Clinical outcome and global gene expression data support the existence of the estrogen receptor-negative/progesterone receptor-positive invasive breast cancer phenotype.

The presence or absence of estrogen and progesterone steroid hormone receptor expression (ER, PR) is an essential feature of invasive breast cancer and determines prognosis and endocrine treatment decisions. Among the four ER/PR receptor phenotypes, the ER-/PR+ is infrequent, and its clinical relevance has been controversially discussed. Thus, we investigated its clinical significance and gene expression pattern in large datasets. In a retrospective clinical study of 15,747 breast cancer patients, we determined the ER/PR subtype survival probabilities using Kaplan-Meier and Cox regression analyses. From The Cancer Genome Atlas (TCGA) breast cancer dataset, PAM50 expression signature and pathway analyses were performed to test for distinct molecular features. In our cohort, the ER-/PR+ phenotype has been observed at a frequency of 4.1 % and was associated with an improved 10-year survival for stage I cancers compared to the ER+/PR+ reference subtype (median; 95 % CI 88.1 %; 83-93 vs. 84.3 %; 82-86 %, P = 0.024) as was confirmed by multivariate analysis over the entire follow-up (HR 0.59, 95 % CI 0.38-0.92, P = 0.021). This association lacked significance when including all stages. ER-/PR+ patients treated with antihormonal agents (34.5 %) had shorter survival compared to their non-treated counterparts (Log-rank P = 0.0001). PAM50 signatures suggest a distinct configuration for the ER-/PR+ phenotype. This specific phenotype has been further separated by a set of 59 uniquely expressed genes. Our study supports the notion of the existence of an ER-/PR+ phenotype with clinical and molecular features distinct from the large group of ER+/PR+ patients.

[Symptom-oriented follow-up of early breast cancer compared to intensive surveillance. Results of a prospective multicentre study: update and 10-year overall survival]. / Symptomorientierte Nachsorge nach Mammakarzinom im Vergleich zur intensiv-apparativen Nachsorge. Ergebnisse einer prospektiven multizentrischen Studie: Update und 10-Jahres-Überlebenszeit.

BACKGROUND AND OBJECTIVE: In a prospective, non-randomised, multicentre cohort study we compared intensive surveillance to symptom-oriented control in the follow-up of patients with early breast cancer after curative surgical treatment. Five-year overall survival had shown that symptom-oriented follow-up was not inferior to intensive control. However, a more intensive, instrumental based follow-up is still claimed by many patients and their physicians. In this context the recent data of 10-year overall survival (OS) are reported. PATIENTS AND METHODS: In the prospective, non-randomised, multicentre cohort study carried out between 1995 and 2000, 244 patients underwent an intensive follow-up (scheduled laboratory tests including CEA and CA 15-3, chest X-rays and liver ultrasound). 426 patients were monitored in a symptom-oriented manner (additional tests only in the case of symptoms indicating possible recurrence). Mammography, structured histories and physical examinations were done regularly in both groups. RESULTS: In the clinical follow-up group, 90 deaths (21.2 %) were observed with an estimated 10-year overall survival rate of 83.0 % (95 % CI 79.1 -86.3 %).  In the intensive follow-up group, 59 deaths (24.2 %) were observed with an estimated 10-year overall survival rate of 78.5 % (95 % CI 72.6 -83.2 %). The Cox proportional hazards model for OS includes the variables follow-up form, stage of primary tumor and lymph nodes, hormone receptor status, grading and age at diagnosis. This model resulted in a hazard ratio of 1.10 (95 % CI 0.78-1.54) for the follow-up protocol (intensive vs. clinical). Welleks' test for non-inferiority showed that clinical follow-up is not inferior in comparison to intensive follow-up (p < 0.05) for a non-inferiority limit of + 7 % at 10-years. CONCLUSION: This analysis of 10-year overall survival of patients with early breast cancer after curative primary treatment confirms that follow-up without regular imaging and laboratory tests is not inferior in the sense of a relevant higher mortality. To what extent new concepts in the treatment of breast cancer have any influence on follow-up care has to be examined in further studies.

