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1.
J Urol ; : 101097JU000000000000061503, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31886713
2.
Front Physiol ; 10: 1155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31607938

RESUMO

Background: Gonadotoxic treatment of malignant diseases as well as some non-malignant conditions such as cryptorchidism in young boys may result in infertility and failure to father children later in life. As a fertility preserving strategy, several centers collect testicular biopsies to cryopreserve spermatogonial stem cells (SSCs) world-wide. One of the most promising therapeutic strategies is to transplant SSCs back into the seminiferous tubules to initiate endogenous spermatogenesis. However, to obtain sufficient numbers of SSC to warrant transplantation, in vitro propagation of cells is needed together with proper validation of their stem cell identity. Materials and Methods: A minute amount of testicular biopsies (between 5 mg and 10 mg) were processed by mechanical and enzymatic digestion. SSCs were enriched by differential plating method in StemPro-34 medium supplemented with several growth factors. SSC-like cell clusters (SSCLCs) were passaged five times. SSCLCs were identified by immunohistochemical and immunofluorescence staining, using protein expression patterns in testis biopsies as reference. Quantitative polymerase chain reaction analysis of SSC markers LIN-28 homolog A (LIN28A), G antigen 1 (GAGE1), promyelocytic leukemia zinc finger protein (PLZF), integrin alpha 6 (ITGA6), ubiquitin carboxy-terminal hydrolase L1 (UCHL1) and integrin beta 1 (ITGB1) were also used to validate the SSC-like cell identity. Results: Proliferation of SSCLCs was achieved. The presence of SSCs in SSCLCs was confirmed by positive immunostaining of LIN28, UCHL1 and quantitative polymerase chain reaction for LIN28A, UCHL1, PLZF, ITGA6, and ITGB1, respectively. Conclusion: This study has demonstrated that SSCs from infant boys possess the capacity for in vitro proliferation and advance a fertility preservation strategy for pre-pubertal boys who may otherwise lose their fertility.

3.
J Urol ; : 101097JU0000000000000615, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642739

RESUMO

PURPOSE: One of the concerns regarding cryptorchidism is the risk of impaired fertility. Current guidelines recommend orchidopexy for cryptorchidism between 6 to 12 months to optimize the fertility outcome. The aim of this study was to evaluate the fertility potential of boys with non-syndromic cryptorchidism who underwent orchidopexy within the recommended age in order to clarify the need for eventual supplemental treatment modalities. MATERIALS AND METHODS: A retrospective evaluation of mini-puberty hormones (follicle stimulating hormone, luteinizing hormone, and inhibin B) and testicular biopsies from boys with cryptorchidism who underwent early orchidopexy within the first year, between 2010 and 2019, was performed. Based on histological examination, the germ cell number and the type A dark (Ad) spermatogonia number per seminiferous tubule cross-section (G/T and AdS/T, respectively) were analyzed in relation to normal values. RESULTS: 25% (83/333) of the boys with non-syndromic cryptorchidism (21% bilateral cryptorchidism) had reduced G/T. 21% of the boys (70/333) had low serum inhibin B. Of these boys having low serum inhibin B, 46% (32/70) boys had decreased G/T and 33% (23/70) boys decreased AdS/T (<0.01). Totally, 23% (75/333) of the boys had no Ad spermatogonia present. CONCLUSIONS: Despite early and successful orchidopexy 20-25% of boys with cryptorchidism may risk later infertility based on hormonal and histological data. Blood test and testicular biopsies are mandatory to identify boys with a high risk of infertility where additional treatment modalities and follow-up may be needed.

