Recurrent transitional cell carcinoma in a scrotal abscess.
We discuss a case of recurrent transitional cell carcinoma to the scrotum 5 years after cystectomy, along with its postoperative management and implications.
Abscess↗
Biomedical subjects
John L Phillips
Publications and source records attributed to John L Phillips.
Re: Urinary fistulas following external radiation or permanent brachytherapy for the treatment of prostate cancer.
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Brachytherapy↗
Aneuploidy in bladder cancers: the utility of fluorescent in situ hybridization in clinical practice.
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Aneuploidy↗
Digital rectal examination is barrier to population-based prostate cancer screening.
OBJECTIVES: To determine whether use of the digital rectal examination (DRE) results in decreased participation in prostate cancer (PCa) screening, which, in turn, would result in lower detection. Population-based PCa screening includes prostate-specific antigen (PSA) measurement with or without a DRE. PSA and DRE screening provide greater sensitivity than PSA alone; however, the increased participation rate resulting from PSA-alone screening may result in a greater detection rate. METHODS: We performed a survey of 13,580 healthy men undergoing PSA-only population-based screening. In addition to the basic demographic information, the survey asked whether the participant would still be willing to participate in the screening if it included a DRE. We modeled the willingness to participate to assess the effect of PSA screening versus PSA and DRE screening on the basis of previously published data and our results. RESULTS: The results of our study indicated that only 78% of men would participate in screening that included both DRE and PSA. Thus, 7800 men of a theoretical population of 10,000 would participate in a screening that included both DRE and PSA. The positive screen rate (PSA > or = 4.0 ng/mL and/or abnormal DRE) would then have been 2013, with 472 PCa cases and 1540 negative biopsies. In the PSA-alone arm, all 10,000 men would have agreed to participate, and the positive screen rate (PSA > or = 4.0 ng/mL) would have been 1480, with 499 PCa cases and 980 negative biopsies. The PSA-alone arm would thus have detected 27 more cancers and performed 560 fewer negative biopsies. CONCLUSIONS: The results of our study have demonstrated that DRE is a significant barrier to participation in PCa screening. PSA plus DRE-based programs result in fewer cases of PCa detected, with a significant increase in negative biopsies. We, therefore, suggest that future mass screening efforts include only PSA determination and omit the DRE.
Adult↗
Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location.
von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome linked to alteration of the VHL tumor suppressor gene. Affected patients are predisposed to develop pheochromocytomas and cystic and solid tumors of the kidney, CNS, pancreas, retina, and epididymis. However, organ involvement varies considerably among families and has been shown to correlate with the underlying germline alteration. Clinically, we observed a paradoxically lower prevalence of renal cell carcinoma (RCC) in patients with complete germline deletion of VHL. To determine if a relationship existed between the type of VHL deletion and disease, we retrospectively evaluated 123 patients from 55 families with large germline VHL deletions, including 42 intragenic partial deletions and 13 complete VHL deletions, by history and radiographic imaging. Each individual and family was scored for cystic or solid involvement of CNS, pancreas, and kidney, and for pheochromocytoma. Germline deletions were mapped using a combination of fluorescent in situ hybridization (FISH) and quantitative Southern and Southern blot analysis. An age-adjusted comparison demonstrated a higher prevalence of RCC in patients with partial germline VHL deletions relative to complete deletions (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy was not seen for cystic renal lesions or for CNS (p=0.22), pancreas (p=0.72), or pheochromocytoma (p=0.34). Deletion mapping revealed that development of RCC had an even greater correlation with retention of HSPC300 (C3orf10), located within the 30-kb region of chromosome 3p, immediately telomeric to VHL (52.3 vs. 18.9%, p <0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC. Careful correlation of genotypic data with objective phenotypic measures will provide further insight into the mechanisms of tumor formation.
Adult↗
Bilateral testicular adrenal rests after bilateral adrenalectomies in a cushingoid patient with von Hippel-Lindau disease.
We report a case of bilateral testicular masses in a 25-year-old man with von Hippel-Lindau disease presenting with cushingoid symptoms. His medical history was significant for bilateral adrenalectomies secondary to pheochromocytomas, and he began steroid therapy at that time. After exhaustive endocrinologic, radiographic, and physical examinations, the testicular masses were postulated to be active adrenal rest tissue. Bilateral testicular venous sampling found elevated glucocorticoids that were responsive to dexamethasone suppression, which confirmed the testicular masses as testicular adrenal rests without the need for surgical intervention. Successful conservative management consisted of appropriate steroid manipulation and radiographic evaluation and resulted in the resolution of presenting symptoms, a decrease in size of the bilateral testicular masses, and testicular conservation in this young man.
