Gleason Score Evolution and the Effect on Prostate Cancer Outcomes.

OBJECTIVES: We evaluated how the changes in Gleason grading affected the long-term outcomes of a large prostatectomy cohort. METHODS: We obtained long-term follow-up (16.7 years) in 581 patients having undergone radical retropubic prostatectomy between 1985 and 1995. We excluded those with seminal vesicle and/or lymphatic involvement. We regraded the specimens according to contemporary guidelines and compared how this affected outcomes compared with their original (pre-1995) Gleason scoring. In total, 499 patients were evaluable. RESULTS: A Gleason score of 6 or less declined from 73% to 29%, and the number increased from 25% to 63% for a Gleason score of 7 and from 5% to 8% for a Gleason score of 8 to 9. As a result, for a Gleason score less than 7, biochemical failure decreased from 28% to 23%, metastatic disease 5% to 2%, and prostate cancer death from 5% to 3%. The same results were 50% to 37%, 11% to 7%, and 10% to 6% for a Gleason score of 7 and 86% to 71%, 43% to 32%, and 29% to 26% for a Gleason score more than 7, respectively. With the most recent grade grouping, for groups 1 to 5, biochemical failure occurred in 23%, 32%, 45%, 69%, and 78%, respectively. Metastatic disease occurred in 2%, 4%, 12%, 24%, and 56%, respectively. Prostate cancer-related death occurred in 2%, 4%, 9%, 21%, and 44%, respectively. CONCLUSIONS: The revised Gleason scores improved the outcomes in all risk groups. Based on Gleason score, patients with prostate cancer will appear to have better outcomes than they did before 2005, making any comparison tenable. The current grading system shows a consistent increased risk in biochemical failure, metastatic disease, and prostate cancer-related death with each successive grade.

Diagnosing Osteomyelitis: A Histology Guide for Pathologists.

Histopathologic examination of bone specimens coupled with bone culture is considered the gold standard for the diagnosis of osteomyelitis (OM). Despite this, studies have demonstrated interpathologist agreement in the diagnosis of OM as low as 30%, largely stemming from a lack of specific definitions and diagnostic criteria. Review of the literature has provided insight into the lifecycle of OM, illustrating the histologic progression of OM phases from acute to chronic, and provides support for defining subcategories of OM. Using an algorithmic histopathologic tool consisting of 15 criteria, each with an associated score, we defined 5 categories of OM: (1) acute OM, (2) acute and chronic OM, (3) chronic OM, (4) chronic active OM, and (5) chronic inactive OM. We reviewed 462 microscopic slides from 263 patients with suspected OM, and for each slide, we determined an algorithm-derived diagnosis, which was then used to calculate a total histopathologic load score (Jupiter score). Algorithm-derived diagnoses recapitulated original clinical diagnoses and diagnosed cases as OM that had not been originally diagnoses. These novel cases were more likely to have subsequent clinical complications. Finally, pathologic load scores were assessed for association with the category of OM.

A pilot study in intraparenchymal therapy delivery in the prostate: a comparison of delivery with a porous needle vs standard needle.

BACKGROUND: New biologic therapies directly injected into the prostate are in clinical trials for prostatic diseases. There is a need to understand distribution of injected therapies as a function of prostatic anatomy, physiology, and device design. METHODS: A needle with a porous length of customizable-length was tested and its performance compared with a standard needle. Injections of magnetic resonance contrast reagent were placed into ex-vivo human prostates after surgical excision in standard of care therapy for invasive bladder cancer patients. Magnetic resonance images were acquired using sequences to quantify volume delivered, distributed, and backflow. RESULTS: Magnetic resonance images analysis revealed heterogeneity distribution with injection into the specimens. There was low resistance to flow along ductal pathways and high resistance to flow into glandular nodules and smooth muscle/fibrous parenchyma. Data confirm previous studies showing injection loss via urethra backflow, urethra, and prostatic ducts. Tissue fraction of dose was significantly higher with porous needle compared with standard needle (p = .03). We found that a greater volume of distribution divided by the amount infused (Vd/Vi) increased by 80% with the porous needle, though no statistically significant association due to small sample size. CONCLUSIONS: This study demonstrated that prostatic tissue is anatomically heterogenic and limits distribution of needle injection. There is greater distribution in the ex-vivo prostate using a porous needle. The complexity of intra prostatic flow pathways suggests preoperative imaging and pre-treatment planning will enhance therapy.

