Assessing cancer in people with profound and multiple disabilities.

BACKGROUND: Cancers are as common in individuals with intellectual disabilities as in the general population (GP). For the subgroup of people with profound and multiple disabilities (PMD) who present with both severe intellectual disability and major motor disorders, the frequency and distribution of cancers are currently not known, preventing proper cancer surveillance. METHODS: We carried out a systematic and synthetic review of the medical literature, including a focused search of Japanese data. RESULTS: The total risk of cancer in individuals with PMD is thought to be lower than in the GP, possibly due to a shorter life expectancy. They have reduced exposure to cancer risk factors, such as alcohol, tobacco, sunlight, human papillomavirus infection, occupational toxins, and being overweight. On the other hand, individuals with PMD present a greater frequency of gastroesophageal reflux disease, Helicobacter pylori gastritis, chronic cystitis, and cryptorchidism, which increase the risk for cancer of the esophagus, stomach, urinary bladder, and testes. In addition, certain genetic disorders underlying compromised motor and cognitive functions are associated with higher risk of childhood cancers. An analysis of 135 cancers in persons with PMD in Japan suggested that they present a particular tumor profile, with certain cancers rarer than in the GP, whereas cancers of the digestive tract are frequent. Cancers of the digestive tract occurred significantly earlier than in the GP (colon: average age 48.3 years vs. 71.3 years in the GP, esophagus: 39 years vs. 72 years in the GP). An increasing number of therapeutic successes in children and adults with PMD have been reported in different countries when cancers are discovered early. CONCLUSION: Individuals with PMD must be appropriately monitored for cancer. Screenings for breast and colon cancer, as well as regular monitoring of the esophagus, stomach, urinary bladder, and testicles, are necessary. Population-based epidemiological studies are needed to better understand risk factors, frequency, and distribution of cancers in the PMD population.

A tumor profile in Patau syndrome (trisomy 13).

Individuals with trisomic conditions like Down syndrome and Edwards syndrome are prone to certain types of malignancy. However, for Patau syndrome (constitutional trisomy 13), which occurs in 1/10,000-1/20,000 live births, the tumor profile has not been well characterized. An awareness of susceptibility to malignancies can improve care of affected individuals, as well as further our understanding of the contribution of trisomy to carcinogenesis. Therefore, we conducted an extensive review of the literature; we found 17 malignancies reported in individuals with Patau syndrome. These comprised eight embryonic tumors, three leukemias, two malignant germ cell tumors, two carcinomas, a malignant brain tumor, and a sarcoma. Benign tumors were mainly extragonadal teratomas. The small number of reported malignant tumors suggests that there is not an increased risk of cancer in the context of trisomy 13. The tumor profile in Patau syndrome differs from that observed in Edwards syndrome (trisomy 18) and Down syndrome (trisomy 21), suggesting that the supernumerary chromosome 13 could promote particular tumor formations as it does particular malformations. No general and direct relationships of tumor occurrence with organ weight, congenital malformations, histological changes, or presence of tumor suppressor genes on chromosome 13 were observed. However, some tumors were found in tissues whose growth and development are controlled by genes mapping to chromosome 13. Recent reports of successful outcomes following surgical treatment and adapted chemotherapy indicate that treatment of cancer is possible in Patau syndrome.

A tumor profile in Edwards syndrome (trisomy 18).

Constitutional trisomy 18 causes Edwards syndrome, which is characterized by intellectual disability and a particular set of malformations. Although this condition carries high mortality during prenatal and early postnatal life, some of the rare infants who survive the first months develop benign and malignant tumors. To determine the tumor profile associated with Edwards syndrome, we performed a systematic review of the literature. This review reveals a tumor profile differing from those of Down (trisomy 21) and Patau (trisomy 13) syndromes. The literature covers 45 malignancies: 29 were liver cancers, mainly hepatoblastomas found in Japanese females; 13 were kidney tumors, predominantly nephroblastomas; 1 was neuroblastoma; 1 was a Hodgkin disease; and 1 was acute myeloid leukemia in an infant with both trisomy 18 and type 1 neurofibromatosis. No instances of the most frequent malignancies of early life-cerebral tumors, germ cell tumors, or leukemia--are reported in children with pure trisomy 18. Tumor occurrence does not appear to correlate with body weight, tissue growth, or cancer genes mapping to chromosome 18. Importantly, the most recent clinical histories report successful treatment; this raises ethical concerns about cancer treatment in infants with Edwards syndrome. In conclusion, knowledge of the Edwards' syndrome tumor profile will enable better clinical surveillance in at-risk organs (i.e., liver, kidney). This knowledge also provides clues to understanding oncogenesis, including the probably reduced frequency of some neoplasms in infants and children with this genetic condition. © 2016 Wiley Periodicals, Inc.

A very rare cancer in Down syndrome: medulloblastoma. Epidemiological data from 13 countries.

