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1.
Int J Oncol ; 57(1): 289-300, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32377699

RESUMO

Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. The prognosis of advanced stage RMS remains poor, and metastatic invasion is a major cause of treatment failure. Therefore, there is an urgent need for treatment alternatives focusing on metastatic invasion and drug resistance. The stromal cell­derived factor­1 (SDF­1)/chemokine receptor 4 (CXCR4) axis is a crucial factor for metastatic invasion in RMS. Clinical data has revealed that high CXCR4 expression is associated with a poor outcome and a high metastatic rate in several malignancies, including RMS. Thus, targeting CXCR4 in addition to classical chemotherapy may improve the effectiveness of RMS treatment. In the present study, flow cytometry and reverse transcription­quantitative PCR were used to assess the effects of the combined treatment with a CXCR4 antagonist and chemotherapy on CXCR4 expression in the embryonal RMS (RME) cell line RD and in the alveolar RMS (RMA) cell line RH30. The functional effect of CXCR4 expression on the migratory behavior of RMS cells was analyzed using Transwell assays. Treatment with cytotoxic agents modulated CXCR4 expression in RMS cells in a dose­, drug­ and cell line dependent manner; however, this was not observed in RD cells with vincristine. The expression levels of CXCR4 significantly increased the migratory behavior of RMA and did not affect RME cell migration towards stromal cell­derived factor­1α (SDF­1α). AMD3100 markedly reduced the migration of RH30 cells in the Transwell assays compared with SDF­1α alone, and the cytotoxic agents doxorubicin and vincristine increased this effect. The results of the combined treatment in RMS cells using the CXCR4 antagonist AMD3100 together with cytotoxic drugs demonstrated that this approach may be a promising alternative for the treatment of advanced stage pediatric RMS. The observed effects of circumventing metastatic invasion and drug resistance should be further investigated in vivo.

2.
Medicine (Baltimore) ; 99(7): e19146, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049838

RESUMO

The aim of this study was to test the hypothesis that computed tomography texture analysis (CTTA) is accurate for response assessment of Hodgkin lymphoma (HL).A total of 100 patients with HL were identified. CTTA in baseline and interim staging was performed generating volume of interests in lymphoma tissue from which CTTA features including 1st, 2nd, and higher order textural features were extracted. Baseline and interim 2-deoxy-fluor-glucose positron emission tomography results were used to determine therapy response and compared to CTTA in terms of patient outcome.At interim, 1st-order features yielded a significant drop (e.g., entropy of heterogeneity, P = .01) or a significant rise (deviation, P < .001), whereas 2nd and higher order features decreased (e.g., entropy of co-occurrence matrix, P < .001). Patients achieving complete remission at end of treatment had a significantly lower entropy of heterogeneity at baseline and interim compared to patients achieving partial remission (P < .05).CT textural features change in parallel to metabolic therapy response, and are therefore a feasible diagnostic tool for a more accurate response assessment of HL.


Assuntos
Fluordesoxiglucose F18 , Doença de Hodgkin/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
4.
Am J Case Rep ; 21: e919751, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32005796

RESUMO

BACKGROUND Conjunctival squamous cell carcinoma is the most common non-pigmented malignancy of the ocular surface. This report illustrates the clinical management of squamous cell carcinoma of the conjunctiva. CASE REPORT A 33-year-old female was referred to our eye hospital with a tumorous lesion on the nasal bulbar conjunctiva of the right eye. A topical therapy with antibiotic and corticosteroid eye drops did not change the lesion. The conjunctival tumor was widely resected. The histopathological diagnosis suggested a squamous cell carcinoma. After resection, a treatment with topical mitomycin C (MMC) 0.02% eye drops were started 4 times daily for 14 days. Two cycles of treatment were done with a 2-week interval during which only artificial tears eye drops were administered. At the 12-month follow-up, there was no sign of recurrence. CONCLUSIONS This case illustrates the effective and successful clinical management of squamous cell carcinoma of the conjunctiva with excision and postoperative treatment with MMC 0.02% eye drops.

