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1.
Analyst ; 148(20): 5022-5032, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37702617

RESUMO

While infrared microscopy provides molecular information at spatial resolution in a label-free manner, exploiting both spatial and molecular information for classifying the disease status of tissue samples constitutes a major challenge. One strategy to mitigate this problem is to embed high-dimensional pixel spectra in lower dimensions, aiming to preserve molecular information in a more compact manner, which reduces the amount of data and promises to make subsequent disease classification more accessible for machine learning procedures. In this study, we compare several dimensionality reduction approaches and their effect on identifying cancer in the context of a colon carcinoma study. We observe surprisingly small differences between convolutional neural networks trained on dimensionality reduced spectra compared to utilizing full spectra, indicating a clear tendency of the convolutional networks to focus on spatial rather than spectral information for classifying disease status.


Assuntos
Aprendizado Profundo , Microscopia , Redes Neurais de Computação , Aprendizado de Máquina
2.
Pathobiology ; 90(2): 71-80, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35691289

RESUMO

INTRODUCTION: Studies on pancreatic neuroendocrine tumors (PanNETs) regarding loss of ATRX, DAXX, or frequency of microsatellite instability (MSI) show inconclusive results. So far, data on corresponding metastaseshave not been published. METHODS: We performed immunohistochemistry (IHC) of ATRX, DAXX, MSH2, MSH6, MLH1, and PMS2 on 74 PanNETs and 19 metastases. ATRX- and DAXX-negative PanNETs were further sequenced for mutations. We used polymerase chain reaction for MSI on cases with IHC loss of MSH2, MSH6, MLH1, and PMS2. RESULTS: Immunohistochemical loss of DAXX and ATRX was observed in 8/74 (11%) and 6/74 (8%) PanNETs. Loss of DAXX immunoreactivity was statistically associated with higher tumor grade and showed a tendency toward a decreased overall survival. Sequencing of DAXX- (7/11 [64%]) and ATRX-negative (5/11 [45%]) PanNETs revealed a mutation in 6/7 (86%) and 2/5 (40%). The specificity of immunohistochemical loss of DAXX and ATRX for mutation was 80% and 67%, respectively. The expression status of DAXX compared to primary tumor differs in 2/12 (17%) lymph node metastases. We further identified 3/74 (4%) tumors as MSI, associated with a poor prognosis. DISCUSSION/CONCLUSION: Our study supports the hypothesis that a loss of DAXX immunoreactivity can identify a more aggressive subtype of PanNET with high confidence, while ATRX loss is a weaker indicator. Our results also strengthen the role of DAXX immunolabeling as a prognostic marker. We could show that ATRX might be less suitable as a surrogate for sequencing. Our results indicate that IHC of DAXX and ATRX may identify PanNET subtypes as targets for more aggressive therapy.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Proteína Nuclear Ligada ao X/genética , Proteína Nuclear Ligada ao X/metabolismo , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Instabilidade de Microssatélites , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/análise , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo
3.
Proc Natl Acad Sci U S A ; 116(51): 25860-25869, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31796589

RESUMO

Environmental triggers acting at the intestinal barrier are thought to contribute to the initiation of autoimmune disorders. The transforming growth factor beta inhibitor Smad7 determines the phenotype of CD4+ T cells. We hypothesized that Smad7 in intestinal CD4+ T cells controls initiation of opticospinal encephalomyelitis (OSE), a murine model of multiple sclerosis (MS), depending on the presence of gut microbiota. Smad7 was overexpressed or deleted in OSE CD4+ T cells to determine the effect on clinical progression, T cell differentiation, and T cell migration from the intestine to the central nervous system (CNS). Smad7 overexpression worsened the clinical course of OSE and increased CNS inflammation and demyelination. It favored expansion of intestinal CD4+ T cells toward an inflammatory phenotype and migration of intestinal CD4+ T cells to the CNS. Intestinal biopsies from MS patients revealed decreased transforming growth factor beta signaling with a shift toward inflammatory T cell subtypes. Smad7 in intestinal T cells might represent a valuable therapeutic target for MS to achieve immunologic tolerance in the intestine and suppress CNS inflammation.


