[Prostate cancer in Luxembourg from 1982 to 2006. Incidence and mortality. Survival of a hospital cohort]. / Le Cancer de la Prostate au Luxembourg de 1982 à 2006. Incidence et mortalité. Survie d'une cohorte hospitalière.

Prostate cancer incidence has tripled in Luxembourg as in many other western countries. From 1982 to 2006, new cases increased from 80 to 309 per year, while the incidence (world stand.pop.) rose from 29.5 to 85 per 100 000 men. Since 1991 prostate cancer is the most frequent male cancer in Luxembourg, exceeding colo-rectal, lung and stomach cancer. Prostate cancer deaths have diminished from 64 in 1982 to 45 in 2006. This represents less than 10% of male cancer related deaths; it represents the third most frequent cancer death, behind lung and colo-rectal cancers. Annual mortality rate has decreased from 29 to 10 per 100 000 men during the same period, this difference between incidence and mortality is explained on the one hand by the widespread use of PSA since the 1990's and on the other hand by a better local control as well as a multidisciplinary approach of advanced disease. The increase of the incidence is particularly important in the 60 to 70 age group, while for men older than 70, the peak incidence was reached in 2002. A lowering of the age at diagnosis is confirmed by the 5-year age group analysis. The hospital cohort consists of 628 patients from the urological department of the Centre Hospitalier de Luxembourg diagnosed with prostate cancer between 1st January 1982 and 31st December 2006; follow-up ended 31st December 2011. During this period, age at diagnosis decreased from 71.5 to 68.9 years whereas the proportion of localized clinical stages increased from 44 to 70%. Median PSA dropped from 14.5 to 9 ng/ml. Furthermore the analysis of cancer specific mortality confirms the negative effects of an advanced clinical stage (10-year survival: 90% for localized disease, 60% for advanced disease) or a high PSA level at diagnosis (10-year survival: 97% if PSA < 4 ng/nl, 94% if 4 < PSA < 10, and 72% if PSA > 10 ng/ml), as well as a poor differentiation (60% 10-year survival compared to 90% for differentiated tumors). Kaplan-Meier curves show that long term surveillance is necessary as even tumors with a good initial prognosis may relapse after 10-12 years.

Evolution of colorectal cancer epidemiology in a setting of opportunistic screening. A 20 year national survey in Luxembourg.

UNLABELLED: Invasive colorectal cancer (CRC) is the second leading cause of cancer death in Luxembourg. There is no organized screening programme in Luxembourg. This study aims to obtain a precise epidemiological description of the evolution of invasive CRC and high grade intraepithelial neoplasia (HGIEN) from 1990 to 2009, extracted from the database of the Morphologic Tumor Registry. Tumor stages and observed survival rates were also recorded. They were compared to the change in use of colonoscopic procedures. During the 20-year period, 4810 invasive CRC cases and 1180 HGIEN were recorded. Incidence rose from 1990 to 2005 and declined thereafter, especially in women. A sharp rise in HGIEN was noted from 2004 onwards, paralleling the rates of colonoscopies. 76% of CRC cases were found in advanced stages pT3 and pT4. The pT stage distribution did not change over the observation period. Observed survival rates improved during the study period. CONCLUSION: Under opportunistic screening conditions, mainly through colonoscopy, the incidence of CRC was declinig in recent years, whereas HGIEN incidence is rising in Luxembourg. Tumor pT staging remained unchanged whereas survival rates improved. We conclude that opportunistic screening is of little benefit for CRC prevention. A national organized screening programme is warranted.

Oesophageal intraepithelial and invasive neoplasia of squamous cell type: epidemiology and outcome in Luxembourg, 1980-2001.

