Byron Crawford

Small nonpolypoid carcinomas of the large intestine

Two small carcinomas of the colon were examined, one an intramucosal carcinoma and the other a small carcinoma invading the submucosa. Serial sections did not reveal any adenomatous hyperplasia or polyps in the vicinity. The colonoscopist must be aware of the potential clinical importance of any small mucosal excrescence. Although several studies have indicated that most colonic carcinomas develop from an adenomatous polyp, some carcinomas apparently arise de novo. Further study of the epidemiologic, etiologic, and prognostic factors relating to these apparently uncommon lesions is indicated.

Primary myxoma of the temporal bone in a 17-year-old boy: case report.

OBJECTIVE AND IMPORTANCE Only two cases of primary intracranial myxomas have been described previously in the literature: one patient had a primary intracranial myxoma in the pituitary fossa, and the other patient’s myxoma was located in the posterior fossa. CLINICAL PRESENTATION A rare case of primary myxoma of the temporal bone in a 17-year-old boy is described. The patient presented with a history of progressive left-sided hearing loss and increasing headaches of a few months’ duration. INTERVENTIONAn initial draining procedure in the left ear revealed extant mucous material, and further investigation showed a large calcified lesion involving the petrous and temporal bones and filling the middle fossa. At surgery, a large mucoid-appearing tumor was removed. The tumor pathology revealed a primary myxoma with bone and meningeal involvement. No clinical or histopathological evidence that it was a metastatic lesion was found. CONCLUSIONThe features of myxomas on computed tomographic and magnetic resonance imaging, the histopathology, and surgical considerations are discussed.

Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer

Purpose: The causes of disproportionate incidence and mortality of prostate cancer among African Americans (AA) remain elusive. The purpose of this study was to investigate the mechanistic role and assess clinical utility of the splicing factor heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) in prostate cancer progression among AA men. Experimental Design: We employed an unbiased functional genomics approach coupled with suppressive subtractive hybridization (SSH) and custom cDNA microarrays to identify differentially expressed genes in microdissected tumors procured from age- and tumor grade–matched AA and Caucasian American (CA) men. Validation analysis was performed in independent cohorts and tissue microarrays. The underlying mechanisms of hnRNPH1 regulation and its impact on androgen receptor (AR) expression and tumor progression were explored. Results: Aberrant coexpression of AR and hnRNPH1 and downregulation of miR-212 were detected in prostate tumors and correlate with disease progression in AA men compared with CA men. Ectopic expression of miR-212 mimics downregulated hnRNPH1 transcripts, which in turn reduced expression of AR and its splice variant AR-V7 (or AR3) in prostate cancer cells. hnRNPH1 physically interacts with AR and steroid receptor coactivator-3 (SRC-3) and primes activation of androgen-regulated genes in a ligand-dependent and independent manner. siRNA silencing of hnRNPH1 sensitized prostate cancer cells to bicalutamide and inhibited prostate tumorigenesis in vivo. Conclusions: Our findings define novel roles for hnRNPH1 as a putative oncogene, splicing factor, and an auxiliary AR coregulator. Targeted disruption of the hnRNPH1-AR axis may have therapeutic implications to improve clinical outcomes in patients with advanced prostate cancer, especially among AA men. Clin Cancer Res; 22(7); 1744–56. ©2015 AACR.

Robotic-assisted transaxillary parathyroidectomy of an atypical adenoma.

Abstract The advancement of minimally invasive surgical technologies over the past several years has led to improved surgical outcomes and greater patient satisfaction. Particularly for patients undergoing parathyroidectomies, endoscopic surgeries resulted in smaller surgical scars when compared with the open approach. Early endoscopic methods, however, were still restricted in their ability to provide adequate dexterity, two-dimensional views of the operative field; and while smaller than open surgeries, still left the presence of a small cervical scar. The limitations of endoscopic surgery led to application of the da Vinci S surgical robot system (Intuitive Surgical, Sunnyvale, CA, USA) and a novel transaxillary approach for parathyroidectomy (15). This surgical technique and approach is ideal for patients with primary hyperparathyroidism. This case report demonstrates that parathyroidectomy with en bloc thyroid lobectomy for atypical parathyroid adenomas using robotic- assisted transaxillary surgery is safe and feasible.

