Características do melanoma em idosos / Characteristics of melanoma in the elderly

RESUMO Objetivo: Avaliar características do melanoma em idosos. Método: Pesquisa retrospectiva mediante revisão de prontuários de idosos diagnosticados com melanoma cutâneo primário, no período de 2013 a 2017, atendidos no Hospital Erasto Gaertner, em Curitiba-Paraná. Resultados: Amostra com 139 pacientes, mulheres (52,5%), média de 70,3 anos de idade, com lesão em membro superior ou membro inferior (32,3%) e cabeça (24,4%), sinais de ulceração (33,8%) e classificação em tipo histológico nodular (29,5%), extensivo superficial (27,3%) e acral (11,5%). Média do índice de Breslow de 3,7 mm. Metástases ocorreram em 33% dos pacientes, para linfonodos (36%) e sistema nervoso central (20%). Pesquisa do linfonodo sentinela foi realizada em 41,7% e tratamento cirúrgico isolado em 70% dos casos. Houve recidiva em 34,5% pacientes e 17,9% evoluíram com óbito. Esses achados apontam características prognósticas sombrias relacionadas ao diagnóstico e tratamento tardio da neoplasia. Conclusões: Melanoma em membros e cabeça, índice de Breslow intermediário, metastático para linfonodos e sistema nervoso central, recidiva e tem desfecho fatal. Há necessidade de direcionar estratégias para melhor abordagem da doença em idosos, como prevenção, detecção precoce e oferta de tratamento uniforme e adequado.

ABSTRACT Objective: This study evaluates melanoma characteristics in the elderly. Methods: A retrospective descriptive analytical study was carried out by reviewing the medical records of patients aged 60 years or older, diagnosed with primary cutaneous melanoma, and treated at Hospital Erasto Gaertner, Curitiba, Paraná, from 2013 to 2017. Results: We studied 139 patients aged 60-98 years (average, 70.3 years) and found melanoma to be more common in women (52.5%) than in men. Lesions mainly affected the limbs (32.3%) and head (24.4%), showed signs of ulceration (33.8%), and could be classified into the nodular histological (29%), extensive superficial (27%), and acral (12%) types. The average Breslow index was 1.2 mm. Metastasis occurred in 33% of the patients and mainly affected lymph nodes (36%) and the central nervous system (CNS, 20%). The first procedure conducted in 79% of the cases was surgical resection. Sentinel node mapping was carried out in 41.7% of the cases, and surgical treatment alone was indicated in 70% of the patients. The disease recurred in 34.5% of the patients, and 17.9% succumbed to the disease. These results indicate that the elderly have poorer prognosis when cancer treatment is delayed. Conclusion: Melanoma of the limbs and head, intermediate Breslow index, metastatic lymph node and CNS metastases, and relapse result in fatal outcomes. Direct strategies, such as prevention and early detection, as well as uniform and adequate treatment, are needed to improve disease management in the elderly.

Association between tumor-infiltrating lymphocytes and sentinel lymph node positivity in thin melanoma

Abstract: Background: Sentinel lymph node biopsy in thin invasive primary cutaneous melanoma (up to 1mm thick) is a controversial subject. The presence of tumor-infiltrating lymphocytes could be a factor to be considered in the decision to perform this procedure. Objective: To evaluate the association between the presence of tumor-infiltrating lymphocytes and lymph node metastases caused by thin primary cutaneous melanoma. Methods: Cross-sectional study with 137 records of thin invasive primary cutaneous melanoma submitted to sentinel lymph node biopsy from 2003 to 2015. The clinical variables considered were age, sex and topography of the lesion. The histopathological variables assessed were: tumor-infiltrating lymphocytes, melanoma subtype, Breslow thickness, Clark levels, number of mitoses per mm2, ulceration, regression and satellitosis. Univariate analyzes and logistic regression tests were performed as well the odds ratio and statistical relevance was considered when p <0.05. Results: Among the 137 cases of thin primary cutaneous melanoma submitted to sentinel lymph node biopsy, 10 (7.3%) had metastatic involvement. Ulceration on histopathology was positively associated with the presence of metastatic lymph node, with odds ratio =12.8 (2.77-59.4 95% CI, p=0.001). The presence of moderate/marked tumor-infiltrating lymphocytes was shown to be a protective factor for the presence of metastatic lymph node, with OR=0.20 (0.05-0.72 95% CI, p=0.014). The other variables - clinical and histopathological - were not associated with the outcome. Study limitations: The relatively small number of positive sentinel lymph node biopsy may explain such an expressive association of ulceration with metastatization. Conclusions: In patients with thin invasive primary cutaneous melanoma, few or absent tumor-infiltrating lymphocytes, as well as ulceration, represent independent risk factors for lymph node metastasis.

