Repeated Occurrences of Basal Cell Cancer in Patients With Inflammatory Bowel Disease Treated With Immunosuppressive Medications.

INTRODUCTION: There are limited data on repeated basal cell cancer (BCC) occurrences among patients with inflammatory bowel disease (IBD), especially the impact of continuing immunosuppressive medications. METHODS: We conducted a retrospective cohort study of 54,919 patients with IBD followed in the Veterans Affairs Healthcare System. We identified patients who had an incident BCC after their IBD diagnosis. We defined patients' exposure based on their IBD medications use as follows: (i) only aminosalicylate (5-ASA) use, (ii) only active thiopurine (TP) use, (iii) past TP use (discontinued >6 months ago) and no antitumor necrosis factor (TNF) use, (iv) anti-TNF use after previous TP use, (v) only anti-TNF use, and (vi) active anti-TNF and TP use. The outcome of interest was the repeated occurrence of BCC. Adjusted and unadjusted hazard ratios with 95% confidence intervals were used to estimate the risk of repeated BCC occurrence. RESULTS: A total of 518 patients developed BCC after their IBD diagnosis. The numbers of repeated BCC occurrences per 100 person-years were 12.8 (5-ASA use only), 34.5 (active TP use), 19.3 (past TP use and no anti-TNF use), 25.4 (anti-TNF use after previous TP use), 17.8 (only anti-TNF use), and 22.4 (active anti-TNF and TP use). Compared with 5-ASA use alone, only active TP use was associated with an increased risk for repeated BCC occurrence (adjusted hazard ratio 1.65, 95% confidence interval 1.24-2.19; P = 0.0005). However, the increased risk was no longer present for other exposure categories. DISCUSSION: Among IBD patients who developed an incident BCC while taking a TP and continued it, there was an increased risk of repeated BCC occurrences.

Decision tree analysis to stratify risk of de novo non-melanoma skin cancer following liver transplantation.

PURPOSE: Non-melanoma skin cancer (NMSC) is the most common de novo malignancy in liver transplant (LT) recipients; it behaves more aggressively and it increases mortality. We used decision tree analysis to develop a tool to stratify and quantify risk of NMSC in LT recipients. METHODS: We performed Cox regression analysis to identify which predictive variables to enter into the decision tree analysis. Data were from the Organ Procurement Transplant Network (OPTN) STAR files of September 2016 (n = 102984). RESULTS: NMSC developed in 4556 of the 105984 recipients, a mean of 5.6 years after transplant. The 5/10/20-year rates of NMSC were 2.9/6.3/13.5%, respectively. Cox regression identified male gender, Caucasian race, age, body mass index (BMI) at LT, and sirolimus use as key predictive or protective factors for NMSC. These factors were entered into a decision tree analysis. The final tree stratified non-Caucasians as low risk (0.8%), and Caucasian males > 47 years, BMI < 40 who did not receive sirolimus, as high risk (7.3% cumulative incidence of NMSC). The predictions in the derivation set were almost identical to those in the validation set (r2 = 0.971, p < 0.0001). Cumulative incidence of NMSC in low, moderate and high risk groups at 5/10/20 year was 0.5/1.2/3.3, 2.1/4.8/11.7 and 5.6/11.6/23.1% (p < 0.0001). CONCLUSIONS: The decision tree model accurately stratifies the risk of developing NMSC in the long-term after LT.

Incidencia y mortalidad del cáncer cutáneo en España: revisión sistemática y metaanálisis / Skin Cancer Incidence and Mortality in Spain: A Systematic Review and Meta-Analysis

