[Cohort study of cancer incidence in patients with type 2 diabetes: record linkage of encrypted data from an external cohort with data from the epidemiological Cancer Registry of North Rhine-Westphalia]. / Kohortenstudie zur Krebsinzidenz bei Patienten mit Diabetes mellitus Typ 2 : Record Linkage von kryptografierten Daten einer externen Kohorte mit Daten des Epidemiologischen Krebsregisters Nordrhein-Westfalen.

INTRODUCTION: German epidemiologic cancer registries may store only encrypted personal identifiers. Thus, record linkage with secondary databases needs to be performed via procedures that are based on encrypted identifiers. In this paper, we describe the linkage of patient data from a statutory health insurance company (AOK NordWest) and from the Disease Management Program for diabetes mellitus type 2 with the database of the cancer registry. We report the cancer incidence in patients with type 2 diabetes (T2D). METHODS: Personal identifying variables of the patient cohort were encrypted before being sent electronically to the cancer registry and submitted to a probabilistic record linkage with registry data. The study included T2D patients who were residents of the Münster, Detmold, or Arnsberg districts and who were aged 40-79 years. Only primary cancers occurring between the date of enrolment and the censoring date (31 December 2010) were included. The standardized incidence ratio (SIR) was calculated relative to the number of incident cases expected on the basis of the averaged incidence rates in the general population. RESULTS: The record linkage took about 3 weeks of processing time. A total of 67,447 T2D (49.2 % men) cases were included for analyses. Incident cancer was diagnosed in 2,086 men and 1,578 women. Cohort members showed an elevated risk for cancer of the liver (SIR =1.86; 95% CI =1.47-2.31), pancreas (SIR = 1.62; 95 % CI =1.36-1.91), lung (SIR = 1.21; 95% CI 1.11-1.32), and uterus (SIR = 1.34; 95 % CI 1.08-1.65), and they were less likely to be diagnosed with prostate cancer (SIR =0.72; 95% CI = 0.65-0.79). DISCUSSION: The findings of this study suggest that record linkage of secondary databases with cancer registry data for research purposes can be effectively carried out in compliance with strict data-protection regulations.

[Linkage of secondary data with cancer registry data on the basis of encrypted personal identifiers - results from a pilot study in North Rhine-Westphalia]. / Abgleich von Sekundärdaten mit einem epidemiologischen Krebsregister auf der Basis verschlüsselter Personendaten - Ergebnisse einer Pilotstudie in Nordrhein-Westfalen.

BACKGROUND: The Cancer Registry of North-Rhine-Westphalia stores exclusively encrypted personal identifiers of registered cancer patients. Therefore, comparisons with secondary data sets can only be performed by record linkage procedures that are based on encrypted personal identifiers. We report on a pilot study which linked encrypted personal data from the disease management program for patients with diabetes mellitus type 2 (DMP-DM2) with the database of the EKR NRW in order to test the feasibility and efficiency of these record linkage procedures. METHODS: Personal identifying variables of the DMP records were encrypted in a 2-stage process before being sent electronically to the EKR NRW where they were subsequently submitted to a probabilistic record linkage with the registry data. The study included 27 450 participants who were insured at the AOK NordWest, residents of the district Münster and who were aged 40-79 years at the time of first enrolment to the DMP-DM2 between June 2003-July 2008. RESULTS: The electronic processing time of the semi-automatic record linkage procedure took about 24 h. Approximately 2% of the records had to be reviewed manually. After exclusion of prevalent cancer cases, multiple primaries and inadequate data, 26 742 participants (47.3% men; 52.7% women) remained in the data set. About 1 364 cohort members (759 men, 605 women) were diagnosed with cancer after submission to the disease management program. DISCUSSION: The DMP-DM2 records were encrypted and linked to cancer registry data with a moderate personnel and financial input and high efficiency. Linked records were instantly usable for epidemiological analyses. Experiences of the pilot study suggest that future linkage studies can further advance the level of data protection, without losses in efficiency, by moderately complex software modifications and amendments of the data flow.

[Linkage of data of the medical service of the health insurances with data of a cancer registry]. / Abgleich von Verwaltungsdaten des Medizinischen Dienstes der Krankenversicherung mit Krebsregisterdaten.

