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1.
Biomed Res Int ; 2022: 1915458, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35707387

RESUMO

Background: It was gradually accepted that endoscopic fragment biopsy (EFB) diagnosis cannot accurately guarantee the absence of higher-grade neoplasms within the lesion of the digestive tract. There are no well-established predictors for histopathologically upgrade discrepancies between EFB diagnosing colorectal low-grade intraepithelial neoplasia (LGIN) and endoscopic resection (ER) specimens. Methods: A total of 918 colorectal LGINs was histopathologically diagnosed by EFB, including 162 cases with upgrade discrepancy and 756 concordant cases. We compared clinicopathological data of EFB and ER specimens between these two groups. Multivariate analysis was performed to identify predictors for this upgrade histopathology. Results: The predominant upgrade discrepancy of LGINs diagnosed by EFB was upgrades to high-grade dysplasia (114/918, 12.4%), followed by upgrades to intramucosal carcinoma (33/918, 3.6%), submucosal adenocarcinoma (10/918, 1.1%), and advanced adenocarcinoma (5/918, 0.5%). NSAID history (OR 4.83; 95% CI, 2.27-10.27; p < 0.001), insufficient EFB number (OR 2.99; 95% CI, 1.91-4.68; p < 0.001), maximum diameter ≥ 1.0 cm (OR 6.18; 95% CI, 1.32-28.99; p = 0.021), lobulated shape (OR 2.68; 95% CI, 1.65-4.36; p < 0.001), erythema (OR 2.42; 95% CI, 1.50-3.91; p < 0.001), erosion (OR 7.12; 95% CI, 3.91-12.94; p < 0.001), surface unevenness (OR 2.31; 95% CI, 1.33-4.01; p = 0.003), and distal location of the target adenoma (OR 3.29; 95% CI, 1.68-6.41; p < 0.001) were associated with the histologically upgrade discrepancies. Conclusion: NSAID history, insufficient EFB number, adenoma size and location, and abnormal macroscopic patterns are potential predictors for upgrade histopathology of LGINs diagnosed by EFBs. The standardization of EFB number and advanced imaging techniques could minimize the risk of neglecting the potential of this upgrade histopathology.


Assuntos
Adenocarcinoma , Adenoma , Carcinoma in Situ , Neoplasias Colorretais , Neoplasias Gástricas , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenoma/diagnóstico , Adenoma/patologia , Adenoma/cirurgia , Anti-Inflamatórios não Esteroides , Biópsia/métodos , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Gastroscopia/métodos , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Instrumentos Cirúrgicos
2.
Arch Soc Esp Oftalmol (Engl Ed) ; 97(6): 337-339, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35676026

RESUMO

An atypical Advancing Wavelike Epitheliopathy case, consecutive to topical treatment for a 360º Conjunctival Intraepithelial Neoplasia, is presented. Mitomycin (0.2 mg/mL) and interferon (1 MUI/mL) drops were used. An atypical presentation, with migrating limbal focus, non clearly delimited in its hourly site through its evolution. Treated with flurometholone drops plus artificial tears, working to complete resolution.


Assuntos
Carcinoma in Situ , Neoplasias da Túnica Conjuntiva , Doenças da Córnea , Administração Tópica , Carcinoma in Situ/complicações , Carcinoma in Situ/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Doenças da Córnea/tratamento farmacológico , Humanos , Mitomicina/uso terapêutico
3.
J Low Genit Tract Dis ; 26(3): 229-244, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35763611

RESUMO

ABSTRACT: The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).


Assuntos
Carcinoma in Situ , Melanoma , Doença de Paget Extramamária , Lesões Intraepiteliais Escamosas , Neoplasias Vulvares , Carcinoma in Situ/patologia , Colposcopia , Feminino , Humanos , Imiquimode/uso terapêutico , Gravidez , Neoplasias Cutâneas , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgia
4.
BMJ Open ; 12(6): e061740, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35667715

