Gunter Haroske

Tumor Necrosis Factor-α Inhibitor-Induced Psoriasis or Psoriasiform Exanthemata

Tumor necrosis factor-α (TNFα) inhibition is effective in the treatment of moderate-to-severe psoriasis. We report on 120 patients from the literature including six new patients (three women and three men) who developed pustular lesions during treatment with TNFα inhibitors. We identified 72 women and 36 men (several papers did not specify the gender of patients) with an age range of 13–78 years (mean 42.3 years). The primary diagnoses were rheumatoid arthritis (n = 61), ankylosing spondylitis (n = 21), psoriasis (n = 10), Crohn disease (n = 8), SAPHO (synovitis acne pustulosis hyperostosis osteitis) syndrome (n = 3), psoriatic arthritis (n = 2), and other diagnoses (n = 15). Psoriasis (except palmoplantar pustular type) was the most common adverse effect during anti-TNFα treatment (n = 73), followed by palmoplantar pustular psoriasis (n = 37) and psoriasis of the nail (n = 6), sometimes combined in the same patient. Palmoplantar pustulosis and psoriasiform exanthema was the diagnosis in ten patients each. A positive personal history of psoriasis was recorded in 25 patients. A positive family history was noted in eight patients. No data about personal (n = 7) or family history (n = 46) were available in a number of patients. Newly induced psoriasis was diagnosed in 74 patients whereas an exacerbation or aggravation of a pre-existing psoriasis was noted in another 25 patients.All three TNFα inhibitors available on the market were involved: infliximab (63 patients), etanercept (37 patients), and adalimumab (26 patients). Several patients were treated with more than a single TFNα inhibitor. The timing of cutaneous adverse effects (psoriasis and psoriasiform rash) varied considerably among patients, ranging from after a single application to a delayed response of up to 63 months after initiation of treatment. The mean time to appearance of the cutaneous adverse effect for all TNFα inhibitors was 9.5 months.

Loss of caveolin expression in type I pneumocytes as an indicator of subcellular alterations during lung fibrogenesis

Abstract Caveolin is a major structural protein of caveolae, also known as plasmalemmal vesicles, which are particularly abundant in type I pneumocytes and capillary endothelial cells of lung parenchyma. Here we demonstrate that caveolin expression in the alveolar epithelium of rats and mini pigs is strikingly downregulated after irradiation-induced lung injury. Indirect immunoperoxidase staining with polyclonal anti-caveolin antibodies, confirmed by double fluorescence studies with type I cell-specific monoclonal anti-cytokeratin antibodies or lectins, revealed a dramatic loss of caveolin immunoreactivity in type I pneumocytes. In contrast, caveolin expression increased in endothelial cells. Immunoblotting of lung homogenates from normal and irradiated rats using specific anti-caveolin antibodies confirmed the presence of caveolin in normal tissue and its marked decrease of expression in fibrotic tissue. The loss of caveolin as an important structural protein of caveolae in alveolar epithelial cells may be an early indicator of serious type I cell injury during fibrogenesis. The increase of caveolin immunoreactivity in endothelia of blood vessels may indicate that different types of caveolae and/or different regulatory mechanisms of caveolin expression exist.

Histological Grading of Breast Cancer: Interobserver, Reproducibility and Prognostic Significance

A study was conducted to assess the reproducibility and prognostic significance of the histopathological grading by using the criteria of Bloom and Richardson. 166 breast carcinomas of the invasive ductal type (NOS - not otherwise specified) according to the WHO criteria, selected from the biopsy material of the years 1980 to 1988 were investigated. 85 of the patients presented axillary lymph node metastases in the mastectomy specimens. A satisfactory correlation of histopathological grades assessed by three pathologists was found in 72.3% of all cases. Fifteen cases (9%) were over- and 31 cases (18.7%) were underestimated compared with an experts grade. A disagreement of two grades occurred in one case only. In comparison of grade 1 and grade 3 tumours as well as of grade 2 and grade 3 tumours significant differences in the overall survival could be found. Irrespective of statistically significant differences between the three grades in actuarial survival, the histopathological grading is of rather low value for the prediction of prognosis of individual patients.

