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Robin T Vollmer

Publications and source records attributed to Robin T Vollmer.

At least 19 recordsLinked to original sources
PubMed2007

Entropy and information content of laboratory test results.

This article introduces the use of information theoretic concepts such as entropy, S, for the evaluation of laboratory tests results, and it offers a new measure of information, 1 - S, which tells us just how far toward certainty a laboratory test result can predict a binary outcome. The derived method is applied to the serum markers troponin I and prostate-specific antigen and to histologic grading of HER-2/neu staining, to cytologic diagnosis of cervical specimens, and to the measurement of tumor thickness in malignant melanoma. Not only do the graphic results provide insight for these tests, they also validate prior conclusions. Thus, this information theoretic approach shows promise for evaluating and understanding laboratory test results.

Cervix Uteri↗
PubMed2006

Pancreatic and bile duct brushing cytology in 1000 cases: review of findings and comparison of preparation methods.

BACKGROUND: Duct brushing cytology is an important tool in evaluation of the extrahepatic biliary tract and large pancreatic ducts. The emergence of neoadjuvant therapies underscores the importance of accurate preoperative diagnosis by noninvasive means. Liquid-based preparation methods, such as ThinPrep, have become popular for nongynecologic cytology specimens. METHODS: Findings from bile and pancreatic duct brushings were reviewed over the 10-year period of 1994-2003. Cytologic material, imaging reports, and clinical data were reviewed and pathologic and clinical follow-up data were obtained. The slides were prepared by direct smear only (18.8%), direct smear plus cytospin (14.4%), or direct smear plus ThinPrep (66.8%). RESULTS: A total of 1118 specimens were identified (1008 bile duct, 110 pancreatic duct) from 864 patients. The cytologic findings were: 53.5% negative, 16.5% malignant, 18.2% suspicious for malignancy, 11% atypical/inconclusive, 0.8% inadequate. Follow-up in the form of either histology or at least 6 months clinical observation was available for 82.2% of cases (n = 971). Overall operating characteristics were: 52.6% sensitivity, 99.4% specificity, 98.9% positive predictive value, 67.1% negative predictive value, and 75.7% accuracy. Diagnostic agreement between cytology and follow-up was the main variable analyzed. Agreement was significantly affected by characteristics of the sampled lesion, with ductal narrowing having the lowest rate of malignancy. In addition, the ThinPrep method showed superior sensitivity and accuracy compared with other preparation methods (P = .02). Nonsignificant associations were noted for patient age and gender, site of lesion, and the presence of either stones or prior stent. CONCLUSION: In a large dataset from a single institution, brushing cytology showed modest sensitivity and high specificity. Diagnostic agreement was considerably better for benign cases. The combination of direct smear and the ThinPrep method showed superior sensitivity and accuracy.

Adolescent↗
PubMed2006

Lymph nodes in colorectal carcinoma. The Poisson probability paradigm.

This article introduces use of the Poisson probability density function and Bayes probability rule to understand and analyze lymph nodal metastases in colorectal carcinoma. We apply these models to 370 patients who underwent resection of their tumors. In 213 cases with negative lymph nodes, we found that the Bayes-estimated probability of missed metastases was related significantly to subsequent survival (P = .0006). In 157 cases with lymph nodal metastases, we found that the estimated value of the Poisson parameter a was associated more closely with subsequent survival than pN stage (P = 9 10(-6)). Consequently, we believe that the Poisson model provides insight and useful results in colorectal carcinoma.

Adenocarcinoma↗
PubMed2006

Predicting prostate biopsy results: The importance of PSA, age, and race.

