An algorithm for expanding the TNM staging system.

AIM: We describe a new method to expand the tumor, lymph node, metastasis (TNM) staging system using a clustering algorithm. Cases of breast cancer were used for demonstration. MATERIALS & METHODS: An unsupervised ensemble-learning algorithm was used to create dendrograms. Cutting the dendrograms produced prognostic systems. RESULTS: Prognostic systems contained groups of patients with similar outcomes. The prognostic systems based on tumor size and lymph node status recapitulated the general structure of the TNM for breast cancer. The prognostic systems based on tumor size, lymph node status, histologic grade and estrogen receptor status revealed a more detailed stratification of patients when grade and estrogen receptor status were added. CONCLUSION: Prognostic systems from cutting the dendrogram have the potential to improve and expand the TNM.

An Algorithm for Creating Prognostic Systems for Cancer.

The TNM staging system is universally used for classification of cancer. This system is limited since it uses only three factors (tumor size, extent of spread to lymph nodes, and status of distant metastasis) to generate stage groups. To provide a more accurate description of cancer and thus better patient care, additional factors or variables should be used to classify cancer. In this paper we propose a hierarchical clustering algorithm to develop prognostic systems that classify cancer according to multiple prognostic factors. This algorithm has many potential applications in augmenting the data currently obtained in a staging system by allowing more prognostic factors to be incorporated. The algorithm clusters combinations of prognostic factors that are formed using categories of factors. The dissimilarity between two combinations is determined by the area between two corresponding survival curves. Groups from cutting the dendrogram and survival curves of the individual groups define our prognostic systems that classify patients using survival outcomes. A demonstration of the proposed algorithm is given for patients with breast cancer from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute.

The clinical implications of integrating additional prognostic factors into the TNM.

BACKGROUND AND OBJECTIVES: The management of solid tumors is governed by host and tumor factors that traditionally have incorporated TNM staging with additional pathologic, biologic, and clinical host factors. Beyond the anatomic-based TNM, increasingly new prognostic and predictive factors are being discovered that have important survival and treatment implications. However, because the TNM is based on a "bin" model, additional prognostic factors would rapidly overwhelm the current system. This communication demonstrates the clinical implications and improved patient prognosis derived from a new algorithmic model based on clustering analysis. METHODS: A new algorithm is described that integrates additional factors into the TNM and calculates survival. RESULTS: The results indicate that additional factors can be integrated into the TNM staging system providing additional patient stratification without changing the TNM definitions. Adding prognostic factors to traditional TNM staging increases substratification of given stages and identifies and separates favorable and unfavorable clinical outcomes for specific TNM stages. CONCLUSION: Integration of additional prognostic factors into the TNM by a clustering algorithm can change the stratification of patient outcome. This may guide the clinician to select a more rational management program based on the additional factors and improve cohort selection for clinical trials.

Assessment of K-Ras mutant frequency and micronucleus incidence in the mouse duodenum following 90-days of exposure to Cr(VI) in drinking water.

Chronic exposure to high concentrations of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) in drinking water induces duodenal tumors in mice, but the mode of action (MOA) for these tumors has been a subject of scientific debate. To evaluate the tumor-site-specific genotoxicity and cytotoxicity of SDD in the mouse small intestine, tissue pathology and cytogenetic damage were evaluated in duodenal crypt and villus enterocytes from B6C3F1 mice exposed to 0.3-520mg/L SDD in drinking water for 7 and 90 days. Allele-competitive blocker PCR (ACB-PCR) was used to investigate the induction of a sensitive, tumor-relevant mutation, specifically in vivo K-Ras codon 12 GAT mutation, in scraped duodenal epithelium following 90 days of drinking water exposure. Cytotoxicity was evident in the villus as disruption of cellular arrangement, desquamation, nuclear atypia and blunting. Following 90 days of treatment, aberrant nuclei, occurring primarily at villi tips, were significantly increased at ≥60mg/L SDD. However, in the crypt compartment, there were no dose-related effects on mitotic and apoptotic indices or the formation of aberrant nuclei indicating that Cr(VI)-induced cytotoxicity was limited to the villi. Cr(VI) caused a dose-dependent proliferative response in the duodenal crypt as evidenced by an increase in crypt area and increased number of crypt enterocytes. Spontaneous K-Ras codon 12 GAT mutations in untreated mice were higher than expected, in the range of 10(-2) to 10(-3); however no treatment-related trend in the K-Ras codon 12 GAT mutation was observed. The high spontaneous background K-Ras mutant frequency and Cr(VI) dose-related increases in crypt enterocyte proliferation, without dose-related increase in K-Ras mutant frequency, micronuclei formation, or change in mitotic or apoptotic indices, are consistent with a lack of genotoxicity in the crypt compartment, and a MOA involving accumulation of mutations late in carcinogenesis as a consequence of sustained regenerative proliferation.

