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Peter A Humphrey

Publications and source records attributed to Peter A Humphrey.

15 recordsLinked to original sources
PubMed2003

Multiple measures of carcinoma extent versus perineural invasion in prostate needle biopsy tissue in prediction of pathologic stage in a screening population.

The capacity of perineural invasion by carcinoma in prostate needle biopsy tissue to independently predict pathologic stage in radical prostatectomy tissues remains uncertain. We sought to determine, in a prostate specific antigen-based screening population, the ability of needle biopsy histologic grade, tumor extent, and perineural invasion to independently predict pathologic stage and margin status in the whole prostate gland. Perineural invasion, Gleason grade, percentage Gleason pattern 4/5 carcinoma, and multiple measures of needle biopsy tumor extent, including number of positive cores, percentage of positive cores, total percentage of carcinoma, greatest percentage of carcinoma in a single core, and total carcinoma length in millimeters, were captured for 215 men from a prostate specific antigen-based screening program diagnosed with prostate cancer in a median of six procured needle biopsy cores. Pathologic stage and surgical margin status were evaluated in corresponding completely embedded radical prostatectomy specimens. A logistic regression model was used to relate the endpoints of extraprostatic extension by carcinoma and/or positive margins to needle biopsy tissue findings. In univariate analyses, total percentage of carcinoma (p = 0.003), greatest percentage of carcinoma in a single core (p = 0.004), total tumor length in millimeters (p = 0.009), and fraction of positive cores (p = 0.02) were all significantly associated with extraprostatic (pT3) carcinoma, whereas all five measures of carcinoma extent in needle biopsy tissue were related to positive margins. Correlation coefficient determinations showed that all five measures of needle biopsy carcinoma extent were highly interrelated. In multivariate analyses, total percentage of carcinoma was significantly related to pathologic T stage (p = 0.003) and positive margins (p = 0.0002). In a multivariate model with the radical prostatectomy whole gland endpoint of either pT3 disease or positive margins, fraction of positive cores (p = 0.00001) was the only variable with significant predictive value. Perineural invasion by carcinoma in needle biopsy tissue was detected in 11% of cases. Neither presence nor absence of perineural carcinoma nor number nor percentage of positive nerves related to pathologic stage in univariate or multivariate analyses. Amount of carcinoma in prostate needle biopsy tissue, using multiple measurements but not perineural invasion, is a significant histologic attribute predictive of pathologic stage and margin status for men with prostate specific antigen screening detected prostatic carcinoma. Reporting of several measures of carcinoma extent in needle biopsy tissue is recommended.

Adult↗
PubMed2003

Evaluation of a vessel sealing system, bipolar electrosurgery, harmonic scalpel, titanium clips, endoscopic gastrointestinal anastomosis vascular staples and sutures for arterial and venous ligation in a porcine model.

PURPOSE: We assessed the usefulness of the LigaSure (Valleylab, Boulder, Colorado) vessel sealing system for vascular control during laparoscopic surgery and compared it with other available hemostatic modalities. MATERIALS AND METHODS: A total of 31 domestic pigs were divided into 5 groups. In groups 1 and 2 the vessel sealing system was compared with titanium clips and Endo-GIA (United States Surgical, Stamford, Connecticut) staples. In group 3 the vessel sealing system was compared with standard Klepinger (Karl Storz, Culver City, California) bipolar forceps. In group 4 the harmonic scalpel and Trimax (United States Surgical) bipolar forceps were compared. In group 5 in vivo laparoscopic application of the vessel sealing system was evaluated. RESULTS: The 5 mm. laparoscopic vessel sealing system sealed arteries up to 6 mm. and veins up to 12 mm. in diameter at supraphysiological bursting pressure. We evaluated 13 arteries with a diameter of 6 mm. or less at a mean bursting pressure of 662 mm. Hg (range 363 to 1,985) and 11 veins with a diameter of 12 mm. or less with a mean bursting pressure of 233 mm. Hg (range 63 to 440). Collateral tissue damage extended 1 to 3 mm. from the application site. Standard bipolar energy with Klepinger and Trimax forceps was less reliable and in some cases vessel sealing could not be accurately assessed before vessel division. Collateral tissue injury was 1 to 6 mm. The harmonic scalpel did not reliably seal vessels larger than 3 mm. but resulted in the least acute collateral tissue injury of 0 to 1 mm. CONCLUSIONS: In the porcine model the LigaSure system is a viable option for laparoscopic management of arteries up to 6 mm. and veins up to 12 mm. in diameter.