INTRODUCCIÓN Y OBJETIVOS: El objetivo de la revisión sistemática es describir la incidencia y mortalidad en España del carcinoma basocelular, carcinoma espinocelular, melanoma y carcinoma de células de Merkel. MATERIAL Y MÉTODOS: Se realizó una búsqueda en Medline, Embase y revisión de artículos de la Red Española de Registros de Cáncer (REDECAN) y la Agencia Internacional de Investigación sobre el Cáncer (IARC). Se evaluó la calidad metodológica de los estudios. La heterogeneidad estadística se midió usando el estadístico I2. Para el metaanálisis de los datos se empleó un modelo de efectos aleatorios debido a la heterogeneidad de los resultados. RESULTADOS: Se incluyeron un total de 32 trabajos en la revisión sistemática. La tasa de incidencia del carcinoma basocelular global cruda fue 113,05 (IC 95%: 89,03-137,08)/100.000 personas-año para los estudios que emplean la metodología de los registros de cáncer (contando un solo tumor por persona y diagnóstico histológico). La tasa de incidencia mediante criterios clínicos e histológicos, y contando tumores en lugar de personas, fue de 253,23 (IC 95%: 273,01-269,45)/100.000 personas-año. La incidencia de carcinoma espinocelular fue de 38,16 (IC 95%: 31,72-39,97)/100.000 personas-año, de 8,76 (IC 95%: 7,50-10,02)/100.000 personas-año para el melanoma y 0,28 (IC 95%: 0,15-0,40)/100.000 personas-año para el carcinoma de células de Merkel. CONCLUSIONES: La tasa de incidencia del carcinoma basocelular y espinocelular en España está probablemente infraestimada al utilizar el método habitual de los registros. La tasa de incidencia del melanoma cutáneo es baja en comparación con otros países europeos, al igual que la tasa de incidencia del carcinoma de células de Merkel

INTRODUCTION AND OBJECTIVES: The aim of this systematic review was to describe the incidence and mortality of basal cell carcinoma, squamous cell carcinoma, melanoma, and Merkel cell carcinoma in Spain. MATERIAL AND METHODS: We performed a search of the MEDLINE and Embase databases and reviewed articles from the Spanish Network of Cancer Registries (REDECAN) and the International Agency for Research on Cancer (IARC). The methodological quality of the studies was evaluated and statistical heterogeneity was measured using the I2 index. A random-effects model was used to perform the meta-analysis because of the heterogeneity of the data. RESULTS: Thirty-two papers were included in the systematic review. The crude incidence rate for basal cell carcinoma was 113.05 (95% CI, 89.03-137.08) cases per 100 000 person-years for the studies based on the registration methodology normally used by registries (in which only 1 tumor with histological confirmation is counted per person). However, the same incidence rate calculated on the basis of clinical and histologic criteria and counting tumors rather than individual patients was 253.23 (95% CI, 273.01-269.45) cases per 100 000 person-years. The incidence was 38.16 (95% CI, 31.72-39.97) cases per 100 000 person-years for squamous cell carcinoma, 8.76 (95% CI, 7.50-10.02) cases per 100 000 person-years for melanoma, and 0.28 (95% CI, 0.15-0.40) cases per 100 000 person-years for Merkel cell carcinoma. CONCLUSIONS: The registration methodology normally used by cancer registries probably underestimates the incidence rates of basal cell and squamous cell carcinoma in Spain. The incidence rates of cutaneous melanoma and Merkel cell carcinoma are lower in Spain than in other European countries

Correspondencia entre diagnóstico clínico e histopatológico de los tumores de los anexos oculares / Correspondence between clinical and histopathological diagnosis of tumors of the ocular adnexa

Fundamento: los tumores de los anexos oculares constituyen una causa frecuente de visita a la consulta de Oftalmología. Una adecuada relación clínico patológica es importante para su pronóstico. Objetivo: describir la correspondencia entre el diagnóstico clínico e histopatológico de los tumores de los anexos oculares. Métodos: estudio de serie de casos sobre los pacientes atendidos en la consulta de Oculoplastia del Centro Oftalmológico del Hospital General Universitario Dr. Gustavo Aldereguia, de Cienfuegos, desde enero del 2014 hasta igual mes del 2015, a los que por criterio de sospecha de malignidad se les realizó estudio histopatológico. Se analizó: edad, color de piel, tipo de tumor, correspondencia entre diagnóstico clínico e histopatológico y margen de seguridad de la cirugía. Resultados: la correspondencia entre el diagnóstico clínico y el histopatológico fue del 79,1 por ciento. El grupo etario más afectado fue el de 40-59 años, con mayor incidencia en el sexo femenino; la localización más frecuente fue a nivel palpebral en pacientes de color de piel blanca. Primaron las lesiones benignas tanto de párpado como de la conjuntiva; el carcinoma de conjuntiva y el carcinoma basal fueron los tumores malignos más representativos; el margen de seguridad fue de 2, 19 por ciento. Conclusiones: se observó un porciento adecuado de correspondencia entre el diagnóstico presuntivo y el histopatológico, el margen de seguridad logrado fue satisfactorio(AU)