We studied whether age and race have a significant role in predicting the results of prostate biopsy after consideration of prostate-specific antigen (PSA) alone. We evaluated the results of 884 prostate biopsies performed on 695 men, including 188 black men. We used logistic regression analysis to evaluate relationships between presence of cancer in the biopsy specimen and the key predictor variables of PSA, age and black race. We also evaluated the importance of a Bayes-derived positive predictive value (PPV), which used age- and race-specific values of specificity and sensitivity of PSA and age- and race-specific Surveillance, Epidemiology, and End Results incidences of prostate cancer. In univariate analysis, the Bayes PPV was associated significantly with presence of cancer (chi2 = 216; P approximately .000); however, serum PSA provided more information (chi2 = 248; P approximately .000). With serum PSA in the logistic model, the Bayes PPV provided no further information (P > .08), and as additional variables, neither age nor black race contributed further information (P > .1). Serum PSA provides the most predictive information about the results of biopsy of the prostate, probably because it naturally correlates with age and race. Decisions about whether to biopsy should rest on values of serum PSA and need not consider age and race.

Age Factors↗
PubMed2006

Analysis of turnaround times in pathology: an approach using failure time analysis.

This article introduces the use of failure time analysis methods for studying turnaround times in pathology. The key to understanding the approach is to view a laboratory specimen like a living patient. When the specimen enters the laboratory, the time is analogous to the time of diagnosis for a patient. When the specimen's analysis is completed, the event is analogous to a patient who has died. To illustrate the approach, I use data previously published and data generated at the Durham, NC, Veterans Affairs Medical Center. I demonstrate that the Kaplan-Meier plotting method, the log-rank test, and the Cox model can all be applied to turnaround times and provide useful results.

Efficiency↗
PubMed2006

Predictive probability of serum prostate-specific antigen for prostate cancer: an approach using Bayes rule.

This article introduces the use of Bayes probability rule to calculate age and serum prostate-specific antigen (PSA)-specific positive predictive values (PPVs) for prostate cancer. The PPV is the conditional probability of having prostate cancer, given a value of PSA and a particular age group. The formulation uses values of sensitivity obtained from previously reported studies of more than 2,700 men with prostate cancer, and it uses values of specificity obtained from previously reported studies of more than 99,000 men without prostate cancer. The formulation also introduces the use of a population-based and age-specific probability of prostate cancer, and for this it relies on the National Cancer Institute-sponsored Surveillance, Epidemiology and End Results data. The Bayes PPV suggests that in younger men, cut points defining an elevated PSA level should be raised rather than lowered. The Bayes formulation also provides estimates of the PPV for narrow intervals of PSA, and these tabulated results may provide useful guidelines for the implications of serum PSA levels at specific age groups.

Adenocarcinoma↗
PubMed2005

Expression of HIF-1alpha, CA IX, VEGF, and MMP-9 in surgically resected non-small cell lung cancer.

Endogenous hypoxia markers have been studied as prognostic indicators because they appear to be associated with tumor aggressiveness. This study was undertaken to compare the expression of two endogenous hypoxia markers, Hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase IX (CA IX), with regard to their prognostic significance. We also compared spatial distribution of HIF-1alpha and CA IX and examined their relationship with expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9, which may be regulated by hypoxia. We studied 74 resected stage I/II non-small cell lung cancers (NSCLCs) for expression of HIF-1alpha, CA IX, VEGF, and MMP-9 by immunohistochemistry, and the extent of tumor necrosis. Univariate and multivariate analyses were performed to assess prognostic implications of these markers for disease free survival. HIF-1alpha expression was strongly correlated with CA IX (r=0.667, p<0.001) and was co-localized with CA IX in corresponding areas. HIF-1alpha and CA IX expression were higher in areas with moderate to severe tumor necrosis relative to areas with minimal necrosis, suggesting their relationship with hypoxia. VEGF expression also showed a modest relationship with HIF-1alpha (p=0.07); however, there was no relationship between HIF-1alpha and MMP-9 expression (p>0.99). Expression of HIF-1alpha and CA IX above the median value was significantly associated with shorter disease free survival in univariate analysis (p<0.05). However, only high CA IX expression and pathologic stage were independent prognostic indicators in a multivariate analysis. Of the markers considered in this study, CA IX expression status was the most reliable hypoxia marker for predicting tumor aggressiveness.

Aged↗
PubMed2005

Pancreatic FNA in 1000 cases: a comparison of imaging modalities.