Failure of Ploidy and Proliferative Fraction to Predict Long-Term Outcome After Prostatectomy.

BACKGROUND: Historically, ploidy and S phase percentage appeared to be promising predictors for prostate cancer recurrence. Lack of uniformity and consistency hampered their development. We evaluated ploidy and S phase for prostate cancer death in a cohort of patients with long-term follow-up. METHODS: We identified 127 patients that had ploidy and S phase determined at the time of their radical prostatectomy for prostate cancer. With 15 years of follow-up, we determined the risk of biochemical failure and risk of death from prostate cancer. We correlated the S phase and ploidy findings with standard pathology findings. RESULTS: A total of 107 (84%) had diploid and 20 (16%) had non-diploid cancers. The median S phase was 6.6%. There was no correlation of ploidy (P = 0.472) or S phase with preoperative PSA or Gleason score. On univariate analysis, EPE, margin positivity, seminal vesicle involvement, lymph node involvement, high Gleason score and PSA > 10 ng/mL were all predictive of biochemical failure. Ploidy and S phase were not. For prostate cancer death, only Gleason score was predictive. CONCLUSIONS: With long-term follow-up in our cohort, Gleason score was predictive of prostate cancer death. Ploidy and S phase were not predictive for biochemical failure or prostate cancer mortality.

TTF-1 and napsin A do not differentiate metastatic lung adenocarcinomas from primary esophageal adenocarcinomas: proposal of a novel staining panel.

CONTEXT: When adenocarcinomas arise within the esophagus, particularly when located away from the gastroesophageal junction, it may be important in some patients to differentiate between a primary esophageal adenocarcinoma and metastasis from another site. Lung adenocarcinoma is one tumor that has been reported to frequently metastasize to the esophagus. OBJECTIVES: To create a panel of immunohistochemical markers that can reliably distinguish between an esophageal and pulmonary primary; within the gastrointestinal pathology literature, including published articles and textbooks, common lung immunohistochemical markers, such as TTF-1, are assumed to be negative in esophageal adenocarcinoma, yet, to our knowledge, no study has yet investigated the veracity of that presumption. DESIGN: In this study, 24 cases each of pulmonary and esophageal adenocarcinomas were stained with TTF-1, napsin A, CDX2, 34ßE12, N-cadherin, and IMP3 in an attempt to define an optimal panel for differentiation. Esophageal adenocarcinomas occurring at the gastroesophageal junction were excluded in this study because a gastric primary tumor cannot be excluded in those cases. RESULTS: Surprisingly, TTF-1 and napsin A were positive in similar proportions of tumors from both sites. Those markers that differentiated statistically between esophageal and pulmonary adenocarcinoma were IMP3, CDX2, and N-cadherin. CONCLUSIONS: When differentiating the origin of a tumor as either esophageal or pulmonary, an immunohistochemical panel consisting of IMP3, CDX2, and N-cadherin is superior to either TTF-1 or napsin A.

Pathologist workforce in the United States: I. Development of a predictive model to examine factors influencing supply.

