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The manuscript summarizes the consensus of the Austrian Society of Nephrology on the diagnosis and therapy of lupusnephritis, which is built on existing studies and literature. We discuss in detail the immunosuppressive treatment in proliferative forms of lupusnephritis (III and IV⯱ V) and in pure lupusnephritis V with nephrotic-range proteinuria. Furthermore, the supportive medication in lupusnephritis is summarized in the consensus. The figures were designed to provide the reader a guidance through the therapeutical approach in lupusnephritis for the daily practice.
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Nefrite Lúpica , Nefrologia , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Áustria , ConsensoRESUMO
We report a case of a patient double-seropositive for anti-glomerular basement membrane (anti-GBM) and anti-neutrophil cytoplasmic antibodies (ANCA) who reported retrosternal chest pain during a regular hemodialysis session associated with ST-segment depression in electrocardiogram and an increase of serum high-sensitivity troponin T. Urgent coronary angiography excluded obstructive coronary artery disease, suggesting the diagnosis of ischemia with non-obstructive coronary arteries. This case illustrates an unusual presentation of cardiovascular involvement in a patient with double-positive ANCA/anti-GBM disease, emphasizing the possible relevance of coronary microvascular dysfunction and the need for close cardiovascular follow-up in this patient population.
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Secondary infections contribute significantly to covid-19 mortality but driving factors remain poorly understood. Autopsies of 20 covid-19 cases and 14 controls from the first pandemic wave complemented with microbial cultivation and RNA-seq from lung tissues enabled description of major organ pathologies and specification of secondary infections. Lethal covid-19 segregated into two main death causes with either dominant diffuse alveolar damage (DAD) or secondary pneumonias. The lung microbiome in covid-19 showed a reduced biodiversity and increased prototypical bacterial and fungal pathogens in cases of secondary pneumonias. RNA-seq distinctly mirrored death causes and stratified DAD cases into subgroups with differing cellular compositions identifying myeloid cells, macrophages and complement C1q as strong separating factors suggesting a pathophysiological link. Together with a prominent induction of inhibitory immune-checkpoints our study highlights profound alterations of the lung immunity in covid-19 wherein a reduced antimicrobial defense likely drives development of secondary infections on top of SARS-CoV-2 infection.
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Immunoglobulin G4 (IgG4)-releated disease is typically associated with interstitial nephritis, but rare cases of idiopathic membranous nephropathy as a renal manifestation have been described. Obinutuzumab was successfully used in refractory membranous nephropathy, but evidence for the treatment of IgG4-related disease with obinutuzumab is lacking. We report one patient's case with membranous nephropathy associated with IgG4-related disease who was treated with obinutuzumab following an anaphylactic reaction to rituximab. Obinutuzumab treatment resulted in a sustained complete remission of membranous nephropathy and a decrease of IgG4 to the normal range. This case demonstrates that membranous nephropathy associated with IgG4-related disease can be treated successfully with obinutuzumab.
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Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Duodenite/induzido quimicamente , Duodenite/patologia , Apoptose , Endoscopia Gastrointestinal , Feminino , Humanos , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidoresRESUMO
BACKGROUND: Cancer-to-cancer metastasis is very rare with less than 50 cases described in literature. This article reports a case of breast cancer with synchronous metastasis to clear cell renal cell cancer. CASE DESCRIPTION: A 79-year-old woman was diagnosed with a bilateral breast carcinoma. Sonographic staging investigation of the abdomen revealed a 6â¯cm wide expansion of the right kidney. Bilateral mastectomy and nephrectomy of the right kidney was performed. The histology revealed a clear cell renal cell carcinoma and in the center of the tumor a 0.5â¯cm metastasis of the breast cancer. The patient's comorbidities and performance status precluded chemotherapy und she received palliative radiotherapy, targeted monoclonal antibody therapy and antihormonal treatment. CONCLUSIONS: Even if cancer-to-cancer metastasis is a very rare phenomenon, the simultaneous or consecutive finding of a renal tumor in women with breast cancer should be carefully evaluated.