BACKGROUND: Image-guided FNA is a popular method for evaluating pancreatic lesions, but few large studies on pancreatic FNA exist. METHODS: Cytologic material, imaging reports, and clinical follow-up information were reviewed from pancreatic FNA cases performed over a 5-year period. RESULTS: A total of 1050 pancreatic FNAs were obtained by EUS (n = 843), US (n = 140), and CT (n = 67). On-site assessment was performed in 89.2% (n = 937) of cases. Findings were as follows: positive for neoplasm 48.9% (n = 503), negative 29.1% (n = 306), descriptive 10% (n = 105), suspicious 5.9% (n = 62), atypical/inconclusive 4.6% (n = 48), and nondiagnostic/inadequate 1.5% (n = 26). Follow-up in the form of histology or at least 6 months of clinical observation was available for 61.2% (n = 643). There was an overall false-positive rate of 0.3% and a false-negative rate of 14.3%. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were as follows: 79.4, 99.0, 99.4, 67.9, 84.5 for the total series, respectively; 79.9, 98.8, 99.2, 72.5, 86.5 for EUS, respectively; 77.9, 100, 100, 48.6, 81.7 for US, respectively; and 78.6, 100, 100, 47.1, 82.0 for CT, respectively. In general, accuracy was not influenced by lesion size or site, number of FNA passes, or number of procedures per patient. After controlling for lesion size, EUS resulted in greater accuracy than US or CT when evaluating lesions <3 cm ( p = 0.015). CONCLUSIONS: All imaging modalities showed moderate to high sensitivity, specificity, and accuracy. Logistic regression analysis showed that for lesions <3 cm, the EUS method had higher accuracy than US or CT. No statistically significant difference was seen for larger lesions or for the number of FNA passes.

Adenocarcinoma↗
PubMed2005

Erythropoietin and erythropoietin receptor expression in human prostate cancer.

Erythropoietin is a hematopoietic cytokine that regulates the production of red blood cells. Erythropoietin is normally produced in the adult kidney in a hypoxia-inducible manner. The recombinant form of human erythropoietin is in clinical use for the prevention and treatment of anemia that is associated with cancer and its treatment with chemoradiation therapy. A series of recent studies from our laboratory and others have reported the expression of receptors for erythropoietin in several different types of human cancer cells. In the present study, we investigated the expression of erythropoietin receptor and its ligand erythropoietin in human prostate cancer. In clinical specimens of prostate cancer, we found abundant expression of erythropoietin receptor protein in all primary tumors examined using immunohistochemistry. Furthermore, we observed erythropoietin coexpression in prostate cancer cells by immunohistochemical analysis. To determine whether monolayer cultures of continuous cell lines derived from prostate cancer also express erythropoietin receptor and erythropoietin, we studied well-characterized hormone-responsive (LNCaP) and hormone-refractory (PC-3) prostate cancer cell lines. We performed reverse-transcription and polymerase chain reaction assays to detect erythropoietin receptor and erythropoietin mRNA transcripts, and also immunoprecipitation and immunoblotting to detect erythropoietin receptor protein expression in prostate cancer cells. These experiments revealed the expression of both erythropoietin receptor and erythropoietin in LNCaP and PC-3 cells suggesting that these prostate cancer cell lines may serve as useful experimental models for further studies of erythropoietin and erythropoietin receptor function in prostate cancer. The coexpression of erythropoietin receptor and its ligand erythropoietin in human prostate cancer cells suggests the potential for growth regulation by erythropoietin-erythropoietin receptor in an autocrine or paracrine manner.

Animals↗
PubMed2005

Analysis of lymph nodal metastases in malignant melanoma using the poisson probability paradigm and Bayes rule.

This article deals with and formalizes 2 notions common to the practice of pathology. The first is that the number of lymph nodes found positive for metastasis relates directly to the total number of lymph nodes examined. The second is that for any patient, there is a chance that the absence of lymph node metastases is a false-negative result. I introduce the Poisson probability density function to deal with the first notion and the Bayes probability rule to deal with the second. To illustrate the insight these 2 models provide, I apply them to data regarding lymph nodal metastases in malignant melanoma. In this preliminary study, the results of these 2 models correlate well with observed survival probabilities in patients with stage N0 melanoma and with observed rates of false-negative results in sentinel lymph node biopsy technology. With further development, the combination of these models should provide a way to estimate the probability of nodal metastasis when, in fact, none have been observed. Thus, these models might provide useful tools for evaluating patients with stage N0 malignant neoplasms.