Surgical pathology of lung cancer.

The diagnosis, treatment, and management of lung tumors represent a complex set of decision algorithms and require the cooperation and interaction of a team of experts and support systems. The surgical pathologist, an early, important member of the diagnostic team, uses clinical and radiological evidence to differentiate benign from malignant tumors and renders a unique diagnosis that provides both prognostic and treatment information. Using routine histopathologic criteria, histochemical and immunohistochemical stains, and molecular and genetic testing, surgical pathologists and cytopathologists may distinguish between small cell and other bronchogenic carcinomas, separate adenocarcinomas from squamous cell carcinomas, differentiate between pleural carcinomas and diffuse malignant mesotheliomas, and discriminate among the varieties of neuroendocrine carcinomas. Among adenocarcinomas, the pathological examination stratifies those tumors with absent or minimal central invasive cores that have an excellent prognosis from the more common adenocarcinomas with larger invasive components. These distinctions are necessary based on differences in tumor biology, response to therapy, and prognosis for these different histological types. Histopathologic analysis should attempt to provide a precise diagnosis and limit the usage of the term non-small cell carcinoma. The team approach also enables the optimal use of tumor tissue for diagnostic purposes as well as molecular genetic testing and the discovery of targetable sites for therapeutic management. Though low-stage tumors tend to be initially treated with surgical resection, more advanced stages will be approached with limited tissue acquisition, necessitating a strategy for best practices of scarce tissue resources. The awareness of diagnostic modalities and tissue handling by all members of the team ensures the best patient-centered care.

Effects of IL2/anti-IL2 antibody complex on chikungunya virus-induced arthritis in a mouse model.

Chikungunya virus (CHIKV) is characterized by disabling joint pain that can cause persistent arthritis in approximately one-fourth of patients. Currently, no standard treatments are available for chronic CHIKV arthritis. Our preliminary data suggest that decreases in interleukin-2 (IL2) levels and regulatory T cell (Treg) function may play a role in CHIKV arthritis pathogenesis. Low-dose IL2-based therapies for autoimmune diseases have been shown to up-regulate Tregs, and complexing IL2 with anti-IL2 antibodies can prolong the half-life of IL2. A mouse model for post-CHIKV arthritis was used to test the effects of IL-2, an anti-IL2 monoclonal antibody (mAb), and the complex on tarsal joint inflammation, peripheral IL2 levels, Tregs, effector (Teff) T cells, and histological disease scoring. The complex treatment resulted in the highest levels of IL2 and Tregs, but also increased Teffs, and therefore did not significantly reduce inflammation or disease scores. However, the antibody group, which had moderately increased levels of IL2 and activated Tregs, resulted in a decreased average disease score. These results suggest the IL2/anti-IL2 complex stimulates both Tregs and Teffs in post-CHIKV arthritis, while the anti-IL2 mAb increases IL2 availability enough to shift the immune environment towards a tolerogenic one.

Effects of rIL2/anti-IL2 antibody complex on chikungunya virus-induced chronic arthritis in a mouse model.

Chikungunya virus (CHIKV) is characterized by disabling joint pain that can cause persistent arthritis in approximately one-fourth of patients. Currently, no standard treatments are available for chronic CHIKV arthritis. Our preliminary data suggest that decreases in interleukin-2 (IL2) levels and regulatory T cell (Treg) function may play a role in CHIKV arthritis pathogenesis. Low-dose IL2-based therapies for autoimmune diseases have been shown to up-regulate Tregs, and complexing IL2 with anti-IL2 antibodies can prolong the half-life of IL2. A mouse model for post-CHIKV arthritis was used to test the effects of recombinant IL2 (rIL2), an anti-IL2 monoclonal antibody (mAb), and the complex on tarsal joint inflammation, peripheral IL2 levels, Tregs, CD4 + effector T cells (Teff), and histological disease scoring. The complex treatment resulted in the highest levels of IL2 and Tregs, but also increased Teffs, and therefore did not significantly reduce inflammation or disease scores. However, the antibody group, which had moderately increased levels of IL2 and activated Tregs, resulted in a decreased average disease score. These results suggest the rIL2/anti-IL2 complex stimulates both Tregs and Teffs in post-CHIKV arthritis, while the anti-IL2 mAb increases IL2 availability enough to shift the immune environment towards a tolerogenic one.