Anastomosis, Surgical↗
PubMed2003

Basal cell hyperplasia in the peripheral zone of the prostate.

Basal cell hyperplasia in the prostate is often viewed as a transition zone proliferation, related to usual, nodular glandular, and stromal hyperplasia. Basal cell hyperplasia in the prostatic peripheral zone, the most common site for development of prostatic intraepithelial neoplasia and carcinoma, has not been previously characterized. We characterized the incidence and histomorphological attributes of basal cell hyperplasia in a series of 500 consecutive sextant needle core biopsy samples and in 26 completely embedded prostate glands from radical prostatectomy specimens. Comparative proliferation indices (by MIB-1 staining) and apoptotic indices (by TUNEL labeling) were quantitated for peripheral zone versus transition zone basal cell hyperplasia versus normal basal cells. The incidence of basal cell hyperplasia in prostate needle biopsy tissue was 10.2% (51 of 500 cases). Usual basal cell hyperplasia was detected in 8.2% of the 500 cases, and basal cell hyperplasia with prominent nucleoli, in 2.0% of cases. Basal cell hyperplasia in needle biopsy tissue was typically focal and associated with inflammation, which was usually lymphocytic, in 84% of cases. Peripheral zone basal cell hyperplasia was found in 23% of whole prostate glands. Peripheral zone basal cell hyperplasia was not observed to be in direct physical continuity with intraepithelial or invasive neoplasia. Peripheral zone and transition zone basal cell hyperplasia exhibited similar mean proliferation and apoptotic indices, at 1% and 0.07%, respectively. This proliferation index was elevated, and apoptotic index was decreased, relative to normal basal cells (P = 1 x 10(-7)). Basal cell hyperplasia in the peripheral zone is present in a significant minority of prostate needle biopsy samples and whole prostate glands. The presence of prominent nucleoli in basal cell hyperplasia may cause diagnostic concern for a neoplastic proliferation. The increase in cell number in basal cell hyperplasia appears to be due to a coordinate increase in proliferation index coupled with a diminished apoptotic index. The presence of inflammation in the majority of basal cell hyperplasia foci suggests that peripheral zone basal cell hyperplasia in untreated patients may represent a stereotyped response to injury such as that sustained because of inflammation.

Adult↗
PubMed2003

Tumor volume in prostate cancer and serum prostate-specific antigen. Analysis from a kinetic viewpoint.

Many have observed poor correlations between serum prostate-specific antigen (PSA) and tumor volume, and this noise undoubtedly reduces the diagnostic specificity of PSA. To explore this phenomenon, we addressed the problem from a theoretical viewpoint. Specifically, we used a compartmental model and first-order kinetics to develop the mathematics necessary to relate serum PSA to tumor volume. We found that the resulting model fit well the observed kinetic data of PSA measured after biopsy or prostatectomy. The model also predicted a linear relationship between PSA and the sum of volumes of benign and malignant tissues, but the coefficients for this linear equation are more complex than previously thought. They reflect not only how much PSA may be present in each tissue but also 3 rate parameters and the volume of serum. Much of the noise in the linkage between PSA and tumor volume is due to individual patient differences in the 3 rate parameters and in serum volume. Our model predicts that without ways to directly measure the several involved rate parameters, we will not be able to accurately predict tumor volume from PSA. Nevertheless, surrogates for the missing parameters may exist and could lead to statistical models that could improve the prediction of tumor volume.