Assuntos
Autoimunidade/fisiologia , Linfócitos T CD4-Positivos/imunologia , Sistema Nervoso Central/metabolismo , Esclerose Múltipla/metabolismo , Proteína Smad7/metabolismo , Animais , Diferenciação Celular , Modelos Animais de Doenças , Encefalomielite/metabolismo , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Microbioma Gastrointestinal/fisiologia , Regulação da Expressão Gênica , Humanos , Tolerância Imunológica , Inflamação , Intestinos/patologia , Camundongos , Camundongos Transgênicos , Esclerose Múltipla/patologia , Transdução de Sinais , Proteína Smad7/genética , Medula Espinal/patologia , Fator de Crescimento Transformador beta/metabolismo
4.
Pathologe ; 43(2): 157-166, 2022 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-35171314

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent chronic liver diseases with a rising incidence in industrial countries. This is accompanied by an increased prevalence for NAFLD-associated liver cirrhosis and an increased risk for developing hepatocellular carcinoma. The current gold standard in the diagnostics is a liver biopsy. The histopathological evaluation is performed through semiquantitative scoring. To optimize the standardization and quantification of the existing scoring systems, in the coming years procedures with artificial intelligence, such as deep learning models could be used. Fields of application could be the supplementation of conventional histopathological diagnostics, the identification of new predictive parameters for estimating the prognosis and the prediction of a possible response to treatment.


Assuntos
Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Inteligência Artificial , Biópsia , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/patologia
5.
Pathologe ; 41(5): 495-504, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32588138

RESUMO

Hepatic involvement is one of the most common manifestations in cancer of unknown primary (CUP) syndrome. The most frequent secondary neoplasms of the liver are carcinomas and malignant melanomas. Most common carcinoma metastases are adenocarcinomas originating from the digestive system or metastases of breast and lung carcinomas. Therefore, hepatic CUP syndrome is an exclusion diagnosis. Immunohistochemistry and molecular examinations are an important part of histopathological diagnosis. They do not only serve to identify the tissue of histologically origin or possible primary tumor, but also contribute to the selection of a personalized targeted therapy by detecting so-called druggable targets in the interdisciplinary management.


Assuntos
Adenocarcinoma , Neoplasias Hepáticas , Neoplasias Primárias Desconhecidas , Humanos , Imuno-Histoquímica , Fígado , Neoplasias Hepáticas/diagnóstico , Neoplasias Pulmonares , Neoplasias Primárias Desconhecidas/diagnóstico
6.
Arch Gynecol Obstet ; 300(3): 651-660, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31338659

RESUMO

BACKGROUND: Chronic ectopic pregnancy (CEP) is a variant of ectopic pregnancy (EP) characterized by low or absent serum human chorionic gonadotropin (hCG) levels, resistance to methotrexate (MTX), and an adnexal mass with fibrosis, necrosis, and blood clots due to repeated and gradual fallopian tube wall disintegration. CEP may complicate the course of patients with EP and is difficult to diagnose. CASE PRESENTATION: The case of a 36-year-old woman with EP, low serum hCG levels, a small echogenic adnexal mass, and resistance to MTX is presented. Salpingectomy was performed and histology demonstrated CEP with fibrosis, necrosis, and a hematocele within degenerated chorionic villi. SYSTEMATIC LITERATURE REVIEW: In a database search, 19 case reports, 3 case-control studies, and 3 case series describing 399 patients with CEP were identified. Serum hCG was negative in 40/124 cases (32%) with reported levels of serum hCG. The most common presenting symptom was abdominal pain (284/399 [71%]), followed by irregular vaginal bleeding (219/399 [55%]), and fever (20/399 [5%]). 73/399 (18%) women were asymptomatic. An adnexal mass was seen in 144/298 (48%) cases with perioperative ultrasound examination and with a mean largest diameter of 6.8 cm. Data on treatment modalities and outcomes were available for 297 women. Of these, 89% underwent surgery as first-line therapy. Laparoscopy was performed in most cases. MTX was the first-line therapy in a minority of cases. Complete resolution was achieved by first-line therapy in 287/297 (97%) cases. Adverse events were reported in 218 patients with CEP. Among those, adverse events ≥ grade 3 were seen in 186/218 (85%) cases. There was no case of treatment-related mortality. CONCLUSION: CEP is a variant of EP with low or absent trophoblast activity. A prolonged clinical course is typical and surgery is the mainstay of treatment.