Cutaneous angiosarcoma. Analysis of 434 cases from the Surveillance, Epidemiology, and End Results Program, 1973-2007.

Cutaneous angiosarcoma is an aggressive malignant mesenchymal vasoformative neoplasm that accounts for 1% of all soft tissue sarcomas. Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program, we analyzed the demographics and survival of cutaneous angiosarcoma. The Surveillance, Epidemiology, and End Results program recorded 434 cases of cutaneous angiosarcoma from 1973 to 2007. The incidence was nearly the same in men (222 cases) and women (212 cases). Most patients were white (88%) with a mean age of 73 years. African Americans made up only 4% of the cases. Two hundred seventy (62%) cases were tumors of the head and neck, whereas 106 (24%) cases arose in the skin of the trunk. Grade was recorded in 194 cases (45%): 28 were grade I, 44 were grade II, 60 were grade III, and 62 were grade IV. Survival rates of cutaneous angiosarcoma correlated with age, anatomical site, and stage of disease. Patients younger than 50 years had a 10-year relative survival rate of 71.7%, whereas patients 50 years and older had a 36.8% 10-year survival rate. Tumors of the scalp and neck resulted in a 13.8% 10-year relative survival rate, whereas tumors arising in the trunk resulted in a 75.3% 10-year survival rate. Tumors localized to the skin had better prognosis (53.6% 10-year relative survival rate) than those with regional or distant stage (19.0% and 6.2%). Twenty-six percent of patients with angiosarcoma had a prior primary. Cutaneous angiosarcomas arise predominantly in the head and neck of white individuals older than 60 years.

A Mouse Model for Studying Post-Acute Arthritis of Chikungunya.

Chikungunya virus (CHIKV) was introduced to the Americas in 2013, causing two million infections across over thirty countries. CHIKV causes a chronic debilitating arthritis in one fourth of infected individuals and currently evidence-based targeted therapies for the treatment of CHIKV arthritis are lacking. Multiple mouse models of chikungunya have been developed to study acute CHIKV infection. In humans, post-CHIKV arthritis may persist for months to years after viremia from a CHIKV infection has resolved. Therefore, the development of a mouse model of post-acute arthritis of chikungunya may facilitate the study of potential novel therapeutics for this arthritis. In this article we describe the development of a wild-type immunocompetent C57BL/6 mouse model for post-acute arthritis of chikungunya, including a histologic inflammation scoring system, as well as suggestions for how this mouse model may be used to examine the efficacy of novel therapies for CHIKV arthritis.

Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor arising predominantly on sun-exposed skin of older and usually immunosuppressed individuals. METHODS: Using data from NCI's SEER (Surveillance, Epidemiology, and End Results) Program from 1973 to 2006, we analyzed the demographics and survival of MCC. RESULTS: SEER had recorded 3870 cases of MCC. The incidence was higher in men (2380 cases, 61.5%) than in women (1490 cases, 38.5%). Most patients were White (94.9%) between 60 and 85 years of age. MCC was rare in Blacks. The most common location was the head and neck. The salivary glands, nasal cavity, lip, lymph nodes, vulva, vagina and esophagus were the most common extracutaneous sites. The 10-year relative survival rate was higher in women than men (64.8% vs. 50.5%, p < 0.001). Patients 50-69 years had the highest 10-year relative survival rate (59.6%). Stage of disease was the best predictor of survival. CONCLUSIONS: MCC arises predominantly in the skin of head and neck in White men above 70 years of age. Cases also occurred in extracutaneous sites. Age did not predict survival, yet gender, site and tumor size revealed clear differences. The most significant predictor of survival was tumor stage.

The Association Between Race, Obesity, and Sperm Quality Among Men Attending a University Physician Practice in Washington, DC.