[Cystic gastric tumor with calcifications]. / Zystischer Magentumor mit Verkalkungen.

In imaging techniques was seen a thickness of the gastric wall in a patient with pain for several months and loss of weight. Biopsies taken out of the tumor mass by gastroscopy and laparoscopy have not been ground-breaking. For this disease pattern is it not unusual that the diagnosis of heterotopic pancreatic tissue with pancreatitis is not confirmed until a resection of the stomach.

Clinical impacts of histological subtyping primary breast cancer.

BACKGROUND: Treatment decisions in breast cancer depend on TNM classification and the assessment of additional variables with have an impact on survival. We examined whether histological subtyping breast cancer as either ductal or lobular is related to disease outcome. PATIENTS AND METHODS: We examined a large data base of 14198 breast cancer patients. RESULTS: Histological sub-classification of invasive breast cancer as either ductal or lobular is not correlated with disease outcome. However, the data further showed that invasive lobular carcinomas have a higher probability of being oestrogen receptor (ER)- and progesterone receptor (PR)-positive and a lower probability of being c-erbB2-positive. They also showed a higher average age at the time of diagnosis in comparison with invasive ductal carcinoma. Local recurrence rates were lower in invasive lobular carcinoma in comparison with invasive ductal carcinoma (3.5% vs. 6.2%; p = 0.031). The multivariable Cox regression analysis showed that ER, PR, nodal status, grade and tumour size predicted disease outcome with statistical significance, while the histological subtype (invasive ductal or lobular) was not a significant predictor of disease outcome. CONCLUSION: Histological sub-classification of invasive breast cancer as either ductal or lobular is not correlated with disease outcome. On the other hand our data gives some indication that lobular and ductal breast cancer appear to be different biological entities.

Hospital accreditation and the surgeon: the Canadian experience.

Accreditation is an internationally recognised process through which healthcare organisations are able to improve the safety and quality of services delivered to patients. The focus of accreditation is to help organisations understand what they are doing well and what opportunities are available for improvement. The Canadian approach to accreditation is a rigorous peer review process comprised of a self-assessment against a set of standards, an on-site survey and follow-up action on recommendations that arise from the survey. The accreditation standards can be used effectively to guide the surgical teams in the transformation of the specialty. The 17 standards that are used to evaluate surgical teams relate to the activities that represent the continuum of clinical care as well as aspects related to learning. Within the subsections and standards are opportunities for surgeons and surgical teams to use the standards to effectively deliver services and to continuously improve patient care. In 38 recent Canadian Accreditation AIM surveys, that included at least one surgical team, there were a total of 75 recommendations made to the teams. Most recommendations related to process as opposed to outcome issues, implying that surgeons need to become more proactive in the functioning of the surgical team and to participate more effectively in management issues related to surgical care. Attention to these details will position surgical programmes to effectively deal with the rapid pace of change that is inherent in a modern surgical practice.

Is first-line single-agent mitoxantrone in the treatment of high-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial.