Biomarkers, Tumor↗
PubMed2002

Patterns of multiple recurrences of superficial (Ta/T1) transitional cell carcinoma of bladder and effects of clinicopathologic and biochemical factors.

BACKGROUND: Although multiple sequential recurrences are one of the most important characteristics of superficial transitional cell carcinoma (TCC) of the bladder, few studies have examined multiple sequential recurrence patterns and the clinicopathologic and biochemical factors associated with these patterns. METHODS: Two hundred seventy superficial TCC bladder carcinoma patients were followed. Clinical, pathologic, and tumor marker (p53, MIB-1, bcl-2, c-erb B-2, and epidermal growth factor receptor) data were collected at baseline and during followup. The Kaplan-Meier (KM) method was used to describe multiple recurrences. The Wei, Lin, and Weissfeld (WLW) marginal proportional hazards model was used to assess the effects of clinicopathologic and immunohistochemic factors on multiple recurrences. RESULTS: Among the 270 patients, 126 (46.7%) had one or more recurrences, 38 (14.1%) had two or more recurrences, and 14 (5.2%) had three or more recurrences during the followup. The median times for the first, the second, and the third recurrences were 23 months, 15 months, and 13 months, respectively. In KM analysis, Stage T1, higher grades, and Ki-67 stain positivity were associated with the first recurrence, and p53 stain positivity was marginally significant. Other markers were not significant. For the second recurrence, only p53 stain positivity was significant. In multivariate analysis (WLW method), stage was significantly associated with the first recurrence (risk ratio [RR] = 2.03), and Ki-67 was marginally significant (RR = 1.49). For the second recurrence, only p53 positivity was statistically significant (RR = 2.73). CONCLUSIONS: Among superficial TCC bladder carcinoma patients, multiple recurrences are common phenomena. The time for recurrence becomes shorter as the number of recurrences increases. In addition to tumor stage and grade, Ki-67 can be used to identify patients at high risk for a first recurrence; and p53 can be used to identify patients at high risk for a second recurrence.

Biomarkers, Tumor↗
PubMed2002

Molecular characterization of a metastatic neuroendocrine cell cancer arising in the prostates of transgenic mice.

The features and functions of prostatic neuroendocrine (NE) cells remain ill-defined. Neuroendocrine differentiation (NED) in adenocarcinoma of the human prostate (CaP) is associated with more aggressive disease, but the underlying mediators are poorly understood. We examined these issues in transgenic mice that utilize regulatory elements from the cryptdin-2 gene (Defcr2) to express simian virus 40 large T antigen (TAg) in prostatic NE cells. CR2-TAg mice develop prostatic intraepithelial neoplasia at 8 weeks of age, 1 week after the onset of TAg expression. An invasive phase follows 2-4 weeks later, with lymph node, liver, lung, brain, and bone metastases appearing within 16 weeks. DNA microarray studies revealed 122 mRNAs that were increased >/=2-fold in duplicate assays of 16-week-old CR2-TAg versus normal prostates. Thirty two transcripts encode proteins associated with neurons and endocrine cells (e.g. basic helix loop helix, SRY-related high mobility group box and sine-oculis homeobox transcription factors, Hu RNA-binding proteins, neuronatin, Racgap1, collapsin response mediator protein-1, synaptotagmin-1, proprotein convertase, and secretogranins). Follow-up studies of candidate mediators and biomarkers of differentiation/growth in the microarray data set involved real time quantitative reverse transcriptase-PCR assays of laser capture microdissected NE cells from CR2-TAg prostates plus liver metastases, and immunohistochemical comparisons of transgenic mouse prostates and 35 human CaP samples. Our findings include (a) expression of the bHLH mouse achaete-scute homolog (mASH1) in normal and CR2-TAg NE cells and foci of NED in human CaP, (b) glutamic acid decarboxylase and its product (gamma-aminobutyric acid) in neoplastic NE cells juxtaposed next to cohorts of normal gamma-aminobutyric acid receptor expressing secretory cells (a potential route for paracrine interactions between these two epithelial lineages), and (c) aromatic l-amino-acid decarboxylase, but not its dopamine/serotonin products, in CR2-TAg NE cells and NED. These results underscore the value of CR2-TAg mice for characterizing normal NE cell biology and tumorigenesis.

