Implementation of various approaches to study the prevalence, incidence and progression of disseminated neoplasia in mussel stocks.

Marine mussel production is of substantial economic interest in numerous coastal areas worldwide, making crucial the study of pathologies that affect them. Disseminated neoplasia (DN) has recently been suggested to be linked to blue mussel, Mytilus edulis, mortality outbreaks observed in France since 2014, although the evidence remains indirect. In order to improve DN detection and monitoring, we compared the sensitivity of four diagnostic tools, namely haemocytology, histology, flow cytometry, and genetics. Haemocytological examination gave the best results in sensitivity and had the advantage of being non-invasive, allowing disease progression to be followed in affected mussels. Using this approach, we showed that DN progression is usually slow, and we provide evidence of remission events. We observed a high diversity of forms and mitotic features of neoplastic cells located in the vesicular connective tissue but rarely in the haemolymph. Circulating cells occur as four main types but are homogenous in morphology and DNA content within a single individual. Polyploidy proved very high, from 8 N to 18 N. Genetic analysis of haemolymph DNA showed that a Mytilus trossulus genetic signal was associated with almost all the DN cases here diagnosed by haemocytological examination, regardless of the DN type. This result corroborates DN is a transmissible cancer that first originated in a M. trossulus host and subsequently crossed into M. edulis. No pre-neoplastic conditions were detectable. The prevalence of the disease was quite low, which, together with the low morbidity observed in the lab, suggest DN is unlikely to be the direct cause of mortality outbreaks in France.

ETIOSARC study : environmental aetiology of sarcomas from a French prospective multicentric population-based case-control study-study protocol.

INTRODUCTION: Sarcomas are rare tumours of connective tissue. The exact overall incidence of sarcomas is unknown due to diagnostic difficulties and the various histological subtypes (over 80 subtypes). However, the apparent increasing incidence of sarcomas suggests environmental causes such as pesticides. Except for some specific factors (ie, ionising radiation, vinyl chloride, dioxin and genetic predispositions) the scientific knowledge on the aetiology of sarcomas is sparse and inconsistent. France is a particularly appropriate country to set up a study investigating the causes of sarcoma occurrence due to the French organisation in treatment and care of sarcoma patients, which is highly structured and revolved around national expert networks. The main objective of the ETIOlogy of SARcomas (ETIOSARC) project is to study the role of lifestyle, environmental and occupational factors in the occurrence of sarcomas among adults from a multicentric population-based case-control study. METHODS AND ANALYSIS: Cases will be all incident patients (older than 18 years) prospectively identified in 15 districts of France covered by a general population-based cancer registry and/or a reference centre in sarcoma's patient care over a 3-year period with an inclusion start date ranging from February 2019 to January 2020 and histologically confirmed by a second review of the diagnosis. Two controls will be individually matched by sex, age (5 years group) and districts of residence and randomly selected from electoral rolls. A standardised questionnaire will be administered by a trained interviewer in order to gather information about occupational and residential history, demographic and socioeconomic characteristics and lifestyle factors. At the end of the interview, a saliva sample will be systematically proposed. This study will permit to validate or identify already suspected risk factors for sarcomas such as phenoxyherbicides, chlorophenol and to generate new hypothesis to increase our understanding about the genetic and environmental contributions in the carcinogenicity process. ETHICS AND DISSEMINATION: The present study is promoted by the French National Institute of Health and Medical Research (identification number C17-03). This study received National French Ethic committee (CPP Sud Méditerrannée I) approval (identification number 18-31) and French Data Protection Authority (CNIL) approval (identification number 918171). Results of this study will be published in international peer-reviewed journals. Technical appendix, statistical code and dataset will be available in the Dryad repository when collection data are completed. TRIAL REGISTRATION NUMBER: NCT03670927.

Increased Prevalence of Subcutaneous Lipomas in Patients With Wilson Disease.