Study of skin neoplasms in a university hospital: integration of anatomopathological records and its interface with the literature

Abstract: Background: Skin cancer is a highly prevalent condition with a multifactorial etiology resulting from genetic alterations, environmental and lifestyle factors. In Brazil, among all malignant tumors, skin cancers have the highest incidences. Objective: To retrospectively evaluate the incidence, prevalence and profile of basal cell carcinoma, squamous cell carcinoma and cutaneous melanoma in Campos dos Goytacazes and region. Methods: In total, 2,207 histopathological reports of a local reference hospital were analyzed between January 2013 and December 2015, of which 306 corresponded to the neoplasms studied. Results: Of the 306 reports evaluated, 232 basal cell carcinomas (75.9%), 55 squamous cell carcinomas (18%) and 19 cutaneous melanomas (6.5%) were identified. The face was the most involved anatomical site (58.8%) and women (51%) were the most affected gender. The temporal analysis revealed a decrease in the overall incidence of 3.4% from 2013 to 2014 and 5.4% from 2014 to 2015. There was a 10.1% increase in basal cell carcinomas and 38% in melanomas in this period; however, there was a decrease in the number of squamous cell carcinomas of 14.8% during the studied years. Study limitations: Some samples of cutaneous fragments had no identification of the anatomical site of origin. Conclusion: Research that generates statistical data on cutaneous tumors produces epidemiological tools useful in the identification of risk groups and allows the adoption of more targeted and efficient future prevention measures.

Hereditary melanoma: a five-year study of Brazilian patients in a cancer referral center - phenotypic characteristics of probands and pathological features of primary tumors

Abstract: BACKGROUND: Approximately five to 10% of all melanomas occur in families with hereditary predisposition and the main high-risk melanoma susceptibility gene is the CDKN2A. OBJECTIVES: To describe, after a five-years study, the clinical data of patients (probands) from familial melanoma kindreds, and the pathological characteristics of their melanoma. METHODS: The inclusion criteria were melanoma patients with a family history of melanoma or pancreatic cancer (first- or second-degree relatives) or patients with multiple primary melanomas (MPM). RESULTS: A total of 124 probands were studied, where 64 were considered familial cases and 60 MPM. Mean age at diagnosis was 50 years. Our results show that the following characteristics were prevalent: skin phototype I/II (89.5%), sunburn during childhood (85.5%), total number of nevi ≥50 (56.5%), Breslow thickness ≤1.0mm (70.2%), tumors located on the trunk (53.2%) and superficial spreading melanomas (70.2%). STUDY LIMITATIONS: Analyses of probands' relatives will be demonstrated in future publication. CONCLUSIONS: Our findings are in agreement with previous familial melanomas reports. Fifteen new melanomas in 11 patients were diagnosed during follow up, all of which were ≤1.0 mm. This is the largest dataset of Brazilian melanoma prone kindreds to date, thus providing a complete database for future genetic studies.

Diphencyprone as a therapeutic option in cutaneous metastasis of melanoma. A single-institution experience

Abstract: Diphencyprone has been reported as a local immunotherapy for cutaneous melanoma metastases. We aim to report cases of melanoma patients treated with diphencyprone in a single Brazilian institution and highlight their outcomes. Since 2012, we have treated 16 melanoma patients with cutaneous metastases with topical diphencyprone. To date, we have had 37.5% of complete response, 25% of partial responses, and 31.25% patients without any response. Treatment was well tolerated and local toxicity was easily controlled. We believe topical diphencyprone is a feasible treatment that can be another option for treating melanoma patients, especially in cases of in-transit or extensive disease.

Conservative surgical management of in situ subungual melanoma: long-term follow-up

Abstract Subungual melanoma represents 20% of all melanomas in Hispanic population. Here, we report the outcome of 15 patients with in situ subungual melanoma treated with resection of the nail unit with a 5-mm margin without amputation, followed up for 55.93 ± 43.08 months. The most common complications included inclusion cysts and nail spicules. We found no evidence of local or distant recurrences at the last visit of our follow up. Functional outcome was good, with only one patient reporting persistent mild pain. These results support functional, non-amputative surgical management of in situ subungual melanomas.