RESUMO

INTRODUCTION: High-risk human papilloma virus (HPV)-associated cervical cancer is the fourth most common cancer in women worldwide. Current treatments of high-grade squamous intraepithelial lesion (HSIL) of the cervix are based on invasive surgical interventions, compromising cervical competence and functionality. APRICITY is a multicentre, prospective, double-blind, randomised controlled phase 3 study further evaluating the efficacy and safety of Cevira, an integrated drug-delivery and light-delivery device for hexaminolevulinate photodynamic therapy, which shows promise as a novel, non-invasive outpatient therapy for women with HSIL. METHODS AND ANALYSIS: Patients with biopsy-confirmed HSIL histology are invited to participate in the study planned to be conducted at 47 sites in China and 25 sites in Ukraine, Russia and the European Union. The aim is to include at least 384 patients, which will be randomised to either Cevira or placebo group (2:1). All patients will be assessed 3 months after first treatment and a second treatment will be administered in patients who are HPV positive or have at least low-grade squamous intraepithelial lesion. Primary endpoint is the proportion of the responders 6 months after first treatment. Secondary efficacy and safety endpoints will be assessed at 6 months, and data for secondary performance endpoints of the Cevira device will be collected at 3 months and 6 months, in case second treatment was administered. All patients in the Cevira group will be enrolled in an open, long-term extension study for 6 months to collect additional efficacy and safety data (study extension endpoints). ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the Peking Union Medical College Hospital and Hannover Medical University, Germany. Findings will be disseminated through peer review publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04484415; clinicaltrials.gov.


Assuntos
Carcinoma in Situ , Infecções por Papillomavirus , Fotoquimioterapia , Lesões Intraepiteliais Escamosas , Neoplasias do Colo do Útero , Ácido Aminolevulínico/análogos & derivados , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Estudos Multicêntricos como Assunto , Infecções por Papillomavirus/complicações , Fotoquimioterapia/métodos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias do Colo do Útero/patologia
5.
World J Surg Oncol ; 20(1): 190, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35681223

RESUMO

BACKGROUND: Hepatopancreaticoduodenectomy (HPD) is one of the most complex procedures, and it is very rarely reported. Laparoscopic HPD (LHPD) is even rarer. To date, there are only 3 reports of LHPD for locally advanced gallbladder cancer (GBC) or extrahepatic cholangiocarcinoma (ECC). This is the first report of LHPD for synchronous GBC and ECC. CASE PRESENTATION: A 75-year-old female patient complained of jaundice for 2 weeks without fever or abdominal pain. She was diagnosed with synchronous GBC and ECC. After a comprehensive preparation, she underwent a laparoscopic pancreaticoduodenectomy and resection of hepatic segments of IVb and V, and her digestive tract reconstruction followed Child's methods. She was discharged on the 12th day postoperatively without pancreatic leakage, biliary leakage, or liver failure. CONCLUSIONS: LHPD is safe and feasible for selected cases of GBCs or ECCs.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma in Situ , Colangiocarcinoma , Neoplasias da Vesícula Biliar , Laparoscopia , Idoso , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma in Situ/patologia , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Feminino , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Hepatectomia/métodos , Humanos , Laparoscopia/métodos
6.
Surg Pathol Clin ; 15(2): 389-405, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35715167

RESUMO

A number of changes have been introduced into the 5th Edition of the World Health Organization (WHO) Classification of squamous and glandular neoplasms of the vulva and vagina. This review highlights the major shifts in tumor classification, new entities that have been introduced, recommendations for p16 immunohistochemical testing, biomarker use, molecular findings and practical points for pathologists which will affect clinical care. It also touches upon several issues that still remain answered in these rare but undeniably important women's cancers.


Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Neoplasias Vulvares , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Vagina/patologia , Vulva/patologia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/patologia
7.
Pathol Res Pract ; 234: 153937, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35561522