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Neoplasias da Mama , Carcinoma de Células Renais , Neoplasias Renais , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/secundário , Neoplasias da Mama/cirurgia , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Mastectomia , NefrectomiaRESUMO
BACKGROUND: Microangiopathic hemolytic anemias and thrombocytopenias in pregnant or postpartum women constitute an interdisciplinary diagnostic and therapeutic challenge in the evaluation of thrombotic microangiopathies (TMA), where urgent care must be considered. CASE PRESENTATION: We here report the case of a 21-year-old Somali woman, who was delivered by emergency caesarean section at 35 weeks of gestational age with acute dyspnea, placental abruption and gross edema due to severe preeclampsia/HELLP syndrome. After delivery, she developed acute kidney failure and thrombotic microangiopathy as revealed by kidney biopsy. The lack of early response to plasma exchange prompted extensive laboratory workup. Ultimately, the patient completely recovered with negative fluid balance and control of severe hypertension. CONCLUSIONS: This case report emphasizes the importance to differentiate between primary TMA syndromes and microangiopathic hemolytic anemias due to systemic disorders. Delayed recovery from preeclampsia/HELLP syndrome and malignant hypertension can clinically mimic primary TMA syndromes in the postpartum period.
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Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Gerenciamento Clínico , Cuidado Pós-Natal/métodos , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/terapia , Injúria Renal Aguda/complicações , Cesárea/efeitos adversos , Cesárea/tendências , Feminino , Humanos , Troca Plasmática/métodos , Troca Plasmática/tendências , Gravidez , Adulto JovemRESUMO
BACKGROUND: Tumor budding, meaning a detachment of tumor cells at the invasion front of colorectal carcinoma (CRC) into single cells or clusters (<=5 tumor cells), has been shown to correlate to an inferior clinical outcome by several independent studies. Therefore, it has been discussed as a complementary prognostic factor to the TNM staging system, and it is already included in national guidelines as an additional prognostic parameter. However, its application by manual evaluation in routine pathology is hampered due to the use of several slightly different assessment systems, a time-consuming manual counting process and a high inter-observer variability. Hence, we established and validated an automatic image processing approach to reliably quantify tumor budding in immunohistochemically (IHC) stained sections of CRC samples. METHODS: This approach combines classical segmentation methods (like morphological operations) and machine learning techniques (k-means and hierarchical clustering, convolutional neural networks) to reliably detect tumor buds in colorectal carcinoma samples immunohistochemically stained for pan-cytokeratin. As a possible application, we tested it on whole-slide images as well as on tissue microarrays (TMA) from a clinically well-annotated CRC cohort. RESULTS: Our automatic tumor budding evaluation tool detected the absolute number of tumor buds per image with a very good correlation to the manually segmented ground truth (R2 value of 0.86). Furthermore the automatic evaluation of whole-slide images from 20 CRC-patients, we found that neither the detected number of tumor buds at the invasion front nor the number in hotspots was associated with the nodal status. However, the number of spatial clusters of tumor buds (budding hotspots) significantly correlated to the nodal status (p-value = 0.003 for N0 vs. N1/N2). TMAs were not feasible for tumor budding evaluation, as the spatial relationship of tumor buds (especially hotspots) was not preserved. CONCLUSIONS: Automatic image processing is a feasible and valid assessment tool for tumor budding in CRC on whole-slide images. Interestingly, only the spatial clustering of the tumor buds in hotspots (and especially the number of hotspots) and not the absolute number of tumor buds showed a clinically relevant correlation with patient outcome in our data.