4.
Hematol Oncol ; 37(4): 375-382, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31408531

RESUMO

In large B-cell lymphoma (LBCL), MYC translocation and MYC/BCL2 or MYC/BCL6 double hit (DH) are associated with poor prognosis, and there is an unmet need for novel treatment targets in this patient group. Treatments targeting the PD-L1/PD-1 pathway are still poorly elucidated in LBCL. PD-L1 expression might predict response to treatment targeting the PD-L1/PD-1 pathway. We therefore investigated the relationship between PD-L1 protein and mRNA expression levels and MYC and DH translocation in LBCL. We detected MYC, BCL2, and BCL6 translocation by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 had DH and 81 without MYC translocation. PD-L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD-L1 mRNA expression by next-generation RNA sequencing (NGS) in another 77 patients. Twenty-four patients overlapped, ie, were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences. PD-L1 protein expression level was significantly lower in patients with MYC (n = 42, median = 3.3%, interquartile range [IQR] 0.0-10.8) or DH translocations (n = 31, median = 3.3%, IQR 0.0-10.0) compared with patients with no MYC (n = 35, median = 16.7%, IQR 3.3-30.0) or no DH translocations (n = 46, 13.3%, IQR 2.5-30.0), P = .004 and P ≤ .001, respectively. PD-L1 mRNA expression was also significantly lower in patients with MYC or DH translocations, P = .001 and P = .006, respectively. Higher PD-L1 protein and mRNA expression levels were associated with non-germinal centre (GC) type compared with germinal centre B-cell (GCB)-type diffuse LBCL (DLBCL), P = .004 and P = .002, respectively. In conclusion, we report an association between low PD-L1 expression and MYC and DH translocation in patients with LBCL. Our findings may indicate that patients with MYC or DH translocation may benefit less from treatment with PD-L1/PD-1-inhibitors compared with patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.


Assuntos
Antígeno B7-H1/biossíntese , Regulação Neoplásica da Expressão Gênica , Genes myc , Linfoma Difuso de Grandes Células B/metabolismo , Proteínas de Neoplasias/biossíntese , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Translocação Genética , Adulto , Idoso , Subpopulações de Linfócitos B/metabolismo , Subpopulações de Linfócitos B/patologia , Antígeno B7-H1/genética , Feminino , Perfilação da Expressão Gênica , Genes bcl-2 , Centro Germinativo/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas Proto-Oncogênicas c-bcl-6/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Estudos Retrospectivos
5.
J Pediatr Surg ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31327540

RESUMO

BACKGROUND/AIM: Cryptorchidism, or undescended testis (UDT) occurs in 1%-4% of newborn males and leads to a risk of infertility and testicular malignancy. Recent research suggests that infertility and malignancy in UDT may be caused by abnormal development of the neonatal germ cells, or gonocytes, which normally transform into spermatogonial stem cells (SSC) or undergo apoptosis during minipuberty at 2-6 months in humans (2-6 days in mice). We aimed to identify the current knowledge on how UDT is linked to infertility and malignancy. METHODS: Here we review the literature from 1995 to the present to assess the possible causes of infertility and malignancy in UDT, from both human studies and animal models. RESULTS: Both the morphological steps and many of the genes involved in germ cell development are now characterized, but the factors involved in gonocyte transformation and apoptosis in both normal and cryptorchid testes are not fully identified. During minipuberty there is evidence for the hypothalamic-pituitary axis stimulating gonocyte transformation, but without known direct control by LH and androgen, although FSH may have a role. An arrested gonocyte maybe the origin of later malignancy at least in syndromic cryptorchid testes in humans, which is consistent with the recent finding that gonocytes are normally absent in a rodent model of congenital cryptorchidism, where malignancy has not been reported. CONCLUSION: The results of this review strengthen the view that malignancy and infertility in men with previous UDT may be caused by abnormalities in germ cell development during minipuberty. TYPE OF STUDY: Systematic review (secondary, filtered) LEVEL OF EVIDENCE: Level I.