Transmission of glioblastoma multiforme through liver transplantation

The 47-year-old woman had a frontal lobe glioma removed. 4 months later, 1 week after resection of a local tumour recurrence, she deteriorated neurologically, and brain death was diagnosed. Informed consent of the legally responsible relatives was obtained, and her liver and both kidneys were harvested for transplantation. At necropsy, no other cancer or metastases were found. 5 months after transplantation, the 29-year-old immunosuppressed liver transplant recipient died after rapid clinical deterioration. Necropsy showed multiple intrahepatic, adrenal gland, lymph-node and leptomeningeal metastases of a gliomatous tumour. No coexisting malignant disease was found. Both kidney recipients are doing well without any signs of cancer at 52 months after transplantation. In cases of possible transmitted cancer, there must be certainty that the cancer came from the donor and was derived from the primary tumour. To our knowledge, this is the first case in which both criteria were fulfilled. Histopathological examination of the primary and recurrent brain tumour and of all metastatic lesions showed the classic features of glioblastoma multiforme. Immunoreactivity was negative for epithelial differentiation markers (KL-1, vimentin, desmin), for S-100P and for Blymphocyte marker L26. The primary glioblastoma was the only lesion to express glial fibrillary acidic protein (GFAP). Loss of GFAP expression during disease progression coincided with the less differentiated histological appearance of the locally recurrent and metastatic lesions and is directly associated with glioma dissemination. 2 All findings were

Short-term outcome of extra-levator abdominoperineal excision for rectal cancer

BackgroundExtra-levator abdominoperineal excision (ELAPE) has been introduced to avoid oncologic problems encountered with conventional abdominoperineal excision (APE) such as high rates of inadvertent bowel perforation and of positive circumferential resection margin. We compare our short-term results of this new approach with a historic patient cohort.Patients and methodsFrom 1997 until 2010, we performed 46 consecutive conventional APE and 28 ELAPE after neoadjuvant therapy with a macroscopically complete resection in the true pelvis. Patient data was prospectively collected in our colorectal tumor database. Patient and tumor characteristics were compared as were the rates of inadvertent bowel perforation, of circumferential margin involvement, and of wound abscesses.ResultsThe rates of inadvertent bowel perforation, of circumferential margin involvement, and of wound abscesses were 15.2% vs. 0 (p = 0.04), 4.9% vs. 0 (p = 0.511), and 17.4% vs. 10.7% (p = 0.518), respectively, in the conventional APE vs. ELAPE group.ConclusionWith a significant reduction of the bowel perforation rate and a reduction of circumferential margin involvement and wound abscess formation, ELAPE improves important surrogate parameters for local recurrence rate and survival.

Diagnostic telepathology: long-term experience of a single institution

ObjectivesThe paper reviews the development of the application of telepathology in a department of surgical pathology between 1991 and 2003. The goal of the efforts during this time was to give up the concept of programming a single application, available only between two fixed workstations with sophisticated devices and special software, and to find the virtual “largest common denominator” for implementing as many different applications as possible with the same basic system.MethodsA new telepathology system was designed as a client–server system with a relational database at its centre. The clients interact together by transferring the questions (texts and images) to a record (case) in the database on the server and by transferring the answers to the same record on the database.ResultsThe new “open” telepathology system iPath (http://telepath.patho.unibas.ch) has been very well accepted by many groups around the world. The main application fields are: consultations between pathologists and medical institutions without a pathologist (e.g. for frozen section diagnoses or for surgical diagnoses in hospitals in South Asia or Africa), tumour boards, field studies and distance education (http://teleteach.patho.unibas.ch).ConclusionsHaving observed that with iPath we have succeeded in satisfying all our telepathology needs, we are inclined to put the emphasis on the nature of the tasks being performed, as opposed to the methods or technical means for performing a given task. The three organisation models proposed by Weinstein et al. (2001) [24] can be reduced to only two models: the model of discussion groups and the model of expert groups (virtual institutes).

Tumescent suction curettage versus minimal skin resection with subcutaneous curettage of sweat glands in axillary hyperhidrosis.