Tratamento cirúrgico do câncer de pele pelo cirurgião plástico / Surgical treatment of skin cancer by the plastic surgeon

Introdução: O câncer de pele é a neoplasia mais frequente no Brasil e corresponde a 25% de todos os tumores malignos. O melhor tratamento é a ressecção cirúrgica em fases iniciais. O cirurgião plástico, juntamente com uma equipe multiprofissional, participa no tratamento desta doença. O objetivo é analisar a eficácia dos procedimentos cirúrgicos realizados pelo cirurgião plástico no tratamento do câncer de pele. Método: Foram analisados 404 prontuários de pacientes operados no período de fevereiro de 2009 a dezembro de 2012 e analisados gênero, idade, diagnóstico, localização e evolução. Resultados: Faixa etária com média de 62 anos. 53% de casos de carcinoma basocelular, 25,5% melanoma e 15,1% carcinoma espinocelular. Houve predomínio de mulheres nos carcinomas basocelulares (56%) e no melanoma (54%) e de homens nos carcinomas espinocelulares (61%). Os carcinomas basocelulares (92,99%) e espinocelulares (72,13%) tiveram sua predominância na região de cabeça e pescoço; enquanto o melanoma predominou em região de tronco (36,89%) e membros inferiores (24,27%). Foram realizadas 67 cirurgias com pesquisa de linfonodo sentinela, com positividade em 14,93%. 7,76% dos pacientes de melanoma apresentaram metástases e 2,91% vieram a óbito. Conclusão: O cirurgião plástico é um dos profissionais importantes para o tratamento do câncer de pele, sendo o mais apto para realizar as reconstruções após as ressecções tumorais, pois tem em sua formação os conceitos de reparação, utilizando-se de enxertos e retalhos e considerando o aspecto estético dos pacientes. Cabe-lhe também a realização da cirurgia de pesquisa de linfonodo sentinela e o seguimento dos pacientes com câncer de pele.

Introduction: Skin cancer is the most common neoplasm in Brazil and it corresponds to 25% of all diagnosed malignant tumors. The best treatment is surgical resection in early stages. The disease is treated by a plastic surgeon along with a multidisciplinary team. The objective is to assess the effectiveness of surgical procedures performed by plastic surgeons to treat skin cancer. Methods: We analyzed medical records of 404 patients operated on between February 2009 and December 2012. Data analyzed included gender, age, diagnosis, localization and evolution. Results: Patients' mean age was 62 years. A total of 53% of patients had basal cell carcinoma, 25.5% melanoma and 15.1% squamous cell carcinoma. There was a predominance of women in basal cell carcinomas (56%) and melanoma (54%) and predominance of men in squamous cell carcinomas (61%). Basal cell carcinomas (92.99%) and squamous (72.13%) were predominant in the head and neck, melanoma predominated in the trunk region (36.89%) and in lower limbs (24.27%). We performed 67 surgeries with sentinel lymph node, with positivity in 14.93%. Patients with melanoma who had metastasis accounted for 7.76% and 2.91% patients died. Conclusion: Plastic surgeons are one of the important professionals for skin cancer treatment. These professionals are the most skilled one to perform reconstructions after tumor resections, because during education they learn repair concepts using grafts and flaps especially focused on aesthetic appearance of patients. They can also perform surgery for sentinel lymph node and offer follow-up to patients with skin cancer.

Study of the histopathological types of cutaneous melanoma in Palmas-TO from 2001 to 2011