Assuntos
Dor Abdominal/etiologia , Febre/etiologia , Gravidez Ectópica , Salpingectomia , Hemorragia Uterina/etiologia , Doenças dos Anexos/diagnóstico por imagem , Doenças dos Anexos/cirurgia , Adulto , Estudos de Casos e Controles , Gonadotropina Coriônica/sangue , Feminino , Humanos , Gravidez , Complicações na Gravidez , Gravidez Ectópica/diagnóstico , Gravidez Ectópica/etiologia , Gravidez Ectópica/imunologia , Gravidez Ectópica/cirurgia , Útero/cirurgia
7.
BMC Cancer ; 18(1): 530, 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29728073

RESUMO

BACKGROUND: Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for this type of malignancy based on controlled trials. METHODS: We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials describing the management and outcome of women with NECC. RESULTS: Three thousand five hundred thirty-eight cases of NECC in 112 studies were identified. The pooled proportion of NECC among women with cervical cancer was 2303/163470 (1.41%). Small cell NECC, large cell NECC, and other histological subtypes were identified in 80.4, 12.0, and 7.6% of cases, respectively. Early and late stage disease presentation were evenly distributed with 1463 (50.6%) and 1428 (49.4%) cases, respectively. Tumors expressed synaptophysin (424/538 cases; 79%), neuron-specific enolase (196/285 cases; 69%), chromogranin (323/486 cases; 66%), and CD56 (162/267; 61%). The most common primary treatment was radical surgery combined with chemotherapy either as neoadjuvant or adjuvant chemotherapy, described in 42/48 studies. Radiotherapy-based primary treatment schemes in the form of radiotherapy, radiochemotherapy, or radiotherapy with concomitant or followed by chemotherapy were also commonly used (15/48 studies). There is no standard chemotherapy regimen for NECC, but cisplatin/carboplatin and etoposide (EP) was the most commonly used treatment scheme (24/40 studies). Overall, the prognosis of women with NECC was poor with a mean recurrence-free survival of 16 months and a mean overall survival of 40 months. Immune checkpoint inhibitors and targeted agents were reported as being active in three case reports. CONCLUSION: NECC is a rare variant of cervical cancer with a poor prognosis. Multimodality treatment with radical surgery and neoadjuvant/adjuvant chemotherapy with cisplatin and etoposide with or without radiotherapy is the mainstay of treatment for early stage disease while chemotherapy with cisplatin and etoposide or topotecan, paclitaxel, and bevacizumab is appropriate for women with locally advanced or recurrent NECC. Immune checkpoint inhibitors may be beneficial, but controlled evidence for their efficacy is lacking.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/terapia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias do Colo do Útero/terapia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Colo do Útero/patologia , Colo do Útero/cirurgia , Quimiorradioterapia Adjuvante/métodos , Ensaios Clínicos como Assunto , Feminino , Humanos , Histerectomia , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
8.
Neuropathology ; 38(3): 288-292, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29226425

RESUMO

Primary leptomeningeal melanocytic tumors (PLMTs) are rare. They usually arise along the spinal cord and at the skull base. Here we report on a patient with a very rare intraventricular melanocytoma. Histologically, a melanocytic tumor was clearly diagnosed. However, to make the uncommon diagnosis of an intraventricular melanocytoma, metastatic melanoma needed to be excluded. Next generation sequencing covering gene mutations that may occur in PLMTs and cutaneous melanoma was performed. The unique gene mutation profile detected, consisting of an activating CYSLTR2 L129Q mutation and EIF1AX G9R mutation and a lack of mutations in genes known to occur in metastatic melanoma (i.e. BRAF or NRAS) confirmed the diagnosis of an intraventricular melanocytoma. This case report is the second intraventricular melanocytoma published to date and demonstrates the value of applying novel genetic assays to make this diagnosis.