Background: tumors of the ocular adnexa are a common cause of patient visits to the Ophthalmology consultation. An adequate clinical-pathological relationship is important for prognosis. Objective: to describe the correspondence between clinical and histopathological diagnosis of tumors of the ocular adnexa. Methods: a case series study was conducted in patients who underwent a histopathological study due to suspicion of malignancy treated at the Oculoplastic Service of the Ophthalmology Center of the Dr. Gustavo Aldereguía University General Hospital, from January 2014 to the same month of 2015. The variables analyzed were: age, skin color, type of tumor, correspondence between clinical and histopathological diagnosis and safety margin. Results: correspondence between clinical and histopathological diagnosis was 79.1 percent. The 40-59 age group was the most affected, with a higher incidence in females. The most common location was the eyelid region in white patients. Benign lesions of the eyelid and conjunctiva predominated. Conjunctival carcinoma and basal cell carcinoma were the most common malignancies; the safety margin was 2.19 percent. Conclusions: an adequate correspondence between presumptive and histopathological diagnosis was observed. The safety margin achieved was satisfactory(AU)

Comparative vaccine-specific and other injectable-specific risks of injection-site sarcomas in cats.

OBJECTIVE: To compare associations between vaccine types and other injectable drugs with development of injection-site sarcomas in cats. DESIGN: Case-control study. ANIMALS: 181 cats with soft tissue sarcomas (cases), 96 cats with tumors at non-vaccine regions (control group I), and 159 cats with basal cell tumors (control group II). PROCEDURES: Subjects were prospectively obtained from a large pathology database. Demographic, sarcoma location, basal cell tumor, and vaccine and other injectable history data were documented by use of a questionnaire and used to define case, control, and exposure status. Three control groups were included: cats with sarcomas at non-vaccine sites, cats with basal cell tumors, and a combined group of cats with sarcomas at non-vaccine sites and cats with basal cell tumors. χ(2) tests, marginal homogeneity tests, and exact logistic regression were performed. RESULTS: In the broad interscapular region, the frequency of administration of long-acting corticosteroid injections (dexamethasone, methylprednisolone, and triamcinolone) was significantly higher in cases than in controls. In the broad rear limb region, case cats were significantly less likely to have received recombinant vaccines than inactivated vaccines; ORs from logistic regression analyses equaled 0.1, with 95% confidence intervals ranging from 0 to 0.4 and 0 to 0.7, depending on control group and time period of exposure used. CONCLUSIONS AND CLINICAL RELEVANCE: This case-control study measuring temporal and spatial exposures efficiently detected associations between administrations of various types of vaccines (recombinant vs inactivated rabies) and other injectable products (ie, long-acting corticosteroids) with sarcoma development without the need to directly measure incidence. These findings nevertheless also indicated that no vaccines were risk free. The study is informative in allowing practitioners to weigh the relative merits and risks of commonly used pharmaceutical products.

Upper lip malignant neoplasms. A study of 59 cases

Objectives: To present the demographic data, clinico-pathologic features and therapeutic outcome of a series of upper lip malignancies. Study Design: Retrospective study at a single Cancer Institution in Mexico City during a 14-year period. Results: There were 59 cases, (30 males and 29 females); age range: 14 to 106 years (mean: 73 yr.). Antecedents of ultraviolet light and tobacco exposure were found in 20 (33.9%) and 16 cases (27%) respectively. There were 35 squamous cell carcinomas (59.3%), 19 basal cell carcinomas (32.2%) and one case each (1.7%) of adenocarcinoma NOS, adenoid cystic carcinoma, angiosarcoma, Merkel cell carcinoma and melanoma. There were 14 cases in stage I (23.7%), 14 in stage II (23.7%), 3 in stage III (5.1%) 14 in stage IV (23.7%) and 14 were not classified (23.7%). There were no significant differences with respect to the overall survival curve and the disease-free survival curve among surgical treatment and radiotherapy. In addition, there was not statistically significant difference in the overall survival and disease-free survival among squamous cell carcinoma and basal cell carcinoma cases with respect to the type of treatment. Conclusions: Upper lip malignant neoplasms are infrequent lesions. The present series describes the main clinicopathological features in a hospital-based population in Mexico city and demonstrates some differences with respect to those found in the lower lip (AU)

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Basal breast cancer: a complex and deadly molecular subtype.