5.
J Cutan Pathol ; 47(5): 439-445, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31904134

RESUMO

BACKGROUND: Aplasia cutis congenita (ACC) is a rare and heterogeneous disorder characterized by congenital absence of skin. The scalp is the most commonly affected site and lesions may overlie deeper ectodermal abnormalities. The exact etiology is still unknown, and histopathologic features are poorly defined. METHODS: A series of 10 cases from nine patients was analyzed to characterize the clinicopathologic spectrum and age-related changes of ACC of the scalp. Hematoxylin and eosin, S100, Elastica van Gieson, and Weigert elastic stains were performed, and clinical information was retrieved from archived medical files. RESULTS: Patient ages ranged from 1 day to 39 years (median 57 months). All cases resembled deep-reaching scars with almost complete loss of all adnexal structures. Isolated residual hair follicles were present in 8/10 and sweat glands and ducts in 2/10 cases. The subcutis was thinned or absent. Elastic fibers were always more fragmented than in normal tissue, and the thickness and density increased over time. There was no gain of adnexal structures with increasing age. CONCLUSIONS: ACC represents a congenital scarring alopecia with permanent loss of skin appendages. Histopathologic changes resemble a deep-reaching scar with fragmented elastic fibers and differentiate ACC from all other forms of non-traumatic congenital alopecias.

7.
Rofo ; 192(2): 119-122, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31779027
8.
Virchows Arch ; 475(4): 479-488, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31451895

RESUMO

Recent studies have shown that re-expression of stem cell factors contribute to pathogenesis, therapy resistance, and recurrent disease in ovarian carcinomas. In this study, we compare the expression and co-expression of stem cell markers ALDH1 and SOX2 in different types of serous ovarian tumors. A total of 215 serous ovarian tumors (161 high-grade serous carcinomas (HGSC), 17 low-grade serous carcinomas (LGSC), 37 atypical proliferative serous tumors (APST)), and 10 cases of serous tubal intraepithelial carcinoma (STIC) were analyzed. Double immunostaining experiments addressed the association of cell proliferation (Ki67) with ALDH1 and the potential co-expression of SOX2 and ALDH1. The prognostic effect was analyzed in the cohort of HGSC. Expression of ALDH1and/or SOX2 was detected with increased frequency in HGSC (88.8%), compared with LGSC (70.5%) and APST (36.4%), while ALDH1 alone was significantly more frequently expressed in LGSC. The majority of all tumor types showed expression of ALDH1 and SOX2 in different cells. Only a minority of HGSC (4.6%) and STIC (20%) showed SOX2/ALDH1 co-expression in > 10% of tumor cells. Double staining also revealed that ALDH1 is associated with the non-proliferating Ki67-negative fraction consistent with a stem cell phenotype. Co-expression of ALDH1 and SOX2 or ALDH1 and Ki67 has no effect on survival. Expression of stem cell factors ALDH1 and/or SOX2 shows increased frequency in high-grade serous ovarian carcinomas compared to low-grade carcinomas and borderline tumors, supporting the concept that stem cell markers play different biological roles in low-grade versus high-grade serous neoplasia of the ovary.


Assuntos
Cistadenocarcinoma Seroso/patologia , Isoenzimas/análise , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/patologia , Retinal Desidrogenase/análise , Fatores de Transcrição SOXB1/análise , Adulto , Biomarcadores Tumorais/análise , Feminino , Humanos , Isoenzimas/biossíntese , Pessoa de Meia-Idade , Retinal Desidrogenase/biossíntese , Fatores de Transcrição SOXB1/biossíntese
10.
Rofo ; 191(10): 891-894, 2019 10.
Artigo em Alemão | MEDLINE | ID: mdl-31121606
11.
Genome Med ; 11(1): 28, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039795