AbstractBACKGROUND:Cutaneous melanoma (CM) is considered serious for causing frequent metastasis, presenting high mortality, resistance to available therapies and incidences in laboring activity.OBJECTIVES:To study the histopathological types of cutaneous melanoma in Palmas-TO from 2001 to 2011, according to risk factors, location of lesions, Clark levels and Breslow thickness.METHODS:A descriptive, retrospective and quantitative research in reports of the Serviços de Anatomia Patológica in Palmas (SAPP) and Registro de Câncer de Base Populacional de Palmas (RCBPP).RESULTS:The years of highest incidences were: 2004 (8 cases/17.8%), 2008 and 2011 (7 cases each/15.6%) and 2010 (6 cases/13.3%). Among the 45 cases studied, there were predominance in patients between 41 and 60 years old, women, caucasians, farmers, located in trunk, in situ type, superficial extensive and metastatic cutaneous, Clark levels I (20%) and IV (17.7%), Breslow thickness ≤1 mm (35.5%) and 2.01 to 4 mm (24.4%).CONCLUSIONS:The most common histopathological types were: cutaneous melanoma in situ, superficial extensive and metastatic, followed by nodular cutaneous melanoma, and finally, by other forms. In this study, Clark levels and Breslow thickness pointed to greater importance of thin melanomas and sun exposure without appropriate protection in farmers.

Conjunctival melanoma: survival analysis in twenty-two Mexican patients / Melanoma conjuntival: análise de sobrevivência em vinte e dois pacientes mexicanos

Purpose: To describe the cases of conjunctival melanoma (CM) and report the disease-free interval (DFI) and overall survival (OS). Methods: The charts of 22 patients who were admitted to two hospitals between 1985 and 2006 were reviewed for pertinent data, including demographics, site of involvement in the conjunctiva and sub-sites, surgical treatment, and adjuvant treatment. Results: There were 10 (45.45%) males and 12 (54.55%) females. Mean age was 52.3 years. In this group, 15 patients (68.1%) involved the bulbar conjunctiva, and 7 (31.9%) involved the palpebral conjunctiva. Of the 22 patients, 72.72% had a history of conjunctival melanosis. The average tumor size was 20.4 mm. Eight (36.36%) patients underwent orbital exenteration, 2 (9.06%) had enucleation, 5 (22.72%) had wide excision of the lesion followed by radiotherapy, 2 (9.06%) had orbital exenteration with neck dissection, and the remaining 5 patients (22.72%) were considered adequately treated only with wide excision. Eight (36.36%) patients received adjuvant treatment. Disease-free survival at 5 years was 51% and the overall survival at 5 and 10 years was 50% and 37%, respectively. Conclusion: Conjunctival melanoma is a rare entity. Tumor behavior is aggressive, and the optimal treatment is surgery with adjuvant therapy. .

Objetivo: Descrever o intervalo livre de doença (DFI) e sobrevida global (OS) de pacientes com melanoma conjuntival (CM). Método: Prontuários de 22 pacientes que foram internados em dois hospitais entre 1985 e 2006 foram revisados para dados pertinentes, incluindo dados demográficos, local de envolvimento na conjuntiva e outros locais de acometimento, tratamento cirúrgico e tratamento adjuvante. Resultados: Dez (45,45%) homens e 12 (54,55%) mulheres foram selecionados. A média de idade foi de 52,3 anos. Em 15 pacientes (68,1%) CM envolveu a conjuntiva bulbar, e em 7 (31,9%) envolveu a conjuntiva palpebral. Dos 22 pacientes, 72,72% tinham história de melanose conjuntival. O tamanho médio do tumor foi de 20,4 mm. Oito (36,36%) pacientes foram submetidos à exenteração orbital, 2 (9,06% ) à enucleação, 5 (22,72%) à ampla excisão da lesão seguida de radioterapia, 2 (9,06%) à exenteração orbital com esvaziamento cervical e os restantes 5 pacientes (22,72%) foram considerados adequadamente tratados apenas com excisão ampla. Oito (36,36%) pacientes receberam tratamento adjuvante. Sobrevida livre de doença em 5 anos foi de 51% e sobrevida global em 5 e 10 anos foi de 50% e 37%, respectivamente. Conclusão: Melanoma conjuntival é uma entidade rara. Comportamento do tumor é agressivo, e o melhor tratamento é a cirurgia com terapia adjuvante. .