BACKGROUND AND STUDY AIMS: Oesophageal intraepithelial neoplasia of squamous cell type (INSC) and invasive oesophageal squamous cell carcinoma (IOSCC) are infrequent diseases in Western Europe. The aim of the present study was to collect population-based data of both entities over a 20 year-period and to look for concomitant neoplastic affections in order to define an adequate diagnostic strategy. PATIENTS AND METHODS: The National Morphologic Tumour Registry allowed to review the data of all patients with INSC and IOSCC diagnosed between 1980 and 2001 and to record the time trends in incidence, the oncologic co-morbidity and the outcome of the patients. RESULTS: 29 patients with INSC and 363 cases of IOSCC were identified. The overall age-standardized (world) incidence rate of intraepithelial neoplasia and invasive squamous cell carcinoma were 0.2 and 4.2 per 10(5), respectively, the M/F-ratio for both 3:1. During the study period, the incidence rate of invasive cancer remained stable in males but showed a 3-fold increase in females. There was a 2-fold increase of the intraepithelial neoplasia incidence in the last decade. The precancerous/cancerous-ratio increased slightly over the last 5 years. 31% of the patients with an INSC and 17.6% of those with IOSCC had concomitant precancerous and cancerous lesions especially of head and neck (laryngopharyngeal) or pulmonary origin. The observed 5-year survival rate was 8.8 +/- 3% (95% confidence interval) for IOSCC and 27.6% +/- 17% for INSC. CONCLUSIONS: The incidence of invasive oesophageal squamous cell carcinomas remains stable whereas that of detected intraepithelial squamous cell neoplasias is remarkably low, indicating potential underdiagnosis. Considering the overall low incidence rates, mass screening for oesophageal cancer does not seem reasonable in Luxembourg. Nevertheless, patients at high-risk for oesophageal or head and neck or broncho-pulmonary cancer should be identified and surveilled by endoscopy, possibly with vital staining.

Cervical screening in Luxembourg: 1990-1999.

For quality assurance purposes, the results of the 1990's obtained by the National Cervical Cancer Screening Programme (NCCSP) launched in 1962 were reviewed. The positive cytodiagnosis, the histologically verified in situ and invasive cervical cancers and the mortality rates were reported.

Atypical squamous cells of undetermined significance: audit and the impact of potential litigation. Retrospective review of 682 cases.

For quality assurance purposes, the frequency of 'abnormal' cytological diagnoses of the non-systematic National Cervical Cancer Screening Programme (NCCSP) was evaluated. In 1999, an unexpected high number of Class (Cl) III cases (i.e. atypical squamous cells of undetermined significance) was reported. The cytological and histological results were reviewed in order to detect a possible cause for this threefold increase. The abnormal Papanicolaou (PAP) smears examined by conventional methods from 1 January 1990 to 31 December 2002 were analysed. The smears of 682 cases diagnosed in 1999 with a Cl III category were reviewed in 2000 and correlated with the available histological diagnoses provided by the Central Department of Pathology. Of the 682 Cl III cases, 176 cases (26.1%) had no follow-up, 314 cases (46.0%) had repeat cytology and 192 cases (28.2%) an histological correlate corresponding to 90 (46.9%) benign lesions, 78 (40.6%) squamous intraepithelial lesions, two (1%) invasive cervical cancers (one squamous and one glandular). Twenty-two Cl III cases (11.5%) were histologically within normal limits. Retrospective smear review confirmed 330 Cl III diagnoses (48.3%), 127 cases (18.6%) were recategorized as Cl IIIG (i.e. atypical glandular cells of undetermined significance), 22 cases (3.2%) as Cl IIID (i.e. mild to moderate dysplasia) and six cases (0.9%) as Cl IVa (i.e. severe dysplasia and/or carcinoma in situ). A total of 197 original Cl III cases had to be reclassified in the Cl II category (28.9%), only two cases showing mild and moderate dysplasia on histology. Thus, 195 cases (28.6%) comprised cytological overdiagnoses. The Cl III category being, by definition, a delicate and often subjective diagnosis, all external influences such as pressure of litigation should be avoided to reduce cytological overdiagnoses as a result of an unnecessary 'fear-factor'.

Consequences of a National Mammography Screening Program on diagnostic procedures and tumor sizes in breast cancer. A retrospective study of 1540 cases diagnosed and histologically confirmed between 1995 and 1997.