GOALS: To determine the prevalence and characteristics of lipomas in patients with Wilson disease. BACKGROUND: Wilson disease is an autosomal recessive disorder resulting in copper accumulation in the liver and the central nervous tissue. Subcutaneous lipomas were often noted by the authors during clinical examinations of patients with Wilson disease. This is the first study to analyze the prevalence and progression of lipoma development in patients with Wilson disease. STUDY: Eighty consecutive patients attending a tertiary care center were examined for the presence of subcutaneous lipomas. RESULTS: Subcutaneous lipomas could be detected during the examination of 21 (26%) of the 80 patients with Wilson disease. Multiple subcutaneous lipomas were present in 16 (76%) of the 21 affected patients. Lipomas were mainly found on the extremities and the trunk. Neither initial presentation nor decoppering treatment influenced the presence or course of lipomas in these patients. CONCLUSIONS: Subcutaneous lipoma formation is more common in patients with Wilson disease than in the general population. We suggest that the presence of lipomas contributes to the differential diagnosis of Wilson disease.

Adherence to treatment guidelines for primary sarcomas affects patient survival: a side study of the European CONnective TIssue CAncer NETwork (CONTICANET).

BACKGROUND: The impact of adherence to clinical practice guidelines (CPGs) for loco-regional treatment (i.e. surgery and radiotherapy) and chemotherapy on local disease control and survival in sarcoma patients was investigated in a European study conducted in an Italian region (Veneto). PATIENTS AND METHODS: The completeness of the adherence to the Italian CPGs for sarcomas treatment was assessed by comparing the patient's charts and the CPGs. Propensity score-adjusted multivariate survival analysis was used to assess the impact of CPGs adherence on patient clinical outcomes. RESULTS: A total of 151 patients were included. Adherence to CPGs for loco-regional therapy and chemotherapy was observed in 106 out of 147 (70.2%) and 129 out of 139 (85.4%) patients, respectively. Non-adherence to CPGs for loco-regional treatment was independently associated with AJCC stage III disease [odds ratio (OR) 1.77, P = 0.011] and tumor-positive excision margin (OR 3.55, P = 0.003). Patients not treated according to the CPGs were at a higher risk of local recurrence [hazard ratio (HR) 5.4, P < 0.001] and had a shorter sarcoma-specific survival (HR 4.05, P < 0.001), independently of tumor stage. CONCLUSIONS: Incomplete adherence to CPGs for loco-regional treatment of sarcomas was associated with worse prognosis in patients with non-metastatic tumors.

Elevated risk of second primary cancer in patients with cutaneous malignant melanoma: a nationwide cohort study in Taiwan.

BACKGROUND: It has been described that Caucasian patients with cutaneous malignant melanoma (CMM) are at an increased risk of developing second primary cancer. However, no large-scale study of second primary cancer in CMM patients has been conducted among Asians, who have distinctly different skin types. OBJECTIVE: We sought to access the risk of second primary cancer among CMM patients based on data from a nationwide database in Taiwan. METHODS: Utilizing the catastrophic illness database of Taiwan's National Health Insurance Research Database, we identified 2665 CMM patients without prior cancers in the period from 1997 to 2008. The standard incidence ratio (SIR) of each cancer was calculated. RESULTS: The mean age ± standard deviation at diagnosis of CMM was 62.2 ± 17.4 years. The mean annual incidence was 0.9 cases per 100,000 people. The overall cancer risk was elevated (SIR: 2.54), with younger patients having a higher risk. The risk remained elevated during the first five years after the CMM diagnosis. CMM patients had a higher risk of developing cancers of eye (SIR: 275.68), connective tissue (SIR: 43.45), brain (SIR: 21.03), and non-melanoma skin cancer (SIR: 17.71). CONCLUSION: CMM patients have a 2.54-fold risk of second primary cancer, with younger patients at increased risk. The risk remains elevated during the first five years after the diagnosis of CMM. The sites with highest risk of second primary cancer are eye, connective tissue, brain, and non-melanoma skin cancer.