RESUMO

BACKGROUND: The differential diagnosis between flat urothelial lesions [reactive urothelial atypia (RUA), atypia of unknown significance (AUS), urothelial dysplasia (UD) and carcinoma in situ (CIS)] has relevant prognostic and therapeutic implications. This crucial distinction could be very challenging but it is currently performed on hematoxylin and eosin (H&E) slides, with a great amount of partially discordant and/or not conclusive findings of the potential adjunctive role of immunohistochemistry. Herein, we tested double staining (DS) for p53/CK20 to verify if p53(+) cells, CK20(+) cells and double-positive cells (DPCs) are differentially expressed among these lesions and if p53/CK20 could be a useful tool in this diagnostic setting. METHODS: We tested 50, 9, 36 and 29 consecutive and retrospectively enrolled cases of RUA, AUS, UD and CIS, respectively. p53(+) cells, CK20(+) cells and DPCs were evaluated and compared by adopting the appropriate statistic tests (Mann-Whitney U and Kruskal-Wallis tests). RESULTS: We found that p53(+) cells (p = 0.000), CK20(+) cells (p = 0.000) and DPCs (p = 0.000) showed statistically significant differences among the different flat urothelial lesions. Besides, when dichotomized, both CIS and RUA are easily differentiable from their histological mimickers adopting all these markers; by contrast, AUS and UD did not reach statistically significant differences able to differentiate them from each other [p53(+) cells, p = 0.123; CK20(+) cells, p = 0.567; DPCs, p = 0.409], except if compared to CIS [AUS VS CIS: p53(+) cells, p = 0.013; CK20(+) cells, p = 0.000; DPCs, p = 0.000; UD vs CIS: p53(+) cells, p = 0.000; CK20(+) cells, p = 0.000; DPCs, p = 0.000]. CONCLUSIONS: p53(+) cells, CK20(+) cells and DPCs are differently expressed by flat urothelial lesions and p53/CK20 could be a time- and money-saving tool for the appropriate management of these lesions if applied to a routine scenario.


Assuntos
Carcinoma in Situ , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , Corantes , Humanos , Queratina-20/análise , Queratina-20/metabolismo , Estudos Retrospectivos , Coloração e Rotulagem , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
8.
World J Surg Oncol ; 20(1): 155, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35549728

RESUMO

BACKGROUND: C20orf54 has been identified as an esophageal squamous cell carcinoma (ESCC) susceptibility gene in previous genome-wide association studies. Here, we attempted to clarify the expression level of C20orf54 in ESCC, non-tumoral esophageal tissues, and esophageal squamous intraepithelial neoplasia (ESIN). METHODS: We assessed C20orf54 expression in 146 ESCC, 108 non-tumoral esophageal tissues, and 148 ESIN using immunohistochemistry on tissue microarrays. We also evaluated the possible correlations of C20orf54 expression with clinicopathological characteristics. The survival rates were analyzed using the Kaplan-Meier method and log-rank test. RESULTS: C20orf54 expression was significantly lower in ESCC, high-grade ESIN, and low-grade ESIN than in the non-tumoral esophageal tissues. The level observed for ESCC was also significantly lower than that in low-grade ESIN and high-grade ESIN, whereas no difference was observed between high-grade ESIN and low-grade ESIN. Furthermore, the C20orf54 defective expression correlated significantly with differentiation, lymph node metastasis, and invasion depth. The overall survival time was inversely associated with lymph node metastasis, an advanced TNM stage (III + IV), and deeper invasion. CONCLUSIONS: This study provides the first evidence of C20orf54 defective expression in ESCC and precancerous lesions, demonstrating a potential role in tumor progression and metastasis. C20orf54 could be used as a potential biomarker for the early detection of ESCC.


Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Estudo de Associação Genômica Ampla , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Prognóstico
9.
Rev Assoc Med Bras (1992) ; 68(5): 664-669, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35584493

RESUMO

OBJECTIVE: This study aimed to examine the prognostic effect of the tumor-stroma ratio, which has been shown to have prognostic value in various cancers, in patients with gallbladder cancer who have undergone curative resection. METHODS: The records of gallbladder cancer patients who underwent surgical treatment in our clinic between December 2005 and March 2021 were analyzed retrospectively. The hematoxylin and eosin-stained sections representing the tumors were evaluated under light microscopy to determine tumor-stroma ratio, and based on the results, <50% was defined as the stroma-rich and ≥50% as the stroma-poor groups. RESULTS: A total of 28 patients, including 20 females and 8 males, with a mean age of 64.6 years, were included in this study. Stroma-poor and stroma-rich tumors were detected in 15 and 13 patients, respectively. There was no statistically significant relationship identified between tumor-stroma ratio and advanced age, gender, serum levels of carbohydrate antigen 19-9 and carcinoembryonic antigen, incidental or nonincidental diagnosis, jaundice, adjacent organ or structure resection, tumor location, grades 1-2 or 3, T1/T2 or T3/T4, N0 or N1/N2, M stage, American Joint Committee on Cancer stage, lymphovascular invasion, and perineural invasion. The stroma-poor and stroma-rich groups had a 5-year survival rate of 30% and 19.2% and a median overall survival of 25.7 and 15.1 months, respectively, with no statistically significant difference between the groups (p=0.526). CONCLUSIONS: A low tumor-stroma ratio tended to be a poor prognostic factor in gallbladder cancer, although not to a statistically significant degree. This can be considered one of the preliminary studies, as further studies involving larger groups are needed.