In 1992, a national screening mammography program, including female patients between 50 and 64 years of age, was launched in Luxembourg. The effects of this campaign on the different diagnostic procedures, especially fine needle aspirations (FNA), large core needle biopsies (LCNB), and surgical specimens, were analyzed. From 1983 to 1997, the National Cancer Registry recorded 3167 new cases of invasive female breast cancer, all histologically diagnosed in one central pathology department. In 1996, the population consisted of 418,300 inhabitants (212,900 females). The number of breast cancer, tumor size, the nature of the diagnostic procedures, their diagnostic value as well as the number of physicians, "aspirators", and "biopsists" were evaluated. Between 1992 and 1994, the incidence of invasive breast cancers increased, concomitant with the launching of a National Screening Mammography Program. The diagnosis of in situ cancers tripled, and the mean size of invasive breast cancer decreased from 2.1-2.4 cm to 1.1-1.4 cm. Since 1994, the number of FNA had remained stable, LCNB had increased by 417.5%, and surgical biopsies had decreased by 18.95%. Between 1995 and 1997, 28.37% of 1075 FNA, and only 9.6% of 465 LCNB yielded inadequate samples. FNA were done by 77 different doctors (53.25% being gynecologists) and LCNB by 34 (52.94% being radiologists). The first diagnoses of all invasive cancers (n = 790) were made by using frozen sections from surgical specimens in 58.35% (n = 461), LCNB in 18.23% (n = 144), mastectomy in 10.13% (n = 80), formalin-fixed biopsies in 9.49% (n = 75), and FNA in 3.17% (n = 25). There are beneficial effects (increase in the number of diagnoses of in situ cancer; decrease in tumor sizes) not only for the "target" age group (50-64 years), but also for all female age groups (> 15 years). For quality assurance purposes, it is absolutely recommended to carry out pathological, radiological, and diagnostic work in specialized centers.

Accuracy of frozen section diagnoses of breast lesions after introduction of a national programme in mammographic screening.

AIMS: By introducing mammography screening programmes, the size of the detected breast lesions became smaller and the histopathological interpretation problems greater. The study's aim was to analyse the risks and possible limitations of the frozen section method. METHODS AND RESULTS: Frozen section consultations of breast lesions (n=559) 2 years before and 6 years after launching a national mammographic screening programme in 1992 were evaluated in regard of the benign/malignant ratio, tumour size, preoperative frozen section results and final permanent section diagnoses. The breast frozen section examinations of 1990 compared with those from 1998 declined from 70.7% (299/423) to 62.2% (260/418) (P < 0.01), the benign/malignant ratio from 1.09 to 0.54 (P < 0.0001), the rate of the conclusive, correct frozen section diagnoses from 96.3% to 91.9% (P < 0.03). The sensitivity dropped from 92.3% to 87.6%, the negative predictive value from 95.7% to 88.3%, whereas the negative likelihood ratio rose from 0.08 to 0.12. The 'small' (< or = 10 mm) invasive breast carcinomas increased from 14.2% to 22.3% (P < 0.01) and the 'in situ' carcinomas from 2.1% to 6.6% (P < 0.05). CONCLUSIONS: The declining sizes of breast tumours (< or = 10 mm), especially from radiologically detected lesions and sometimes without a macroscopic correlate, create new limitations and changing indications in the histopathological interpretation. Considering the performance of new diagnostic methods (i.e. large core needle biopsies), frozen sections of surgical specimens should not be the primary diagnostic procedure for breast lesions and should be performed only after other preoperative methods have failed.

Cervical cancer screening in Luxembourg.