RESUMO

BACKGROUND: Although mutated HLA ligands are considered ideal cancer-specific immunotherapy targets, evidence for their presentation is lacking in hepatocellular carcinomas (HCCs). Employing a unique multi-omics approach comprising a neoepitope identification pipeline, we assessed exome-derived mutations naturally presented as HLA class I ligands in HCCs. METHODS: In-depth multi-omics analyses included whole exome and transcriptome sequencing to define individual patient-specific search spaces of neoepitope candidates. Evidence for the natural presentation of mutated HLA ligands was investigated through an in silico pipeline integrating proteome and HLA ligandome profiling data. RESULTS: The approach was successfully validated in a state-of-the-art dataset from malignant melanoma, and despite multi-omics evidence for somatic mutations, mutated naturally presented HLA ligands remained elusive in HCCs. An analysis of extensive cancer datasets confirmed fundamental differences of tumor mutational burden in HCC and malignant melanoma, challenging the notion that exome-derived mutations contribute relevantly to the expectable neoepitope pool in malignancies with only few mutations. CONCLUSIONS: This study suggests that exome-derived mutated HLA ligands appear to be rarely presented in HCCs, inter alia resulting from a low mutational burden as compared to other malignancies such as malignant melanoma. Our results therefore demand widening the target scope for personalized immunotherapy beyond this limited range of mutated neoepitopes, particularly for malignancies with similar or lower mutational burden.


Assuntos
Antígenos de Neoplasias/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Transcriptoma , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/metabolismo , Carcinoma Hepatocelular/imunologia , Exoma , Feminino , Genômica/métodos , Humanos , Neoplasias Hepáticas/imunologia , Masculino , Pessoa de Meia-Idade , Taxa de Mutação
12.
Fertil Steril ; 111(1): 186-193, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30611405

RESUMO

OBJECTIVE: To report our experience with the screening and selection of potential recipients and living donors of our uterus transplantation (UTx) program. DESIGN: Part of an observational program. SETTING: University hospital. PATIENT(S): Patients with absolute uterine factor infertility (AUFI). INTERVENTION(S): Screening by e-mail and telephone, selection during surgical consultation, and preoperative investigations according to a multistep procedure for living donation. MAIN OUTCOME MEASURE(S): Age, cause of AUFI, exclusion reasons, and preoperative workup. RESULT(S): A total of 212 potential recipients expressed interest in participation. Among the 46 potential recipients and 49 directed donors were 4 potential recipients, each with 2 directed donors. Mean (range) age of potential recipients was 29.6 (19-41) years. Of the potential recipients, 39 (84.8%) had congenital AUFI and 7 (17.3%) had acquired AUFI. Ultimately, 15 potential recipients with 16 directed donors were selected for participation, with 1 potential recipient having 2 directed donors. Mean age of included potential recipients was 28.9 (22-35) years, and mean donor age was 51.3 (37-62) years. Fourteen potential recipients (93.3%) had congenital AUFI, and one potential recipient (6.7%) had undergone hysterectomy for obstetric complications. CONCLUSION(S): The number of potential candidates for UTx is not inconsiderable, with congenital AUFI being the leading cause of AUFI in our cohort. However, our findings highlight that large numbers of AUFI patients need to be screened, considering our exclusion rates were >50%, owing to ABO incompatibility, unavailability of a directed donor, and self-withdrawal. Moreover, meticulous preoperative screening, including in-depth psychological assessment, is mandatory to maximize living donor safety and UTx success.