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Adesão Celular , Movimento Celular , Neoplasias Colorretais/patologia , Interpretação de Imagem Assistida por Computador , Imuno-Histoquímica , Idoso , Automação Laboratorial , Biomarcadores Tumorais/análise , Análise por Conglomerados , Neoplasias Colorretais/química , Feminino , Humanos , Queratinas/análise , Aprendizado de Máquina , Masculino , Invasividade Neoplásica , Redes Neurais de Computação , Variações Dependentes do Observador , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Análise Serial de TecidosRESUMO
BACKGROUND & AIMS: The lysyl oxidase-like protein 2 (LOXL2) promotes stabilization of the extracellular matrix, chemotaxis, cell growth and cell mobility. We aimed to (i) identify stimuli of LOXL2 in cholangiopathies, (ii) characterize the effects of LOXL2 on biliary epithelial cells' (BECs) barrier function, (iii) compare LOXL2 expression in primary sclerosing cholangitis (PSC), primary biliary cholangitis, and disease controls, and (iv) to determine LOXL2 expression and its cellular sources in four mouse models of cholangiopathies. METHODS: Cultured murine BECs were challenged with well-known triggers of cellular senescence, hypoxia, phospholipid-deficient Abcb4-/- mouse bile and chenodeoxycholic acid and investigated for LOXL2, SNAIL1 and E-cadherin expression and transepithelial electrical resistance with and without LOX-inhibition. In vivo, LOXL2 expression was studied in PSC livers, and controls and mouse models. We compared LOXL2 serum levels in patients with PSC, secondary SC, primary biliary cholangitis, and controls. RESULTS: Cellular senescence, hypoxia, Abcb4-/- bile and chenodeoxycholic acid induced LOXL2 and SNAIL1 expression, repressed E-cadherin expression, and significantly reduced transepithelial electrical resistance in BECs. Notably, all of the pathological changes could be recovered via pharmacological LOX-inhibition. Mouse models showed induced LOXL2 expression in the portal region and in association with ductular reaction. LOXL2 serum levels were significantly elevated in patients with cholangiopathies. In PSC, LOXL2 expression was located to characteristic periductal onion skin-type fibrosis, ductular reaction, Kupffer cells, and fibrotic septa. Importantly, in PSC, LOXL2 overexpression was paralleled by E-cadherin loss in BECs from medium-sized bile ducts. CONCLUSIONS: Reactive BECs produce LOXL2, resulting in increased tight junction permeability, which can be ameliorated by pharmacological LOX-inhibition in vitro. Reactive BECs, portal myofibroblasts, and Kupffer cells are the main sources of LOXL2 in cholangiopathies. LAY SUMMARY: In this study, we investigate the role of lysyl oxidase-like protein 2 (LOXL2), an enzyme pivotal in the development of organ fibrosis, in the pathogenesis of cholangiopathies (diseases of bile ducts), such as primary sclerosing cholangitis. We found LOXL2 to be expressed in association with bile duct epithelial injury and uncovered mechanisms for its upregulation and the subsequent effects in vitro and in vivo. Our findings support testing of anti-LOXL2 treatment strategies for patients with primary sclerosing cholangitis.
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Aminoácido Oxirredutases/metabolismo , Doenças Biliares , Sistema Biliar/metabolismo , Caderinas/metabolismo , Colestase , Células Epiteliais/metabolismo , Animais , Doenças Biliares/metabolismo , Doenças Biliares/patologia , Proliferação de Células/fisiologia , Células Cultivadas , Senescência Celular/fisiologia , Colestase/metabolismo , Colestase/patologia , Modelos Animais de Doenças , CamundongosRESUMO
Acute kidney injury is common in patients with liver disease and associated with significant morbidity and mortality. Besides bacterial infections, fluid loss, and use of nephrotoxic drugs AKI in liver disease may be triggered by tubular toxicity of cholephiles. Cholemic nephropathy, also known as bile cast nephropathy, supposedly represents a widely underestimated but important cause of renal dysfunction in cholestasic or advanced liver diseases with jaundice. Cholemic nephropathy describes impaired renal function along with characteristic histomorphological changes consisting of intratubular cast formation and tubular epithelial cell injury directed towards distal nephron segments. The underlying pathophysiologic mechanisms are not entirely understood and clear defined diagnostic criteria are still missing. This review aims to summarize (i) the present knowledge on clinical and morphological characteristics of cholemic nephropathy, (ii) available preclinical models, (iii) potential pathomechanisms especially the potential role of bile acids, and (iv) future diagnostic and therapeutic strategies for cholemic nephropathy. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