Malignant melanoma in Chile: different site distribution between private and state patients

BACKGROUND: The body site location of primary Malignant Melanoma (MM) has been correlated with prognosis and survival. Ethnic, genetics, sun exposure factors are related to the anatomical distribution of MM. Low and high socioeconomic strata in Chile differ in ethnic, genetic and cultural conditions. The purpose of this study was to analyze the anatomical MM distribution in the Chilean population in both strata searching for differences due to their ethno-genetic-cultural differences. Records of 1148 MM, 575cases from state hospitals (Low Socioeconomic Strata, LSS) and 573 cases from private clinics (High Socioeconomic Strata, HSS) were analyzed by body site. RESULTS: Females from LSS showed a higher number of MM in soles, cheeks, and around the eye area. Females from the HSS showed a higher number of MM in dorsal feet and dorsal hands. Males from LSS showed a higher number of MM in soles, around the eye area, and cheeks. However, males from HSS showed a higher number of MM in the trunk, and in the arms. Acral MM was significantly higher in LSS than in the HSS in both sexes. The Chilean population from the HSS and LSS showed differences in the distribution of MM by site. Furthermore, gender differences in the proportion of MM analyzed by anatomical site are observed in both strata. CONCLUSIONS: Results show evidence that differential genetics factors, sun exposure, or other environmental or cultural factors of both strata may account for these differences.

Epidemiological and histopathological profile of cutaneous melanoma at a center in northeastern Brazil from 2000 to 2010 / Perfil epidemiologico e histopatologico do melanoma cutaneo em um centro do nordeste brasileiro de 2000 a 2010

BACKGROUND: While representing only 3-4% of malignant skin tumors, cutaneous melanoma is the most aggressive and lethal. Statistical knowledge about the biological behavior of this tumor is essential for guiding daily outpatient practice and aiding public health policies. OBJECTIVES: To analyze the profile of patients with cutaneous melanoma attending a pathology department in Teresina (state of Piauí) between 2000 and 2010. METHODS: Retrospective study of melanoma patients diagnosed between 2000 and 2010 in the São Marcos Hospital in the city of Teresina. The pathology laboratory reports were studied and all the statistical analyses performed using SPSS 19.0. RESULTS: A total of 25 in situ, 199 invasive and 89 metastatic melanomas of unknown primary site were observed. Histological types found were nodular (52.8%), superficial spreading melanoma (18.6%), acral (10.6%) and lentigo maligna (9.5%). In 144 (73.4%) cases the Breslow thickness was >1 mm. Metastasis was found in 28.6% of invasive melanomas and nodular melanoma, Clark IV/ V, Breslow > 1 mm, mitotic index > 6 and ulcerated lesions were more likely to metastasize. CONCLUSION: Most melanomas presented Breslow> 1mm. The main factors associated with metastasis were nodular type, Clark IV / V, Breslow> 1mm, mitotic index > 6 and ulcerated lesions. .

FUNDAMENTOS: Apesar de representar apenas 3-4% dos tumores malignos de pele, o melanoma cutâneo é o mais agressivo e letal deles. O conhecimento estatístico do comportamento biológico deste tumor em nosso meio ambiente é fundamental para orientar a prática ambulatorial diária e para auxiliar políticas de saúde pública. OBJETIVOS: Analisar o perfil de pacientes com melanoma cutâneo diagnosticados em serviço de referência em patologia em Teresina-Piauí no período de 2000 a 2010. MÉTODOS: Estudo retrospectivo de pacientes com melanoma diagnosticados entre 2000 e 2010 no Hospital São Marcos, Teresina-Piauí-Brasil. Estudou-se laudos histopatológicos e realizou-se análises estatísticas com o programa SPSS 19,0. RESULTADOS: Um total de 25 melanomas in situ, 199 invasivos e 89 metastáticos de sítio primário desconhecido foram observados. Tipos histológicos encontrados foram nodular (52,8%), melanoma extensivo superficial (18,6%), acral (10,6%) e lentigo maligno (9,5%). Em 144 (73,4%) casos o índice de Breslow foi >1 mm. Verificou-se metástases em 28,6% dos melanomas invasivos e melanoma nodular, Clark IV/V, Breslow >1 mm, índice mitótico ≥6 e lesões ulceradas estavam mais propensos a metástases. CONCLUSÃO: Melanomas com Breslow >1mm foram os casos predominantes. Principais fatores ...

Perfil clinicoepidemiológico dos melanomas cutâneos em duas instituições de referência na cidade de Manaus, Brasil / Clinical and epidemiological profile of cutaneous malignant melanomas in two referral institutions in the city of Manaus, Brazil

O conhecimento da frequência e das características clinicoepidemiológicas do melanoma cutâneo nas diversas regiões do Brasil é importante para avaliar a magnitude do problema e direcionar adequadamente as ações de saúde. Neste estudo, revisaram-se os dados de 55 pacientes com melanoma cutâneo atendidos em duas instituições de saúde da cidade de Manaus. Verificou-se maior frequência entre homens pardos, na oitava década de vida, com lesões do tipo melanoma acrolentiginoso nos membros inferiores, com Breslow maior que 1mm e Clark nível V.