6.
Asian J Androl ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31274480

RESUMO

Cryptorchidism is associated with infertility in adulthood. Early orchiopexy is suggested to reduce the risk. Information is lacking on the potential link between infant germ cell maturation and the risk of future infertility. The objective of the study was to evaluate age-related germ cell development in cryptorchidism. Immunostaining for markers of germ cell development (octamer-binding transcription factor 3/4 [OCT3/4], placental alkaline phosphatase [PLAP], KIT proto-oncogene [C-KIT], podoplanin [D2-40], Lin-28 homolog A [LIN28], and G antigen 7 [GAGE-7]) was performed in testicular biopsies from 40 cryptorchid boys aged 4-35 months. Germ cell numbers and distributions were evaluated in cross sections of seminiferous tubules, with and without immunostaining. OCT3/4, D2-40, and LIN28 were generally expressed in the early stages of germ cell development, as shown by positive expression in germ cells in the central region of seminiferous tubules. In contrast, PLAP and GAGE-7 were expressed in both central and peripheral parts of the tubules in the early stages of development and expressed mainly in a peripheral position with advancing age. Germ cell maturation was delayed in this study population as compared with that observed in our previous study on germ cell markers in a healthy population. The number of GAGE-7-positive germ cells per tubular cross section obtained by immunostaining was significantly higher than that obtained by standard hematoxylin and eosin staining. Double immunostaining revealed heterogeneity in germ cell development in cryptorchid testes. These results shed light on the pathophysiology of germ cell development in boys with cryptorchidism.

7.
BMJ Case Rep ; 12(4)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30948396

RESUMO

We report a case of a 79-year-old woman with urinary incontinence who presented at a urogynaecology appointment. Her medical history included rheumatoid arthritis (RA) treated with methotrexate (MXT) for 22 years. A polypoidal lesion was protruding from the meatus urethrae. The histoimmunocytology confirmed a primary superficial spreading malignant melanoma. The tumour was extensively excised, but 8 months later, due to a lymphatic nodal swelling, a positron emission tomography/CT was performed showing a process suspicious of malignant melanoma and multiple distant metastasis. The subsequent treatment was palliative and 1 year later, the patient died. The aetiology of malignant melanomas in the urethra is poorly understood. There is consistent evidence that RA is associated with a number of cancers, but it remains controversial whether this risk is increased with MXT. This case emphasises the importance of gynaecological examination even in patients with only weak symptoms from the pelvic region, especially in patients undergoing immunosuppressive treatment.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Melanoma/induzido quimicamente , Metotrexato/efeitos adversos , Neoplasias Uretrais/induzido quimicamente , Idoso , Feminino , Humanos , Uretra/efeitos dos fármacos
8.
BMJ Open ; 9(3): e023566, 2019 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-30833314

RESUMO

INTRODUCTION: Richter's transformation (RT) refers to the development of an aggressive lymphoma in patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma. Studies have shown that 2-10% of patients with CLL develop RT including diffuse large B-cell lymphoma (DLBCL) and less common Hodgkin lymphoma (HL). This study aims to assess the risk factors for RT of CLL in a nationwide cohort. Additionally, we want to examine prognostic factors in patients with RT. These findings may guide management of treated as well as untreated patients with CLL in the risk of RT. METHODS: Clinical data for patients diagnosed with CLL between 2008 and 2016 will be retrieved from the Danish National CLL registry (DCLLR). Using the Danish unique person identification number, clinical data will be merged with histologically verified DLBCL and/or HL diagnoses retrieved from the Danish National Pathology Data Bank. This will ensure complete follow-up for all patients.The DCLLR includes data from more than 4000 patients with CLL ensuring a median follow-up of 3 years. With the reported incidences (2-10%) of RT, we expect to identify 80-200 CLL patients with RT enabling analysis of overall survival following RT. From time of CLL diagnosis, estimates of cumulative incidence of RT will be calculated using the Aalen-Johansen estimator. From time of RT diagnosis, survival analysis will be performed by Kaplan-Meier method. Cox proportional hazards models will be used for multivariable survival analysis. ETHICS AND DISSEMINATION: Approvals for data collection and analysis was obtained from the Danish Data Protection Agency and the Danish Health Authorities. All data will be managed confidentially according to guidelines and legislation. The dissemination will include a publication of scientific papers and/or presentations of the study findings at international conferences.

