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1.
Pathologe ; 41(4): 411-424, 2020 Jul.
Article in German | MEDLINE | ID: mdl-32430586

ABSTRACT

Molecular tumor diagnostics is rapidly evolving, driven by technological advances in high-throughput sequencing and bioinformatics, and paralleled by the emergence of novel therapeutic approaches, not least in the field of immune oncology. Molecular stratification of common tumor entities such as colorectal carcinoma and the discovery of paradigmatic molecular changes such as NTRK fusions illustrate how molecular pathological investigations can be performed under diagnostic or predictive conditions and can also provide prognostic information. Promising recent developments include "liquid biopsy" and tumor agnostic strategies. A functioning interdisciplinary cooperation between oncology, bioinformatics and molecular pathology is prerequisite for modern oncological diagnostics based on the current state-of-the-art knowledge and decisive for optimal care of oncological patients.


Subject(s)
Biomarkers, Tumor , Molecular Diagnostic Techniques , Biomarkers, Tumor/genetics , High-Throughput Nucleotide Sequencing , Humans , Medical Oncology , Pathology, Molecular
2.
Br J Ophthalmol ; 85(10): 1208-12, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11567966

ABSTRACT

AIM: To evaluate the cell proliferation activity in posterior uveal melanomas after Ru-106 brachytherapy. METHODS: Eyes containing choroidal or ciliary body melanoma from seven ocular oncology centres, which were enucleated after first being treated by Ru-106 brachytherapy and which had enough melanoma tissue to enable histological assessment, were included. The 57 eligible specimens were divided into a group of 44 eyes that were enucleated because of tumour regrowth, and a non-recurrent group of 13 eyes that were enucleated because of complications such as neovascular glaucoma. 46 non-irradiated eyes harbouring uveal melanoma served as a control group. All specimens underwent routine processing. They were cut into 5 microm sections, and were stained with two main cell proliferation markers: PC-10 for PCNA and MIB-1 for Ki-67. The stained sections were assessed, and the cells that were positive in the immunostaining were counted in each section. The results were evaluated by various statistical methods. RESULTS: The PC-10 score showed a statistically significant difference across the three groups (p = 0.002). The control group showed the highest PC-10 score (median 31.0 PCC/HPF) followed by the tumour regrowth group (median 4.9 PCC/HPF). The lowest PC-10 scores were found in the non-recurrent tumours (median 0.05 PCC/HPF). The MIB-1 score in the control group (median 5.77 PCC/HPF) was similar to the regrowth group (median 5.4 PCC/HPF). In contrast, the MIB-1 score in the non-recurrent tumours was statistically significantly lower (median 0.42 PCC/HPF). The PC-10 and MIB-1 scores were similar in tumours composed of either spindle cells or epithelioid cells in all groups. CONCLUSIONS: The non-recurrent melanomas demonstrate significantly lower cellular proliferation activity than melanomas that showed regrowth or that were not irradiated at all. In our hands, PCNA gave more meaningful information than Ki-67. Our findings strongly support the need for treating regrowing posterior uveal melanoma either by enucleation or re-treatment by brachytherapy. On the other hand, also in the non-recurrent uveal melanomas there are viable cells with potential for proliferation, although fewer in number, with unknown capacity for metastatic spread. Therefore, the irradiated tumours should be followed for many years, probably for life.


Subject(s)
Melanoma/radiotherapy , Ruthenium Radioisotopes/therapeutic use , Uveal Neoplasms/radiotherapy , Analysis of Variance , Antigens, Nuclear , Brachytherapy/methods , Cell Division/radiation effects , Choroid Neoplasms/pathology , Choroid Neoplasms/radiotherapy , Ciliary Body , Female , Humans , Ki-67 Antigen/analysis , Male , Melanoma/pathology , Middle Aged , Neoplasm Recurrence, Local/pathology , Nuclear Proteins , Proliferating Cell Nuclear Antigen/analysis , Staining and Labeling/methods , Statistics, Nonparametric , Uveal Neoplasms/pathology
3.
Klin Monbl Augenheilkd ; 216(1): 17-24, 2000 Jan.
Article in German | MEDLINE | ID: mdl-10702938

ABSTRACT

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome. In this survey we report about two further patients with CAR, who were referred to the University Eye Hospital of Tuebingen within a few months. The most common primary tumor associated with CAR is small cell carcinoma of the lung. Case reports about rhabdomyosarcoma, carcinoma of the endometrium, prostate and mamma were also described. The exact pathogenesis of CAR is still unknown. Specific autoantibodies were found against the photoreceptor protein recovering (23-kd retinal CAR antigen). However, this reaction is not present in all patients, and probably other antigens are also involved. Most of the patients experience symptoms of CAR before the primary tumor is detected. Besides glare sensitivity and flashing lights, a rapidly progressive, often asymmetric visual loss may occur. Although paracentral and mid-peripheral scotomas can be found frequently, visual field defects are often quite heterogeneous. Typically, the responses in the electroretinogram (ERG) are markedly reduced, but normal ERGs were also described. The fundus picture in CAR shows sheathing of the retinal vessels, narrowing of the arterioles and clumbing of the retinal pigment epithelium. The prognosis is poor. Frequently there is progression to bilateral loss of vision within a few months. Treatment of the primary tumor does not seem to alter the ocular prognosis. Systemic corticosteroids may be helpful in some patients. Nevertheless, no proven therapeutic regimen is currently available.