In 1962, a programme for early detection of cervical cancer was established at the national level. The programme is based on the collaboration of different groups of doctors and not on a system of sending out invitations to every woman. This programme was re-adapted twice according to the needs for assuring quality in a system of mainly liberal medicine. At present the programme is 'institutionalised' and is carried out according to the criteria defined in 1990. This includes a centralisation of the smear readings and handing out the material needed to take the smears. The contribution of the doctors is regulated by a system of bonuses given by the government and a reimbursement by the Health Fund. The annual cervical smear is free of charge for every woman. The participation of the women targeted by the programme (>15 years old) has increased by approximately 50% every decade from the early 1970s increasing from 10950 in 1972 to 70441 in 1999. Between 1980 and 1999, the number of women at risk taking part in the programme increased from 10.80 to 38.92%. The number of all the doctors taking smear samples increased from 68 to 105 and the number of gynaecologists increased from 19 (ratio Gyn/GP (gynaecologists/General Practitioners) of 28%) to 52 (ratio Gyn/GP of 50%). The mortality rate has decreased continuously from 6. 1/100000 in 1990 to 0.9/100000 in 1997. In conclusion, to be successful, a cervical cancer screening programme should be flexible enough to allow short-term adaptations to unexpected local situations and needs a highly motivated team of the different participants involved in the regional and national health policy.

Colorectal high-grade adenomas: incidence, localization and adenoma-adenocarcinoma ratio in a retrospective and comparative population-based study of 225 consecutive cases between 1988 and 1996.

Colorectal high-grade adenomas can be regarded as precancerous lesions. This study collected epidemiological data from a defined region (Luxembourg) that can serve as reference data for designing a national screening program for early colorectal cancer detection. Nine pathologists diagnosed and reviewed slides retrospectively from 288 new colorectal and anal in situ carcinomas from the period 1988-1996 (63 were excluded for various reasons). In all, 225 new colorectal high-grade adenomas were considered. There were 129 men (57%) and 96 women (42%), and 78% of patients were aged over 60 years. Over this period we found an increase in incidence of high-grade colorectal adenomas (11 cases in 1988, 40 cases in 1996) for both sexes. The overall incidence rate was 2.9 x 100,000 in 1988 and 9.6 x 100,000 in 1996. The average annual age-standardized incidence rate for this period was 3.7+/-0.5 (95% confidence interval); the cumulative rate (0-74 years) was 0.4%. Three-fourths of the adenomas were situated in the rectum (n=78, 35%) or sigmoid colon (n=92, 41%). Histological diagnosis was provided by 160 total polypectomy specimens (71%), 30 surgical resections (13.3%), and 35 biopsy specimens (16%). Over the study period there was an increased incidence of new colorectal adenocarcinomas. There were eight times as many adenocarcinomas (n=1782) as adenomas (n=225); the distribution of anatomical sites was comparable. These epidemiological data on 225 new colorectal high-grade adenomas can be the basis for quality assurance in clinical and histological diagnostic procedures, especially in regard to the 1:8 ratio between high-grade adenomas and invasive adenocarcinomas and may provide additional data for the design of a regional or national colorectal cancer screening program.

[Prostatic cancer in the Grand Duchy of Luxembourg. Role of PSA]. / Le cancer prostatique au Grand-Duché de Luxembourg. Rôle du PSA.

We reviewed the trends in prostate cancer incidence and mortality in Luxembourg between 1983 and 1995 to discuss the importance of total and free PSA in early detection. The study was performed on all the new cases recorded by the National Cancer Registry (Registre Morphologique des Tumeurs). Total and free PSA were measured with the automated Immulite System (DPC, Los Angeles) using a chemoluminescent immunometric assay. The performance of free-to-total serum PSA was analysed by a hospital based study of 113 patients (55 PC, 58 BPH). The age standardized incidence rate increased from 29.3/100,000 in 1983 to 71.5/100,000 in 1995. Mortality rates only changed slightly. The widespread use of PSA testing from 1988 on is probably the main cause of this incidental increase; however no major changes in the age-specific-incidence have been found suggesting the absence of a systematic screening policy by the PSA. The superiority of free-to-total serum PSA ratio in discriminating between cancer and benign condition was confirmed. Early health-conscious man over 50 should be proposed prostate cancer screening by digital rectal examination and PSA. However a systematic screening policy cannot been recommended since a benefit in survival after early treatment has not yet been proven.

[Rothmund-Thomson syndrome with reduced DNA repair capacity]. / Syndrome de Rothmund-Thomson avec anomalie de l'excision-réparation de l'ADN.