[Tumors of the footbones- a report from the Hamburg Bone Tumor Registry]. / Tumoren des Fussskeletts - Ein Erfahrungsbericht des Hamburger-Knochentumorregisters.

Aim of the present study was a systematic examination of the tumors of the foot registered in the Hamburg Bone Tumor Registry regarding age, sex, location, diagnosis and morphological characteristics. The registry files and histological specimens of 367 tumors and tumor-like lesions of the foot were reviewed. Males were more frequently affected (ratio 4 : 3). Some 20.4 % of all mass forming tumors were malignant. Cartilage tumors (146 cases), cystic (132 cases) and osteoblastic lesions (33 cases) were most common. Several tumors showed a strong predilection for certain parts of the foot. In the calcaneus a solitary bone cyst was the most common lesion. Lesions in the talus and metatarsals with a similar morphology mostly represented intraosseous ganglion cysts. Other tumors in the calcaneus were mainly cartilaginous. Besides chondroblastoma, chondrosarcoma was regularly diagnosed. Chondroma was extremely rare at this site. Contrary to that chondroma was regularly found at the metatarsal and phalangeal bones, it was 4 times more common than chondrosarcoma. An even distribution showed aneurysmal bone cysts and osteoidosteoma. Very rare lesions were fibrous dysplasia, eosinophilic granuloma and intraosseous lipoma. The knowledge of the distribution of tumors in the foot is important for an exact differential diagnosis and thereby for biopsy planning, diagnosis and therapy.

Gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are mesenchymal gut tumors that differ dramatically from other histologically similar neoplasms, such as leimomyomas, leiomyosarcomas (LMS), and neural tumors. Complete surgical removal remains the best current therapy for GISTs, but even major resections are associated with recurrence in approximately 90% of cases. GISTs are remarkably resistant to irradiation and standard chemotherapy; there is no role for treatment with those modalities. Treatment of advanced GIST patients with STI571, a novel selective tyrosine kinase inhibitor, results in remission rates that approach 60% and overall tumor control rates of 85%. Selected groups of patients, as based on tumor mutational status, have response rates as high as 80%. To date, STI571 therapy remains the only systemic treatment for GISTs to have meaningful clinical activity. Though other molecularly targeted therapies exist in oncology (eg, trastuzumab), STI571 is one of the first that applies a drug specifically designed to inhibit the product of a constitutively-activating mutation that drives pathogenesis of a solid tumor. Its use can serve as a paradigm for designing molecularly targeted therapies for other malignancies.

[Secondary malignant neoplasms in patients with breast cancer]. / Sekundäre maligne Neoplasien bei Patientinnen mit Mammakarzinom.

OBJECTIVE: This report analyzes the occurrence of secondary malignancies among patients with breast cancer. MATERIAL AND METHODS: We evaluated all women diagnosed with breast cancer who were reported to the National Cancer Institute of the former GDR in 1976. There was a follow up of 5,485 patients from 1976 to 1988 (38,231 person-years at risk). Cancer incidence rates of the whole female population specific for age and calendar year were used for calculation of the standardized incidence ratio (SIR). RESULTS: Significantly increased risks were observed for neoplasms of the bilateral breast (SIR 2.44; 95% CI 2.04-2.93), colon (SIR 1.53; 95% CI 1.06-2.12), rectum (SIR 1.65; 95% CI 1.10-2.40), endometrium (SIR 1.55; 95% CI 1.02-2.27), and ovary (SIR 1.71; 95% CI 1.09-2.57). Neoplasms of the lung (SIR 1.65; 95% CI 0.93-2.73), kidney (SIR 1.51; 95% CI 0.69-2.87), bladder (SIR 1.32; 95% CI 0.48-2.87), connective tissue (SIR 3.54; 95% CI 0.73-10.34), and multiple myeloma (SIR 1.98; 95% CI 0.54-5.06) were also increased, not reaching statistical significance. Risk reduction was observed for malignant tumors of the gallbladder (SIR 0.36; 95% CI 0.12-0.83). CONCLUSION: In proposing recommendations for the follow-up and management of women with breast cancer, it is important to recognize their long-term predisposition to an array of secondary cancers.