Assuntos
Infertilidade Feminina/cirurgia , Doadores Vivos , Transplantados , Útero/transplante , Adulto , Feminino , Humanos , Infertilidade Feminina/diagnóstico , Doadores Vivos/psicologia , Pessoa de Meia-Idade , Transplante de Órgãos/métodos , Transplante de Órgãos/psicologia , Seleção de Pacientes , Transplantados/psicologia
13.
Ann Transplant ; 24: 30-35, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30643112

RESUMO

BACKGROUND Therapy of peritoneal metastases (PM) in solid organ transplant recipients is challenging. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) might constitute a new therapeutic opportunity for these patients. MATERIAL AND METHODS This was a single-center, retrospective analysis of prospective registry data (NCT03210298) in a tertiary care center between 1.7.2016 and 31.12.2017. Intraperitoneal administration of oxaliplatin 92 mg/m² body surface or a combination of cisplatin 7.5 mg/m² and doxorubicin 1.5 mg/m², repeated every 6 weeks. Objective tumor response was documented via histology (Peritoneal Regression Grading Score, PRGS), adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) 4.0. RESULTS Out of 71 consecutive patients treated with PIPAC, 2 patients (2.8%) were solid organ transplant recipients. The first patient had metachronous PM of colonic cancer origin after liver transplantation. The second patient had synchronous PM of pancreatic cancer origin after combined kidney-pancreas transplantation. After repeated combined systemic and PIPAC chemotherapy, objective histological response was documented in both patients. No adverse events >CTCAE 2 were recorded. There was no measurable liver or renal toxicity. PIPAC procedures could be repeated (2, resp. 3 cycles) without any interruption of immunosuppressive medication or impairment of respective plasmatic drug levels. The first patient passed away 7 months after the first PIPAC, the second patient was still alive after 8 months. CONCLUSIONS PIPAC can induce objective regression of PM in solid organ transplant recipients without inducing organ toxicity or interfering with immunosuppressive therapy.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Administração por Inalação , Antineoplásicos/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Neoplasias do Colo/patologia , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/patologia , Neoplasias Peritoneais/secundário , Estudos Retrospectivos
14.
Urology ; 123: 273-279, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30312669

RESUMO

OBJECTIVE: To develop a novel device for cryobiopsy of the upper urinary tract (UUT) and to evaluate its feasibility in a standardized preclinical setting. MATERIALS AND METHODS: Flexible cryoprobes (diameter 0.9 mm; cooling agent CO2) were developed and used to extract biopsies in porcine UUTs. Cryosamples obtained by ureterorenoscopy were systematically compared with biopsy specimens obtained with standard of care devices in terms of physical characteristics (deflection angle and irrigation flow rates) and histologic criteria (assessability). RESULTS: Irrigation flow rates were significantly higher with introduced BIGopsy (2.8 ± 0.1) compared with standard forceps (0.94 ± 0.06; P < .001) and cryoprobe (1.1 ± 0.1; P < .001). Angular deflection was significantly reduced by the inserted cryoprobe (130.7° ± 1.2° vs 166.9° ± 1.1° [BIGopsy] or 161.4° ± 1.9° [standard forceps]; both P < .001). Significantly larger UUT tissue samples were obtained by the cryoprobe (mean specimen area 7.5 ± 2.5 vs 4.6 ± 2.5 mm² [BIGopsy] or 1.4 ± 1.4 mm² [standard forceps]; both P < .001). No crush artifacts were observed in cryosamples. Superior histologic assessability scores were achieved in samples obtained by the cryoprobe (mean 2.8 ± 0.8) and BIGopsy (2.3 ± 1.9) when compared with standard forceps (0.4 ± 0.9; P < .001). CONCLUSION: Cryobiopsy in the UUT is feasible and represents a viable new option to improve the diagnostic accuracy of histopathologic evaluation. Larger and more representative tissue samples can be obtained using a cryoprobe and artifacts may be avoided. Further optimization of the probe will reduce possible restrictions of ureterorenoscopy handling when the device is inserted.