Persons with Down syndrome (DS) uniquely have an increased frequency of leukemias but a decreased total frequency of solid tumors. The distribution and frequency of specific types of brain tumors have never been studied in DS. We evaluated the frequency of primary neural cell embryonal tumors and gliomas in a large international data set. The observed number of children with DS having a medulloblastoma, central nervous system primitive neuroectodermal tumor (CNS-PNET) or glial tumor was compared to the expected number. Data were collected from cancer registries or brain tumor registries in 13 countries of Europe, America, Asia and Oceania. The number of DS children with each category of tumor was treated as a Poisson variable with mean equal to 0.000884 times the total number of registrations in that category. Among 8,043 neural cell embryonal tumors (6,882 medulloblastomas and 1,161 CNS-PNETs), only one patient with medulloblastoma had DS, while 7.11 children in total and 6.08 with medulloblastoma were expected to have DS. (p 0.016 and 0.0066 respectively). Among 13,797 children with glioma, 10 had DS, whereas 12.2 were expected. Children with DS appear to be specifically protected against primary neural cell embryonal tumors of the CNS, whereas gliomas occur at the same frequency as in the general population. A similar protection against neuroblastoma, the principal extracranial neural cell embryonal tumor, has been observed in children with DS. Additional genetic material on the supernumerary chromosome 21 may protect against embryonal neural cell tumor development.

Challenges in Diagnosis and Treatment of Lung Cancer in People with Intellectual Disabilities: Current State of Knowledge.

As the life expectancy of people with intellectual disability (ID) has progressed, they have become similarly at risk of cancer as individuals of the general population. Epidemiological studies indicate a reduced incidence and mortality from lung cancer in the total population of persons with ID. However, the pattern is heterogeneous and the risk is strongly correlated with the impairment level; persons with mild intellectual impairment have higher cancer risk, and this subgroup also has the highest tobacco consumption (the major risk factor for lung cancer) compared to individuals with more severe impairment. Clinical presentation of lung cancer in persons with ID is often atypical, with symptoms frequently hidden by the mental state and communication impairments. Treatment can be impeded by incomplete understanding and lack of cooperation on the part of the patient; nevertheless, general principles for treating lung cancer must be applied to persons with ID. Early diagnosis and implementation of an adapted treatment plan may result in lung cancer outcomes similar to those of individuals in the general population. Physicians facing the difficult task of treating lung cancer in persons with ID are called to carry out their mission of care in a responsible, free, and creative way.

A mucoepidermoid carcinoma in a young man with intellectual disability: review of oral cancer in people with intellectual disability.

Oral tumors in patients with intellectual disabilities (ID) remain poorly documented, despite cancer incidence suggesting that malignancies are globally as frequent in this group as in the general population. A clinical case of a 36-year-old man with severe ID presenting with a mucoepidermoid carcinoma of intermediate grade in the right mandible is reported. Delayed diagnosis and problems managing complementary chemotherapy and radiotherapy are described. The literature review reported only 27 cases of malignant tumors in patients with ID. This finding indicates that oral tumors in patients with ID may be less frequent than in the general population, are usually diagnosed at an advanced stage, and may occur in patients who are younger than the general population. Diagnosis and treatment are difficult, implying a comprehensive knowledge of the underlying condition of each individual and the need for good communication skills to obtain patient cooperation, including an understanding of how the patient expresses pain.

Respiratory symptoms and cigarette smoking in 3,197 pulmonologist-based asthmatic patients with a highly prevalent use of inhaled corticosteroid.

The relation between smoking and risk of asthma has been well-examined; however little attention has been paid to the correlation between smoking and asthma symptoms. The aims of this study were to examine respiratory symptoms in asthmatics with a highly prevalent use of inhaled corticosteroid (ICS) and to assess the effects of smoking and its cessation. A cross-sectional study of pulmonologist-based 3197 asthmatics (men 45.2%, ages 20-97) was performed using a questionnaire about smoking habits, the incidence and frequency of symptoms (sputum, cough and wheezing, night symptoms, and shortness of breath), physical activity interference, and medication. Although 81.4% of the patients used ICS according to the international guideline, 14.9% had activity interference, and daily symptoms remained in 43.3%. At the time of the questionnaire, 21.6% were current and 25.1% were ex-smokers. In multiple logistic regression analysis, the factors of significance (p < 0.0001) were (1) smoking; for all four symptoms, (2) age and duration of asthma; for shortness of breath. Current smokers were at a risk of sputum (age-adjusted odds ratio 2.32 [95% confidence interval 1.73-3.11]; 2.09 [1.57-2.79]), of cough and wheezing (2.38 [1.81-3.14]; 1.78 [1.35-2.36]), of night symptoms (1.95 [1.41-2.60]; 1.47 [1.09-1.98]), and of shortness of breath (1.70 [1.26-2.28]; 1.30 [0.97-1.75]) in men and women, respectively. These ratios in ex-smokers decreased to the level similar to nonsmokers. Although 81.4% of asthmatic patients used ICS, 43.3% complained of daily respiratory symptoms, especially sputum. It is suggested that the effects of ICS on asthma symptoms may be interfered with by smoking and therefore more emphasis should be placed on cessation of smoking.

Familial aggregation of uterine myomas in Japanese women.

To assess the familial aggregation of uterine myomas in Japanese women with myomas, one hundred forty four women requiring surgery for myomas and 288 age-matched healthy controls were studied in Hokkaido, Japan. The incidence of positive first-degree family history of myomas among women aged 45-54 years with myomas was greater than that among controls (31.5% versus 15.2%, respectively, p < 0.01). Analyses categorized by the status of parity and familiality among subjects showed that the risk for myomas was the greatest in women who had both fewer births (parity = 0 or 1) and the positive family history of myomas as compared with those who had both more births (parity > or = 2) and the negative familiality of myomas (odds ratio = 5.8, 95% confidence interval = 2.3 - 14.6). The results of this study suggest that Japanese middle-aged women with myomas have the familial predisposition of uterine myomas. Furthermore, nulliparous women with the familial aggregation of myomas may be at increased risk of the disease.