During the last decade, gene expression profiling of breast cancer has revealed the existence of five molecular subtypes and allowed the establishment of a new classification. The basal subtype, which represents 15-25% of cases, is characterized by an expression profile similar to that of myoepithelial normal mammary cells. Basal tumors are frequently assimilated to triple-negative (TN) breast cancers. They display epidemiological and clinico-pathological features distinct from other subtypes. Their pattern of relapse is characterized by frequent and early relapses and visceral locations. Despite a relative sensitivity to chemotherapy, the prognosis is poor. Recent characterization of their molecular features, such as the dysfunction of the BRCA1 pathway or the frequent expression of EGFR, provides opportunities for optimizing the systemic treatment. Several clinical trials dedicated to basal or TN tumors are testing cytotoxic agents and/or molecularly targeted therapies. This review summarizes the current state of knowledge of this aggressive and hard-to-treat subtype of breast cancer.

Increased risk of nonmelanoma skin cancers among individuals with inflammatory bowel disease.

BACKGROUND & AIMS: There are limited data on the risk of nonmelanoma skin cancer (NMSC) among individuals with inflammatory bowel disease (IBD), including those with or without exposure to immunosuppressant medications. METHODS: Individuals with IBD (n = 9618) were identified from the University of Manitoba IBD Epidemiology Database and matched with randomly selected controls (n = 91,378) based on age, sex, and postal area of residence on the date of IBD diagnosis (index date). Groups were followed up from the index date until a diagnosis of any invasive cancer (including NMSC), death, migration from the province, or the end of the study (December 31, 2009), whichever came first. Cox regression analysis was performed to calculate the relative risk of NMSC among the individuals with IBD, adjusting for frequency of ambulatory care visits and socioeconomic status. RESULTS: Of the individuals followed, 1696 were diagnosed with basal cell skin cancer (BCC) and 341 were diagnosed with squamous cell skin cancer (SCC). Individuals with IBD had an increased risk for BCC, compared with controls (hazard ratio, 1.20; 95% confidence interval [CI], 1.03-1.40). Among patients with IBD, use of thiopurines increased the risk of SCC (hazard ratio, 5.40; 95% CI, 2.00-14.56), compared with controls. Use of thiopurines also was associated with SCC in a case-control, nested analysis of individuals with IBD (odds ratio, 20.52; 95% CI, 2.42-173.81). CONCLUSIONS: The risk of BCC could be increased among individuals with IBD. Use of thiopurines increases the risk of SCC among individuals with IBD.

Metastatic breast cancer in a Nigerian tertiary hospital.

BACKGROUND: Late presentation of breast carcinoma is common in resource-limited countries with attendant poor outcome. OBJECTIVE: To describe the pattern of clinical presentation and challenges of treating patients presenting with metastatic breast carcinoma in a Nigerian hospital. METHOD: Clinical records of all patients who presented with metastatic breast carcinoma between January 1991 and December 2005 at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria were reviewed. RESULTS: More than half of all histologically confirmed breast cancer patients seen within the study period presented with metastatic disease. Their ages ranged between 20-81 years with a mean age of 45.9 years. Only 3% (6 of 202) were males. Two-thirds had more than one secondary site on initial evaluation and the commonest sites were liver (63%), lung parenchyma (51%), pleura (26%) and contralateral breast in 25%. On immunohistochemistry, basal like tumours were found in 46.1%. Mastectomy was done in 37 patients with fungating breast masses while only one third of those referred to a nearby center for radiotherapy had it done. One year survival rate was 27%. CONCLUSION: Metastatic disease is common in Nigeria and treatment is limited due to resource limitations. Improved awareness of the disease is advocated to reduce late presentation.

Minireview: Basal-like breast cancer: from molecular profiles to targeted therapies.