Assuntos
Carcinoma in Situ , Neoplasias da Vesícula Biliar , Carcinoma in Situ/patologia , Feminino , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
10.
J Med Case Rep ; 16(1): 196, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35590335

RESUMO

BACKGROUND: The spread of cervical squamous cell carcinoma to the inner surface of the uterus with replacement of the endometrium is rare. Continuity of the lesion must be demonstrated to confirm superficial spread and rule out concomitant endometrial cancer. CASE PRESENTATION: We present the case of a 66-year-old white woman with superficial spreading squamous cell carcinoma of the cervix that involved the endometrium. Her relevant past history included conization of the cervix to treat cervical intraepithelial neoplasia III with positive margins. She subsequently had three negative cervical vaginal cytology results, each with a positive high-risk human papillomavirus test. Transvaginal ultrasound showed occupation of the entire uterine cavity by dense material consistent with pyometra in addition to myometrial thinning due to tension and cervical dilation. The patient presented with greenish vaginal discharge of 3 months' duration. The cervix was not visible during speculum examination. Access for endometrial sampling was not possible, raising suspicion of post-conization cervical stenosis. The patient was treated with laparoscopic hysterectomy with double adnexectomy. Histologic examination showed superficial squamous cell carcinoma invading the cervix to a depth of 2.8 mm; superficial spreading squamous cell carcinoma in situ was also observed in the lower uterine segment and endometrium. The patient was free of symptoms 12 months after surgery. CONCLUSIONS: Squamous cell carcinoma of the cervix with superficial spread to the endometrium is not included in the 2020 (fifth edition) World Health Organization Classification of Female Genital Tract Tumors or the 2018 International Federation of Gynecology and Obstetrics cervical cancer staging system. More clinical cases are needed to identify other prognostic factors and inform clinical practice guidelines on the management of this disease.


Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Idoso , Carcinoma in Situ/diagnóstico por imagem , Carcinoma in Situ/cirurgia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/cirurgia , Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Endométrio/diagnóstico por imagem , Endométrio/patologia , Feminino , Humanos , Histerectomia , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/cirurgia
11.
Clin Transl Med ; 12(5): e874, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35608199

RESUMO

BACKGROUND: High-grade intraepithelial neoplasia (HIN) is the precursor of oesophageal squamous cell carcinoma. The molecular and functional properties of HIN are determined by intrinsic origin cells and the extrinsic microenvironment. Yet, these factors are poorly understood. METHODS: We performed single-cell RNA sequencing of cells from HINs and adjacent tissues from the human oesophagus. We analysed the heterogeneity of basal layer cells and confirmed it using immunostaining. Aneuploid cells in HIN were studied using primary cell culture combined with karyotype analysis. We reconstructed the lineage relationship between tumour and normal populations based on transcriptome similarity. Integration analysis was applied to our epithelial data and published invasive cancer data, and results were confirmed by immunostaining and 3D organoid functional experiments. We also analysed the tumour microenvironment of HIN. RESULTS: The basal layer contained two cell populations: KRT15high STMN1low and KRT15high STMN1high cells, which were located mainly in the interpapillary and papillary zones, respectively. The KRT15high STMN1low population more closely resembled stem cells and transcriptome similarity revealed that HIN probably originated from these slow-cycling KRT15high STMN1low cells. 3D Organoid experiments and RNA-sequencing showed that basal-cell features and the differentiation ability of the normal epithelium were largely retained in HIN, but may change dramatically in tumour invasion stage. Moreover, the tumour microenvironment of HIN was characterised by both inflammation and immunosuppression. CONCLUSIONS: Our study provides a comprehensive single-cell transcriptome landscape of human oesophageal HIN. Our findings on the origin cells and unique microenvironment of HIN will allow for the development of strategies to block tumour progression and even prevent cancer initiation.