CONTEXT: Results of prior pathology workforce surveys have varied between a state of equilibrium and predictions of shortage. OBJECTIVE: To assess the current and future supply of pathologists, and apply a dynamic modeling tool for assessing the effects of changing market forces and emerging technologies on the supply of pathologists' services through 2030. DESIGN: Data came from various sources, including the literature, College of American Pathologists' internal data, and primary research through custom-developed surveys for the membership and for pathology practice managers RESULTS: Through 2010, there were approximately 18 000 actively practicing pathologists in the United States (5.7 per 100 000 population), approximately 93% of whom were board certified. Our model projects that the absolute and per capita numbers of practicing pathologists will decrease to approximately 14 000 full-time equivalent (FTE) pathologists or 3.7 per 100 000 in the coming 2 decades. This projection reflects that beginning in 2015, the numbers of pathologists retiring will increase precipitously, and is anticipated to peak by 2021. Including all types of separation, the net pathologist strength will begin falling by year 2015. Unless workforce entry or exit rates change, this trend will continue at least through 2030. These changes reflect the closure of many training programs 2 to 4 decades ago and the substantially decreased number of graduating residents. CONCLUSIONS: This comprehensive analysis predicts that pathologist numbers will decline steadily beginning in 2015. Anticipated population growth in general and increases in disease incidence owing to the aging population, to be presented in a companion article on demand, will lead to a net deficit in excess of more than 5700 FTE pathologists. To reach the projected need in pathologist numbers of nearly 20 000 FTE by 2030 will require an increase from today of approximately 8.1% more residency positions. We believe a pathologist shortage will negatively impact both patient access to laboratory services and health care providers' abilities to deliver more effective health care to their patient populations.

TRIG on TRACK: educating pathology residents in genomic medicine.

Genomic technologies are dramatically changing the practice of medicine. Next-generation sequencing has allowed prognostic stratification of cancer patients, personalized drug therapy and the identification of genetic risk factors for a multitude of diseases. As the physicians who oversee tissue- and laboratory-based diagnostic testing, pathologists must understand and utilize this new technology for the benefit of patients; however, only a minority of pathology residency programs currently provide training in genomics. In response to this urgent need, the Training Residents in Genomics (TRIG) Working Group has made significant progress towards creating, implementing, evaluating and disseminating a national curriculum in genomic pathology. Although presented in the context of pathology training, the approach described in this review can serve as model for education in genomic medicine of students, trainees or professionals in other areas of healthcare.

Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study.

BACKGROUND: Optimum management of clinically localised prostate cancer presents unique challenges because of the highly variable and often indolent natural history of the disease. To predict disease aggressiveness, clinicians combine clinical variables to create prognostic models, but the models have limited accuracy. We assessed the prognostic value of a predefined cell cycle progression (CCP) score in two cohorts of patients with prostate cancer. METHODS: We measured the expression of 31 genes involved in CCP with quantitative RT-PCR on RNA extracted from formalin-fixed paraffin-embedded tumour samples, and created a predefined score and assessed its usefulness in the prediction of disease outcome. The signature was assessed retrospectively in a cohort of patients from the USA who had undergone radical prostatectomy, and in a cohort of randomly selected men with clinically localised prostate cancer diagnosed by use of a transurethral resection of the prostate (TURP) in the UK who were managed conservatively. The primary endpoint was time to biochemical recurrence for the cohort of patients who had radical prostatectomy, and time to death from prostate cancer for the TURP cohort. FINDINGS: After prostatectomy, the CCP score was useful for predicting biochemical recurrence in the univariate analysis (hazard ratio for a 1-unit change [doubling] in CCP 1·89; 95% CI 1·54-2·31; p=5·6×10(-9)) and the best multivariate analysis (1·77, 1·40-2·22; p=4·3×10(-6)). In the best predictive model (final multivariate analysis), the CCP score and prostate-specific antigen (PSA) concentration were the most important variables and were more significant than any other clinical variable. In the TURP cohort, the CCP score was the most important variable for prediction of time to death from prostate cancer in both univariate analysis (2·92, 2·38-3·57, p=6·1×10(-22)) and the final multivariate analysis (2·57, 1·93-3·43; p=8·2×10(-11)), and was stronger than all other prognostic factors, although PSA concentration also added useful information. Heterogeneity in the hazard ratio for the CCP score was not noted in any case for any clinical variables. INTERPRETATION: The results of this study provide strong evidence that the CCP score is a robust prognostic marker, which, after additional validation, could have an essential role in determining the appropriate treatment for patients with prostate cancer. FUNDING: Cancer Research UK, Queen Mary University of London, Orchid Appeal, US National Institutes of Health, and Koch Foundation.

Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710).

OBJECTIVE: • To determine whether the effect of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) on the survival of patients with locally advanced urothelial carcinoma (UC) of the bladder treated with radical cystectomy varies with the presence of non-urothelial components in the tumour. PATIENTS AND METHODS: • This is a secondary analysis of the Southwest Oncology Group-directed intergroup randomized trial S8710 of neoadjuvant MVAC followed by cystectomy versus cystectomy alone for treatment of locally advanced UC of the bladder. • For the purpose of these analyses, tumours were classified based on the presence of non-urothelial components as either pure UC (n= 236) or mixed tumours (n= 59). Non-urothelial components included squamous and glandular differentiation. • Cox regression models were used to estimate the effect of neoadjuvant MVAC on all-cause mortality for patients with pure UC and for patients with mixed tumours, with adjustment for age and clinical stage. RESULTS: • There was evidence of a survival benefit from chemotherapy in patients with mixed tumours (hazard ratio 0.46; 95% CI 0.25-0.87; P= 0.02). Patients with pure UC had improved survival on the chemotherapy arm but the survival benefit was not statistically significant (hazard ratio 0.90; 95% CI 0.67-1.21; P= 0.48). • There was marginal evidence that the survival benefit of chemotherapy in patients with mixed tumours was greater than it was for patients with pure UC (interaction P= 0.09). CONCLUSION: • Presence of squamous or glandular differentiation in locally advanced UC of the bladder does not confer resistance to MVAC and in fact may be an indication for the use of neoadjuvant chemotherapy before radical cystectomy.

Quality of pathologic response and surgery correlate with survival for patients with completely resected bladder cancer after neoadjuvant chemotherapy.

BACKGROUND: In a retrospective study of Southwestern Oncology Group (SWOG)-S8710/INT-0080 (radical cystectomy [RC] alone vs 3 cycles of neoadjuvant chemotherapy [NC] with methotrexate, vinblastine, doxorubicin, and cisplatin before RC for bladder cancer), factors found to be associated with improved overall survival (OS) included pathologic complete response, defined as P0; treatment with NC; completion of RC with negative surgical margins; and >or=10 pelvic lymph nodes (LNs) removed. METHODS: The authors used stratified Cox regression to retrospectively study the association of quality of pathologic response after RC with OS in the subset of S8710 patients who received NC and RC with negative surgical margins. RESULTS: Of 154 patients who received NC, 68 (44.2%) were

Selective inhibition of prostaglandin E2 receptors EP2 and EP4 induces apoptosis of human endometriotic cells through suppression of ERK1/2, AKT, NFkappaB, and beta-catenin pathways and activation of intrinsic apoptotic mechanisms.

Endometriosis is a benign chronic gynecological disease of reproductive-age women characterized by the presence of functional endometrial tissues outside the uterine cavity. It is an estrogen-dependent disease. Current treatment modalities to inhibit biosynthesis and actions of estrogen compromise menstruation, pregnancy, and the reproductive health of women and fail to prevent reoccurrence of disease. There is a critical need to identify new specific signaling modules for non-estrogen-targeted therapies for endometriosis. In our previous study, we reported that selective inhibition of cyclooxygenase-2 prevented survival, migration, and invasion of human endometriotic epithelial and stromal cells, which was due to decreased prostaglandin E(2) (PGE(2)) production. In this study, we determined mechanisms through which PGE(2) promoted survival of human endometriotic cells. Results of the present study indicate that 1) PGE(2) promotes survival of human endometriotic cells through EP2 and EP4 receptors by activating ERK1/2, AKT, nuclear factor-kappaB, and beta-catenin signaling pathways; 2) selective inhibition of EP2 and EP4 suppresses these cell survival pathways and augments interactions between proapoptotic proteins (Bax and Bad) and antiapoptotic proteins (Bcl-2/Bcl-XL), facilitates the release of cytochrome c, and thus activates caspase-3/poly (ADP-ribose) polymerase-mediated intrinsic apoptotic pathways; and 3) these PGE(2) signaling components are more abundantly expressed in ectopic endometriosis tissues compared with eutopic endometrial tissues during the menstrual cycle in women. These novel findings may provide an important molecular framework for further evaluation of selective inhibition of EP2 and EP4 as potential therapy, including nonestrogen target, to expand the spectrum of currently available treatment options for endometriosis in women.