The classification of breast cancer into molecular subtypes with distinctive gene expression signatures that predict treatment response and prognosis has ushered in a new era of personalized medicine for this remarkably heterogeneous and deadly disease. Basal-like breast cancer (BLBC) is a particularly aggressive molecular subtype defined by a robust cluster of genes expressed by epithelial cells in the basal or outer layer of the adult mammary gland. BLBC is a major clinical challenge because these tumors are prevalent in young woman, often relapsing rapidly. Additionally, most (but not all) basal-like tumors lack expression of steroid hormone receptors (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2, limiting targeted therapeutic options for these predominantly triple-negative breast cancers. This minireview will focus on new insights into the molecular etiology of these poor-prognosis tumors that underlie their intrinsic genomic instability, deregulated cell proliferation and apoptosis, and invasive tumor biology. We will also review ongoing efforts to translate these fundamental insights into improved therapies for women with BLBC.

Genetic variants in telomere-maintaining genes and skin cancer risk.

Telomere-related genes play an important role in maintaining the integrity of the telomeric structure that protects chromosome ends, and telomere dysfunction may lead to tumorigenesis. We evaluated the associations between 39 SNPs, including 38 tag-SNPs in telomere-related genes (TERT, TRF1, TRF2, TNKS2, and POT1) and one SNP (rs401681) in the TERT-CLPTM1L locus which has been identified as a susceptibility locus to skin cancer in the previous GWAS, and the risk of skin cancer in a case-control study of Caucasians nested within the Nurses' Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 870 controls. Of the 39 SNPs evaluated, ten showed a nominal significant association with the risk of at least one type of skin cancer. After correction for multiple testing within each gene, two SNPs in the TERT gene (rs2853676 and rs2242652) and one SNP in the TRF1 gene (rs2981096) showed significant associations with the risk of melanoma. Also, the SNP rs401681 in the TERT-CLPTM1L locus was replicated for the association with melanoma risk. The additive odds ratio (OR) [95% confidence interval (95% CI)] of these four SNPs (rs2853676[T], rs2242652[A], rs2981096[G], and rs401681[C]) for the risk of melanoma was 1.43 (1.14-1.81), 1.50 (1.14-1.98), 1.87 (1.19-2.91), and 0.73 (0.59-0.91), respectively. Moreover, we found that the rs401681[C] was associated with shorter relative telomere length (P for trend, 0.05). We did not observe significant associations for SCC or BCC risk. Our study provides evidence for the contribution of genetic variants in the telomere-maintaining genes to melanoma susceptibility.

Skin growths of the head and neck region in elderly patients--analysis of two five-year periods in General Hospital Karlovac, Croatia.

Skin lesions, benign and malignant, are more common in the older than younger people. Due to the aging of the skin and greater exposure to the impact of ultraviolet rays, their long-term cumulative negative effect, skin lesions are more common in the head and neck area than on other parts of the skin. This paper analyses the pathohistological diagnosis of material after the surgical excision of tumors of the skin on the head and neck of persons older than 60, at the General Hospital Karlovac through two five-year period. The first period is the period from 2006 to 2010 and the second one from 1996 to 2000. The aim was to determine for each period the type and variety of skin lesions, the prevalence of the disease, the age and gender structure, and finally to compare the two periods. The total number of excisions in the first period was 1200, and in the second 513. In both periods more excisions was done in women than men, if compared it comes to 1.4:1. The ratio of malignant (basocellular carcinoma, squamous cell carcinoma and melanomas), and benign tumors (seborrheic keratoses, moles and others) in the first period was 49.3 to 46.3%, and in the second 56.7 to 42.1%. Precancerous lesions (actinic keratoses and Mb Bowen's disease) accounted for 4.3% of lesions in the first and 1.2% in the second period. The total number of basocellular carcinoma was 481/232, which makes 81.3% of all malignant tumors in the first, or 79.7% in the second period. Our results showed that around half of all skin lesions removed in both periods consisted of malignant tumors, among which the most common were basal cell carcinomas. High prevalence of malignant non-melanoma skin cancers, 48.7 and 56%, indicate the importance of protection from UV radiation, and early detection and treatment of skin cancer and precancerous lesions.

Identification of patients with nonmelanoma skin cancer using health maintenance organization claims data.