BACKGROUND: The aim of this study was to examine whether a linkage of data sets of the Epidemiological Cancer Registry North Rhine-Westphalia (EKR-NRW) and the Medical Service of the Health Insurances (MDK WL) is feasible, which problems may occur during execution and what could be a solution strategy. METHODS: Data of the EKR-NRW were used to identify all cancer cases in the district of Munster, for which an expert opinion regarding nursing needs from the period 2004-2008 was available at the MDK WL. For this purpose factually anonymised data of the EKR-NRW and the MDK WL were linked by means of a semi-automatic probabilistic record linkage. RESULTS: Data linkage yielded 18 877 cancer cases but required great technical and temporal input. The processing of management data and the use of "routine channels" (ISDN connection), which provide the necessary safety for data transfer, but are designed for a considerably smaller amount of data, accounted for this. The interface problem (converting data from text format to a hierarchical XML format) can be solved with Excel or SAS. CONCLUSION: A record linkage with factually anonymised data from the MDK WL and the EKR-NRW is feasible. This allows, among other things, quantifying the needs for nursing care in persons with a cancer diagnosis.

The tumor-protective effect of selenium in an experimental model.

The possibility of a tumor-protective effect of selenium on the growth of benzpyrene-induced sarcoma was studied in an assay with Balb/c mice. The animals received 4 parts/10(6) selenium in their drinking water for 12 months prior to subcutaneous injection of benzpyrene to induce sarcomas. In contrast to unpretreated controls, the selenium-exposed animals developed significantly less and smaller tumors in a given time. These results are compared to those of other authors. Several mechanisms for selenium influence on benzpyrene metabolism are discussed.

Macrophages and T lymphocytes infiltrating the rat mammary carcinoma HH9-cl 14 in progressive and regressive tumor growth. An immunohistological study.

Ascites tumor cells (2 X 10(6] of a DMBA-induced rat mammary adenocarcinoma (HH9-cl 14) were injected s.c. into tumor-free syngeneic female rats and produced a continuously growing solid tumor in all animals of this group. Inoculation of 2 X 10(7) cells induced a first brief period of tumor growth, followed by complete tumor regression from the 2nd until the 5th week after injection. Both the progressive and the regressive tumors were analyzed immunohistologically at different stages with monoclonal antibodies against different T lymphocytes and macrophages. Obviously these cells appear in different quantity and quality, during the hosts immune response. Possible interactions of T lymphocytes and macrophages with tumor cells are discussed.

The relationship between characteristics of the tumor cells and sex of the patients in primary malignant melanomas.

Sex is a well proven prognosticator in primary malignant melanoma. We studied 19 parameters of tumor cells in primary malignant melanoma from 391 patients, the purpose being to determine if melanomas in men and women are alike. Apart from results in thin melanomas, no difference was seen between the sex groups. Thin melanomas showed a significant difference for the melanoma-associated antigen G7-E2 (higher expression in women) and the histocompatibility antigen HLA-DR (higher expression in men). The results suggest that sex-related prognostic differences are due more to host than to tumor characteristics.

Comparative studies of cardia carcinoma and infracardial gastric carcinoma.

In a part retrospective, part prospective study, 354 carcinomas of the cardia were compared with 1259 infracardial gastric carcinomas with regard to the age and sex of the patients, macroscopic classification, microscopic classifications, depth of invasion, and survival rates. Mortality rates are generally higher in cardia carcinoma than in stomach carcinoma. The difference is due to the significantly poorer survival of cardia carcinoma patients in stage I, while mortality rates in stages II, III, and IV of both types are approximately similar. Highly significant differences were also found with regard to sex ratio, incidence of macro- and microscopic subtypes, and invasive growth. The typical cardia carcinoma occurs preferentially in men, is mostly well-delineated, and is manifested as an ulcerated or polypoid, well-differentiated tumor of expansive growth, corresponding to Laurén's intestinal type. These results confirm the concepts of McPeak and Warren, MacDonald, and Siewert et al., that the carcinoma located in the cardia must be seen as a separate entity of gastric carcinoma.

Clinical features of superficial spreading melanomas with zones of regression.