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Injúria Renal Aguda/etiologia , Ácidos e Sais Biliares/toxicidade , Colestase/complicações , Icterícia Obstrutiva/complicações , Túbulos Renais/patologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Animais , Ácidos e Sais Biliares/metabolismo , Ductos Biliares/citologia , Ductos Biliares/efeitos dos fármacos , Ductos Biliares/metabolismo , Ductos Biliares/patologia , Bilirrubina/metabolismo , Bilirrubina/toxicidade , Colagogos e Coleréticos/farmacologia , Colagogos e Coleréticos/uso terapêutico , Colestase/tratamento farmacológico , Colestase/patologia , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Icterícia Obstrutiva/tratamento farmacológico , Icterícia Obstrutiva/patologia , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Eliminação Renal , Ácido Ursodesoxicólico/análogos & derivados , Ácido Ursodesoxicólico/farmacologia , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
AIM: Hepatic innervation represents a potentially underestimated regulator of liver function and regeneration. The muscarinic 3 receptor (M3 -R) is the primary cholangiocyte receptor for the afferent parasympathetic innervation of bile ducts. We aimed to determine the specific role of the M3 -R in bile formation and models for cholestatic liver disease in mice. METHODS: We compared bile flow and composition in M3 -R knock-out mice (M3 -R-/- ) and wild type littermates (WT). Furthermore, we compared liver inury of M3 -R-/- and WT mice after 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding, a well-characterized preclinical model of cholestatic liver disease. To analyze the possible role of the M3 -R as a therapeutic target, we treated 4-week-old Mdr2-/- mice, a preclinical model for sclerosing cholangitis, with the M3 -R agonist bethanechol for 4 weeks. RESULTS: M3 -R-/- mice showed significantly reduced bile flow compared to WT mice, most likely due to decreased biliary HCO3- secretion. However, even aged M3 -R-/- mice did not spontaneously develop liver injury or cholestasis. Challenging M3 -R-/- and WT littermates with DDC feeding showed substantially aggravated liver injury in M3 -R-/- mice. After 4 weeks bethanechol treatment, Mdr2-/- mice showed less liver injury compared to controls. CONCLUSION: Our experimental findings suggest that M3 -R-signalling significantly influences bile formation. Loss of the M3 -R increases susceptibility to cholestatic injury in DDC-fed mice. Since treatment of Mdr2-/- mice with a M3 -R agonist decreases liver injury, M3-R signaling may represent a therapeutic target in specific cholangiopathies.
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BACKGROUND & AIMS: Severe cholestasis may cause cholemic nephropathy that can be modeled in common bile duct ligated (CBDL) mice. We aimed to explore the therapeutic efficacy and mechanisms of norursodeoxycholic acid (norUDCA) in cholemic nephropathy. METHODS: In 8-week CBDL mice fed with norUDCA (prior or post CBDL) or chow we evaluated serum urea levels, urine cytology and urinary neutrophil gelatinase associated lipocalin (uNGAL), kidney and liver tissue quantification of fibrosis by hydroxyproline content and gene chip expression looking at key genes of inflammation and fibrosis. Moreover, we comprehensively analysed bile acid profiles in liver, kidney, serum and urine samples. RESULTS: NorUDCA-fed CBDL mice had significantly lower serum urea and uNGAL levels and less severe cholemic nephropathy as demonstrated by normal urine cytology, significantly reduced tubulointerstitial nephritis, and renal fibrosis as compared to controls. NorUDCA underwent extensive metabolism to produce even more hydrophilic compounds that were significantly enriched in kidneys. CONCLUSION: NorUDCA ameliorates cholemic nephropathy due to the formation of highly hydrophilic metabolites enriched in kidney. Consequently, norUDCA may represent a medical treatment for cholemic nephropathy. LAY SUMMARY: The term cholemic nephropathy describes renal dysfunction together with characteristic morphological alterations of the kidney in obstructive cholestasis that can be mimicked by ligation of the common bile duct in mice. Feeding the hydrophilic bile acid norUDCA to bile duct ligated mice leads to a significant amelioration of the renal phenotype due to the formation of highly hydrophilic metabolites enriched in the kidney and may therefore represent a medical treatment for cholemic nephropathy.