High circulating estrogens and selective expression of ERβ in prostate tumors of Americans: implications for racial disparity of prostate cancer

Although estrogen receptor beta (ERβ) has been implicated in prostate cancer (PCa) progression, its potential role in health disparity of PCa remains elusive. The objective of this study was to examine serum estrogens and prostate tumor ERβ expression and examine their correlation with clinical and pathological parameters in African American (AA) versus Caucasian American (CA) men. The circulating 17β-estradiol (E2) was measured by enzyme immunoassay in blood procured from racially stratified normal subjects and PCa patients. Differential expression profile analysis of ERβ was analyzed by quantitative immunohistochemistry using ethnicity-based tissue microarray encompassing 300 PCa tissue cores. In situ ERβ expression was validated by quantitative reverse transcription-PCR in matched microdissected normal prostate epithelium and tumor cells and datasets extracted from independent cohorts. In comparison with normal age-matched subjects, circulating E2 levels were significantly elevated in all PCa patients. Further analysis demonstrates an increase in blood E2 levels in AA men in both normal and PCa in comparison with age- and stage-matched counterparts of CA decent. Histochemical score analysis reveals intense nuclear immunoreactivity for ERβ in tumor cores of AA men than in CA men. Gene expression analysis in microdissected tumors corroborated the biracial differences in ERβ expression. Gene expression analysis from independent cohort datasets revealed correlation between ERβ expression and PCa progression. However, unlike in CA men, adjusted multivariate analysis showed that ERβ expression correlates with age at diagnosis and low prostate-specific antigen recurrence-free survival in AA men. Taken together, our results suggest that E2-ERβ axis may have potential clinical utility in PCa diagnosis and clinical outcome among AA men.

In vivo proteomic analysis of cytokine expression in laser capture-microdissected urothelial cells of obstructed Ureteropelvic junction procured by laparoscopic dismembered pyeloplasty

BACKGROUND AND PURPOSE Ureteropelvic junction obstruction (UPJO) is defined as an impediment to urinary flow from the renal pelvis into the ureter. The exact cause remains an enigma despite investigations along embryologic, anatomic, and histologic lines. Our goal was to investigate in vivo the expression profile of cytokines in hyperplastic urothelial cells as a means of determining the source of UPJO. MATERIALS AND METHODS Cellular proteomes of matched normal and hyperplastic urothelial cells were analyzed by laser capture microdissection (LCM) and tissue microdissection and human cytokine proteomic chips. All specimens (N = 9) were surgically obtained from patients undergoing laparoscopic dismembered pyeloplasty and were immediately embedded in O.C.T. solution and flash-frozen in liquid nitrogen. Tissue sections (6 microm) were mounted on uncoated glass slides using a cryostat, fixed in 70% ethanol, stained with hematoxylin and eosin, and sequentially dehydrated in ethanol and xylene. Typically, paired samples of normal and hyperplastic urothelial cells were procured on separate caps from serial sections of each specimen by the Arcturus PixCell II LCM system using 3000 laser pulses and a spot diameter of 30 microm. Total proteins were harvested and quantitated. Differential expression profile analysis of 43 cytokines in normal and hyperplastic cells were performed using human protein chips. Briefly, the membranes were initially probed with protein (150 ng) from normal or hyperplastic cells and sequentially reacted with a cocktail of biotinylated cytokine antibodies and horseradish peroxidase-conjugated streptavidin. The membranes were developed using enhanced chemiluminescence and analyzed by densitometry. RESULTS Comparative densitometric analysis revealed twofold to fourfold upregulation of growth-related oncogene alpha (GRO-alpha), interleukin (IL)-1alpha, interferon (INF)-gamma, IL-8, tumor necrosis factor (TNF)-alpha, RANTES, and macrophage inflammatory protein-1beta (MIP-1beta) and twofold to fourfold downregulation of transforming growth factor (TGF)-beta and IL-10 in hyperplastic urothelial cells compared with paired control cells. CONCLUSIONS We here report the efficient application of LCM and proteomic array chips for expression profile analysis of cytokines in vivo. Because the etiology and pathogenesis of UPJO are still fragmentary, the marked heterogeneity of the observed cytokine alterations reported here may be of significance. Further studies are required to elucidate the functional significance of the differentially expressed cytokines in the pathogenesis of the disease.

Primary Peripheral Nerve Sheath Tumors of the Thyroid Gland

BACKGROUND Primary peripheral nerve sheath tumors (PNSTs) of the thyroid gland are exceptionally rare tumors that usually present as asymptomatic neck nodules in adults. This article presents a literature review of these tumors. SUMMARY PNSTs of the thyroid can be classified into benign and malignant. Only three cases of malignant PNSTs have been reported. Benign PNSTs of the thyroid include neurofibromas and schwannomas. Only two cases of isolated neurofibroma of the thyroid have been reported. Schwannomas are typically benign, slow-growing tumors that originate from neuronal schwann cells, with a clinical picture depending on the anatomic size and site. Pathologically, schwannomas are classified into Antoni A and Antoni B. Only 17 cases of schwannomas of the thyroid exist in literature to date. CONCLUSIONS Schwannomas of the thyroid gland are extremely rare and usually asymptomatic. Complete surgical resection is mandatory for care.

A web page to teach neurology and neuropathology to medical students.