Assuntos
Carcinoma in Situ , Neoplasias Esofágicas , Epitélio/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Humanos , Transcriptoma/genética , Microambiente Tumoral/genética
12.
Clin. transl. oncol. (Print) ; 24(5): 902-908, mayo 2022.
Artigo em Inglês | IBECS | ID: ibc-203792

RESUMO

PurposeTo explore the underlying risk factors and to prevent misdiagnosis of cervical intraepithelial neoplasia (CIN) coexisted with vaginal intraepithelial neoplasia (VaIN).MethodsClinical data of patients pathologically diagnosed with CIN were collected from January 2017 to December 2018. A total of 446 cases were analyzed, including 406 cases of single lesions (‘CIN single’ group) and 40 cases complicated with VAIN (‘VAIN concurrent’ group).ResultsThe median age of the VAIN concurrent group was 53 years (46.25–59 years), and the median age of the CIN single group was 44 years (36–50 years). Regarding menopausal status, there were 28 cases (70.0%) in the VAIN concurrent group and 89 cases (21.9%) in the CIN single group (P < 0.005). The median load of high-risk human papillomavirus (Hr-HPV) in the VAIN concurrent and CIN single group was 923.4 relative light units/cutoff (RLU/CO) (145–2172.2 RLU/CO) and 229.155 RLU/CO (18.615–638.1275 RLU/CO), respectively (P = 0.037). The results revealed that the menopausal status was an independent risk factor for VAIN occurrence in CIN patients. The risk of VAIN in menopausal patients was higher than that in non-menopausal CIN patients (OR = 8.311, 95% CI 4.062–17.005). Age and HPV load were also related to the concurrence of VAIN and CIN.ConclusionExaminations regarding vaginal screening are of great importance in the diagnosis of perimenopausal and postmenopausal CIN patients, especially patients with Hr-HPV load. Colposcopy and tissue biopsy should also be performed, when necessary, to avoid misdiagnosis and the appearance of vaginal lesions.This is a preview of subscription content, access via your


Assuntos
Humanos , Carcinoma in Situ/epidemiologia , Neoplasia Intraepitelial Cervical/patologia , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/patologia , Gravidez , Neoplasias Vaginais/complicações
13.
Cells ; 11(10)2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35626644

RESUMO

Skeletal muscle wasting critically impairs the survival and quality of life in patients with pancreatic ductal adenocarcinoma (PDAC). To identify the local factors initiating muscle wasting, we studied inflammation, fiber cross-sectional area (CSA), composition, amino acid metabolism and capillarization, as well as the integrity of neuromuscular junctions (NMJ, pre-/postsynaptic co-staining) and mitochondria (electron microscopy) in the hindlimb muscle of LSL-KrasG12D/+; LSL-TrP53R172H/+; Pdx1-Cre mice with intraepithelial-neoplasia (PanIN) 1-3 and PDAC, compared to wild-type mice (WT). Significant decreases in fiber CSA occurred with PDAC but not with PanIN 1-3, compared to WT: These were found in the gastrocnemius (type 2x: -20.0%) and soleus (type 2a: -21.0%, type 1: -14.2%) muscle with accentuation in the male soleus (type 2a: -24.8%, type 1: -17.4%) and female gastrocnemius muscle (-29.6%). Significantly higher densities of endomysial CD68+ and cyclooxygenase-2+ (COX2+) cells were detected in mice with PDAC, compared to WT mice. Surprisingly, CD68+ and COX2+ cell densities were also higher in mice with PanIN 1-3 in both muscles. Significant positive correlations existed between muscular and hepatic CD68+ or COX2+ cell densities. Moreover, in the gastrocnemius muscle, suppressor-of-cytokine-3 (SOCS3) expressions was upregulated >2.7-fold with PanIN 1A-3 and PDAC. The intracellular pools of proteinogenic amino acids and glutathione significantly increased with PanIN 1A-3 compared to WT. Capillarization, NMJ, and mitochondrial ultrastructure remained unchanged with PanIN or PDAC. In conclusion, the onset of fiber atrophy coincides with the manifestation of PDAC and high-grade local (and hepatic) inflammatory infiltration without compromised microcirculation, innervation or mitochondria. Surprisingly, muscular and hepatic inflammation, SOCS3 upregulation and (proteolytic) increases in free amino acids and glutathione were already detectable in mice with precancerous PanINs. Studies of initial local triggers and defense mechanisms regarding cachexia are warranted for targeted anti-inflammatory prevention.