To assess the significance of spontaneous regression in superficial spreading melanoma (SSM), 36 patients with clinical signs of regression in their primary tumor were compared to 200 patients with regular SSMs (controls). SSMs with regression were found to have the following, distinctive clinical features, which were significantly different from controls (P less than 0.05): (1) male predominance (69%), (2) preferential localization on the trunk (80.6%), (3) lower tumor thickness (Breslow), (4) clustering in Clark levels II and III, and (5) a larger surface area. The incidence of metastases was lower in patients with regressing SSMs (13.9%) compared to controls (20.5%) although the time until relapse was slightly shorter (20.6 months versus 28.1 months for controls). These prognostic parameters were not significantly different. However, of the patients who died, 2 of 4 with zones of regression had thin melanomas (less than or equal to 1.5 mm), compared to only 1 of 27 without regression zones (P less than 0.05). SSMs with regression therefore have unique clinical features, which may be related to their pathogenesis, and they may have some prognostic significance.

Association of macrophages detected with monoclonal antibody 25 F 9 with progression and pathobiological classification of gastric carcinoma.

Using monoclonal antibody 25 F 9, which reacts with a determinant of mature macrophages, the inflammatory infiltrate of 66 gastric carcinomas was evaluated using a counting grid. The ratio tumor cells/macrophages was determined for every tumor. For a threshold value of 5, carcinomas with a better prognosis, such as the intestinal type according to Lauré, the expanding type according to Ming and the differentiated carcinomas according to the WHO had a significantly smaller relative content of 25 F 9-positive macrophages (a minimum of P less than 0.05) than the diffuse type, infiltrative type, and undifferentiated carcinomas. Furthermore, the relative macrophage content tended to increase with the stage of carcinomas spread (P less than 0.1). The results suggested that 25 F 9-positive macrophages in gastric carcinoma are of greater significance in tumor spread than in any defensive reaction against the tumor.

[Record linkage with cryptographic identification data in a population-based cancer registry. Development, implementation and error rates]. / Record Linkage mit kryptografierten Identitätsdaten in einem bevölkerungsbezogenen Krebsregister. Entwicklung, Umsetzung und Fehlerraten.

BACKGROUND: Population-based cancer registries depend on the completeness of their case notification. At present, restrictive legal regulations in Germany requesting written informed consent of cancer patients hinder some health professionals, for example pathologists, from reporting to cancer registries. New cryptographic methods may be used to obtain record linkage based on anonymised data. OBJECTIVES: To assess the feasibility of a record linkage in the Münster Cancer Registry (EKR-MS) using cryptographic methods as compared to traditional methods based on personal identifiers. METHODS: We generated so called control numbers--a sequence of 23 alphanumeric signs--for 19 name related characteristics employing consecutively two different chiffrations. Record linkage was carried out using a semi-automatic computer program (AUTOMATCH) that generates probabilities of identity for pairs of case notifiation based on the information of control numbers only. Probabilities exceeding present limits lead to automatic decisions whereas the remaining linkage has to be decided manually. Plausibility-based rules helped to considerably reduce the amount of manual decisions. RESULTS: We compared traditional and cryptographic record linkage for all new reports received in the EKR-MS during 1998 (n = 27,262) against the background of n = 101,880 known cases in the registry data base. Setting traditional, text-based record linkage results to be the reference the cryptographic method resulted in a synonomous error (false creation of a new case) of almost 2% and a homonymous error (false link to a known case) of less than 0.5%. CONCLUSION: Cryptographic methods may be feasible procedures of record linkage in cancer registries. The size of the database of the EKR-MS prohibits extrapolation of findings to smaller registries. The error rates resulting in slight overestimation of disease rates that may seem acceptable. It should be noted though that cryptographic data are in many situations prohibitive for further epidemiologic research limiting the usefulness of the method exclusively to cancer registration under the given legal coercion.

[Adjuvant chemotherapy in addition to radical surgical treatment of regional lymph node metastases in malignant melanoma]. / Adjuvante Polychemotherapie zusätzlich zur radikalen operativen Behandlung regionaler Lymphknotenmetastasen beim malignen Melanom.

Thirty-three patients with malignant melanoma and regional lymph node metastases who underwent lymph node dissection were additionally given polychemotherapy with carmustine, hydroxycarbamide and dacarbazine immediately before surgery and up to five times postoperatively. Twenty-nine patients were only treated surgically. These two groups were comparable as regards prognostic criteria, in particular tumour size, ulceration and the number of lymph nodes affected, although the individual follow-up periods varied considerably. The group given chemotherapy showed better results than the control group undergoing surgery alone. The log rank test yielded a significant difference (P less than 0.05) with respect to the probability of relapse-free survival but not as regards probability of survival time. Patients with ulcerated primary melanomas and with a large number of affected lymph nodes had a less favourable prognosis. The major side effects of chemotherapy were transient nausea and bone marrow depression.