9.
Sex Dev ; 13(2): 74-82, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30889614

RESUMO

Postnatal maturation of Sertoli cells is crucial for male fertility. The aim of this study was to assess the association between the Sertoli cell number per tubule cross-section (SC/T), the serum level of the Sertoli cell-produced inhibin B, and the A-dark spermatogonia number per tubule (Ad/T) in cryptorchid boys. Forty infant cryptorchid boys aged 4-35 months (median: 13 months) were included in the study. During orchiopexy, blood samples for serum inhibin B, luteinizing hormone (LH), and follicle stimulating hormone (FSH) and testicular biopsies were obtained. Histological sections were evaluated by quantitative immunohistochemical and immunofluorescence analysis including VASA and SOX9 (Sertoli cell marker) in order to measure the tubular germ cell number (G/T), Ad/T, and SC/T. The SC/T correlated negatively with age (p < 0.0002) and positively with G/T, Ad/T, inhibin B, FSH, and LH (all p < 0.01). Inhibin B correlated with LH (p < 0.0001), but not with FSH (p = 0.2077). The SC/T:G/T ratio positively correlated with age (p < 0.0001). Boys with Ad spermatogonia at surgery had a higher number of Sertoli cells compared to boys without Ad spermatogonia. In conclusion, a correlation between Sertoli cell number and inhibin B was proven, indicating that inhibin B possibly reflects the function of Sertoli cells in infant cryptorchid boys.

10.
Eur J Haematol ; 102(5): 395-406, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30737994

RESUMO

OBJECTIVE: In patients with large B-cell lymphoma (LBCL) according to WHO, the prognostic significance of MYC translocation is still not sufficiently clarified. We therefore aimed to investigate whether prognostication could be improved in patients with MYC translocation positive LBCL by additional stratification according to MYC and BCL2 protein expression levels or MYC translocation partner gene as well as concurrent BCL2 and/or BCL6 translocation (DH). METHODS: From an unselected consecutive cohort of >600 patients with LBCL investigated with fluorescent in situ hybridization (FISH), 64 patients were diagnosed with MYC translocation positive LBCL and included in the study. They were further investigated for supplemental translocations with FISH and MYC and BCL2 protein expression with immunohistochemistry (IHC). RESULTS: MYC expression >75% was associated with both reduced progression-free survival (PFS) and overall survival (OS) (PFS: HR 6.8 (95% CI 1.5-31), P = 0.004. OS: HR 4.3 (95% CI 0.9-21), P = 0.05). Immunoglobulin (IG) MYC translocation partner gene was related to high MYC protein expression (P = 0.047) but was not prognostic for PFS (P = 0.8) or OS (P = 0.6). DH did not confer a worse outcome compared to MYC single hit (SH). These findings were confirmed in a comparable, independent validation cohort of 28 patients with MYC translocation positive LBCL. All patients included in the survival analyses were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOEP (R-CHOP + etoposide). CONCLUSION: These findings suggest that in patients with LBCL stratification by MYC protein expression level significantly improves the prognostic impact associated with MYC translocation.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Linfoma de Células B/genética , Linfoma de Células B/mortalidade , Proteínas Proto-Oncogênicas c-myc/genética , Translocação Genética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfoma de Células B/diagnóstico , Linfoma de Células B/terapia , Masculino , Estadiamento de Neoplasias , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-myc/metabolismo
11.
Oncol Lett ; 17(2): 1477-1482, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30675202