Assuntos
Carcinoma in Situ , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Aminoácidos , Animais , Caquexia , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Ciclo-Oxigenase 2/metabolismo , Progressão da Doença , Feminino , Glutationa/metabolismo , Humanos , Inflamação , Masculino , Camundongos , Músculo Esquelético/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Qualidade de Vida , Proteína Supressora de Tumor p53
14.
Arkh Patol ; 84(3): 32-39, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35639841

RESUMO

Bladder cancer is one of the most common onco-urological diseases, ranked second in frequency among all tumors of the urinary system after prostate cancer. At the time of detection of the primary tumor, approximately 75% of patients have no invasion into the muscularis layer (non-muscle-invasive carcinoma), with tumor growth limited to the basal membrane (stage Ta) or submucosal base (stage T1). Removal of the tumor in a «unified block¼ (laser en-bloc resection or L-ERBT), unlike routine transurethral resection, allows to obtain qualitative biopsy material for precise pathomorphological staging of the tumor process. In order to accurately stratify a patient into one or another risk group, verification of the following morphological parameters is required: degree of tumor differentiation and its malignancy, depth of invasion, foci of carcinoma in situ at resection margins, presence or absence of lymphovascular invasion. Identification of tumor variant histology is also recommended. Information on presence or absence of detrusor elements in the specimen is necessary in the morphological report, as this parameter is considered as a criterion of radically performed tumor removal. According to ICCR recommendations (International Collaboration on cancer reporting), it is recommended to use subclassification of T1 stage using all possible criteria: volume and/or depth of invasion (assessed in mm), and/or width of invasion «spot¼ (assessed in mm), and/or involvement of anatomical structure - muscularis mucosae. Full morphological examination of the material obtained during the primary resection of the tumor is an important step in the diagnosis and treatment of bladder cancer, as it allows to stratify the patient into one or another risk group and, accordingly, allows to develop a personalized postoperative management.


Assuntos
Carcinoma in Situ , Neoplasias da Bexiga Urinária , Biópsia , Humanos , Lasers , Masculino , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/cirurgia
15.
Nat Commun ; 13(1): 2665, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562376

RESUMO

Pancreatic intraepithelial neoplasia (PanIN) is a precursor of pancreatic ductal adenocarcinoma (PDAC), which commonly occurs in the general populations with aging. Although most PanIN lesions (PanINs) harbor oncogenic KRAS mutations that initiate pancreatic tumorigenesis; PanINs rarely progress to PDAC. Critical factors that promote this progression, especially targetable ones, remain poorly defined. We show that peroxisome proliferator-activated receptor-delta (PPARδ), a lipid nuclear receptor, is upregulated in PanINs in humans and mice. Furthermore, PPARδ ligand activation by a high-fat diet or GW501516 (a highly selective, synthetic PPARδ ligand) in mutant KRASG12D (KRASmu) pancreatic epithelial cells strongly accelerates PanIN progression to PDAC. This PPARδ activation induces KRASmu pancreatic epithelial cells to secrete CCL2, which recruits immunosuppressive macrophages and myeloid-derived suppressor cells into pancreas via the CCL2/CCR2 axis to orchestrate an immunosuppressive tumor microenvironment and subsequently drive PanIN progression to PDAC. Our data identify PPARδ signaling as a potential molecular target to prevent PDAC development in subjects harboring PanINs.


Assuntos
Carcinoma in Situ , Carcinoma Ductal Pancreático , PPAR delta , Neoplasias Pancreáticas , Animais , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/patologia , Humanos , Ligantes , Camundongos , PPAR delta/genética , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Microambiente Tumoral/genética
16.
Pathol Res Pract ; 234: 153919, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35512522

RESUMO

Numerous studies show that some biomarkers are aberrantly expressed in endometrial endometrioid adenocarcinoma (EMAC) and endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (EAH/EIN) compared to endometrial benign lesions. Because of low sensitivity and/or specificity, the utility of these markers to distinguish EMAC and EAH/EIN from benign endometrial lesions is limited. YTH domain family 2 (YTHDF2) is a functional N6-methyladenosine (m6A)-specific reader protein that mainly regulates mRNA stability. Aberrant YTHDF2 expression has been reported in many cancers and plays important functions in tumorigenesis and cancer progression. However, its expression in endometrial benign and malignant lesions has not been investigated. We evaluated YTHDF2 mRNA and protein expression in EMAC and normal endometrium using the UALCAN database and validated the bioinformatic results in EMAC cells using qRT-PCR, Western blot, and immunohistochemical (IHC) staining. We found that YTHDF2 was weakly expressed in normal endometrium, benign endometrial lesions, endometrial hyperplasia without atypia, and adenomyosis. In contrast, YTHDF2 was upregulated in EAH/EIN and EMAC. These results indicate that YTHDF2 immunostaining may be a useful tool to distinguish EAH/EIN from EHWA. Finally, YTHDF2 expression can accurately assess the depth of myometrial invasion (DMI) in EMAC when EMAC coexists with adenomyosis.