Assuntos
Rim/patologia , Ureter/patologia , Animais , Biópsia/instrumentação , Biópsia/métodos , Criocirurgia , Desenho de Equipamento , Estudos de Viabilidade , Suínos
15.
Acad Radiol ; 26(2): 247-256, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29731419

RESUMO

RATIONALE AND OBJECTIVES: This study aimed to test the hypothesis that ultrastructural wall abnormalities of lymphoma vessels correlate with perfusion computed tomography (PCT) kinetics. MATERIALS AND METHODS: Our local institutional review board approved this prospective study. Between February 2013 and June 2016, we included 23 consecutive subjects with newly diagnosed lymphoma, who were referred for computed tomography-guided biopsy (6 women, 17 men; mean age, 60.61 ± 12.43 years; range, 28-74 years) and additionally agreed to undergo PCT of the target lymphoma tissues. PCT was obtained for 40 seconds using 80 kV, 120 mAs, 64 × 0.6-mm collimation, 6.9-cm z-axis coverage, and 26 volume measurements. Mean and maximum k-trans (mL/100 mL/min), blood flow (BF; mL/100 mL/min) and blood volume (BV) were quantified using the deconvolution and the maximum slope + Patlak calculation models. Immunohistochemical staining was performed for microvessel density quantification (vessels/m2), and electron microscopy was used to determine the presence or absence of tight junctions, endothelial fenestration, basement membrane, and pericytes, and to measure extracellular matrix thickness. RESULTS: Extracellular matrix thickness as well as the presence or absence of tight junctions, basal lamina, and pericytes did not correlate with computed tomography perfusion parameters. Endothelial fenestrations correlated significantly with mean BFdeconvolution (P = .047, r = 0.418) and additionally was significantly associated with higher mean BVdeconvolution (P < .005). Mean k-transPatlak correlated strongly with mean k-transdeconvolution (r = 0.939, P = .001), and both correlated with mean BFdeconvolution (P = .001, r = 0.748), max BFdeconvolution (P = .028, r = 0.564), mean BVdeconvolution (P = .001, r = 0.752), and max BVdeconvolution (P = .001, r = 0.771). Microvessel density correlated with max k-transdeconvolution (r = 0.564, P = .023). Vascular endothelial growth factor receptor-3 expression (receptor specific for lymphatics) correlated significantly with max k-transPatlak (P = .041, r = 0.686) and mean BFdeconvolution (P = .038, r = 0.695). CONCLUSION: k-Trans values of PCT do not correlate with ultrastructural microvessel features, whereas endothelial fenestrations correlate with increased intra-tumoral BVs.


Assuntos
Linfoma , Microvasos/ultraestrutura , Imagem de Perfusão/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Correlação de Dados , Feminino , Humanos , Imuno-Histoquímica , Linfoma/metabolismo , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias/irrigação sanguínea , Estudos Prospectivos
16.
Gastroenterol Res Pract ; 2018: 2743985, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30473706

RESUMO

Introduction: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug delivery system with superior pharmacological properties for treating peritoneal metastasis (PM). Safety and efficacy results of PIPAC with cisplatin/doxorubicin or oxaliplatin from a registry cohort are presented. Methods: IRB-approved registry study. Retrospective analysis. No predefined inclusion criteria, individual therapeutic recommendation by the interdisciplinary tumor board. Safety assessment with CTCAE 4.0. Histological assessment of tumor response by an independent pathologist using the 4-tied peritoneal regression grading system (PRGS). Mean PRGS and ascites volume were assessed at each PIPAC. Results: A total of 142 PIPAC procedures were scheduled in 71 consecutive patients with PM from gastric (n = 26), colorectal (n = 17), hepatobiliary/pancreatic (n = 9), ovarian (n = 6), appendiceal (n = 5) origin, pseudomyxoma peritonei (n = 4), and other tumors (n = 3). Mean age was 58 ± 13 years. Patients were heavily pretreated. Mean PCI was 19 ± 13. Laparoscopic nonaccess rate was 11/142 procedures (7.7%). Mean number of PIPAC/patient was 2. All patients were eligible for safety analysis. There was no procedure-related mortality. There were 2.8% intraoperative and 4.9% postoperative complications. 39 patients underwent more than one PIPAC and were eligible for efficacy analysis, and PRGS could be assessed in 36 of them. In 24 patients (67%), PRGS improved or remained unchanged at PIPAC#2, reflecting tumor regression or stable disease. Ascites was present in 24 patients and diminished significantly under therapy. Median survival was 11.8 months (95% CI: 7.45-16.2 months) from PIPAC#1. Conclusion: PIPAC is feasible, safe, and well-tolerated and can induce histological regression in a significant proportion of pretreated PM patients. This trial is registered with NCT03210298.