Assuntos
Neoplasias do Ventrículo Cerebral/diagnóstico , Neoplasias do Ventrículo Cerebral/genética , Melanócitos/patologia , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/genética , Idoso de 80 Anos ou mais , Encéfalo/patologia , Neoplasias do Ventrículo Cerebral/complicações , Fator de Iniciação 1 em Eucariotos/genética , Humanos , Masculino , Neoplasias Meníngeas/complicações , Mutação , Receptores de Leucotrienos/genética
9.
Eur Respir J ; 49(6)2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28663314

RESUMO

The traceability of asbestos fibres in human lungs is a matter of discussion especially for chrysotile. This issue is of high significance for differential diagnosis, risk assessment and occupational compensation. At present no intra-individual longitudinal information is available. This study addresses the question whether the asbestos fibre burden in human lungs decreases with time after exposure cessation.The database of the German Mesothelioma Register was screened for patients with asbestos body counts of at least 500 fibres per gram of wet lung, which had been analysed twice from different tissue excisions at minimum intervals of 4 years.Twelve datasets with individual longitudinal information were discovered with a median interval of about 8 years (range 4-21 years). Both examinations were performed after exposure cessation (median: surgery, 9.5 years; autopsy, 22 years). Pulmonary asbestos fibre burden was stable between both examinations (median 1623/4269 asbestos bodies per gram wet lung). Electron microscopy demonstrated a preponderance of chrysotile (median 80%).This study is the first to present longitudinal intra-individual data about the asbestos fibre burden in living human lungs. The high biopersistence of amphiboles, but also of chrysotile, offers mechanistic explanations for fibre toxicity, especially the long latency period of asbestos-related diseases.


Assuntos
Asbestos Serpentinas/efeitos adversos , Asbestos Serpentinas/análise , Neoplasias Pulmonares/etiologia , Mesotelioma/etiologia , Exposição Ocupacional/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Autopsia , Alemanha , Humanos , Estudos Longitudinais , Pulmão/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Mesotelioma/cirurgia , Microscopia Eletrônica , Pessoa de Meia-Idade , Sistema de Registros
11.
Pathologie (Heidelb) ; 2024 May 02.
Artigo em Alemão | MEDLINE | ID: mdl-38695911

RESUMO

Benign mesothelial tumors are rarer than malignant mesotheliomas and are often found in the peritoneum as incidental findings in women. They include the adenomatoid tumor (AT), the well-differentiated mesothelial tumor (WDPMT), the mesothelioma in situ (MIS), and the solid papillary mesothelial tumor (SPMT). ATs are always benign and predominantly manifest in the genital tract. WDPMTs can develop multifocally and are prone to recurrence, particularly in the case of incomplete resection. Only MISs are considered a confirmed precursor lesion of malignant mesothelioma according to the currently valid World Health Organization (WHO) classifications. As with malignant mesothelioma, alterations of BAP1, MTAP, and p16 are detectable for MIS in contrast to the other three tumors. SPMTs cannot be clearly assigned to the other mesothelial tumors and have so far only been described in the peritoneum in women with a benign course.

12.
Mol Vis ; 19: 1804-14, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23946635

RESUMO

PURPOSE: In recent years, numerous studies have investigated the involvement of immunological mechanisms in glaucoma. Until now, it has not been determined whether the altered antibody pattern detected in patients is harmful to retinal ganglion cells (RGCs) or triggers disease formation in any way. In a model of experimental autoimmune glaucoma, RGC loss can be induced through immunization with certain ocular antigens. In the current study, the time course of the levels of autoreactivity against ocular tissues after immunization was examined. METHODS: Intraocular pressure was measured regularly. Ten weeks after immunization with an optic nerve homogenate antigen (ONA), the number of RGCs was determined. Immunoglobulin G levels in aqueous humor were measured via enzyme-linked immunosorbent assay at the same time point. Serum from different time points was used to analyze the possible occurrence of autoreactive antibodies against the retina or optic nerve in this autoimmune glaucoma model. Additionally, optic nerve and brain sections were evaluated for possible pathological findings. RESULTS: Intraocular pressure stayed within the normal range throughout this study. A continuous increase of autoreactive antibodies against the optic nerve and retina sections was observed. At 4, 6, and 10 weeks, antibody reactivity was significantly higher in ONA animals (p<0.01). Aqueous humor immunoglobulin G levels were also significantly higher in the ONA group (p=0.006). Ten weeks after immunization, significantly fewer RGCs were noted in the ONA group (p=0.00003). The optic nerves from ONA animals exhibited damaged axons. No pathological findings appeared in any brain sections. CONCLUSIONS: Our findings suggest that these modified antibodies play a substantial role in mechanisms leading to RGC death. The slow dissolution of RGCs observed in animals with autoimmune glaucoma is comparable to the slow progressive RGC loss in glaucoma patients, thus making this a useful model to develop neuroprotective therapies in the future.