INTRODUCTION: Rothmund-Thomson syndrome is a genodermatosis associated with early poikilodermal lesions. The condition usually occurs in children. Features include skeletal deformations and increased risk of malignancy. CASE REPORT: A 3 and a half year-old girl with poikilodermal lesions predominating in photoexposed areas presented a rash after exposure to sun. The first manifestations occurred during the first months of life. Examination of DNA repair on a culture of UV irradiated fibroblasts showed reduced DNA repair capacity. DISCUSSION: Other childhood photodermatoses were eliminated by the clinical signs. It would be important to know whether there is a correlation between DNA repair and development of neoplasia in Rothmund-Thomson syndrome.

The cutaneous form of adult T-cell leukemia/lymphoma in a woman from the Ivory Coast. Clinical, immunovirologic studies and a review of the African adult T-cell leukemia/lymphoma cases.

A 36-year-old woman from Ivory Coast, who has lived in France since 1976, had multiple cutaneous nodules and tumors in 1988. Histopathologic studies showed a massive infiltration of the dermis and hypodermis by a diffuse proliferation of mature activated T-cells (CD4-positive, CD25-positive, HLA-DR-positive) with irregular nuclei. The patient did not present with a leukemic picture and only few lymphoid cells with abnormally shaped nuclei were present in the blood. Human T leukemia/lymphoma virus type I (HTLV-I) antibodies were present in the serum and specific HTLV-I pol sequences were detected in the DNA extracted from the tumor nodules and peripheral blood mononuclear cells (PBMC) using the polymerase chain reaction technique. Whereas only a polyclonal integration of HTLV-I provirus was detectable in the PBMC, a clonal integration of three HTLV-I proviruses was demonstrated in the tumor nodules DNA, establishing with certainty the diagnosis of HTLV-I-induced adult T-cell leukemia/lymphoma (ATL). This case illustrates the need for molecular studies to differentiate without ambiguity an ATL from any other type of cutaneous lymphoproliferation, even when it occurs in a HTLV-I-seropositive individual. The situation of HTLV-I-associated ATL in Africa is reviewed.

[Chronicity and diagnostic doubts of Melkersson-Rosenthal syndrome. Analysis of developing ways in 5 cases]. / Chronicité et incertitudes diagnostiques du syndrome de Melkersson-Rosenthal. Analyse des modalités évolutives de cinq cas.

In order to demonstrate the variability of the muco-cutaneous and neurovegetative signs and symptoms of Melkersson-Rosenthal syndrome (MRS), we report the cases of five out of 80 patients suffering from this complex oro-facial syndrome. In the majority of our patients the major symptoms, and in particular recurrent labial or intraoral swellings and/or facial palsy, did not occur simultaneously, which delayed the definite diagnosis of either complete or incomplete type of MRS. However, more than 80 p. 100 of our patients complained of various relapsing cranio-facial neurovegetative troubles that constitute the so-called minor symptoms of MRS, whereas a history or sequelae of facial palsy were found in only 35 p. 100 of our patients followed up for years or decades. In patients with solitary facial palsy or oro-facial oedemas as the initial symptom of putative MRS, the uncovering of concomitant minor symptoms proves to be helpful for substantiating the recognition of incomplete MRS. Thus, in questionable cases of MRS attention should be paid to seemingly incidental disturbances of the cranio-facial neurovegetative system (e. g., relapsing disorders of lacrimation, sweating, migraine-like headache) forming minor but characteristic hints to incomplete or unusual cases of MRS.

No evidence for HTLV-I infection in 24 cases of French and Portuguese mycosis fungoïdes and Sezary syndrome (as seen in France).

A survey in search of evidence for HTLV-I infection was conducted on French and Portuguese patients residing in France with a diagnosis of mycosis fungoïdes or Sezary syndrome. Methods used in this investigation included serological assays (ELISA, Western blot, particle agglutination, indirect immunofluorescence) and DNA molecular studies (Southern blot and polymerase chain reaction). Cultures of peripheral blood mononuclear cells were performed and checked by electron microscopy and reverse transcriptase assay. The results indicate that neither HTLV-I nor a closely related retrovirus are associated with mycosis fungoïde or Sezary syndrome in the cases studied.