Assuntos
Adenomiose , Carcinoma in Situ , Carcinoma Endometrioide , Hiperplasia Endometrial , Neoplasias do Endométrio , Lesões Pré-Cancerosas , Proteínas de Ligação a RNA , Adenomiose/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma in Situ/patologia , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/metabolismo , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Hiperplasia/patologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
17.
Breast Cancer Res Treat ; 194(2): 257-264, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35595928

RESUMO

PURPOSE: The Breast Cancer Surveillance Consortium (BCSC) model predicts risk of invasive breast cancer risk based on age, race, family history, breast density, and history of benign breast disease, including lobular carcinoma in situ (LCIS). However, validation studies for this model included few women with LCIS. We sought to evaluate the accuracy of the BCSC model among this cohort. METHODS: Women with LCIS diagnosed between 1983 and 2017 were identified from a prospectively maintained database. The BCSC score was calculated; those with prior breast cancer, unknown breast density, age < 35 years or > 74 years, or with history of chemoprevention use were excluded. The Kaplan-Meier method was used to estimate incidence rates. Time-dependent receiver operating characteristic (ROC) analysis was used to analyze the discriminative capacity of the model. RESULTS: 1302 women with LCIS were included. At a median follow-up of 7 years, 152 women (12%) developed invasive cancer (6 with bilateral disease). Cumulative incidences of invasive breast cancer were 7.1% (95% CI 5.6-8.7) and 13.3% (95% CI 10.9-15.6), respectively, and the median BCSC risk scores were 4.9 and 10.4, respectively, at 5 and 10 years. The median 10-year BCSC score was significantly lower than the 10-year Tyrer-Cuzick score (10.4 vs 20.8, p < 0.001). The ROC curve scores (AUC) for BCSC at 5 and 10 years were 0.59 (95% CI 0.52-0.66) and 0.58 (95% CI 0.52-0.64), respectively. CONCLUSION: The BCSC model has moderate accuracy in predicting invasive breast cancer risk among women with LCIS with fair discrimination for risk prediction between individuals.


Assuntos
Carcinoma de Mama in situ , Neoplasias da Mama , Carcinoma in Situ , Carcinoma Lobular , Adulto , Carcinoma de Mama in situ/diagnóstico , Densidade da Mama , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Lobular/patologia , Feminino , Seguimentos , Humanos
18.
Pathologica ; 114(2): 138-145, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35481564

RESUMO

Objective: To identify and compare significant or relevant prognostic factors in pre-operatively diagnosed, surgically resectable, gallbladder cancer and in incidentally detected gallbladder cancer cases. Material and methods: Gallbladder resections (October 2009-March 2016) were identified on the histopathology Winpath database. Cases with a final histological diagnosis of gallbladder cancer (GBC) were categorised into: Group A: clinically suspected operable GBC (n = 13). Group B: incidental GBC with staged liver bed resection (n = 5). Group C: incidental GBC without staged liver bed resection (n = 15). The clinicopathological features were analysed in each group separately. Results: The overall incidence of primary (GBC) was 0.66% and all the cases were adenocarcinomas, of which, 6 of 33 (18.2%) were grade 1 and 15 of 33 (45.4%) were grade 3. Male to female ratio is 1:2.3. Of the 33 patients with GBC 14 (42.4%) has died of disease at 18-month follow-up. 15 of 33 had perineural invasion and 10/21 (47.6%) cases showed lymph node matastasis. Six cases had positive surgical margin and 9/15 showed direct liver invasion. Higher stage disease (T3/T4) was seen in 10/14 cases. Conclusion: The prognosis of primary GBC is poor and best clinical outcomes can be achieved with early diagnosis followed by radical cholecystectomy and staged liver resection with negative margins.