Assuntos
Antígenos/imunologia , Doenças Autoimunes/imunologia , Olho/imunologia , Glaucoma/imunologia , Imunidade/imunologia , Imunização , Nervo Óptico/imunologia , Animais , Humor Aquoso/metabolismo , Autoanticorpos/imunologia , Doenças Autoimunes/patologia , Doenças Autoimunes/fisiopatologia , Axônios/patologia , Encéfalo/patologia , Bovinos , Modelos Animais de Doenças , Olho/patologia , Olho/fisiopatologia , Fundo de Olho , Glaucoma/patologia , Glaucoma/fisiopatologia , Imunoglobulina G/metabolismo , Pressão Intraocular , Masculino , Nervo Óptico/fisiopatologia , Ratos , Ratos Endogâmicos Lew , Retina/imunologia , Retina/patologia , Retina/fisiopatologia , Células Ganglionares da Retina/imunologia , Células Ganglionares da Retina/patologia
13.
BMC Cancer ; 13: 490, 2013 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-24144362

RESUMO

BACKGROUND: Chemotherapy for soft tissue sarcomas remains unsatisfactory due to their low chemosensitivity. Even the first line chemotherapeutic agent doxorubicin only yields a response rate of 18-29%. The antibiotic salinomycin, a potassium ionophore, has recently been shown to be a potent compound to deplete chemoresistant cells like cancer stem like cells (CSC) in adenocarcinomas. Here, we evaluated the effect of salinomycin on sarcoma cell lines, whereby salinomycin mono- and combination treatment with doxorubicin regimens were analyzed. METHODS: To evaluate the effect of salinomycin on fibrosarcoma, rhabdomyosarcoma and liposarcoma cell lines, cells were drug exposed in single and combined treatments, respectively. The effects of the corresponding treatments were monitored by cell viability assays, cell cycle analysis, caspase 3/7 and 9 activity assays. Further we analyzed NF-κB activity; p53, p21 and PUMA transcription levels, together with p53 expression and serine 15 phosphorylation. RESULTS: The combination of salinomycin with doxorubicin enhanced caspase activation and increased the sub-G1 fraction. The combined treatment yielded higher NF-κB activity, and p53, p21 and PUMA transcription, whereas the salinomycin monotreatment did not cause any significant changes. CONCLUSIONS: Salinomycin increases the chemosensitivity of sarcoma cell lines - even at sub-lethal concentrations - to the cytostatic drug doxorubicin. These findings support a strategy to decrease the doxorubicin concentration in combination with salinomycin in order to reduce toxic side effects.


Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Piranos/farmacologia , Sarcoma , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/toxicidade , Sinergismo Farmacológico , Humanos , Piranos/toxicidade , Sarcoma/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo
14.
J Refract Surg ; 29(12): 863-4, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24202702

RESUMO

PURPOSE: To investigate the quality and accuracy of three-dimensional spectral-domain optical coherence tomography (OCT)-guided corneal incisions with the Catalys precision femtosecond laser system (OptiMedica, Sunnyvale, CA) in living human tissue. METHODS: In vivo cataract and intrastromal corneal incisions were made with a femtosecond laser designed for cataract surgery with a patient scheduled for enucleation. RESULTS: An accurate correlation between the pre-incision spectral-domain OCT and the post-incision histology was demonstrated. CONCLUSIONS: The OCT-guided femtosecond laser is capable of creating accurate, precise, and histologically demonstrable incisions in preselected intrastromal locations.