Adrenal Gland Neoplasms↗
Early onset hereditary papillary renal carcinoma: germline missense mutations in the tyrosine kinase domain of the met proto-oncogene.
PURPOSE: Hereditary papillary renal carcinoma (HPRC) is characterized by a predisposition to multiple, bilateral papillary type 1 renal tumors caused by inherited activating missense mutations in the tyrosine kinase domain of the MET proto-oncogene. In the current study we evaluated the clinical phenotype and germline MET mutation of 3 new HPRC families. We describe the early onset clinical features of HPRC. MATERIALS AND METHODS: We identified new HPRC families of Italian (family 177), Spanish (family 223) and Cuban (family 268) descent. We evaluated their clinical features, performed MET mutation analysis by denaturing high performance liquid chromatography and DNA sequencing, and estimated age dependent penetrance and survival using Kaplan-Meier analysis. We characterized renal tumors by histology and fluorescence in situ hybridization. RESULTS: Identical germline MET c.3522G --> A mutations (V1110I) were identified in families 177 and 268 but no evidence of a founder effect was found. Affected members of family 223 carried a germline c.3906G --> C.3522G --> A MET mutation (V1238I). Age dependent penetrance but not survival was significantly earlier for the c.3522G -->A mutation than for the c.3906G --> A mutation in these HPRC families. Trisomy of chromosome 7 and papillary renal carcinoma type 1 histology were detected in papillary renal tumors. CONCLUSIONS: HPRC can occur in an early onset form. The median age for renal tumor development in these 3 HPRC families was 46 to 63 years. HPRC associated papillary renal tumors may be aggressive and metastasize, leading to mortality. Median survival age was 60 to 70 years. Families with identical germline mutations in MET do not always share a common ancestor. HPRC is characterized by germline mutations in MET and papillary type 1 renal tumor histology.
Adenocarcinoma, Papillary↗
Patterns of aneuploidy in stage IV clear cell renal cell carcinoma revealed by comparative genomic hybridization and spectral karyotyping.
We report the use of spectral karyotyping (SKY) and comparative genomic hybridization (CGH) to describe the numerous genomic imbalances characteristic of stage IV clear cell renal cell carcinoma (CCRCC). SKY and CGH were performed on 10 cell lines established from nephrectomy specimens, and CGH on uncultured material from five of the primary renal tumors. The mutational status of VHL (3p25) and MET (7q31), genes implicated in renal carcinogenesis, were determined for each case. Each case showed marked aneuploidy, with an average number of copy alterations of 14.6 (+/-2.7) in the primary tumors and 19.3 (+/-4.6) in the cell lines. Both whole-chromosome and chromosome-segment imbalances were noted by CGH: consistent losses or gains included +5q23-->ter (100%), -3p14-->ter (80%), and +7 (70%). All VHL mutations and 83% of the genomic imbalances found in the primary tumors were also found in the cell lines derived from them. SKY showed many complex structural rearrangements that were undetected by conventional banding analysis in these solid tumors. All cases with VHL inactivation had 3p loss and 5q gain related primarily to unbalanced translocations between 3p and 5q. In contrast, gains of chromosome 7 resulted primarily from whole-chromosome gains and were not associated with mutations of MET. SKY and CGH demonstrated that genomic imbalances in advanced RCC were the result of either segregation errors [i.e., whole chromosomal gains and losses (7.8/case)] or chromosomal rearrangements (10.7/case), of which the majority were unbalanced translocations.
Adenocarcinoma, Clear Cell↗
Signal pathway profiling of prostate cancer using reverse phase protein arrays.