Assuntos
Carcinoma in Situ , Neoplasias da Vesícula Biliar , Carcinoma in Situ/cirurgia , Colecistectomia , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Excisão de Linfonodo , Masculino , Margens de Excisão , Prognóstico , Reino Unido/epidemiologia
19.
Int J Gynecol Pathol ; 41(3): 298-306, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35444146

RESUMO

Accurate diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) is challenging, in part due to the sometimes subtle nature of its atypia. Many dVIN lesions demonstrate aberrant p53 staining; however, staining patterns overlap between dVIN and benign/reactive entities. We evaluate a p53/CK17 dual stain in an initial cohort of dVIN (n=30), benign vulvar skin (n=5), lichen sclerosus (LS, n=10), lichen simplex chronicus (LSC, n=10), and pseudoepitheliomatous hyperplasia (PEH, n=10). In the initial cohort, aberrant p53 staining was seen only in dVIN (50%, 15/30). Equivocal p53 staining patterns were seen in dVIN (37%, 11/30), LS (50%, 5/10), LSC (40%, 4/10), and PEH (40%, 4/10). All 30 dVIN cases were positive for CK17 (strong partial-thickness or full-thickness staining), but positive CK17 staining was also seen in LS (70%, 7/10), LSC (50%, 5/10), and PEH (100%, 10/10). In the initial cohort, the combination of aberrant p53 and positive CK17 was seen only for dVIN (50%, 15/30). Forty cases of LS with known follow-up (20 with progression to dVIN, 20 without) were stained to assess prognostic value. Three LS cases showed aberrant p53 staining with CK17 positivity; all progressed to dVIN. Equivocal p53 staining and CK17 positivity were seen in cases with and without progression. The p53/CK17 dual stain is more diagnostically useful than either stain alone. Negative/focal staining for CK17 argues against a diagnosis of dVIN, while aberrant p53 staining with CK17 positivity strongly supports the diagnosis.


Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Lesões Intraepiteliais Escamosas , Proteína Supressora de Tumor p53/metabolismo , Líquen Escleroso Vulvar , Neoplasias Vulvares , Biomarcadores Tumorais , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Corantes , Feminino , Humanos , Líquen Escleroso Vulvar/patologia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/patologia
20.
J Transl Med ; 20(1): 188, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484565

RESUMO

BACKGROUND: Recent studies exploring the roles of invasion-metastasis associated miRNAs in gallbladder cancer (GBC) are limited. In the study, we aimed to identify the invasion-metastasis associated miRNAs in GBC by bioinformatics and experimental validation. METHODS: MiRNAs of different expression were identified by comparing GBC tumor samples with different survival from Gene Expression Omnibus database. MiRTarBase was used for identifying the potential target genes of miRNAs. Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. And miRNA-gene and protein-protein interaction (PPI) network were constructed for hub genes evaluation. We further explored and compared miR-642a-3p and miR-145-5p expression in both The Cancer Genome Atlas database and our hospital data. Finally, quantitative real-time PCR, wound healing assay, and Transwell assay were conducted to validate the invasion-metastasis associated miRNAs in GBC. RESULTS: In GSE104165 database, 25 up-regulated and 97 down-regulated miRNAs were detected with significantly different expression in GBC tumor samples. Then, 477 potential target genes were identified from the 2 most up-regulated miRNAs (miR-4430 and miR-642a-3p) and 268 genes from the 2 most down-regulated miRNAs (miR-451a and miR-145-5p). After GO and KEGG analysis, mTOR and PI3K-Akt signaling pathways were found associated with the potential target genes. Based on PPI network, the top 10 highest degree hub nodes were selected for hub genes. Furthermore, the miRNA-hub gene network showed significant miR-642a-3p up-regulation and miR-145-5p down-regulation in both GBC tissues and cell lines. In the experimental validation, miR-145-5p up-regulation and miR-642a-3p down-regulation were confirmed to suppress GBC invasion and metastasis. CONCLUSIONS: MiR-642a-3p and miR-145-5p were identified as invasion-metastasis associated miRNAs via bioinformatics and experimental validation, and both up-regulation of miR-642a-3p and down-regulation of miR-145-5p would be served as novel treatment options for GBC in the future.


Assuntos
Carcinoma in Situ , Neoplasias da Vesícula Biliar , MicroRNAs , Biologia Computacional , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/patologia , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/genética
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