Assuntos
Extração de Catarata/métodos , Córnea/patologia , Córnea/cirurgia , Terapia a Laser/métodos , Tomografia de Coerência Óptica , Idoso , Humanos , Imageamento Tridimensional , Masculino , Capsulotomia Posterior/métodos , Cicatrização
15.
Brain Sci ; 13(9)2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37759878

RESUMO

BACKGROUND: Reimplantations of autologous skull flaps after decompressive hemicraniectomies (DHs) are associated with high rates of postoperative bone flap resorption (BFR). We histologically assessed the cell viability of explanted bone flaps in certain periods of time after DH, in order to conclude whether precursors of BRF may be developed during their storage. METHODS: Skull bone flaps explanted during a DH between 2019 and 2020 were stored in a freezer at either -23 °C or -80 °C. After their thawing process, the skulls were collected. Parameters of bone metabolism, namely PTH1 and OPG, were analyzed via immunohistochemistry. H&E stain was used to assess the degree of avital bone tissue, whereas the repeated assays were performed after 6 months. RESULTS: A total of 17 stored skull flaps (8 at -23 °C; 9 at -80 °C) were analyzed. The duration of cryopreservation varied between 2 and 17 months. A relevant degree of bone avitality was observed in all skull flaps, which significantly increased at the repeated evaluation after 6 months (p < 0.001). Preservation at -23 °C (p = 0.006) as well as longer storage times (p < 0.001) were identified as prognostic factors for higher rates of bone avitality in a linear mixed regression model. CONCLUSIONS: Our novel finding shows a clear benefit from storage at -80° C, which should be carefully considered for the future management and storage of explanted skull flaps. Our analysis also further revealed a significant degree of bone avitality, a potential precursor of BFR, in skull flaps stored for several weeks. To this end, we should reconsider whether the reimplantation of autologous skull flaps instead of synthetic skull flaps is still justified.

17.
Chirurg ; 93(2): 115-122, 2022 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-34613440

RESUMO

Histopathologic evaluation of tumors after neoadjuvant therapy is performed by tumor regression grading (TRG) systems, which reflect the proportion of vital residual primary tumor in relation to the previous total tumor. The World Health Organization (WHO) tumor grading is replaced by TRG in tumor classification. The histopathological work-up of a tumor is based on the criteria of the TNM classification even after neoadjuvant therapy. A uniform TRG does not exist. For various tumors TRGs based on the tumor entity have been established, consisting of a 3-stage or 5­stage grading system. Complete histopathological tumor regression is only present if no vital tumor cells are detectable in the histopathological examination of the primary surgical specimens (primary tumor and accompanying locoregional lymph nodes) and there are no distant metastases.


Assuntos
Linfonodos , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
18.
Recent Results Cancer Res ; 189: 57-78, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21479896

RESUMO

Malignant mesothelioma is a rare aggressive tumour arising from mesothelial cells of the pleural and peritoneal cavity including pericardium and tunica vaginalis testis. Malignant mesothelioma occurs predominantly in men (>90%). Asbestos exposure is the best known and evaluated risk factor with a long latency period between exposure and onset of malignant mesothelioma ranging from 15 to 60 years. Exposure to erionite leads to higher incidences of mesothelioma and play an important role in environmental exposure (Turkey). Other possible risk factors are radiation, recurrent pleuritis/peritonitis and simian virus 40 (SV 40).Malignant pleural mesothelioma is most common, whereas malignant peritoneal mesothelioma accounts only for 6-10%. Infrequent sites of origin are the pericardium and tunica vaginalis in 1-2%.Malignant mesothelioma shows either diffuse growth pattern or occurs as a localised tumour mass. Diffuse type represents an aggressive tumour with poor prognosis and is incurable in most cases.According to the WHO classification, three histological subtypes are distinguished: epithelioid, sarcomatoid and biphasic malignant mesothelioma.Rare variants are desmoplastic type, a subtype of sarcomatoid mesothelioma, undifferentiated type and deciduoid type. Epithelioid type is the most frequent one, but biphasic malignant mesothelioma occurs in 30%. Pure sarcomatoid or biphasic type is seen less frequently in malignant peritoneal mesothelioma than in its pleural counterpart.Well-differentiated papillary mesothelioma is a generally non-invasive mesothelioma with low malignant potential that arises mostly in females in the peritoneal cavity. Histological type is an important prognostic marker. Longest survival is seen in patients with epithelioid malignant mesothelioma. Sarcomatoid subtype has the worst prognosis.Malignant mesothelioma shows macroscopical and microscopical similarities to benign lesions and other malignancies. Therefore, reactive mesothelial proliferations on the one hand and secondary tumours resembling mesothelial cells as well as benign or rare mesothelial tumours on the other hand have to be distinguished. Additional immunohistochemistry is essential in histopathological assessment using a marker panel of antibodies.