Risk of second malignant neoplasms among long-term survivors of testicular cancer.

BACKGROUND: We have quantified the site-specific risk of second malignant neoplasms among nearly 29,000 survivors (> or = 1 year) of testicular cancer, taking into account the histologic type of initial cancer and the primary therapy used to treat it. METHODS: The study cohort consisted of 28,843 men identified within 16 population-based tumor registries in North America and Europe; over 3300 men had survived more than 20 years. New invasive cancers were identified through a search of registry files. RESULTS: Second cancers were reported in 1406 men (observed-to-expected ratio [O/E] = 1.43; 95% confidence interval = 1.36-1.51), with statistically significant excesses noted for acute lymphoblastic leukemia (O/E = 5.20), acute nonlymphocytic leukemia (O/E = 3.07), melanoma (O/E = 1.69), non-Hodgkin's lymphoma (O/E = 1.88), and cancers of the stomach (O/E = 1.95), colon (O/E = 1.27), rectum (O/E = 1.41), pancreas (O/E = 2.21), prostate (O/E = 1.26), kidney (O/E = 1.50), bladder (O/E = 2.02), thyroid (O/E = 2.92), and connective tissue (O/E = 3.16). Overall risk was similar after seminomas (O/E = 1.42) or nonseminomatous tumors (O/E = 1.50). Risk of solid tumors increased with time since the diagnosis of testicular cancer, yielding an O/E = 1.54 (O = 369) among 20-year survivors (two-sided P for trend = .00002). Secondary leukemia was associated with both radiotherapy and chemotherapy, whereas excess cancers of the stomach, bladder, and, possibly, pancreas were associated mainly with radiotherapy. CONCLUSIONS: Men with testicular cancer continue to be at significantly elevated risk of second malignant neoplasms for more than two decades following initial diagnosis. Patterns of excess second cancers suggest that many factors may be involved, although the precise roles of treatment, natural history, diagnostic surveillance, and other influences are yet to be clarified.

Cancer risks among female farmers in Sweden.

There are few studies on cancer risks among female farmers, particularly on breast cancer and cancer in female genital organs. We have conducted a cohort study of cancer risk among 50,682 women with occupations in agriculture according to the Swedish 1970 census. The cohort was followed up in the nationwide, population-based, Cancer-Environment Register from 1 January 1971 until death or until 31 December 1987. Expected number of cases was based on annual cancer incidence in five-year age groups. The standardized incidence ratio (SIR) was computed as the ratio between observed and expected number of cases. A total of 4,474 cases of cancer were observed in the cohort from 1971 until 1987 cf 5,273 expected, resulting in a significantly decreased SIR of 0.85 (95 percent confidence interval [CI] = 0.82-0.87). SIR for breast cancer was significantly decreased (0.83, CI = 0.78-0.88), as was the SIR for cervix uteri (0.40, CI = 0.31-0.50). For the other female genital organs, SIR was close to one. Other cancer sites with significantly decreased SIRs were: colon (0.90, CI = 0.81-1.00); rectum (0.86, CI = 0.74-1.00); lung (0.46, CI = 0.37-0.57); kidney (0.81, CI = 0.68-0.97); urinary organs (0.57, CI = 0.45-0.72); connective tissue and muscle (0.62, CI = 0.39-0.95); and non-Hodgkin's lymphomas (0.78, CI = 0.63-0.96).

A meta-analysis of exposure to phenoxy acid herbicides and chlorophenols in relation to risk of soft tissue sarcoma.