Adolescent↗
PubMed2005

The importance of total number of sentinel lymph nodes in patients with stage N0 cutaneous melanoma.

Staging of malignant melanoma now relies routinely on the sentinel node (SN) technique. On average, 2.1 SNs are removed per patient. Nevertheless, despite the success of the SN technique, approximately 10% of patients with negative SNs experience metastatic recurrence. Because a prior theoretical analysis using Poisson and Bayes probability models suggested that limited sampling of SNs could cause false-negative results, we undertook this study to see whether the subset of patients with negative SN and only 1 or 2 nodes examined have a shorter time to recurrence than patients with 3 or more nodes examined and found to be negative. Our study cases comprised 178 melanoma cases with SN biopsy: positive SN, 47; negative SN and fewer than 3 nodes examined, 68; and negative SN and more than 2 nodes examined, 63. Patients with negative SNs and fewer than 3 examined had disease-free survival intermediate between patients with positive SNs and those with negative SNs and more than 2 examined (P = .013). These results suggest that among patients with negative SNs, those with fewer than 3 nodes examined have greater risk for recurrence.

Adolescent↗
PubMed2004

Carbonic anhydrase IX in early-stage non-small cell lung cancer.

PURPOSE: Tumor hypoxia is associated with poor prognosis and increased tumor aggressiveness. Carbonic anhydrase (CA) IX, an endogenous marker for tumor hypoxia, catalyzes the hydration of carbon dioxide into carbonic acid and contributes to the pH regulation of tumor cells. Therefore, CA IX might allow tumors to acclimate to a hypoxic microenvironment, promoting tumor cell proliferation. We hypothesized that CA IX expression is related to tumor cell proliferation and poor disease-free survival in patients with early-stage non-small-cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: CA IX expression was measured in 75 resected NSCLC tumors to assess prognostic implications for disease-free survival. The relationship of CA IX expression with microvessel density (MVD) and proliferation (Ki-67) index was assessed via colocalization analysis. RESULTS: All patients had operable NSCLC (stage I, 58; stage II, 17). CA IX expression was present in 54 (72%) of 75 patients and was associated with tumor necrosis (P < 0.05). CA IX-positive tumor areas showed greater cell proliferation as measured by Ki-67 index (P < 0.05) and less MVD (P < 0.05) than did CA IX-negative areas in colocalization analysis. The percentage of CA IX-positive tumor cells was significantly related to postoperative recurrence and poor disease-free survival (P < 0.05). Ki-67 index and pathologic stage were also independent prognostic factors for worse disease-free survival (P < 0.05). CONCLUSIONS: CA IX expression of tumor cells may be an indicator for poor disease-free survival in early-stage NSCLC.

Adenocarcinoma↗
PubMed2004

Diagnostic impact of core-needle biopsy on fine-needle aspiration of non-Hodgkin lymphoma.

We retrospectively reviewed 74 fine-needle aspiration (FNA) cases of presumptive non-Hodgkin lymphoma (NHL). All the cases had cytology and core-needle biopsy and 53 cases had concurrent flow cytometric analysis. FNA (cytology and flow cytometry) and core-needle biopsy were evaluated independently. FNA was diagnostic of diffuse large B-cell lymphoma (DLBL) in 25% (13/53) of cases and small B-cell NHL in 15% (8/53) of cases, whereas core-needle biopsy was diagnostic of DLBL in 37% (27/74) of cases and small B-cell NHL in 8% (6/74) of cases. Subclassification of small B-cell NHL was reached in 3/6 cases by core-needle biopsy. Insufficient cases were observed in both FNA (47%; 25/53) and core-needle biopsy (28%; 21/74) groups. With the combination of FNA and core-needle biopsy, diagnostic cases of DLBL increased to 43% (32/74) and insufficient samples were reduced to 16% (12/74). There was no clear advantage in the diagnosis and classification of small B-cell NHL by adding core-needle biopsy to FNA (14%; 10/74). We conclude that core-needle biopsy is a useful adjunct to FNA in the diagnosis of DLBL and shall be encouraged. In small B-cell NHL, core-needle biopsy does not add to the diagnostic ability of FNA. Cases insufficient for diagnosis may be seen in both core-needle biopsy and FNA. A combined approach reduces the number of insufficient cases and is recommended in routine FNA practice.