RESUMO

The aim of the present study was to describe a rare case of orbital precursor B-lymphoblastic lymphoma (B-LBL) in an adult. A 56-year-old male in complete remission of a gastric precursor B-LBL was referred to our orbital clinic due to rapid development of left-sided painless periorbital swelling, diplopia, and proptosis. Complete ophthalmoplegia was observed. Notably, magnetic resonance imaging showed swelling of the medial and inferior rectus muscles in the left orbit and biopsies were performed. Following histological diagnosis of precursor B-LBL, the patient was treated with radiotherapy (2Gy × 20) and chemotherapy according to the NOPHO ALL 2008 protocol. The disease progressed and the patient succumbed after 5 months. Histomorphologically, a lymphoblastic infiltrate was observed within the skeletal muscle tissue. The tumor cells were small and immature, and stained strongly for cluster of differentiating (CD)10, CD79a, paired box 5 and B cell lymphoma-2. The Ki-67 proliferative index was 90%. Multiplex ligation-dependent probe amplification and array comparative genomic hybridization detected whole chromosomal gain of X and 12, and both hemizygous and homozygous deletion on 9p comprising cyclin dependent kinase inhibitor 2A/B. Furthermore, array comparative genomic hybridization detected copy number imbalances consisting of focal or smaller deletions on chromosomes 1, 9, 10, 11 and 20. The final diagnosis was precursor B-LBL relapse in the extraocular muscles. Orbital precursor B-LBL is extremely rare in adults, and the diagnosis may be challenging to make. It is recommended to obtain material for cytogenetic and molecular analyses.

12.
J Pediatr Surg ; 54(4): 809-814, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29706444

RESUMO

PURPOSE: A meta-analysis including 11,900 cases showed that maternal gestational smoking was associated with increased risk of cryptorchidism. The aim of study was to investigate whether a hormone profile of cryptorchid boys and a supplementing histopathological evaluation of testicular biopsies could add detailed knowledge to the impact of maternal gestational smoking on pathogenesis of cryptorchidism. METHODS: 601 cryptorchid boys aged 4 months to 14 years old were included. Because normal hormones have a pronounced age dependency, we compared results from boys whose mothers had smoked heavily (>10 cigarettes/day) during pregnancy with age matched cryptorchid controls of nonsmoking mothers (1:6). We studied: birthweight, germ-cell number/tubular cross section, frequency of germ cells positive for placental-like alkaline phosphatase (PLAP), gonadotropins and inhibin-B. RESULTS: 501 boys were sons of nonsmokers, 72 boys of intermittent smokers and 28 boys of heavy smokers. 39%, 44% and 61% respectively had bilateral cryptorchidism. Compared to age-matched cryptorchid controls of nonsmoking mothers, sons of heavy smokers had lower birthweight (p = 0.006), germ-cell number/tubular cross section (p = 0.009), frequency of germ cells positive for PLAP (p = 0.037) and inhibin-B (p = 0.042). CONCLUSIONS: All findings could be associated with placental dysfunction with altered human chorionic gonadotropin production well described in women smoking during pregnancy. TYPE OF STUDY: Prognosis study (prospective cohort study with >80% follow-up). LEVEL OF EVIDENCE: Level 1.


Assuntos
Criptorquidismo/patologia , Inibinas/sangue , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fumar/efeitos adversos , Espermatozoides/patologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Criptorquidismo/sangue , Feminino , Gonadotropinas Hipofisárias/sangue , Humanos , Lactente , Masculino , Gravidez , Estudos Prospectivos , Testículo/patologia
13.
Acta Vet Scand ; 60(1): 79, 2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30522494