17.
Int Med Case Rep J ; 11: 161-165, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30100765

RESUMO

Purpose: Nevi of the conjunctiva are usually benign pigmented tumorous lesions located in the bulbar conjunctiva. In most conjunctival nevus cases, the patient wants the lesion to be removed for cosmetic reasons, but excisional biopsies are best for lesions suspicious for malignancy. This case report illustrates the intraoperative surgical management, histological findings, and the course of healing in a conjunctival nevus patient. Case report: A 26-year-old man was referred to our eye hospital with a large bulbar conjunctival nevus of the right eye. Upon examination, there was a large pigmented lesion with numerous small cysts present on the superior bulbar conjunctiva. The conjunctival tumor was resected, and an amniotic membrane transplantation was performed for the bulbar conjunctival reconstruction. The histopathological diagnosis suggested a conjunctival nevus. After the resection, a reduction in the inflammation and healing of the conjunctival lesion could be seen. The epithelialization of the bulbar conjunctiva over the amniotic membrane was complete 4 weeks after the resection. At the 6-month follow-up, there was no sign of recurrence or any postoperative complications. Conclusion: A surgical excision combined with reconstruction via amniotic membrane transplantation is effective and economical for the treatment of large conjunctival lesions.

18.
BMC Med Genet ; 19(1): 144, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30111295

RESUMO

BACKGROUND: The PTEN-hamartoma-tumor-syndrome (PHTS) is caused by germline mutations in Phosphatase and Tensin homolog (PTEN) and predisposes to the development of several typical malignancies. Whereas PTEN mutations have been implicated in the occurrence of malignant mesotheliomas, the genetic landscape of verrucous carcinomas (VC) is largely uncharted. Both VC and malignant peritoneal mesotheliomas (MPM) are exceedingly rare and a potential link between these malignancies and PHTS has never been reported. CASE PRESENTATION: We here describe the clinical course of a PHTS patient who, in addition to a typical thyroid carcinoma at the age of 36 years, developed a highly-differentiated oral VC and an epithelioid MPM six years later. The patient with a history of occupational asbestos exposure underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for MPM. The clinical diagnosis of PHTS was consequently corroborated by a germline PTEN deletion. Sequencing of tumor tissue revealed a second hit in PTEN in the thyroid carcinoma and VC, confirmed by a PTEN loss and activation of the PI3K/AKT pathway in immunohistochemistry. Furthermore, additional somatic mutations in the thyroid carcinoma as well as in the VC were detected, whereas the genetics of MPM remained unrevealing. DISCUSSION AND CONCLUSIONS: We here report the very unusual clinical course of a patient with rare tumors that have a germline mutation first hit in PTEN in common. Since this patient was exposed to asbestos and current evidence suggests molecular mechanisms that might render PHTS patients particularly susceptible to mesothelioma, we strongly recommend PHTS patients to avoid even minimal exposure.


Assuntos
Carcinoma Verrucoso/genética , Mutação em Linhagem Germinativa/genética , Neoplasias Pulmonares/genética , Mesotelioma/genética , Neoplasias Bucais/genética , PTEN Fosfo-Hidrolase/genética , Humanos , Doenças Raras
19.
J Surg Oncol ; 118(1): 167-176, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29953623