Knowledge on the frequency and clinical and pathological characteristics of cutaneous melanoma in the different geographical regions of Brazil is important in evaluating the magnitude of the problem and in directing healthcare actions appropriately. The present study reviewed data from 55 cases of cutaneous melanoma in patients treated at two healthcare institutions in the city of Manaus, Amazonas, Brazil. Rates were higher in brown-skinned males and in individuals of 70-80 years of age. Lesions were most commonly located on the lower limbs, were of the acral lentiginous melanoma type and at advanced stages of the disease, with Breslow thickness > 1 mm and Clark level V.

Melanoma maligno como complicación de transplante renal tratado con interferon alfa-2B / Malignant melanoma how complication of renal transplantation treated with interferon alpha-2B

Caso de paciente masculino 41 años, diabético tipo 1, trasplantado renal con tratamiento inmunosupresor, antecedente de carcinoma basocelular y espinocelular in situ tratado quirúrgicamente. Presentó en 2007 lesión nodular hiperpigmentada en pectoral izquierdo, se realizó exéresis con histopatología junio 2008: melanoma Clark III, Breslow 4 mm, ganglio centinela negativo. Clasificado como melanoma pectoral izquierdo Clark III Breslow 4 mm Estadio II (pT4aN0M0). Sintomatología gástrica noviembre 2009 estudios de imagen: hígado con lesiones nodulares múltiples tipo metastásicas, punción con aguja fina de hígado: melanoma metastásico. Reactivación a hígado múltiples metástasis, y metástasis pulmón derecho en diciembre 2009. Recibió tratamiento con temozolamida por ser paciente inmunosuprimido, con riñón único y baja depuración de creatinina, y limitación de quimioterapia con platino, recibió 3 ciclos, con progresión de enfermedad clínica e imaginológica, recibe segunda línea con interferón alfa-2b dosis modificadas, evolucionando tórpidamente, fallece por insuficiencia hepática complicada encefalopatía e insuficiencia renal crónica reagudizada.

Male patient of 41 years, type 1 diabetes, renal transplant immunosuppressive treatment, history of squamous cell carcinoma spleen in situ treated by surgery with free margins, submitted in 2007 hyperpigmented nodular lesion in the left chest, was performed exéresis with histopathology June 2008: melanoma Clark III, Breslow 4mm, sentinel node negative. Left pectoral classified as Clark III melanoma Breslow 4mm Stadium II (pT4aN0M0) May 2008 with multiple liver reactivation metastases, in November 2009 have gastric symptoms with imaging studies reported multiple nodular liver lesions type metastatic liver biopsy of metastatic melanoma and in right lung December 2009, was treated with temozolomide given immunocompromised patient treated with single kidney and low creatinine clearance with limited platinum-based chemotherapy received three cycles, showing progression of clinical disease and imaging, get second line with interferon alfa-2b dose modified, evolving torpidamente and died from liver failure complicated by encephalopathy and exacerbation of chronic renal failure.

Malignant melanoma in Puerto Rico: an update

A study about the incidence of malignant melanoma in Puerto Rico during the calendar year 1996 was carried out compiling the information submitted by pathological reports to the Puerto Rico Cancer Registry and identifying similar reports at other pathology laboratories. A total of 107 new cases were documented in 1996, resulting in an incidence of 3.03 (+/- 17.9) per 100,000 persons for that particular year. The age of the patients fluctuated between 19 and 88 years with a mean of 61.3 years, most of them being between 50 and 80 years. More than half of the cases (54.2 percent) were located in the head and neck, and the extremities. Thickness measurement of the neoplasm was reported in only 42 percent of the cases. In 60 percent of those cases in which the tumor thickness was reported, it was found to be less than 1.49 mm. Previous data in Puerto Rico from the years 1981 to 1986 had shown a tendency to an increase in the incidence of melanoma per 100,000 inhabitants rising 1.20 to 1.52 respectively. The present study reflects a continuation of the same pattern, with a two-fold increase in the last 10 years (from 1.52 to 3.03)