This analysis combines the results of the epidemiologic studies which appeared in the literature from 1979-1987 concerning the associations between phenoxy acid herbicides (PH) and chlorophenols (CP) and the occurrence of soft tissue sarcoma. Cohort studies and case-control studies are considered separately. After specifying criteria for inclusion, the total number of deaths due to cancer occurring in selected cohorts of people exposed to PH or CP was determined. The proportion of soft tissue sarcoma cases observed versus expected in the cohort studies, calculated using United States SEER registry data, resulted in a proportional mortality ratio of 3.5 (95% confidence interval of 0.7-10.3). Excluding the initial reports, the selected case-control studies had homogeneous risk estimates with a summary odds ratio of 1.1 (95% confidence interval of 0.9-1.4). Other attempts to assess the combined data did not yield results indicating an association. These meta-analyses do not provide strong support for an association between the specified herbicides and soft tissue sarcoma.

Epidemiology of cancer of the connective tissue in Canada during the period 1950-1985.

Canadian patterns of morbidity and mortality from malignancies of the connective tissue were examined for the periods 1970-1982 and 1950-1985, respectively. Age-standardized morbidity rates have risen significantly during 1970-1982 in males (P = 0.005), whereas the increase noted in females was of borderline significance (P = 0.055). Examination of age-specific morbidity rates during this period revealed that rates for the eight age groups studied in males have increased, with rates of increase for males aged 65-74 attaining statistical significance (P = 0.0006), whereas increases for males aged 0-24 and 75-84 years were of borderline significance (P less than 0.08). Age-standardized mortality rates during 1950-1985 have risen significantly for both males (0.013 additional new deaths per 100,000 population per year; P less than 0.0001) and females (0.008 additional new deaths per 100,000 population per year; P less than 0.0001). Significant rates of increase were noted in age-specific mortality rates for seven of the eight age groups studied in males (P less than 0.03) and for five of the eight age groups studied in females (P less than 0.04). The rate of increase for women aged 35-44 years was of borderline significance (P = 0.06). Rates of increase in age-specific mortality rates were greatest in males and females aged 75-84 years at 0.113 and 0.059 additional new deaths per 100,000 population per year, respectively.

Incidence of childhood tumours in Queensland.

The incidence of childhood cancer in Queensland has been studied using the data of the population-based Queensland Childhood Malignancy Registry. During the 7-year period 1973-1979, 454 cases were registered, giving an annual age-specific incidence of 11.34/10(5) for the age group 0-14 years inclusive. There was a male/female ratio of 1.36. The commonest group of diseases was that of the leukaemias, followed by that of CNS tumours. The incidences of the various types of tumour in Queensland have been compared with those from other reported series. The incidence of leukaemia was midway between that of U.S. whites and that of Manchester, while the incidences of lymphoma and Wilms' tumour were much closer to those of the United States. Ewing's tumour was considerably commoner than osteosarcoma.

Incidence of malignant disease in childhood: a 24-year review of the Manchester Children's Tumour Registry data.

The Manchester Children's Tumour Registry data for the period 1954-1977 have been analysed. The overall incidence of malignant disease in children aged 0-14 years in the north-west of England is estimated to be 100 per million person-years. The most common disease group is leukaemia, which forms about one third of the total number of cases. Among solid tumours, by far the most common presenting site is the central nervous system, representing nearly a quarter of all neoplasms. Wilms' tumour, neuroblastoma and soft-tissue sarcomas comprise approximately 5%, 6.5% and 6% respectively of the total. The tumours most frequently seen in adults (e.g. carcinoma of colon, lung and breast) are extremely rare in childhood. A significant excess of males was seen in acute lymphoid leukaemia, non-Hodgkin's lymphoma, Hodgkin's disease, medulloblastoma and hepatoblastoma. A female excess was found among germ-cell tumours. During the study period significant increases in incidence were seen among acute lymphoid leukaemia and epithelial tumours, and an increase in germ cell tumours approached significance.