Induction of peritoneal endometriosis in nude mice with use of human immortalized endometriosis epithelial and stromal cells: a potential experimental tool to study molecular pathogenesis of endometriosis in humans.

OBJECTIVE: To determine whether a mixed population of immortalized human endometriosis epithelial and stromal cells is able to induce peritoneal endometriosis in nude mice. DESIGN: Prospective experimental study. Human immortalized endometriosis epithelial and stromal cells were xenografted into ovariectomized nude mice. Macroscopically, the number of induced endometriosis-like lesions and their color were determined. Microscopically, histomorphology of endometriosis glands and their structure were analyzed, and comparisons were made with tissue from spontaneous endometriosis in women. SETTING: College of Veterinary Medicine and Biomedical Sciences, Texas A&M University. ANIMALS: Seven ovariectomized nude mice. INTERVENTION(S): Minimal invasive procedures were performed to administer estrogen pellets and transplant immortalized human endometriosis epithelial and stromal cells into nude mice. MAIN OUTCOME MEASURE(S): Peritoneal endometriosis-like lesions induced in nude mice were characterized and compared with spontaneous peritoneal endometriosis in women. RESULT(S): Xenografts of human immortalized endometriosis epithelial and stromal cells into the peritoneal cavity of the recipient nude mice are able to proliferate, attach, invade, reorganize, and establish peritoneal endometriosis. Endometriosis glands at different stages of growth were present in induced endometriosis-like lesions. Proliferating cell nuclear antigen, metalloproteinase 2, estrogen receptor-alpha, cyclooxygenase-2, and prostaglandin E(2) receptors EP2 and EP4 proteins were expressed in both endometriosis glandular epithelial and stromal cells of the induced endometriosis-like lesions. CONCLUSION(S): This xenograft model could be used as a potential experimental tool to understand the molecular and cellular aspects of the pathogenesis of endometriosis in humans.

Benign breast disease.

Benign breast disease includes all nonmalignant conditions of the breast, including benign tumors, trauma, mastalgia, mastitis, and nipple discharge. Benign tumors include pathologic changes that do not increase a patient's risk for developing cancer, lesions that confer a slightly increase risk, and lesions that are associated with an up to 50% risk of developing breast cancer. Both benign and malignant breast disorders can present with a palpable mass; skin dimpling, thickening, or erythema; pain; nipple discharge and inversion or distortion; or an abnormal screening mammogram with no clinical findings. Tools available to investigate breast problems include clinical breast examination, mammogram, and ultrasound. This article discusses the gynecologist's role in maintaining breast health, the clinical evaluation of breast problems, and management of benign breast disease.

Cyclooxygenase-2 regulates survival, migration, and invasion of human endometriotic cells through multiple mechanisms.