A decades-long decline in sperm counts in Western countries has coincided with an increase in obesity rates, prompting study into their association. Few of these studies have incorporated men of color, the sperm health of whom is relatively unknown. The present exploratory study evaluated the association between body mass index (BMI), race, ethnicity, and sperm parameters among a diverse sample of U.S. men attending a Washington, DC physician practice. Semen samples were collected and processed at a single laboratory and sperm concentration, motility, morphology, and count were evaluated according to World Health Organization (WHO) 5th edition criteria. Multivariate models accounted for covariates related to sperm health. The study population (n = 128) was largely obese (45.3%) or overweight (34.4%), and 36.0% were black or Hispanic. Black men had lower adjusted sperm concentration compared to white men (75.0 million/mL to 107.4 million/mL, p = .01) and were more likely to have oligozoospermia (p = .01), asthenozoospermia (p = .004), and low sperm count (p < .0001). Hispanic men had higher adjusted sperm concentration compared to non-Hispanic men (124.5 million/mL to 62.1 million/mL, p = .007) and were less likely to have teratozoospermia (p = .001). Obesity and BMI were associated with lower sperm motility and count in crude models only. Given the study's sample size its findings should be interpreted with caution but align with the limited epidemiological literature to date that has evaluated racial and ethnic differences in semen quality. Heightened clinical research attention is needed to ensure men of color are included in representative numbers in studies of urologic and andrologic health.

BP1, a homeoprotein, is significantly expressed in prostate adenocarcinoma and is concordant with prostatic intraepithelial neoplasia.

BP1 is a member of the homeobox gene superfamily of transcription factors that are essential for early development. Significant mRNA expression and immunohistochemical reactivity of BP1 is present in a majority of breast cancers and in all cases of inflammatory breast cancer. This study attempts to determine whether BP1 expression is detectable in prostate cancer, another hormone dependent solid tumor, and whether this expression correlates with histopathologic and prognostic factors. Paraffin sections from radical prostatectomy cancer specimens and from tissue microarray sections of prostate cancer, obtained from the Prostate Cancer Tissue Registry (NIH), were assayed for BP1 immunoreactivity. Immunoreactivity scoring by two independent pathologists, using a three-tiered system (0, 1+, 2+), was recorded and correlated with Gleason scoring and prostatic specific antigen (PSA) biochemical recurrence. Ki-67 (MIB-1) immunoreactivity was performed to assess proliferation. Kappa and Cochran-Mantel-Haenszel statistical analyses were used to assess interobserver agreement and pathobiologic correlations. Significant BP1 immunoreactivity (2+) was identified in approximately 70% of prostatic adenocarcinomas, whether the analysis was performed on tissue sections (50 cases) or tissue microarray platforms (123 cases). BP1 immunoreactivity was seen in <5% of normal acinar cells. The agreement between two separate observers was very good, with kappa-statistics >0.7. In tissue sections, 12 cases with paired carcinoma and prostatic intraepithelial neoplasia (PIN) showed concordance with strong immunoreactivity. Gleason scores or prostatic specific antigen (PSA) biochemical recurrences were not correlated with strong BP1 immunoreactivity. Tumor proliferation, assayed with Ki-67 (MIB-1) immunoreactivity, was higher in cancer cells that were BP1 immunoreactive, relative to those that were BP1 non-reactive. These findings suggest that BP1 is an important upstream factor in the carcinogenic pathway of prostate cancer and that the expression of BP1 may reflect or directly contribute to tumor progression and/or invasion.

Developing prognostic systems of cancer patients by ensemble clustering.

Accurate prediction of survival rates of cancer patients is often key to stratify patients for prognosis and treatment. Survival prediction is often accomplished by the TNM system that involves only three factors: tumor extent, lymph node involvement, and metastasis. This prediction from the TNM has been limited, because other potential prognostic factors are not used in the system. Based on availability of large cancer datasets, it is possible to establish powerful prediction systems by using machine learning procedures and statistical methods. In this paper, we present an ensemble clustering-based approach to develop prognostic systems of cancer patients. Our method starts with grouping combinations that are formed using levels of factors recorded in the data. The dissimilarity measure between combinations is obtained through a sequence of data partitions produced by multiple use of PAM algorithm. This dissimilarity measure is then used with a hierarchical clustering method in order to find clusters of combinations. Prediction of survival is made simply by using the survival function derived from each cluster. Our approach admits multiple factors and provides a practical and useful tool in outcome prediction of cancer patients. A demonstration of use of the proposed method is given for lung cancer patients.

Cancers of the ampulla of vater: demographics, morphology, and survival based on 5,625 cases from the SEER program.