Sir: We describe a computer-based module developed to teach neurology and neuropathology to sophomore medical students, made available on both CD-ROM and the World Wide Web. Student reaction to the module was encouraging and exam scores also appeared to improve in the class that used this module. A medical student must gain a working knowledge of the intricacies of the nervous system and its pathology in a very limited amount of time. In the United States, neuropathology is usually taught during the second year of medical school, over about a 1±3 week period. In recent years there also has been increasing pressure to advance relevant clinical knowledge in the allied ®elds of neurology, neuropsychiatry and neuroradiology within the teaching of neuropathology. Successful teaching of neuropathology involves several factors. Obviously, the main goal is that students learn the material. There are many ways to establish how well this has been accomplished, such as class exams, preceptor evaluations and performance in subsequent clinical rotations in areas such as neurology, neurosurgery and neuroradiology. Standardized exams, such as the National Board of Medical Examiners (NBME) shelf exam, can provide a reasonable means of comparison [6]. Although instructors would like their students to perform well on exams, neuropathology also should be an enjoyable and stimulating experience for the students. How best to accomplish these goals in the teaching of neuropathology has been the subject of research and debate [1,2]. Case-based approaches are increasingly popular [5], as is the use of computer technology [4]. In previous studies we have investigated what students found useful in a web page to teach pathology and have found that students generally like computer-based teaching modules [3]. Students like web pages that provide images and material in a format that is easily organized for review. Student complaints often focused on pages that loaded slowly, or that required complicated or memory-hungry plug-ins. The principles learned from these earlier surveys were applied to construct a web page to teach neuropathology to second year medical students. The same material was provided on a CD-ROM and distributed free to the students during their neuropathology block. The success of this venture was measured in two ways: by examining student scores on the neuropathology portion of the NBME shelf exam; and by surveying student opinions of the course, the web page and the neuropathology computer module. A module was constructed to cover the following topics: congenital malformations; hydrocephalus; brain herniation; intracranial haemorrhage; cerebrovascular disorders and cerebral haemorrhage; degenerative, demyelinating, and neuromuscular diseases; infectious diseases of the nervous system; and tumours and phakomatoses of the nervous system. This module included digital images, case presentations and review questions. All material was written in simple Hypertext Markup Language (HTML). Images were stored as industry-standard formats (jpg; joint expert photographic ®les or gif; graphic interface ®les) so that any web browser could be used. Material was made available to students at the following web address: Http://www.tmc.tulane.edu/ student/2002/neuropathology/start_here.htm. Material was also provided on CD-ROM. Student performance in neuropathology was compared by examining performance in the neuropathology section of the NBME shelf exam for the class that had access to the neuropathology module (class of 2002) to the previous years class (class of 2001). In order to protect the integrity of the NBME exam, and to correct for variations in the comparative dif®culty of different questions on exams from different years, scores are reported as normalized to the national average rather than as raw scores (Figure 1). After the neuropathology block, students were asked to ®ll out a survey that included their overall opinion of the neuropathology CD-ROM (Figure 2) and their preferred media for accessing neuropathology material outside of class (Figure 3). Students were also encouraged to write comments about the neuropathology module in general. Con®dence intervals for percentages were calculated for extrapolation to an in®nite population using an alpha of 0.95. Comparisons between groups were made by student t-test. Neuropathology and Applied Neurobiology (2001), 27, 142±144

Papillary thyroid carcinoma in black thyroids

Black thyroid is a rare condition. It has been considered to be pathognomonic of chronic minocycline ingestion for more than 30 years, although it can also occur in patients with hemochromatosis, ochronosis, mucoviscidosis, and hemorrhage. A possible association of black thyroid with thyroid cancer has been considered, but no direct causal relationship has been established. Hence, the purpose of this article was to identify the malignant potential of such glands.

Black Thyroid Associated with Thyroid Carcinoma

Objective. Black thyroid is a rare pigmented change seen almost exclusively in patients upon minocycline ingestion, and the process has previously been thought to be generally benign. There have been 61 reported cases of black thyroid. We are aware of 13 cases previously reported in association with thyroid carcinoma. This paper reports six patients with black thyroid pigmentation in association with thyroid carcinoma. Design. The medical records of six patients who were diagnosed with black thyroid syndrome, all of whom underwent thyroid surgery, were reviewed. Data on age, gender, race, preoperative fine needle aspiration biopsy (FNA), thyroid function levels, and pathology reports were collected. Main Outcome. The mean age was 60 years. There were 5 females, 4 of whom were African American. All patients were clinically and biochemically euthyroid. Black pigmentation was not diagnosed in preoperative FNA, and only one patient had a preoperative diagnosis of papillary thyroid carcinoma. The other patients underwent surgery and were found to have black pigmentation of the thyroid associated with carcinoma. Conclusions. FNA does not diagnose black thyroid, which is associated with thyroid carcinoma. Thyroid glands with black pigmentation deserve thorough pathologic examination, including several sections of each specimen.