Endometriosis is a debilitating disease characterized by the presence of functional endometrial glandular epithelium and stroma outside the uterine cavity that affects up to 20% of women of child-bearing age. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme in the biosynthesis of prostaglandin E(2) (PGE(2)), is highly expressed in endometriotic tissues and results in increased concentrations of peritoneal PGE(2) in women. In this study, we determined the expression of COX-2 protein in ectopic and eutopic endometria in humans and the role of COX-2 in endometriotic cell survival, migration, and invasion in humans. Our results indicate that COX-2 protein is abundantly expressed in ectopic endometria compared with eutopic endometria. Comparatively, expression of COX-2 protein is higher in eutopic endometria from women with endometriosis compared with women without endometriosis. Inhibition of COX-2 decreases survival, migration, and invasion of endometriotic cells that are associated with decreased production of PGE(2). Cell growth inhibitory effects of COX-2 inhibition/silencing are mediated through nuclear poly (ADP-ribose) polymerase-mediated apoptosis. Cell motility and invasion inhibitory effects of COX-2 inhibition/silencing are mediated through matrix metalloproteinase-2 and -9 activities. Interestingly, effects of COX-2 inhibition is more profound in endometriotic epithelial than in stromal cells. Furthermore, inhibition of COX-2 affects invasion rather than migration of endometriotic epithelial and stromal cells. It is the first evidence showing that inhibition of COX-2 decreases endometriotic epithelial and stromal cell survival, migration, and invasion in humans. Our results support the emerging concept that COX-2/PGE(2) promotes the pathophysiology and pathogenesis of endometriosis in humans.

Global hypomethylation is common in prostate cancer cells: a quantitative predictor for clinical outcome?

This study was designed to determine if cytological detection of 5-methylcytosine (5MC) was feasible on prostate tumor sections and to determine if levels of 5MC differed in malignant compared to normal prostate tissue. We further sought to see if 5MC levels correlated with any clinical outcome data. Thirty prostate tumor sections were obtained from patients who underwent radical prostatectomies from 1988 to 1995; these represented a mix of low to high grade tumors. Clinical data were maintained for each of these patients with a minimum of 7 years of follow up. Sections were stained with a commercially available antibody to 5MC and immunocytochemistry levels were subsequently quantified using a computer-assisted true-color imaging system. Tumor and benign regions of the same archived sections were compared, in addition to a series of 12 normal prostate samples. Prostate cancer cells exhibited a pronounced global decrease in methylation compared with benign and normal tissue. This was observed in 29 of 30 patients (96.7%) studied and densitometric scanning of methylation staining indicated that this value was quantifiable. Overall, higher methylation values were detected in men who had positive surgical margins and recurrent disease. These data suggest that loss of methylation is a feature of prostate cancer, and partial gain of methylation (presumably at promoters of specific genes) is associated with clinical outcome and is measurable using whole-cell assays.

Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer.

BACKGROUND: Despite aggressive local therapy, patients with locally advanced bladder cancer are at significant risk for metastases. We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy. METHODS: Patients were enrolled if they had muscle-invasive bladder cancer (stage T2 to T4a) and were to be treated with radical cystectomy. They were stratified according to age (less than 65 years vs. 65 years or older) and stage (superficial muscle invasion vs. more extensive disease) and were randomly assigned to radical cystectomy alone or three cycles of methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy. RESULTS: We enrolled 317 patients over an 11-year period, 10 of whom were found to be ineligible; thus, 154 were assigned to receive surgery alone and 153 to receive combination therapy. According to an intention-to-treat analysis, the median survival among patients assigned to surgery alone was 46 months, as compared with 77 months among patients assigned to combination therapy (P=0.06 by a two-sided stratified log-rank test). In both groups, improved survival was associated with the absence of residual cancer in the cystectomy specimen. Significantly more patients in the combination-therapy group had no residual disease than patients in the cystectomy group (38 percent vs. 15 percent, P<0.001). CONCLUSIONS: As compared with radical cystectomy alone, the use of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy increases the likelihood of eliminating residual cancer in the cystectomy specimen and is associated with improved survival among patients with locally advanced bladder cancer.

Evaluation of immunohistochemistry and multiple-level sectioning in sentinel lymph nodes from patients with breast cancer.

