RESUMO
OBJECTIVES: Atrophy of the left lateral segment (LLS) is often encountered in liver transplantation (LT) for biliary atresia (BA). To clarify the meaning of the heterogeneous atrophy, we compared the pathological characteristics of the LLS with the right posterior segment (RPS) of BA livers obtained during LT. METHODS: Among the 116 patients with BA who underwent LT at our hospital between 2014 and 2018, 63 patients with persistent cholestasis after the Kasai portoenterostomy (KP) were selected. Three pathologists evaluated tissues from the LLS and RPS for 5 pathological parameters. Positive areas in whole-slide image observed as portal inflammation, fibrosis, cholestasis, and ductular reaction, were analyzed with automated image quantitation. Moreover, we examined the relationship between the pathological score and the Pediatric End-stage Liver Disease (PELD) score. RESULTS: The median age at LT was 7 months (range 4-26 months). Inflammation and fibrosis were significantly greater in the LLS than in the RPS (Pâ<â0.001, for both); however, there were no differences in cholestasis, ductular reaction, and hepatocellular damage (Pâ=â0.3, 0.3, and 0.82). The same results were obtained in automated image quantitation. Moreover, the sums of the 5 pathological scores in the LLS showed a significant positive correlation with the PELD score (Pâ=â0.016, rsâ=â0.3). CONCLUSIONS: More severe inflammation and fibrosis without cholestasis were observed in the LLS. The segmental atrophy may not be associated with poor bile drainage, but with etiopathogenesis of BA. Moreover, the proper site for biopsy during KP could be the LLS.
Assuntos
Atresia Biliar , Doença Hepática Terminal , Atrofia , Atresia Biliar/cirurgia , Criança , Pré-Escolar , Doença Hepática Terminal/cirurgia , Humanos , Lactente , Portoenterostomia Hepática , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND AIM: The incidence of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is progressively increasing. However, the pathophysiology and etiology of NASH progression to HCC are unknown. We hypothesized that steatosis was the key factor in NASH-related hepatocarcinogenesis and aimed to evaluate the effects of long-term liver X receptor (LXR) agonist stimulation on hepatic steatosis induced by a high-fat diet and oxidative stress. METHODS: We used an LXR agonist (T0901317) and CCl4 to induce hepatic steatosis and oxidative stress, respectively. C57BL/6 mice fed with a high-fat diet were treated with either T0901317 + CCl4 (T09 + CCl4 group) or CCl4 alone (CCl4 group). T0901317 (2.5 mg/kg) and CCl4 (0.1 mL/kg) were intraperitoneally administered twice weekly for 24 weeks. RESULTS: The liver-to-body weight ratio was significantly higher in the T09 + CCl4 group than in the CCl4 group. Mice in the T09 + CCl4 group exhibited abnormal lipid metabolism and NASH-like histopathological features. Additionally, all mice in the T09 + CCl4 group developed liver tumors diagnosed as well-differentiated HCC. The genes identified via microarray analysis were related to NASH and HCC development. CONCLUSIONS: By combining long-term LXR agonist stimulation with oxidative stress and a high-fat diet, we successfully reproduced liver conditions in mice similar to those in humans with NASH and progression to HCC. Our results provide new insight into NASH-related HCC progression and therapy.
Assuntos
Carcinoma Hepatocelular/etiologia , Hidrocarbonetos Fluorados/efeitos adversos , Neoplasias Hepáticas/etiologia , Receptores X do Fígado/agonistas , Hepatopatia Gordurosa não Alcoólica/complicações , Estresse Oxidativo , Sulfonamidas/efeitos adversos , Animais , Tetracloreto de Carbono/administração & dosagem , Tetracloreto de Carbono/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Hidrocarbonetos Fluorados/administração & dosagem , Injeções Intraperitoneais , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Sulfonamidas/administração & dosagemRESUMO
Surgical intervention for HB with tumor thrombi extending into the IVC and the RA might requires careful planning of the surgical procedures, including vascular reconstruction and extracorporeal circulation. We herein report a successful case of LDLT for HB with atrial extension of a tumor thrombus by extracorporeal circulation with a transdiaphragmatic approach. The patient was a 5-year-old boy with PRETEXT IV HB with a tumor thrombus that extended into the IVC and the RA. After 4 cycles of chemotherapy and resection of bilateral lung metastases, the size of the primary HB tumor decreased. As the tumor extension from the LHV to the RA had decreased but was still present, we performed LDLT with tumor thrombectomy. The central part of the diaphragm was sagittally incised to expose the suprahepatic IVC and the RA. Venovenous bypass was achieved from the right femoral vein and IMV to the RA En bloc resection of the native liver with the tumor thrombus was then performed. HV anastomosis was made between the newly created orifice on the IVC and the graft LHV. The duration of LDLT was 10 hours and 44 minutes (extracorporeal circulation time: 78 minutes). Pediatric LT for HB with the extension of tumor thrombi into the RA under extracorporeal circulation is a feasible option and allows for the expansion of the indications for transplantation for children with unresectable liver tumors.