Prognostic immunohistochemical markers of primary human melanomas.

BACKGROUND: Several clinical and histological factors of primary melanomas comprise a relatively large quantity of prognostic information. OBJECTIVE: To find immunohistochemical markers that can improve the prognostic accuracy achieved by factors that are available without extra laboratory work, i.e. mitotic rate, tumour thickness, ulceration, localization, gender and age. METHODS: Immunohistochemical markers were determined on frozen sections. Univariate and multivariate Cox regression analyses were performed after 5-10 years follow-up. RESULTS: Seven immunohistochemical markers were related to disease-free and overall survival in univariate Cox regression analysis: Ki-67, human leucocyte antigen (HLA) -DQ, HLA-DP, Muc 18, A-10-33, transferrin receptor, and H-2-8-10. Only Ki-67 (n = 399) and HLA-DQ (n = 452) retained prognostic significance when evaluated in multivariate analyses in several models together with tumour thickness alone and with tumour thickness, gender, mitotic rate, age, localization and ulceration. CONCLUSIONS: Ki-67 and HLA-DQ may be useful for risk assessments in primary melanomas.

Can immunohistochemical markers and mitotic rate improve prognostic precision in patients with primary melanoma?

BACKGROUND: In addition to tumor thickness, several other prognostic parameters have been identified in primary human melanomas. Some are available readily (localization, gender, age, and ulceration). Others must be evaluated with a moderate or even substantial amount of work (mitoses and immunohistochemical markers). This study was undertaken to determine whether this extra effort is justified because it actually improves the precision of prognostic statements. METHODS: Immunohistologic markers were determined on frozen sections from 691 biopsies of human melanomas with the immunoperoxidase method. Univariate and multivariate Cox regression analyses were performed with metastases and with death as endpoints. RESULTS: Fifteen parameters were related to disease free survival in univariate Cox regression analysis: tumor thickness, ulceration, localization, gender, age, mitoses, and the immunohistochemical markers very late antigen (VLA)-2, human leukocyte antigen (HLA)-ABC, HLA-DR, NKI-beteb, Mel 14, intercellular adhesion molecule (ICAM-1), K-1-2, G-7-E2, and H-2-4-7. Three of the easily available parameters exhibited independent significance in multivariate Cox regression analysis: tumor thickness, ulceration, and localization. If mitotic rate was included in this model, then it had independent prognostic significance but ulceration was no longer significant. However, the model that included tumor thickness, localization, and ulceration had a slightly higher overall chi-square test score, indicating a better performance compared with thickness, localization, and mitoses. The model that included tumor thickness, localization, and mitoses could not be improved by any of the immunohistochemical markers in this study. CONCLUSIONS: Nine immunohistochemical markers with established prognostic significance for primary human melanoma were not found to improve a prognostic model that included tumor thickness, localization, and mitoses. If mitoses was replaced by ulceration, then the model performed slightly better, although ulceration was not significant in the presence of mitoses.

[Therapy and prognosis of small breast cancers. Comparison of subcutaneous mastectomy procedures with ablatio mammae]. / Therapie und Prognose des kleinen Mammakarzinomas. Vergleich von subkutanen Mastektomieverfahren und Ablatio mammae.

A retrospective clinical study included 1283 patients with breast cancer. 307 of 762 tumours with known diameter (mm) were classified as stage pT1 (TNM, 70). Four groups were formed to compare the prognosis in subgroups of pT1 cancers: 0-5 mm (n = 22), 6-9 mm (n = 22), 10 mm (n = 53) and 11-20 mm (n = 210). A comparison of three types of surgery was made: Radical subcutaneous mastectomy (12), bilateral modified subcutaneous mastectomy (10, 11), and modified radical mastectomy (Auchincloss, 3). Both forms of subcutaneous mastectomy were combined with adjuvant postoperative radiotherapy to the side of the tumour. In this trial, patients were younger at diagnosis than usually stated in the literature. Small breast cancers had the same localisation and histology as large ones. Axillary lymph node metastases were identified from a tumour diameter of 6 mm upwards. Bilateral tumours were seen in 2 of 22 patients with tumours less than or equal to 5 mm. Multifocal growth was observed also in the same size range. Histologically different simultaneous invasive unilateral cancers were seen starting at a diameter of 8 mm of the larger tumour. Systemic metastases were observed in tumours of 10 mm in diameter. Local recurrences occurred in breast cancers with a diameter of 2 mm and more. There were no recurrences in the area of the nipple or areola in pT1 cancers. Small breast cancers did not appear to be biologically different from larger lesions. No prognostic subgroups of pT1 were evident beyond the established TNM staging. Disease-free survival was not significantly different between the three surgical approaches. Local recurrence was significantly less frequent after breast-conserving surgery. A negative influence of local recurrence on the prognosis was observed to a similar extent irrespective of the type of surgery. The concept of "minimal breast cancer" suggesting ablative surgery for a heterogeneous group of preinvasive and small invasive lesions is outdated. The different forms of subcutaneous mastectomy are a therapeutic alternative in the context of breast-conserving surgery of small infiltrating breast cancers. Especially the modified subcutaneous mastectomy (Beller) combines a good cosmetic result without prognostic impairment and with a potential reduction of the risc of contralateral breast cancer. Further potential applications include prophylactic treatment of high-risk patients with preinvasive lesions.