CONTEXT: Previous investigations on sentinel lymph node biopsies have demonstrated their importance in nodal staging of patients with breast cancer. However, sentinel node biopsy in breast cancer is currently a controversial procedure and continues to provoke debate. OBJECTIVES: We designed our study to determine the usefulness of a standard protocol for evaluating sentinel lymph node metastases and to assess the value of sentinel node biopsy as the only procedure in nodal staging in breast cancer patients. MATERIALS AND METHODS: A retrospective analysis of 84 breast cancer patients with sentinel node biopsies, who also underwent axillary dissection, was conducted using a standard protocol (3 levels of immunohistochemical stains for keratin and 2 levels of hematoxylin-eosin (HE) stains on the first 3 negative lymph nodes). RESULTS: Hematoxylin-eosin staining identified 20 patients (23.8%) with sentinel node metastases. The remaining 64 negative patients (76.1%) were tumor free on sentinel lymph nodes at level 1 HE. Additional immunohistochemical stains for keratin and HE stains on specimens from these 64 patients showed an additional 5 patients (7.8%) to be positive for lymph node micrometastases (<2 mm). The total percentage of cases with sentinel lymph node metastases detected by HE staining and immunohistochemistry was 29.7%. Of the remaining 59 cases that were negative on HE and immunohistochemistry, axillary dissection revealed 3 cases that had metastases in the axillary lymph nodes. The false-negative rate was 10.7%. The concordance rate between sentinel lymph nodes and axillary lymph nodes was 96.4%. The sensitivity was 89% and specificity was 100%. CONCLUSION: Immunohistochemistry and multiple-level sectioning increased detection of metastases by 7.8% in sentinel lymph nodes. Caution should be used in accepting sentinel node biopsy alone as the only procedure for staging due to a high false-negative rate (10.7%). A predictive value of 96.4% confirms that sentinel lymph node biopsy is most likely to contain metastatic carcinoma. Sentinel lymph node examination with the protocol we describe, combined with axillary dissection, increased the yield of metastatic disease by identifying 8 additional cases of nodal metastatic disease (an increase of 28%), as compared to standard axillary nodal dissection and single-section sentinel lymph node examination alone.

Unusual case of stridor and wheeze in an infant: tracheal bronchogenic cyst.

Bronchogenic cysts are congenital anomalies that represent aberrant development of the foregut. Bronchogenic cysts in the mediastinum have been documented in both children and adults, but only one case of tracheal bronchogenic cyst in an infant was found in the literature. We report on a case of an infant with wheeze, stridor, and retractions, caused by a midtracheal bronchogenic cyst. This entity, with its unusual location, should be considered in the differential diagnosis of respiratory distress, cyanotic spells, wheezing, and stridor in infants.

Frozen section diagnosis of metastatic prostate adenocarcinoma in pelvic lymphadenectomy compared with nomogram prediction of metastasis.

OBJECTIVES: To compare the sensitivity and negative predictive values of frozen section analysis of pelvic lymphadenectomy in patients undergoing radical retropubic prostatectomy for prostate adenocarcinoma with the predictive power of published nomograms for metastasis to lymph nodes. METHODS: A retrospective review was performed on all patients who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for prostate adenocarcinoma between 1991 and early 1997. The sensitivity and negative predictive values were computed comparing frozen section analysis, and patients were grouped by risk stratification. Comparison was made using the McNemar text. RESULTS: The sensitivity for detecting lymph node metastasis on frozen section analysis for all risk groups was 33% (9 of 27). The sensitivity for identifying patients at high risk of having nodal metastasis by published nomograms alone was 67% (18 of 27) (P = 0.04). The overall negative predictive value for frozen section analysis was 96.5% (503 of 521). The negative predictive value for uninvolved lymph nodes, using low and intermediate-risk groups stratified by published nomograms, was 97.9% (436 of 445). CONCLUSIONS: Frozen section analysis of pelvic lymph nodes to detect metastatic prostate adenocarcinoma is less sensitive in determining which patients will have lymph nodes involved by metastatic adenocarcinoma than using risk stratification by published nomograms. The negative predictive value of frozen section analysis in all risk groups was very high, up to 97.9%.