Cancer registries usually exclude nonmelanoma skin cancers (NMSC), despite the large population affected. Health maintenance organization (HMO) and health system administrative databases could be used as sampling frames for ascertaining NMSC. NMSC patients diagnosed between January 1, 1988, and December 31, 2007, from such defined US populations were identified by using 3 algorithms: NMSC International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, NMSC treatment Current Procedural Terminology (CPT) codes, or both codes. A subset of charts was reviewed to verify NMSC diagnosis, including all records from HMO-enrollee members in 2007. Positive predictive values for NMSC ascertainment were calculated. Analyses of data from 1988-2007 ascertained 11,742 NMSC patients. A random sample of 965 cases was selected for chart review, and NMSCs were validated in 47.0% of ICD-9-CM-identified patients, 73.4% of CPT-identified patients, and 94.9% identified with both codes. All charts from HMO-health plan enrollees in 2007 were reviewed (n = 1,116). Cases of NMSC were confirmed in 96.5% of ICD-9-CM-identified patients, 98.3% of CPT-identified patients, and 98.7% identified with both codes. HMO administrative data can be used to ascertain NMSC with high positive predictive values with either ICD-9-CM or CPT code, but both codes may be necessary among non-HMO patient populations.

Space-time clustering and seasonality in diagnosing skin cancers in Wallonia (south-east Belgium).

BACKGROUND: In Westernized populations, the number of diagnosed cases of primary cutaneous cancers, particularly malignant melanomas and basal cell carcinomas (BCC), has been previously shown to fluctuate during specific periods of the year. OBJECTIVE AND METHOD: The aim of the present 6-year study was to explore the seasonality if any in skin cancer detection in Wallonia (south-east Belgium). RESULTS: For both malignant melanomas and BCC late spring/early summer and mid-autumn were the periods of highest diagnosis prevalence irrespective of gender. The amplitude of this bimodal evolution remained within the range of 2 standard deviations around the monthly means. Similar seasonal variations were also found in non-neoplastic controls consisting of laboratory samplings of onychomycoses and non-infectious onychodystrophies. CONCLUSION: There is reason to believe that this timing and rhythm is unrelated to any specific cancer chronomics. Rather, the present findings suggest unspecific seasonality in diagnosing skin disorders including malignancies. A variable patient awareness of changing aspects of the skin according to seasons probably represents the major influence of the described space-time clustering of skin cancer diagnosis.

Squamous cell and basal cell carcinoma of the skin in relation to radiation therapy and potential modification of risk by sun exposure.

BACKGROUND: Epidemiologic studies consistently find enhanced risk of basal cell carcinoma of the skin among individuals exposed to ionizing radiation, but it is unclear whether the radiation effect occurs for squamous cell carcinoma. It is also not known whether subgroups of individuals are at greater risk, eg, those with radiation sensitivity or high ultraviolet radiation exposure. METHODS: We analyzed data from a case-control study of keratinocyte cancers in New Hampshire. Incident cases diagnosed in 1993-1995 and 1997-2000 were identified through a state-wide skin cancer surveillance system, and controls were identified through the Department of Transportation and Center for Medicare and Medicaid Service Files (n = 1121 basal cell carcinoma cases, 854 squamous cell carcinoma cases, and 1049 controls). RESULTS: We found an association between history of radiation treatment and basal cell carcinoma. The association was especially strong for basal cell carcinomas arising within the radiation treatment field (odds ratio = 2.6; 95% confidence interval = 1.5-4.3), and among those treated with radiation therapy before age 20 (3.4; 1.8-6.4), those whose basal cell carcinomas occurred 40 or more years after radiation treatment (3.2; 1.8-5.8), and those treated with radiation for acne (11; 2.7-49). Similar age and time patterns of risk were observed for squamous cell carcinoma, although generally with smaller odds ratios. For basal cell carcinoma, early exposure to radiation treatment was a risk factor largely among those without a history of severe sunburns, whereas for squamous cell carcinoma, radiation treatment was a risk factor primarily among those with a sun-sensitive skin type (ie, a tendency to sunburn). CONCLUSIONS: Radiation treatment, particularly if experienced before age 20, seems to increase the long-term risk of both basal and squamous cell carcinomas of the skin. These risks may differ by sun exposure or host response to sunlight exposure.