Algorithms↗
PubMed2004

Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen.

OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth.

Biopsy↗
PubMed2004

Patient age in Spitz nevus and malignant melanoma: implication of Bayes rule for differential diagnosis.

In the differential diagnosis of Spitz nevus vs malignant melanoma, patient age provides a critical piece of clinical information, because Spitz nevi occur mostly in children and melanomas occur mostly in adults. Nevertheless, there is overlap in the age distributions of Spitz nevus and melanoma. The issue to consider is how these age distributions and their governing probability densities can impact the a priori probability that a lesion is a Spitz nevus vs a melanoma. Herein I introduce a quantitative approach that uses Bayes rule together with previous published data on the age distributions in Spitz nevi and melanoma. The resulting algorithm yields plots and a table of predictive a priori probabilities of Spitz nevus, given patient age occurring within narrow intervals, and I believe these provide useful guidelines for using age in the differential diagnosis of Spitz nevus and malignant melanoma.

Adolescent↗
PubMed2004

An abnormal cervicovaginal cytology smear in uterine carcinosarcoma is an adverse prognostic sign: analysis of 25 cases.

Carcinosarcoma of the uterus has been poorly characterized on cervicovaginal (Pap) smears, and we examine whether they effectively screen for carcinosarcoma and whether an abnormal Pap smear result has any clinical importance. Twenty-five patients with histologically confirmed carcinosarcoma had a conventional Pap smear shortly before diagnosis. Eleven smears (44%) originally were read as abnormal (malignant or atypical), and 4 additional cases were read as abnormal on retrospective review (15/25 [60%]). All malignant elements were epithelial, and 2 cases (8%) had atypical spindle cells, but no diagnostic sarcoma. Cervical involvement was the only histologic parameter correlating with an abnormal Pap smear result (P = .04). Univariate analysis found stage III or IV disease was an adverse prognostic sign compared with stage I or II disease (mean survival, 8 vs 36 months, respectively; P = .001), and multivariate analysis indicated that an abnormal Pap smear result correlated with worse survival (P = .023). The conventional Pap smear is insensitive (60%) for detecting carcinosarcoma, but when the result is abnormal, the Pap is an important stage-independent adverse prognosticator.

Carcinosarcoma↗
PubMed2004

Use of Bayes rule and MIB-1 proliferation index to discriminate Spitz nevus from malignant melanoma.

Differentiating Spitz nevus from malignant melanoma is difficult and controversial. Despite helpful lists of differential diagnostic features, uncertainty about the diagnosis often provokes some to stain the tumor for MIB-1 antibody to Ki-67 and measure the proliferation index (PI) of the tumor. Of the many reports about MIB-1 PI in Spitz nevi and melanoma, none have consolidated the information to provide guidelines for the predictive probability that a lesion is a Spitz nevus, given that the MIB-1 PI falls into a certain interval. The present study used previously published data and exponential and gamma probability density functions to model statistical distributions of PI, respectively, in Spitz nevi and melanomas and Bayes rule to estimate the predictive probability that a lesion is a Spitz nevus, given an observed PI. Results indicate that PIs more than 10% favor a melanoma diagnosis and PIs less than 2%, Spitz nevus. PI values between 2% and 10% yield various predictive values for Spitz nevus, depending on the a priori probability that the lesion is a Spitz nevus. The algorithm tabulates guidelines for the predictive probabilities of Spitz nevus given an observed PI.

Bayes Theorem↗