Animals↗
PubMed2002

Prostate-specific antigen cutoff of 2.6 ng/mL for prostate cancer screening is associated with favorable pathologic tumor features.

OBJECTIVES: To evaluate the pathologic characteristics of clinical Stage T1c (nonpalpable, prostate-specific antigen [PSA]-detected) prostate cancers detected in the 2.6 to 4.0-ng/mL PSA range and compare them with Stage T1c cancers concurrently detected in the 4.1 to 10.0-ng/mL PSA range. All cancers were detected in a prostate cancer screening study. METHODS: We studied 94 patients with clinical Stage T1c prostate cancer diagnosed by four or six-sector ultrasound-guided needle biopsy who underwent radical prostatectomy between June 1995 and December 1996. We included all men whose prostatectomy specimens were processed with complete embedding of all prostatic tissue. Of these, 42 had a PSA level of 2.6 to 4.0 ng/mL and 52 a PSA level 4.1 to 10.0 ng/mL at the time of cancer detection. We determined the tumor volume by complete embedding and grid morphometry, pathologic stage, Gleason sum, and surgical margin status and compared the cancer volume and pathologic tumor stages for each group. RESULTS: Men with cancer detected at the 2.6 to 4.0 ng/mL PSA range had significantly smaller cancer volumes (1.1 +/- 1.1 cm(3) versus 1.8 +/- 1.5 cm(3), P = 0.02); however, no difference was found in the proportion (11.9% versus 11.5%, P = 0.9, and 23.8% versus 26.9%, P = 0.7, respectively) of tumors that met previously published criteria of "clinically insignificant" (organ confined, less than 0.2 cm(3) tumor volume, Gleason sum 6 or less) or "clinically unimportant" (organ confined, less than 0.5 cm(3) tumor volume, and Gleason sum 6 or less) tumors. Using the lower PSA cutoff point resulted in the detection of a significantly higher percentage of organ-confined tumors (88% versus 63%, P = 0.01). CONCLUSIONS: The use of a 2.6-ng/mL PSA threshold for screening resulted in the more frequent detection of small, organ-confined tumors without overdetecting possibly clinically insignificant ones.

Aged↗
PubMed2002

Renal hypothermia achieved by retrograde intracavitary saline perfusion.

BACKGROUND AND PURPOSE: Hypothermia during vascular clamping protects the kidney from ischemia-induced nephron loss. Traditionally, cooling is achieved by packing the kidney in ice, which lowers the temperature of the rest of the surgical field as well, and the method cannot be used during laparoscopy. We evaluated the utility of a newly developed ureteral access system for circulating ice-cold saline. MATERIALS AND METHODS: Domestic pigs underwent retrograde endoscopic cooling through an access sheath without (N = 2) or with (N = 3) renal artery occlusion, traditional ice-slush cooling with renal artery occlusion (N = 3), or occlusion without hypothermia (N = 3). Five days later, the pigs were sacrificed and the kidneys and ureters examined histologically. RESULTS: Endoscopic cooling with renal artery occlusion and ice-slush cooling both produced renal hypothermia. The former produced medullary and cortical temperatures of 21.3 degrees C and 27.3 degrees C, respectively, and the latter medullary and cortical temperatures of 28.8 degrees C and 23.7 degrees C, respectively. Histologically, there were minimal changes in the first three groups, whereas venous congestion, multifocal chronic inflammation, and periarteriolar hemorrhage were seen after renal artery occlusion without hypothermia. CONCLUSION: Retrograde endoscopic renal hypothermia is effective and requires no novel equipment or special surgical skills. Clinical application has not yet been attempted.