Assuntos
Mesotelioma/diagnóstico , Neoplasias Pleurais/diagnóstico , Amianto/toxicidade , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Mesotelioma/etiologia , Mesotelioma/secundário , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia , Neoplasias Pleurais/etiologia , Neoplasias Pleurais/patologia , Pleurisia/diagnóstico , Pleurisia/patologia , Prognóstico , Sarcoma/diagnóstico , Sarcoma/patologia , Vírus 40 dos Símios
19.
Int J Comput Assist Radiol Surg ; 16(9): 1517-1526, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34053010

RESUMO

PURPOSE: A precise resection of the entire tumor tissue during surgery for brain metastases is essential to reduce local recurrence. Conventional intraoperative imaging techniques all have limitations in detecting tumor remnants. Therefore, there is a need for innovative new imaging methods such as optical coherence tomography (OCT). The purpose of this study is to discriminate brain metastases from healthy brain tissue in an ex vivo setting by applying texture analysis and machine learning algorithms for tissue classification to OCT images. METHODS: Tumor and healthy tissue samples were collected during resection of brain metastases. Samples were imaged using OCT. Texture features were extracted from B-scans. Then, a machine learning algorithm using principal component analysis (PCA) and support vector machines (SVM) was applied to the OCT scans for classification. As a gold standard, an experienced pathologist examined the tissue samples histologically and determined the percentage of vital tumor, necrosis and healthy tissue of each sample. A total of 14.336 B-scans from 14 tissue samples were included in the classification analysis. RESULTS: We were able to discriminate vital tumor from healthy brain tissue with an accuracy of 95.75%. By comparing necrotic tissue and healthy tissue, a classification accuracy of 99.10% was obtained. A generalized classification between brain metastases (vital tumor and necrosis) and healthy tissue was achieved with an accuracy of 96.83%. CONCLUSIONS: An automated classification of brain metastases and healthy brain tissue is feasible using OCT imaging, extracted texture features and machine learning with PCA and SVM. The established approach can prospectively provide the surgeon with additional information about the tissue, thus optimizing the extent of tumor resection and minimizing the risk of local recurrences.


Assuntos
Neoplasias Encefálicas , Tomografia de Coerência Óptica , Algoritmos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Humanos , Aprendizado de Máquina , Máquina de Vetores de Suporte
20.
Onkologie ; 33(11): 617-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20975309

RESUMO

BACKGROUND: The clinical prognosis of metastatic pancreatic cancer is very poor, with a median survival time of such patients ranging from 3 to 6 months. Current chemotherapy regimens include the combination of oxaliplatin and gemcitabine. CASE REPORT: A 43-year-old woman was diagnosed with pancreatic adenocarcinoma spreading into the regional lymph nodes and into multiple liver segments (pT3, pN1, pM1). Upon diagnosis, she underwent a pylorus-preserving pancreatic head resection, including dissection of regional lymph nodes and atypical resection of a single liver segment, followed by 9 cycles of palliative chemotherapy with gemcitabine and oxaliplatin. 37 weeks after surgery, the patient demonstrated a sustained partial remission, and the chemotherapy was stopped. Surprisingly, 10 months later, she still showed no evidence of tumor progression. Since the time of pancreatic surgery, the patient had taken mistletoe extracts and this adjunctive treatment has been continued until now. CONCLUSIONS: Cases of sustained long-term remission of metastatic pancreatic cancer are extremely rare. Although this single case observation does not allow for firm conclusions regarding potential mechanisms, the adjunctive therapy with mistletoe extracts might have played a role. Therefore, the clinical effects of such treatment in patients with pancreatic cancer warrant further investigation.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Erva-de-Passarinho/química , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/secundário , Extratos Vegetais/uso terapêutico , Adulto , Quimioterapia Adjuvante , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Metástase Linfática , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Fitoterapia/métodos , Resultado do Tratamento , Gencitabina
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