, including age (p =0.20), gender (p=0.84), history of smoking (p=0.25), pathologic Tstage (p=0.38), clinical stage (p=0.60), lymph node metastasis (p=0.17), and distant metastasis (p=0.88). Our data indicate that p53 is frequently expressed in small cell carcinoma of the urinary bladder. However, no correlation is found between p53 expression and clinicopathologic parameters, including long-term survival.

Adult↗