BACKGROUND: To determine whether patients with high-risk metastatic breast cancer draw benefit from combination chemotherapy as first-line treatment. PATIENTS AND METHODS: A total of 260 women with measurable metastatic breast cancer fulfilling high-risk criteria, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either mitoxantrone 12 mg/m(2) or the combination of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) every 3 weeks. Treatment was continued until complete remission plus two cycles, or until disease progression. In the case of partial remission or stable disease, treatment was stopped after 12 cycles. Second-line treatment was vindesine, mitomycin and prednisolone. Gain from treatment was estimated using a modified Brunner's score composed of time to progression, patients' rating of the treatment benefit, alopecia, vomiting and performance status. RESULTS: After recruitment from 1992 to 1997 and observation from 1997 to 1999, the final evaluation showed that single-agent treatment with mitoxantrone does not differ significantly from combination treatment with FEC in terms of response, objective remission rate, remission duration, time to response, time to best response, time to progression or overall survival. There was, however, a significant difference in gain from treatment using a modified Brunner's score favoring the single-agent treatment arm. There was no evidence that any subgroup would fare better with combination treatment. CONCLUSIONS: No significant difference was detected between the treatment with mitoxantrone as a single agent and the combination of low-dose FEC in terms of response or survival; therefore, the imperative of the necessity of first-line combination chemotherapy for patients with high-risk metastatic breast cancer may be questioned. Since toxicity and quality of life score favored the single-agent mitoxantrone treatment arm, this treatment may be offered to patients preferring quality of life to a potential small prolongation of survival.

Primary breast cancer therapy in six regions of Germany.

Studies from six regions of Germany (Aachen (W1), Dresden (E1), Jena (E2), Marburg (W2), Munich (W3), and Stuttgart (C1)) have been compared to verify and assess the quality of healthcare using breast cancer as an example. All of the data collection was carried out in comprehensive cancer centres and is population-based, with the exception of C1. Classic prognostic factors and the initial treatment of 8661 women with breast cancer, diagnosed between 1996 and 1998, were examined. Primary therapy, breast conserving therapy (BCT), and the use of subsequent local radiation and/or systemic therapy (chemotherapy or hormonal therapy) were analysed. BCT was performed on 39.3-57.7% of patients. By pT-category, the proportion of BCT in the six regions were as follows: for pTis between 37.8 and 64.3%, for pT1 between 51.7 and 71.5%, for pT2 between 25.9 and 51.1%, for pT3 between 0 and 13.1% and for pT4 between 0 and 15.2%. Multivariate analyses, adjusted for age and biological factors, showed a significant influence of the treating hospital on the mastectomy rate. The use of radiotherapy after BCT (80%) was quite homogeneous in the six regions. The application of radiotherapy after mastectomy, however, varied between 10.4 and 32.2%. In all regions, for premenopausal patients, the use of adjuvant systemic therapy almost reflected the St. Gallen-Consensus recommendations. In contrast, post-menopausal women with positive lymph nodes were not always treated according to these standards. In all regions, age had an influence on the administration of treatment: elderly breast cancer patients received less BCT, less radiotherapy and less adjuvant therapy than recommended in the St. Gallen-Consensus. Feedback of the results was made available to each hospital, providing a comparative summary of patient care that could be used by the participating hospitals for self-assessment and quality-control.

[Patella dislocation. Therapeutic principles and prevention of late complications]. / Patellaluksation. Behandlingsprincipper og forebyggelse af senkomplikationer.

In this review we have compared the different kinds of treatment of acute dislocation of the patella regarding the effects and the complications. The literature describes a variety of treatments and no standard treatment exists. Most studies are not randomised prospective studies and the follow-up period is often short. We conclude that there is a need for randomised, prospective studies with a large number of patients and with a long follow-up period in order to find the best kind of treatment. Treatment modalities for acute as well as recurrent dislocation are described in the general section of the review. In order to achieve the best results and decrease the number of complications it is necessary to have a clear diagnosis of APD and knowledge of predisposing factors.

[Acute and chronic patella dislocations. Therapeutic strategies in Danish orthopedic departments]. / Akutte og kroniske patellaluksationer. Behandlingsstrategier på danske ortopaedkirurgiske afdelinger.

BACKGROUND: In review of the literature there is no standard treatment of acute- as well as recurrent dislocation of the patella. Most investigations are retrospective or not randomised. Approximately 1500 patients/year with the diagnosis luxatio patellae are seen in Danish hospitals. METHODS: Using a questionnaire we wished to find out how these patients were treated in Danish orthopaedic departments. RESULTS: We found that there was no consensus on the treatment of patellar dislocation. CONCLUSION: We concluded that there is a need for prospective randomised studies involving a large number of patients, with a long follow up time.