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Colestase/complicações , Nefropatias/tratamento farmacológico , Ácido Ursodesoxicólico/análogos & derivados , Animais , Ácidos e Sais Biliares/urina , Modelos Animais de Doenças , Fibrose , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Ligadura , Lipocalina-2/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nefrite Intersticial/tratamento farmacológico , Ácido Ursodesoxicólico/metabolismo , Ácido Ursodesoxicólico/uso terapêuticoAssuntos
Hemoglobinúria Paroxística/diagnóstico , Hemólise , Necrose Tubular Aguda/diagnóstico , Biópsia , Feminino , Testes Hematológicos , Hemoglobinúria Paroxística/sangue , Hemoglobinúria Paroxística/complicações , Hemoglobinúria Paroxística/terapia , Humanos , Necrose Tubular Aguda/sangue , Necrose Tubular Aguda/etiologia , Necrose Tubular Aguda/terapia , Túbulos Renais/patologia , Pessoa de Meia-Idade , Diálise RenalRESUMO
PURPOSE: The study aimed to analyze clinicopathological factors that determine the extent of lymph node retrieval and to evaluate its prognostic impact in patients with colorectal cancer (CRC). METHODS: The number of retrieved lymph nodes was analyzed in 381 CRC specimens. Lymph node count was related to different clinicopathological variables by binary logistic regression. Progression-free survival (PFS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier method and Cox regression models. RESULTS: The median number of retrieved lymph nodes was 20 (mean 21 ± 10, range 1-65) in right-sided, 13 (16 ± 10, 1-66) in left-sided, and 15 (18 ± 11, 3-64) in rectal tumors. The number of retrieved lymph nodes was independently associated with T-classification (p < 0.001), N-classification (p = 0.014), and tumor size (p = 0.005) as well as right-sided tumor location (p = 0.012). There was no association with age, sex, tumor grade, mismatch-repair status, and lymph or blood vessel invasion. The longer the surgical specimen, the higher were the numbers of retrieved and positive lymph nodes (p < 0.001, respectively). In patients with locally advanced (T3/T4) tumors (n = 283), analysis of more than 12 lymph nodes was independently associated with PFS (HR = 0.63, p = 0.025) and CSS (HR = 0.54, p = 0.004). In the subset of T3/T4 N0 patients (n = 130), analysis of more than 12 lymph nodes similarly proved to be an independent predictor of outcome (PFS, HR = 0.48, p = 0.046; OS, HR = 0.41, p = 0.026). CONCLUSION: The number of retrieved lymph nodes is associated with higher tumor stage, tumor size, and right-sided location. Low lymph node count indicates adverse outcome in patients with locally advanced (T3/T4) disease.
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Neoplasias Colorretais/patologia , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Modelos Logísticos , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de SobrevidaRESUMO
Natural killer T (NKT) cells are activated by lipid antigens presented by CD1d molecules and represent a major lymphocyte subset of the liver. NODc3c4 mice spontaneously develop biliary inflammation in extra- and intrahepatic bile ducts. We demonstrated by flow cytometry that invariant NKT (iNKT) cells were more abundant in the thymus, spleen, and liver of NODc3c4 mice compared to NOD mice. iNKT cells in NODc3c4 mice displayed an activated phenotype. Further, NOD and NODCd1d-/- mice were irradiated and injected with NODc3c4 bone marrow, and injection of NODc3c4 bone marrow resulted in biliary infiltrates independently of CD1d expression in recipient mice. Activation or blocking of NKT cells with α-galactosylceramide or anti-CD1d antibody injections did not affect the biliary phenotype of NODc3c4 mice. NODc3c4.Cd1d-/- mice were generated by crossing NODCd1d-/- mice onto a NODc3c4 background. NODc3c4.Cd1d-/- and NODc3c4 mice developed the same extent of biliary disease. This study demonstrates that iNKT cells are more abundant and activated in the NODc3c4 model. The portal inflammation of NODc3c4 mice can be transferred to irradiated recipients, which suggests an immune-driven disease. Our findings imply that NKT cells can potentially participate in the biliary inflammation, but are not the primary drivers of disease in NODc3c4 mice.