BACKGROUND: Cancers of the ampulla are unusual and morphologically heterogeneous. The NCI's SEER Program is now large enough so that unusual cancers can be studied. Based on pathologic and epidemiologic characteristics of cancer of the ampulla available in SEER, important clinicopathological correlations can be made. METHODS: All patients with cancer of the ampulla were identified between 1973 and 2005. Demographic features, distribution of histological types, age-specific incidence rates, and 5-year survival rates according to stage and histologic type were compared. RESULTS: There were 5,625 cases of ampullary cancer. Ampullary cancer has been increasing since 1973. In both African Americans and Caucasians, the disease is more common in men. Adenocarcinomas, NOS comprised 65% of all histological types. Survival depends on stage, grade, and histologic type. Papillary carcinomas had a more favorable survival than other types; carcinomas arising in adenomas had a more favorable survival than adenocarcinomas not associated with adenomas. Logarithmic transformation of age-related incidence data demonstrates that cancers having differing histopathologic phenotypes represent a single population of tumors. CONCLUSIONS: Prognostic factors include histologic type, grade, stage, and coexisting adenomas. These data should be included in pathology reports. Although certain histologic types exhibit morphologic differences, their pathogenesis appears to be similar.

Carcinoid tumors and small-cell carcinomas of the gallbladder and extrahepatic bile ducts: a comparative study based on 221 cases from the Surveillance, Epidemiology, and End Results Program.

Primary neuroendocrine tumors of the gallbladder (GB) and extrahepatic biliary ducts (EHBDs) include carcinoid tumors and small-cell carcinomas (SCCs). They are uncommon, and therefore, little is known about their demographics and clinical course. From National Cancer Institute's Surveillance, Epidemiology, and End Results program (1973-2005), we analyzed the demographics and 10-year relative survival rates of carcinoids and SCCs of the GB and EHBD according to histologic type and stage. There were 119 cases of carcinoid tumors and 54 cases of SCCs in the GB. There were 31 carcinoid tumors and 17 SCCs in the EHBD. The female/male ratios of carcinoids in the GB and EHBD were 2.4 and 1.6, respectively. The ratios for SCC in the GB and EHBD were 2.2 and 1.1, respectively. For the GB, the mean age of diagnosis for carcinoids was 64.5, and for SCC, it was 67.5. For the EHBD, the mean age was 58.2 for carcinoids and 68.4 for SCC. The 10-year survival rates were 36% for carcinoid tumors of the GB and 80% for carcinoid tumors of the EHBD. For SCC, the 10-year survival was 0% in the GB and EHBD. Carcinoid tumors and SCC of the extrahepatic biliary tree are uncommon neoplasms that differ in their demographics and biologic behavior, supporting the distinction of these 2 histopathologic types. Therefore, these tumors should be separately classified and not included in the single generic group of neuroendocrine carcinoma.

Cystic lymphatic malformation of the middle ear.

OBJECTIVES: We review the clinical, radiologic, and histopathologic features of cystic lymphangioma of the middle ear, and discuss the developmental etiology and management of such a lesion. METHODS: We present an unusual location for the development of a cystic lymphangioma with emphasis on etiology, clinical implications, and current treatment. RESULTS: A 10-year-old girl presented with a mass involving the medial surface of the right tympanic membrane. T2-weighted magnetic resonance imaging demonstrated a hyperintense lesion in the anterior-superior middle ear cavity without evidence of vascular abnormalities. CONCLUSIONS: To our knowledge, this is the only report of lymphangioma involving the middle ear represented in the English-language literature. Such a lesion has been demonstrated to arise from abnormalities in growth factors that contribute to the tightly regulated process of lymphangiogenesis. Lymphatic malformations can be diagnosed presumptively by virtue of magnetic resonance imaging in combination with a detailed physical examination. The treatment of choice for lymphangiomas located in the middle ear is surgical excision. Definitive diagnosis of the lesion is then made by identifying specific histopathologic characteristics. Although rare and histologically benign, middle ear lymphangiomas may produce significant patient discomfort and ultimately a conductive hearing loss. Therefore, these lesions warrant early recognition and treatment.

Creating prognostic systems for cancer patients: A demonstration using breast cancer.

Integrating additional prognostic factors into the tumor, lymph node, metastasis staging system improves the relative stratification of cancer patients and enhances the accuracy in planning their treatment options and predicting clinical outcomes. We describe a novel approach to build prognostic systems for cancer patients that can admit any number of prognostic factors. In the approach, an unsupervised learning algorithm was used to create dendrograms and the C-index was used to cut dendrograms to generate prognostic groups. Breast cancer data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute were used for demonstration. Two relative prognostic systems were created for breast cancer. One system (7 prognostic groups with C-index = 0.7295) was based on tumor size, regional lymph nodes, and no distant metastasis. The other system (7 prognostic groups with C-index = 0.7458) was based on tumor size, regional lymph nodes, no distant metastasis, grade, estrogen receptor, progesterone receptor, and age. The dendrograms showed a relationship between survival and prognostic factors. The proposed approach is able to create prognostic systems that have a good accuracy in survival prediction and provide a manageable number of prognostic groups. The prognostic systems have the potential to permit a thorough database analysis of all information relevant to decision-making in patient management and prognosis.