Reverse phase protein arrays represent a new proteomics microarray technology with which to study the fluctuating state of the proteome in minute quantities of cells. The activation status of cell signaling pathways controls cellular fate and deregulation of these pathways underpins carcinogenesis. Changes in pathway activation that occur between early stage prostatic epithelial lesions, prostatic stroma and the extracellular matrix can be analyzed by obtaining pure populations of cell types by laser capture microdissection (LCM) and analyzing the relative states of several key phosphorylation points within the cellular circuitry. We have applied reverse phase protein array technology to analyze the status of key points in cell signaling involved in pro-survival, mitogenic, apoptotic and growth regulation pathways in the progression from normal prostate epithelium to invasive prostate cancer. Using multiplexed reverse phase protein arrays coupled with LCM, the states of signaling changes during disease progression from prostate cancer study sets were analyzed. Focused analysis of phospho-specific endpoints revealed changes in cellular signaling events through disease progression and between patients. We have used a new protein array technology to study specific molecular pathways believed to be important in cell survival and progression from normal epithelium to invasive carcinoma directly from human tissue specimens. With the advent of molecular targeted therapeutics, the identification, characterization and monitoring of the signaling events within actual human biopsies will be critical for patient-tailored therapy.
Antigens, Neoplasm↗
Prostate cancer in Klinefelter syndrome during hormonal replacement therapy.
Prostate cancer detection is a rare occurrence in patients with Klinefelter syndrome, in whom chronically low circulating androgen levels are common findings. Administration of exogenous testosterone has increasingly been used to treat young adolescents diagnosed with Klinefelter syndrome and documented androgen deficiency. Although testosterone replacement in adult patients has been associated with prostatic enlargement, it remains unknown whether chronic supplementation of exogenous testosterone to pubescent males with hypogonadism results in early prostate carcinogenesis. We report a first case of prostate cancer in a patient with Klinefelter syndrome who had undergone long-term testosterone replacement therapy since childhood for chronically depressed levels of testosterone.
Adenocarcinoma↗
The genetic basis of renal cell carcinoma.
The recognition of hereditary forms of renal cancer and the development of high-throughput genetic analysis have led to the identification of genes responsible for familial renal epithelial tumors of differing histologies and cytogenetic features. Some of these genes (VHL) are known to have an important role in sporadic renal neoplasia. This article describes the various epithelial renal tumors most commonly encountered by the urologist, the molecular and cytogenetic distinctions between them, and the hereditary syndromes that predispose to these tumors. Consideration of these syndromes is important for proper treatment when one encounters patients with multiple renal tumors, tumors at an early age of onset, or patients with a positive family history of renal cell carcinoma.
Carcinoma, Renal Cell↗
Assessment of risk for intra-abdominal adhesions at laparoscopy for urological tumors.
PURPOSE: Abdominal wall adhesions at laparoscopy may predispose patients to access related injuries and increase the complexity of the procedure. We have observed concern from referring physicians regarding the safety of laparoscopy in patients who previously underwent surgery because of the risk of abdominal adhesions. To assess the risk of adhesions at laparoscopy a retrospective cohort study was performed. MATERIALS AND METHODS: All patients who underwent a transperitoneal urological laparoscopic procedure in a 6-year period at our institution were included in this study. A chart review was performed to obtain demographic/surgical data and identify preoperative risk factors for adhesions, such as previous abdominal or pelvic surgery, radiation and/or intra-abdominal inflammatory disease. Operative videotapes were reviewed to determine the presence and location of adhesions. Standard statistical analyses were performed. RESULTS: During the study period 127 patients underwent transperitoneal laparoscopy and videotapes on 82 (65%) were available for review. A total of 44 patients (54%) were identified with preoperative risk factors for adhesions (group 1), while 38 (46%) had no risk factors (group 2). The relative risk of adhesions was 1.34 (95% CI 0.89 to 2.01, p = 0.18) when risk factors were identified. There were no differences in the groups in patient age, operative time, access technique, conversion to open surgery or complications. Estimated blood loss was significantly higher in group 2, likely due to the preponderance of cytoreductive laparoscopic nephrectomy in this group. CONCLUSIONS: There was no difference in the risk of intra-abdominal adhesions in patients with and without identifiable preoperative risk factors. Preoperative risk factors for adhesions should not contraindicate the transperitoneal laparoscopic approach for urological oncology procedures.
Abdomen↗
Post-analysis follow-up and validation of microarray experiments.
Measurement of gene-expression profiles using microarray technology is becoming increasingly popular among the biomedical research community. Although there has been great progress in this field, investigators are still confronted with a difficult question after completing their experiments: how to validate the large data sets that are generated? This review summarizes current approaches to verifying global expression results, discusses the caveats that must be considered, and describes some methods that are being developed to address outstanding problems.
Animals↗