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Antígenos CD1d/genética , Doenças dos Ductos Biliares/imunologia , Inflamação/imunologia , Células T Matadoras Naturais/imunologia , Animais , Antígenos CD1d/imunologia , Doenças dos Ductos Biliares/metabolismo , Doenças dos Ductos Biliares/patologia , Modelos Animais de Doenças , Galactosilceramidas/farmacologia , Inflamação/metabolismo , Inflamação/patologia , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Knockout , Células T Matadoras Naturais/efeitos dos fármacos , Células T Matadoras Naturais/metabolismo , Baço/imunologia , Baço/metabolismo , Baço/patologia , Timo/imunologia , Timo/metabolismo , Timo/patologiaRESUMO
AIMS: Verrucous carcinoma (VC) is a variant of well-differentiated squamous cell carcinoma and in the anal region is regarded as synonymous with giant condyloma (Buschke-Löwenstein tumour) (BLT). Aetiology, diagnostic criteria and clinical behaviour of both lesions are controversial. Recent studies suggest that VC at other sites is not associated with human papillomaviruses (HPV). We hypothesized that anal VC is also not related to HPV, while BLT is a HPV-induced lesion. METHODS AND RESULTS: Ten cases of VC and four cases of BLT were included. Several techniques were used for HPV detection: in-situ hybridization for HPV6, 11, 16 and 18, six different polymerase chain reaction (PCR) protocols for detection of at least 89 HPV types from alpha-, beta-, gamma- and mu-PV genera and in-situ hybridization for high-risk HPV E6/E7 mRNA; p16 immunohistochemistry and morphometric analysis were also performed. Alpha-, gamma- and mu-PVs were not found in any case of VC, while HPV6 was detected in all cases of BLT. p16 overexpression was not present in any of the lesions. Among microscopic features, only the absence of koilocytosis and enlarged spinous cells seem to be useful to distinguish VC from BLT. CONCLUSIONS: Our results suggest that anal VC, similarly to VC at other sites, is not associated with HPV infection, and must be distinguished from BLT, which is associated with low-risk HPV. Only with well-set diagnostic criteria will it be possible to ascertain clinical behaviour and optimal treatment for both lesions.
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Neoplasias do Ânus/virologia , Tumor de Buschke-Lowenstein/virologia , Carcinoma Verrucoso/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/patologia , Tumor de Buschke-Lowenstein/patologia , Carcinoma Verrucoso/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Reação em Cadeia da PolimeraseRESUMO
The antiproliferative treatment options for neuroendocrine tumors (NET)/neuroendocrine carcinomas of the gastrointestinal tract critically depend on the proliferation rate, evaluated by immunohistochemical staining for Ki-67. According to their grading, tumors are treated with somatostatin analogs, mTOR inhibitors, or cytotoxic substances. This case illustrates downgrading of a primarily highly proliferative NET achieved by a variation of cytotoxic chemotherapy regimens, followed by a combination therapy using everolimus together with lanreotide. The latter medication might lead to a good clinical response as far as tumor growth is concerned.
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Mucin glycoprotein expression can be altered during the carcinogenic process. The impact on the prognosis of patients with colorectal cancer (CRC) is controversial. We analyzed tumors from 381 patients for MUC1, MUC2, MUC5AC, and MUC6 expression by immunohistochemical staining, using tissue microarrays. Progression-free and cancer-specific survival were determined using the Kaplan-Meier method. Expression of intestinal mucin MUC2 was lost in 85 (23 %) CRCs, and patients with MUC6-negative tumors showed shorter progression-free survival (PFS, p = 0.043). Gastric mucins MUC5AC and MUC6 showed high (>50 %) aberrant expression in 28 (8 %) and 9 (2 %) cases, respectively. High expression of MUC5AC was associated with longer PFS (p = 0.055). High expression of MUC6 was associated with 100 % PFS (p = 0.024) and longer cancer-specific survival (CSS, p = 0.043). MUC1 was expressed in 238 (64 %) tumors and had no impact on outcome. When analysis was restricted to stages II and III, loss of MUC2 was associated with adverse outcome. Overexpression of both MUC5AC and MUC6 significantly predicted favorable PFS and CSS. In conclusion, loss of MUC2 expression proved to be a predictor of adverse outcome, while the gain of aberrant expression of MUC5AC and particularly of MUC6 was associated with favorable outcome in CRC, notably in intermediate stages II and III.