Diagnostic surgical pathology in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition).

OBJECTIVE: The objective of this study was to provide evidence-based background and recommendations for the development of American College of Chest Physicians guidelines for the diagnosis and management of lung cancer. METHODS: A systematic search of the medical and scientific literature using MEDLINE, MDCONSULT, UpToDate, Cochrane Library, NCCN guidelines, and NCI/NIH search engines was performed for the years 1990 to 2006 to identify evidence-based and consensus guidelines. The search was limited to literature on humans and articles in the English language. RESULTS: The pathologic assessment of lung cancers is based on a set of well-accepted findings, including histologic type, tumor size and location, involvement of visceral pleura, and extension to regional and distant lymph nodes and organs. Bronchial-based incipient neoplasia needs to be recognized both grossly and microscopically because these lesions may be multifocal and represent multistep carcinogenesis and may be amenable to therapy. Cytologic assessment of the individual with no symptoms is, as yet, of insufficient clinical benefit for screening of lung cancer. In challenging situations of pathologic differential diagnosis, additional studies may provide information that enables the separation of distinct tumor types. Pathobiological and molecular biological studies may yield prognostic and predictive information for clinical management and should be considered as part of protocol studies. Enhanced pathologic and molecular techniques may identify the presence of micrometastatic disease within lymph nodes; however, the clinical utility of these approaches is still unresolved. Intraoperative consultations have high diagnostic accuracy and may aid ongoing treatment and management decisions. CONCLUSIONS: Pathologic assessment is a crucial component for the diagnosis, management, and prognosis of lung cancer. Selective diagnostic techniques and decision analysis will increase diagnostic accuracy. Cytologic screening, molecular characterization of tumors, and micrometastatic analysis are potential but not yet proved modalities for the evaluation of lung cancers.

Changing patterns in the incidence and survival of thyroid cancer with follicular phenotype--papillary, follicular, and anaplastic: a morphological and epidemiological study.

Thyroid carcinomas with follicular phenotype have demonstrated changing patterns over 30 years (1973-2003) according to data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Papillary carcinomas have significantly increased. They accounted for 74% of all cases of thyroid cancers in 1973 and 87% in 2003. During this period, the incidence rate of papillary carcinoma (including the follicular variant) increased by 189%, the rate of follicular carcinoma remained stable, and the rate of anaplastic carcinoma decreased by 22%. The rate of the follicular variant of papillary carcinoma alone increased by 173%. Thyroid cancer was more common in whites than in blacks and in females more than in males. Papillary carcinomas rapidly increased during adolescence and reached a peak around age 52-56, then declined. Follicular carcinomas increased steadily, but at a lower rate until age 80. After 1988, both papillary and follicular carcinomas, less than 2 cm, increased at the same rate as carcinomas larger than 2 cm. However, papillary carcinomas less than 2 cm were more common. Overall, the 10-year relative survival rate was greater than 90% for blacks and whites with the exception of follicular carcinoma in blacks. The 10-year relative survival rate for anaplastic carcinoma in patients over 40 years of age was 4.7%. The decrease in incidence rate of anaplastic carcinoma may be the result of the successful treatment of papillary and follicular carcinomas.

Gouty Tenosynovitis of the Distal Biceps Tendon Insertion Complicated by Partial Rupture: First Case and Review of the Literature.

Background: Given the appreciable prevalence of gout, gout-induced tendon ruptures in the upper extremity are extremely rare. Although these events have been reported only 5 times in the literature, all in patients with a risk factor for or history of gout, they have conspicuously never been diagnosed in the shoulder or elbow. Methods: A 45-year-old, right-hand-dominant man with a history of gout presented with pain in his right anterior elbow and weakness in his forearm after a trivial injury. Results: Here, we report the first case of gouty tenosynovitis of the distal biceps tendon insertion complicated by partial rupture, a composite diagnosis supported by both intraoperative and histological observations. Conclusions: In patients who are clinically diagnosed with biceps tendon rupture and have a history of gout, it is important to consider the possibility of a gout-related pathological manifestation causing or simulating tendon rupture.