[Clinical importance of histology, grading and ploidies in primary breast cancer]. / Zur klinischen Wertigkeit von Histologie, Grading und Ploidie primärer Mammakarzinome.

OBJECTIVE: In order to characterise carcinoma of the breast the determination of ploidy can be used in addition to established prognostic factors such as histology and grading. The aim of the investigation was to establish the association between histology, grading and ploidy and to indicate the prognostic and predictive value of these parameters in relation to disease free survival (DFS) and overall survival (OS). MATERIAL AND METHODS: 125 consecutive cases of primary breast carcinoma occurring between the years 1992-1995 were surveyed. The median follow up time lasted 45 months. Correlation analyses were carried out using the Chi-square test, Kaplan-Meier (univariate) and Cox (multivariate) methods. RESULTS: Histology and grading showed no correlation to ploidy but seems to be of importance for DFS in node-negative breast carcinoma. Ploidy did not influence neither DFS nor OS. Ductal histology appeared to be a useful factor in predicting the response of cases treated with an anti-oestrogen (Tamoxifen) since in this group a higher relapse rate of 25% occurred. CONCLUSIONS: Ploidy appears not to be of clinical importance.

[Lymphomas and leukemias in population-related cancer registries in Germany]. / Lymphome und Leukämien in bevölkerungsbezogenen Krebsregistern in Deutschland.

BACKGROUND: A German Federal law enacted in 1995 aims at nation-wide cancer registration, the details of realization based on local regulations being left to the individual Federal states. The impact of different approaches and regulations on the results of registration was investigated at three well-established records in the Saarland, Hamburg and North-Rhine Westphalia, taking the group of lymphoma and leukaemia (ICD 200-208) taken as an example. MATERIAL AND METHODS: Incidence and mortality rates calculated by the record files for the period from 1987 to 1994 were compared. The resulting mortality/incidence ratios were compared as well as the percentage of cases in each register with death certificates (DCO) as the only information source. RESULTS: There was a distinct increase of incidence rates visible in Hamburg and Münster. As far as the male patients was concerned, both records attained the level of Saarland at the end of the period. However, the leukaemia and lymphoma mortality figures for males and females was about 10% lower for Saarland than in the comparative regions. The male mortality incidence ratio was 0.55 for Saarland versus 0.60 average in Hamburg and Münster at the end of the period. In Saarland and Hamburg there was a decrease of DCO-cases from 14% to less than 6% in 1994. More constant values around 11% could be observed in the Münster registry. The distribution of diagnosis within the group as well as age-specific incidence rates for the selected diagnosis "lymphatic leukaemia" (ICD 204) and "Hodgkin's disease" (ICD 201) yielded only slight differences. CONCLUSION: The increase of incidence rates in Münster and Hamburg indicates more complete reporting. Assuming that the survival rates are the same in the three regions, the lower mortality in Saarland points to lower morbidity. Hence in spite of a definite approximation the cancer registries in Hamburg and Münster do not reach the level of completeness of the Saarland cancer registry. This may be due to the informed patient consent required by regional law for reports to the registry. To achieve completeness a special reporting procedure for pathological and haematological Institutes is mandatory. Simple indicators should be available in each registry for continuous estimation of completeness. Standardised case definitions and rules for the coding of diagnosis in cancer registries will improve national and international comparability and feasibility of data exchange.