RESUMO

BACKGROUND AND OBJECTIVES: The role of local surgical procedures in patients with metastatic soft tissue sarcoma is still undefined. Few retrospective studies have reported survival benefits for patients with pulmonary metastases after complete surgical resection. Treatment decisions are therefore mainly based on personal experiences rather than on reproducible knowledge. METHOD: A total of 237 patients with metastatic sarcoma, treated between 1982 and 2015 at the University Hospital Tuebingen, Germany, were eligible for inclusion. Out of the 237 screened patients, 102 patients underwent at least one metastasectomy. Overall survival was defined as the primary endpoint in this study. For association of non-linear relationship to the endpoint, significant prognostic factors were included into a recursive partitioning model. A subgroup analysis for long-term survivors was also performed. RESULTS: The median overall survival was 64 months. The 3-, 5-, 10-, and 20-years overall survival rates were 70.7%, 50.3%, 24.7%, and 14.8%, respectively. The number of resections and the progression-free intervals were independent prognostic factors in three statistical models. CONCLUSION: Repeated resections of metastases from different localizations are a strong predictor for prolonged survival. We suggest that the progression-free interval after metastasectomy should be considered as a predictive factor for benefit from further surgery.


Assuntos
Sarcoma/cirurgia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Metastasectomia , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Sarcoma/patologia , Adulto Jovem
20.
Pathol Res Pract ; 214(8): 1136-1141, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29935812

RESUMO

BACKGROUND: Microvessel density is an indicator of tumor-driven neoangiogenesis. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have distinct vascular patterns, which are also reflected in their imaging characteristics. Since a significant proportion of HCC are treated without biopsy confirmation, it is essential to discriminate HCC and ICC radiologically. The aim of our study was therefore to compare microvessel density and expression of VEGFR-2 in HCC and ICC, since these data may ultimately help us to better understand their imaging characteristics. Whereas CD31 documents vessel density, VEGFR-2 expression is an indicator of tumor-related neoangiogenesis. METHODS: CD31 and VEGFR-2 expressing microvessels were quantified on tissue microarrays of 95 resection specimens of HCC and 47 cases of ICC. Microvessel density was evaluated by counting immuno-reactive vascular structures both within the tumor and adjacent liver control tissue, respectively. Further 16 cases of ICC were immunostained for CD31 and VEGFR-2 on full sections. RESULTS: The frequency of VEGFR-2 (46.2/HPF; range 0-150) and CD31 (61.2/HPF; range 2.6-140) expressing vascular structures was significantly increased in HCC compared to adjacent liver parenchyma (VEGFR-2 33.3/HPF, range 0-87, CD31 21.4/HPF, range 0-78, both p < 0,001). ICC revealed significantly less VEGFR2-positive microvessels (15.4/HPF; range 2-77) compared to matched control tissue (42.3/HPF; range 4.6-109), whereas microvessel density with CD31 was comparable between ICC and adjacent liver (32.1/HPF; range 5.3-78 versus 28.0/HPF; range 5.3-57; p = 0.89). In ICC, the tumor-to-normal microvessel density ratio was 0.38 for VEGFR-2 and 1.24 for CD31. These ratios were nearly identical (VEGFR: 0.38; CD31: 0,97) for the 16 cases of ICC studied on whole sections, confirming the validity of the TMA approach. In contrast, ratios of VEGFR-2 and CD31 in HCC vs. adjacent liver were significantly higher (VEGFR: 2.23; CD31: 6.57). Expression of VEGFR-2 by tumor cells was not observed in any of the cases. CONCLUSIONS: HCC and ICC differ significantly in their microvessel density, confirming the hypovascular nature of ICC as compared to the hypervascularity of HCC. Of note, inverse tumor-to-normal ratios of microvascular VEGFR-2 expression between the two neoplasms indicate distinct features of neoangiogenesis. Whether these differences can be exploited for improvements in imaging of hepatic tumors and may play a role for anti-angiogenic treatment strategies requires further studies.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Neoplasias Hepáticas/patologia , Neovascularização Patológica/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Criança , Feminino , Humanos , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Molécula-1 de Adesão Celular Endotelial a Plaquetas/biossíntese , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/análise , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Adulto Jovem
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