RESUMO

BACKGROUND: Eyelid tumours are frequently found in dogs, most of these being benign. In case of an ulcerating eyelid tumour, malignancy must be considered. We report a unique case of a low-grade peripheral T-cell lymphoma in the eyelid of a 9-year-old English Setter. CASE PRESENTATION: A 9-year-old Setter presented with a 6-month history of an eyelid ulcer. A malignant eyelid neoplasm was suspected, and the lesion was surgically excised. No other treatment was applied, and 19 months after excision the dog was still well. Histopathology revealed a diffuse lymphocytic infiltrate in the eyelid skin. Ulceration of the epithelium was seen, and the underlying tumour was composed of round and poorly demarcated pleomorphic tumour cells. The cytoplasm was pale and the nuclei heterogeneous. Numerous mitoses were present. The tumour cells stained strongly for CD3. The final diagnosis was a peripheral T-cell lymphoma not otherwise specified (NOS). CONCLUSIONS: This is the first described case of a solitary T-cell lymphoma NOS in the haired eyelid skin in a dog. Lymphoma should be considered in case of a persistent eyelid ulcer and a biopsy should be performed. T-cell lymphoma is generally an aggressive disease; however, indolent cases are well known, and as this case shows, complete excision of a solitary T-cell lymphoma can be curable. Canine cutaneous epitheliotropic T-cell lymphoma is an important differential diagnosis, which must be recognized as the prognosis is very poor and systemic treatment is mandatory. The sub-classification of canine lymphoma is not complete, and further studies are needed to identify lymphoma subgroups and provide treatment guidelines.


Assuntos
Doenças do Cão/diagnóstico , Neoplasias Palpebrais/veterinária , Pálpebras/patologia , Linfoma Cutâneo de Células T/veterinária , Neoplasias Cutâneas/veterinária , Animais , Doenças do Cão/patologia , Doenças do Cão/cirurgia , Cães , Neoplasias Palpebrais/diagnóstico , Neoplasias Palpebrais/patologia , Neoplasias Palpebrais/cirurgia , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/cirurgia , Masculino , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia
14.
Clin Case Rep ; 6(11): 2246-2251, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30455930

RESUMO

B-cell lymphoblastic lymphoma is an aggressive malignant disease. Necropsy and microscopical examination revealed widespread disease with a high proliferation index. This is the first reported case of B-cell lymphoblastic lymphoma presenting in the ocular region and only the second reported lymphoma of the nictitating membrane.

15.
Artigo em Inglês | MEDLINE | ID: mdl-29922233

RESUMO

Introduction: Orchiopexy for congenital cryptorchid testes is recommended between ½ and 1 year of age to preserve testicular germ cell maturation. Early operation is not enough to preserve fertility in 22 and 36% of cases. Aim of this study was to set up a protocol for optional adjuvant hormonal therapy after orchiopexy and thereafter cryopreservation of testicular biopsies from infants with bilateral cryptorchidism and high infertility risk. Materials and methods: We included 17 boys with bilateral cryptorchidism, normal FSH, and impaired germ cell number per tubular transverse section (G/T) in testicular biopsies at orchiopexy, 7 months to 3½ years old. Postoperatively, optional adjuvant LHRH (kryptocur®) 0.2 mg/0.1 mL 2× every second day in 16 weeks were offered. Ten boys were applicable for age matching according to parent's choice of treatment regime and G/T. Five of them had kryptocur®, and five were controls. Repeat bilateral testicular biopsy evaluation and cryopreservation were offered to all boys 12 months after primary orchiopexy. For cryopreservation, tissue pieces were incubated with a cryoprotectant with a slow program freezing. Results: Two out of five kryptorcur®-treated boys normalized both the average G/T and the number of adult dark spermatogonia (Ad-S). Another kryptocur®-treated boy with initial low G/T and no Ad-S increased the G/T and achieved normal number of Ad-S at time of cryopreservation. In the control group, two patients reached only normal lower range regarding the G/T and the number of Ad-S. None of boys with less than average 0.2 G/T improved significantly, whether they were kryptocur®-treated or not. Conclusion: Based on literature and the present results, we recommend adjuvant LHRH treatment to boys with cryptorchidism and insufficient genuine gonadotropin stimulation at time of surgery, as these patients have high infertility risk. Cryopreservation should be an option in case of treatment failure of adjuvant LHRH. However, to avoid repeat surgery with biopsy, some parents may choose biopsy for cryopreservation at time of the initial bilateral orchiopexy, well informed that the procedure may only be truly indicated in 22 and 36% of the cases.