Animals↗
PubMed2002

Practical application of molecular genetic testing as an aid to the surgical pathologic diagnosis of sarcomas: a prospective study.

The strong correlation of specific reciprocal translocations with individual tumor types and the demonstration that polymerase chain reaction (PCR)-based methods can detect translocations in tissue samples have stimulated interest in the role of molecular genetic testing in diagnostic surgical pathology. To evaluate the clinical utility of PCR-based molecular analysis of soft tissue neoplasms in routine surgical pathology, 131 consecutive soft tissue tumors submitted for molecular genetic testing at a tertiary care teaching hospital were prospectively analyzed over a 36-month period. RT-PCR was used to test tumor RNA for fusion transcripts characteristic of malignant round cell tumors (including Ewing sarcoma/primitive neuroectodermal tumor, desmoplastic small round cell tumor, and alveolar rhabdomyosarcoma), spindle cell tumors (including synovial sarcoma and congenital fibrosarcoma), and fatty tumors (myxoid liposarcoma). DNA sequence analysis was used to confirm the identity of all PCR products, and the PCR results were compared with the histopathologic diagnosis. We found that sufficient RNA for RT-PCR-based testing was recovered from 96% of the 131 cases and the percentage of tumors that tested positive for the associated characteristic fusion transcript was in general agreement with those reported in the literature. DNA sequence analysis of PCR products identified both variant transcripts and spurious PCR products, underscoring the value of product confirmation steps when testing formalin-fixed, paraffin-embedded tissue. Only in rare cases did testing yield a genetic result that was discordant with the histopathologic diagnosis. We conclude that PCR-based testing is a useful adjunct for the diagnosis of malignant small round cell tumors, spindle cell tumors, and other miscellaneous neoplasms in routine surgical pathology practice.

Base Sequence↗
PubMed2002

Exaggerated signet-ring cell change in stromal nodule of prostate: a pseudoneoplastic proliferation.

A stromal nodule of the prostate was incidentally identified in a simple prostatectomy specimen from a 66-year-old man with benign prostatic hyperplasia. Microscopically, the nodule consisted of short spindly cells with bland nuclear features. Many of the cells in the nodule, however, contained a large, clear cytoplasmic vacuole that displaced and indented the nucleus, generating signet-ring cell morphology. Immunohistochemically, these cells were strongly positive for vimentin and weakly positive for desmin, suggesting a myofibroblastic nature. Further immunostains demonstrated the cells to be negative for cytokeratins and prostate-specific antigen, excluding the possibility of signet-ring cell carcinoma. The cytoplasmic vacuoles also stained negative for mucin production. Electron microscopy revealed no intracytoplasmic lumina. Notably, thermal effect or other signs of cellular injury, frequently associated with signet-ring cell change seen in prostate specimens obtained by transurethral resection and needle biopsy, were not appreciated in this stromal nodule. This case demonstrates that signet-ring cell change may occur in benign, hyperplastic, prostatic stromal cells in the absence of cellular damage.

Aged↗
PubMed2002

Conditional loss of Nkx3.1 in adult mice induces prostatic intraepithelial neoplasia.