Subject(s)
Eye Proteins , Lipoproteins , Nerve Tissue Proteins , Paraneoplastic Syndromes/diagnosis , Retinal Diseases/diagnosis , Aged , Autoantibodies/blood , Breast Neoplasms/diagnosis , Breast Neoplasms/immunology , Calcium-Binding Proteins/immunology , Carcinoma/diagnosis , Carcinoma/immunology , Diagnosis, Differential , Electroretinography , Female , Hippocalcin , Humans , Male , Middle Aged , Optic Neuritis/diagnosis , Optic Neuritis/immunology , Paraneoplastic Syndromes/immunology , Recoverin , Retinal Diseases/immunology , Uterine Neoplasms/diagnosis , Uterine Neoplasms/immunology
4.
Curr Opin Ophthalmol ; 10(3): 164-7, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10537773

ABSTRACT

Choroidal metastases and melanomas are the most common intraocular neoplasms. Choroidal metastases may appear clinically similar to other amelanotic tumors, and the diagnosis may be difficult in the absence of a history of extraocular malignancy. Ultrasonography, using A- and B-mode criteria, offers an opportunity for high accuracy in the diagnosis of choroidal tumors. However, a considerable overlapping of ultrasonographic parameters, such as tumor solidity, vascularity, and choroidal excavation, has been demonstrated for choroidal melanomas and metastases. We have found that choroidal metastases are characterized by a significantly lower height-to-base ratio than melanomas, whereas reflectivity is significantly higher in metastases. Thus the combined use of height-to-base ratio and reflectivity provides a highly significant differentiation between choroidal melanomas and metastases. This observation has further improved the diagnostic value of ultrasonography in the differentiation of choroidal tumors.


Subject(s)
Choroid Neoplasms/diagnostic imaging , Melanoma/diagnostic imaging , Choroid Neoplasms/pathology , Choroid Neoplasms/secondary , Diagnosis, Differential , Humans , Melanoma/pathology , Melanoma/secondary , Neoplasm Metastasis/diagnostic imaging , Reproducibility of Results , Ultrasonography
5.
Br J Ophthalmol ; 82(2): 159-61, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9613382

ABSTRACT

AIMS: The purpose of the study was to analyse, whether the shape and the height to base ratio in B-scan ultrasonography are appropriate to differentiate choroidal melanomas from metastases. METHODS: Between 1991 and 1996 16 eyes of 16 patients with choroidal metastases from breast carcinomas and 66 eyes of 66 patients with choroidal melanomas were evaluated ultrasonographically. The diagnosis of choroidal melanoma has been confirmed histologically in all eyes. Irradiated tumours were excluded from the study. Fisher's exact test and chi 2 test were used for statistical analysis. RESULTS: Choroidal metastases demonstrated a significantly lower height to base ratio in B-scan (mean 0.18, SD 0.08) than melanomas (mean 0.6 (0.16); p < 0.001). A polygonal tumour surface was significantly more frequent in metastases (13 out of 16 metastases and in six out of 66 melanomas, p < 0.001). A choroidal excavation could be demonstrated in 38 melanomas and in no metastatic tumour (p < 0.001). The reflectivity was significantly higher in metastases than in melanomas. CONCLUSION: The combined use of height to base ratio and reflectivity enables a highly significant discrimination between choroidal melanomas and metastases from the breast, thus probably constituting appropriate variables for the clinical differentiation.


Subject(s)
Breast Neoplasms/pathology , Choroid Neoplasms/diagnostic imaging , Choroid Neoplasms/secondary , Melanoma/diagnostic imaging , Melanoma/secondary , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Ultrasonography
6.
Surv Ophthalmol ; 42(2): 190-4, 1997.
Article in English | MEDLINE | ID: mdl-9381373

ABSTRACT

Cataract extraction with a Graefe knife incision was the most important development in cataract surgery during the 19th century. To determine the indications, visual outcome, complications, and problems of cataract surgery performed a century ago, we reviewed patient records from the year 1895. With use of Graefe's technique of cataract extraction, the early postoperative visual acuity was 20/200 or better in 63% and 20/40 or better in 5%. A secondary cataract developed in about 30% of eyes. A flat anterior chamber persisted for more than two days in about 20% of eyes. Astigmatism was not regularly measured, but was markedly increased after surgery. Surgery for secondary cataract was performed in only 20 eyes. There was a complication rate of nearly 50% in secondary cataracts. These results demonstrate some of the major problems of cataract surgery 100 years ago: secondary cataract, insufficient wound closure, high astigmatism, and aphakia as a refractive problem.


Subject(s)
Cataract Extraction/history , Cataract Extraction/methods , Germany , History, 19th Century , Humans
7.
Z Exp Angew Psychol ; 36(4): 654-64, 1989.
Article in German | MEDLINE | ID: mdl-2629363

ABSTRACT

A new paradigm was constructed using rats as trained animals in order to examine changes appearing in the scent of mice after a fully allogeneic bone marrow transplantation (BMT). Two rats (CAP), deprived of water 20 hours before each training session, were trained in an olfactometer to discriminate two fully allogeneic mice strains (C3H, C57) via their urine odors. Reinforcement for identification of the St was provided by a drop of water. After discrimination was built-up, the reinforcement schedule was reduced stepwise in defined blocks of trials, in order to allow transfer-of-training tests, to which urine samples of allogeneic reconstituted BMT-chimeras (C57----C3H and C3H----C57) were submitted. It was confirmed that the strain-specific urine odors of the recipients were changed by a fully allogeneic BMT. The results also showed that the urine odors of allogeneic reconstituted chimeras differed from the specific urine odor of the donor strain.


Subject(s)
Bone Marrow Transplantation/physiology , Pheromones/urine , Smell/physiology , Species Specificity , Animals , Discrimination Learning/physiology , Female , Mice , Mice, Inbred Strains , Rats , Rats, Inbred Strains
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