16.
Artigo em Inglês | MEDLINE | ID: mdl-29910774

RESUMO

Background: Positive immunohistochemical expression of testicular cancer markers is often reported beyond 12 months of age in cryptorchid testes, which is assumed to indicate delayed maturation of the fetal germ cells, or neoplastic changes. These findings allowed for questions as to the extent of positive reaction in normal testes. The aim of the study was to clarify the expression of these markers in a normal material up to 2 years. Methods: Testicular material from 69 boys aged 1-690 days, who died of causes with no association of testicular pathology. Histology sections were incubated with primary antibodies including anti-placental-like alkaline phosphatase (PLAP), anti-C-Kit, anti-D2-40, and anti-Oct3/4. The mean germ cell number per tubular transverse section (G/T) was calculated based on the G/T of both testes of every boy. Results: The mean G/T declined through the 690 days. PLAP appeared stably expressed throughout the ages studied. The likelihood of a positive reaction for C-Kit waned with increasing age within the study period. Positive staining for D2-40 and Oct3/4 was demonstrated up to 6 and 9 months respectively. Conclusion: Up to 1 or 2 years of age, normal infantile testes contain germ cells positive for the immunohistochemical markers commonly utilized to aid in the detection of testicular cancer. This finding supports the concept of germ cells undergoing a continuous maturational process in a heterogeneous fashion, and that this process is not complete by 2 years of age.

17.
Clin Case Rep ; 6(3): 490-493, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29531724

RESUMO

Tumor lysis syndrome is rare in diffuse large cell lymphoma, but it is important to recognize the risk in patients with massive tumor burden and reduced kidney function. Very intense vigilance can be necessary despite adequate prophylactic measures and certain drugs may exacerbate electrolyte derangements.

18.
Melanoma Res ; 28(4): 319-325, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29595571

RESUMO

Ultrasound-guided fine-needle aspiration cytology (US-FNAC) is used to evaluate the involvement of lymph nodes in various malignant diseases. Its value in detecting sentinel lymph node (SN) metastasis preoperatively in melanoma patients is controversial and is the subject of this study. In this prospective validation study, 91 consecutive patients with melanoma clinical stage I (n=64) and II (n=27) were examined with US-FNAC before SN biopsy from 2012 to 2014 at a tertiary center. All patients underwent lymphoscintigraphy before the US-FNAC. Lymph nodes that showed any of the Berlin morphologic criteria on ultrasonography were examined using FNAC. The median Breslow thickness of the melanomas was 1.22 mm (range: 0.47-11.5 mm). Twenty-two percent of the patients had metastases in their SNs, 90% of which were smaller than 2 mm in largest diameter. The percentages of metastases with a size more than 1 mm were 50 and 29%, respectively, in the true-positive and false-negative US groups. The sensitivity, specificity, positive predictive value, and negative predictive value for overall US examination were 30, 81, 24, and 83%, respectively. None of the FNACs contained conclusive malignant cells. The specificity of the FNAC was 76%. Our results show that US-FNAC was not a useful diagnostic tool in our setting as it did not add significantly to the staging and management of patients with mainly thin cutaneous melanomas, perhaps because of the often small size of the SN metastases. It may be useful in the early diagnosis of lymph node metastases in a subgroup of melanoma patients with larger metastases.


Assuntos
Biópsia por Agulha Fina/métodos , Melanoma/diagnóstico , Linfonodo Sentinela/cirurgia , Neoplasias Cutâneas/diagnóstico , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Melanoma/diagnóstico por imagem , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Estudos de Validação como Assunto , Adulto Jovem
19.
Malar J ; 17(1): 34, 2018 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-29338760