[Ischemic colitis as a primary manifestation of an embolizing small-cell bronchial carcinoma infiltrating a pulmonary vein]. / Ischämische Kolitis als Primärmanifestation eines in eine Pulmonalvene eingewachsenen, embolisierenden kleinzelligen Bronchialkarzinoms.

CASE REPORT: A 59-year-old male patient was admitted to hospital for general malaise with muscle and bone pain. Some weeks ago he had been treated with roxithromycin because of pneumonia. Physical examination revealed melena. Hemoglobin was 7.6 g/l. Endoscopy of the upper gastrointestinal tract did not show a bleeding source. Colonoscopy and histologic examination revealed hemorrhage caused by ischemic colitis. To rule out cardiac embolies in the presence of paroxysmal tachyarrhythmia absoluta a transesophageal echocardiogram was performed. A mediastinal mass infiltrating the upper left pulmonary vein was detected. The mass had not been visible on routine chest X-ray. Histologic examination of a bronchoscopically taken specimen revealed an oat-cell bronchial carcinoma. CONCLUSION: In this patient invasion of a pulmonary vein by the bronchial carcinoma lead to embolies which caused mesenterial ischemia. According to our researches this is the first report of ischemic colitis as a manifestation of bronchial carcinoma.

Moving to global standards for accreditation processes: the ExPeRT Project in a larger context. External Peer Review Techniques.

The ExPeRT (External Peer Review Techniques) Project, a European Union effort to examine and compare methods of health care evaluation currently in use, includes an assessment of accreditation as one such method. This article contributes to that examination by describing recent work, through the International Society for Quality in Health Care (ISQua), to investigate and to enhance the international comparability of national health care accreditation programs, both existing and newly emerging.

[What do we know about the prevalence of pain caused by malignancy?]. / Tumorpatienten in Deutschland: Was wissen wir über Schmerzprävalenzen?

BACKGROUND: Since there is no epidemiologic assessment of the frequency of pain caused by tumor in Germany, tumor-pain-prevalence is estimated indirectly on the basis of mortality and median survival. Knowing that about 50% of all patients having metastases or incurable locoregional recurrence suffer from pain every day, the product of median survival times mortality was calculated to achieve the number of patients' days with tumor-caused pain per year (82,710,690 days in Germany 1995). By division with 365 (days), it is calculated that 226,605 patients require tumor pain related treatment at one day in Germany. Another calculation based on Bonica's publications that 60-90% of patients suffering from advanced cancer are having pain and based on an estimated tumor prevalence 1989/90 revealed a tumor pain prevalence of 221,826. DISCUSSION: Thus both methods result in the estimation, that about 220,000 patients require tumor-pain-related treatment at one day in Germany.

A comparative analysis of surveyors from six hospital accreditation programmes and a consideration of the related management issues.

PURPOSE: To gather data on how accreditors manage surveyors, to compare these data and to offer them to the accreditors for improvement and to the scientific community for knowledge of the accreditation process and reinforcement of the credibility of these processes. DATA SOURCE: The data were gathered with the aid of a questionnaire sent to all accreditors participating in the study. RESULTS: An important finding in this comparative study is the different contractual relationships that exist between the accreditors and their surveyors. CONCLUSION: Surveyors around the world share many common features in terms of careers, training, work history and expectations. These similarities probably arise from the objectives of the accreditors who try to provide a developmental process to their clients rather than an 'inspection'.

Accreditation programs for hospitals: funding and operation.

Accreditation is a formal process by which an authorized body assesses and recognizes an individual, an organization (like a hospital), a program, or a group as complying with requirements such as standards or criteria. This article analyses and compares the activity and funding of six health care accrediting bodies which operate in five different countries, and which in 1994, accredited over 5000 health centres. The data included in this article could be useful for other institutions who wish to commence accreditation programmes for health care organizations.