BACKGROUND Axillary hyperhidrosis is a common problem with a strong negative impact on professional and social life. Various types of surgical procedures have been developed for its treatment. OBJECTIVE We want to compare efficacy and risk–benefit ratio of two local surgical procedures, i.e., the minimal skin excision with subcutaneous curettage (Method A) and tumescent liposuction curettage (Method B). METHODS A total of 163 patients with primary axillary hyperhidrosis as assessed by positive iodine-starch test were included. The age range of patients was 16 to 61 years (mean 28 years), including 33 males and 129 females. A total of 125 underwent Method A, and 37 were treated by Method B. Both procedures were performed in tumescent anesthesia. The mean follow-up was 21 months (Method A) and 48 months (Method B). The outcome was evaluated by patients global assessment and by Minors starch test. Patient satisfaction was scored as “satisfied,”“partially satisfied,” or “dissatisfied.” Adverse effects, complications, hospitalization time, and time to return to work were recorded and compared for both methods. In patients who underwent Method A, scar formation was assessed only for the first axilla (n=99). RESULTS In Method A, the rate of residual sweating was 12.0%. The relapse rate was 1.0% of patients or 2% of axillae. In Method B, the relapse rate was 16.2% of patients or 14.5% of axillae within 12 months. If we consider both the relapses and the residual sweating, this modified relapse rate per axilla was 12.8% for Method A and 14.5% for Method B. Patients who underwent Method B had significantly less pain, no atrophic or hypertrophic scars, and no complications such as wound infections, bleeding (with the need of a second operation), or delayed healing. Using Method A, the stay in hospital was on average 5.8 days per patient or 3.2 days per axilla. Mean time to return to work was 8.8±3.5 days. For Method B, the procedure was performed in an outpatient setting. The mean time to return to professional work was 1.3±0.8 days. The total satisfaction rate was 97% for Method A and 89.2% for Method B, respectively. CONCLUSIONS As shown by this study, minor skin resection with subcutaneous curettage of axillary sweat glands (Method A) is somewhat more effective in permanent reduction of hyperhidrosis than suction curettage. The minimal invasiveness of suction curettage and the minimal scarring, however, are significant advantages over excisional surgery. Downtime after surgery is significantly shorter for suction curettage. Therefore, suction curettage might be the surgical treatment of choice for axillary hyperhidrosis.

Competence on demand in DNA image cytometry.

Quantitation methods in clinical pathology have to be normalized and standardized both from the instrumental and the methodological point of view to guarantee a defined level of precision and accuracy independent of the site where they are applied. The comparability of results obtained in different laboratories is the basis for the application of standardized diagnostic classification systems and therapeutic schemes. Remote quantitation based on standardized evaluation tools could be a way to reach the goals mentioned above. Diagnostic DNA image cytometry, increasingly used as a routine method in clinical pathology, will serve as an example for demonstrating the feasibility and usefulness of a concept of remote quantitation. We report a system for a remote DNA ploidy analysis, based on client server technology, and accessible via Internet or ISDN connections (Quantitation Server EUROQUANT). This system (i) allows the cytometric measurement of the DNA content of cells for diagnostic purposes, (ii) provides the user with comprehensive quality control of such measurements, (iii) helps in trouble-shooting, and (iv) gives assistance in diagnostic interpretation. The system uses the principles of telepathology and Internet technology. To date, more than 40 laboratories from Europe, USA, and Asia have successfully performed analyses on about 3,000 ploidy data sets.

DNA histogram interpretation based on statistical approaches.

Image cytometric DNA measurements provide data which are most often interpreted as equivalent to the chromosomal ploidy although the chromosomal and the DNA ploidy are not identical. The common link between them is the cell cycle. Therefore, if destined for DNA ploidy interpretations, the DNA cytometry should be performed on a population‐oriented stochastic basis. Using stochastic sampling the data can be interpreted by applying the rules of stochastic processes. A set of statistical methods is given that enables a DNA histogram to be interpreted objectively and without human interaction. These statistics analyse the precision and accuracy of the entire measurement process. They give in error probabilities for accepting a measurement as reliable, for recognition of stemlines, stemline aneuploidy, and for evaluating so‐called rare events. Nearly 300 image cytometric DNA measurements from breast cancers and rat liver imprints examples have been selected to demonstrate the efficiency of the statistics in each step of interpreting DNA histograms.

Late recurrence (10 years or more) of malignant melanoma in south-east Germany (Saxony) A single-centre analysis of 1881 patients with a follow-up of 10 years or more

Background  Late recurrent melanoma (MM) is rare.