RESUMO

BACKGROUND: Iron deficiency is the most widespread nutrient deficiency and an important cause of developmental impairment in children. However, some studies have indicated that iron deficiency can also protect against malaria, which is a leading cause of childhood morbidity and mortality in large parts of the world. This has rendered interventions against iron deficiency in malaria-endemic areas controversial. METHODS: The effect of nutritional iron deficiency on the clinical outcome of Plasmodium chabaudi AS infection in A/J mice and the impact of intravenous iron supplementation with ferric carboxymaltose were studied before and after parasite infection. Plasma levels of the iron status markers hepcidin and fibroblast growth factor 23 were measured in animals surviving and succumbing to malaria, and accompanying tissue pathology in the liver and the spleen was assessed. RESULTS: Nutritional iron deficiency was associated with increased mortality from P. chabaudi malaria. This increased mortality could be partially offset by carefully timed, short-duration adjunctive iron supplementation. Moribund animals were characterized by low levels of hepcidin and high levels of fibroblast growth factor 23. All infected mice had extramedullary splenic haematopoiesis, and iron-supplemented mice had visually detectable intracellular iron stores. CONCLUSIONS: Blood transfusions are the only currently available means to correct severe anaemia in children with malaria. The potential of carefully timed, short-duration adjunctive iron supplementation as a safe alternative should be considered.


Assuntos
Suplementos Nutricionais/análise , Compostos Férricos/administração & dosagem , Ferro/deficiência , Malária/tratamento farmacológico , Desnutrição/tratamento farmacológico , Maltose/análogos & derivados , Plasmodium chabaudi/fisiologia , Animais , Malária/mortalidade , Masculino , Maltose/administração & dosagem , Camundongos , Plasmodium chabaudi/efeitos dos fármacos , Organismos Livres de Patógenos Específicos
20.
Eur J Pediatr Surg ; 28(6): 469-476, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28838001

RESUMO

PURPOSE: Cryptorchidism is a risk factor for testicular malignancy and surgical treatment lowers this risk. This study aimed to investigate the germ cell behavior in prepubertal cryptorchid testes using immunohistochemical markers for germ cell malignancy to understand how early orchiopexy may possibly prevent cancer developing. MATERIALS AND METHODS: Histology sections from 1,521 consecutive testicular biopsies from 1,134 boys aged 1 month to 16.5 years operated for cryptorchidism were incubated with antibodies including antiplacental-like alkaline phosphatase (PLAP), anti-Oct3/4, anti-C-kit, and anti-D2-40. RESULTS: Oct3/4 and D2-40-positive germ cells are found throughout the first 2 years of life, with declining frequency thereafter. After 2 years, they should have disappeared and may indicate neoplasia. PLAP-positive cells were seen in 57 to 82% and C-kit-positive cells in 5 to 21% of cryptorchid testes between 4 and 13 years. Not until puberty did PLAP and C-kit-positive undifferentiated spermatogonial stem cells vanish. Only 0.3% of the present material had obvious prepubertal intratubular germ cell neoplasia (ITGCN) and they all had syndromic cryptorchidism. An additional three boys (0.3%) older than 2 years had weak Oct3/4 expression in undescended testes, but all cases were D2-40 negative. CONCLUSION: Prepubertal ITGCN was rare and mostly seen in syndromic cryptorchidism. In nonsyndromic cryptorchidism PLAP-positive undifferentiated spermatogonial stem cells persisted in a significant proportion of nontreated undescended testes and they will be especially sensitive to long-lasting abnormally high temperature that may be the single most important cause facilitating the accumulation of mutations during cell replication and the development of ITGCN to be prevented by orchiopexy.


Assuntos
Criptorquidismo/cirurgia , Células Germinativas/crescimento & desenvolvimento , Neoplasias Embrionárias de Células Germinativas/prevenção & controle , Orquidopexia , Neoplasias Testiculares/prevenção & controle , Adolescente , Biomarcadores Tumorais/metabolismo , Criança , Pré-Escolar , Criptorquidismo/fisiopatologia , Células Germinativas/metabolismo , Células Germinativas/patologia , Humanos , Imuno-Histoquímica , Lactente , Masculino , Neoplasias Embrionárias de Células Germinativas/etiologia , Neoplasias Embrionárias de Células Germinativas/metabolismo , Fatores de Risco , Neoplasias Testiculares/etiologia , Neoplasias Testiculares/metabolismo
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