The homeodomain-containing transcription factor NKX3.1 is a putative prostate tumor suppressor that is expressed in a largely prostate-specific and androgen-regulated manner. Loss of NKX3.1 protein expression is common in human prostate carcinomas and prostatic intraepithelial neoplasia (PIN) lesions and correlates with tumor progression. Disruption of the murine Nkx3.1 gene results in defects in prostate branching morphogenesis, secretions, and growth. To more closely mimic the pattern of NKX3.1 loss that occurs in human prostate tumors, we have used Cre- and loxP-mediated recombination to delete the Nkx3.1 gene in the prostates of adult transgenic mice. Conditional deletion of one or both alleles of Nkx3.1 leads to the development of preinvasive lesions that resemble PIN. The pattern of expression of several biomarkers (Ki-67, E-cadherin, and high-molecular-weight cytokeratins) in these PIN lesions resembled that observed in human cases of PIN. Furthermore, PIN foci in mice with conditional deletion of a single Nkx3.1 allele lose expression of the wild-type allele. Our results support the role of NKX3.1 as a prostate tumor suppressor and indicate a role for this gene in tumor initiation.

Animals↗
PubMed2002

The morphologic spectrum of metastatic prostatic adenocarcinoma to the lung: special emphasis on histologic features overlapping with other pulmonary neoplasms.

We undertook a detailed histologic study to identify specific morphologic features that may aid in distinguishing prostatic adenocarcinoma with lung metastases (PALM) from other pulmonary tumors with similar histologic features. In 16 cases, we found 3 predominant architectural patterns: microacinar (n = 10), tubulopapillary (ductal; n = 4), and carcinoid-like (n = 2). Characteristic features of PALM included small acinar and/or cribriform growth, frequent lymphangitic permeation, lack of stromal response, uniform round nuclei with prominent nucleoli, intraluminal blue mucin, and prominent cell borders. By immunohistochemical staining, prostate-specific antigen and prostate-specific acid phosphatase were present in 13 of 14 and 13 of 13 cases, respectively. Metastatic prostatic duct adenocarcinoma exhibited morphologic features similar to metastatic colonic adenocarcinoma. Two cases had a carcinoid-like appearance with nested or solid architecture, parachromatin clearing, and prominent nucleoli, but lacked the finely stippled chromatin pattern of carcinoid tumors. Several features that may result in misinterpretation or lack of association of the neoplasm in the lung with a prostatic primary include lung metastasis preceding the detection of a prostatic primary tumor, solitary pulmonary nodule, tubulopapillary (ductal) or carcinoid-like pattern, scant material in which histologic features of metastatic prostate carcinoma are not fully appreciated, and frequent necrosis. Attention to specific discriminating histologic features, supported by immunohistochemical staining, may be useful in the differential diagnosis, which is therapeutically and prognostically critical.

Acid Phosphatase↗
PubMed2002

Carcinoma extent in prostate needle biopsy tissue in the prediction of whole gland tumor volume in a screening population.

Increasing prostate tumor volume has been shown to correlate with numerous adverse prognostic indicators for patients with prostate carcinoma The ability to predict tumor volume from pretreatment parameters is potentially critical in the stratification of patients for different management strategies. We assessed the capacity of preoperative variables to predict tumor volume in 100 men diagnosed with prostate cancer in a prostate-specific antigen (PSA)-based screening program. Preoperative information included total serum PSA concentration and needle biopsy tissue variables, including Gleason score, number of positive cores, linear extent of carcinoma in millimeters, greatest percentage of carcinoma (in a single core), total percentage of carcinoma (all cores), presence of perineural invasion, and percentage of high-grade carcinoma. The postoperative end point was total tumor volume in radical prostatectomy tissue, calculated by image analysis. We determined independently significant factors and generated a predictive modelfor whole gland tumor volume. Total tumor volume was related significantly in multivariate analysis to 3 preoperative variables: linear extent of carcinoma, exponential number of positive cores, and serum PSA. A predictive model generated based on these 3 variables accounted for only 65% of the natural deviance of the data owing to data-point scatter for individual patients, suggesting that additional variables are needed to more accurately predict tumor volume. Findings highlight the importance of reporting quantitative measures of tumor amount in prostate needle biopsy specimens; several measures of tumor extent (vs 1 measure) provide maximal information on prostate cancer size.

Adenocarcinoma↗