Assuntos
Circulação Extracorpórea , Átrios do Coração/cirurgia , Hepatoblastoma/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Pré-Escolar , Humanos , Doadores Vivos , Masculino , Veia Cava Inferior/cirurgiaRESUMO
BACKGROUND: EBV-associated HLH driven by EBV-infected CD8+ T cells is a rare complication after pediatric solid organ transplantation. The etiology and disease spectrum of post-transplant EBV-HLH are poorly understood, and making a precise diagnosis and providing optimal treatment remain a challenge. METHODS/CASE DESCRIPTION/RESULTS: We report a 2-year-old multivisceral transplant recipient who developed fever and cytopenia with a persistent high EBV-load state. Repeated tissue examinations and CT scans could not identify a localized mass, which is the key to the diagnosis of PTLD as per the WHO classification. Hence, EBV-HLH was diagnosed by clinical manifestations as well as characterization of EBV-infected cells, pathological examination on cell block of pleural effusion and clonality analysis. This EBV-HLH did not respond to intensive chemotherapy, resulted in the recipient's death, acting similarly to hematological malignancy. CONCLUSIONS: Characterization of EBV-infected cells in peripheral blood should be considered when persistent high EBV loads develop with symptoms consistent with PTLD, but no evidence of localized mass, and the tissue diagnosis is unavailable after pediatric solid organ transplantation.
Assuntos
Linfócitos T CD8-Positivos/virologia , Infecções por Vírus Epstein-Barr/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Vísceras/transplante , Pré-Escolar , Evolução Fatal , Humanos , Masculino , Estudo de Prova de ConceitoRESUMO
BACKGROUND: LT is an elective treatment choice for children diagnosed with GSD1b that can improve their quality of life and stabilize their glucose intolerance. However, careful attention should be paid to immunosuppression after LT due to the susceptibility to infection because of neutropenia and neutrophil dysfunction in GSD1b patients. This study revealed the immunological features and complications in the early post-LT period. METHODS: We compared findings between 11 (1.9%) children with GSD1b and 273 children with BA. Analyses using the PSM were performed to overcome selection bias. RESULTS: Despite persistent low tacrolimus trough levels in GSD1b patients, none of these children developed TCMR within 1 month after LDLT (GSD1b: 0/11 [0%] vs. BA: 86/273 [31.5%], p = .038). This result was also confirmed in PSM. The incidence of bloodstream infections was higher in GSD1b patients than in BA patients in the early phase of the post-transplant period (GSD1b: 4/11 [36.4%] vs. BA: 33/273 [12.1%], p = .041), but not reach statistical significance in PSM. In a phenotypic analysis, the ratio of CD8+ T cells in GSD1b recipients' peripheral blood mononuclear cell samples was lower than in recipients with BA through the first month after LDLT. CONCLUSIONS: We found that GSD1b recipients were more likely to develop postoperative bloodstream infection than recipients with BA but did not experience TCMR despite low tacrolimus levels in the early post-LDLT period. A tailored immunosuppression protocol should be prepared for GSD1b recipients after LDLT.
Assuntos
Doença de Depósito de Glicogênio Tipo I/imunologia , Doença de Depósito de Glicogênio Tipo I/cirurgia , Transplante de Fígado , Complicações Pós-Operatórias/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Incidência , Lactente , Doadores Vivos , Masculino , Qualidade de VidaRESUMO
X-linked myotubular myopathy (MTM) (OMIM 310400) is a severe neuromuscular disorder caused by mutations in the myotubularin (MTM1) gene. Liver hemorrhaging due to peliosis hepatis (PH) is a fatal complication. We herein report 2 successful cases of living-donor liver transplantation (LDLT) for MTM patients due to liver hemorrhaging caused by PH and review previous reports. A boy who was 9 years and 4 months old initially underwent left lateral segmentectomy due to massive hepatic and intraperitoneal hemorrhaging. As bleeding from the remnant liver continued after hepatectomy, this patient emergently underwent LDLT using a left lateral segment graft from his father. Another boy who was 1 year and 7 months old underwent transcatheter arterial embolization due to hepatic hemorrhaging and was referred to our hospital for LDLT using a left lateral segment graft from his father. The pathological findings in both cases showed sinusoidal dilatation with degenerative changes in reticular fiber and hematoma in the explanted liver, which were consistent with PH associated with MTM. LT should be considered as a treatment option for patients with episodes of hepatic hemorrhaging due to MTM in order to protect against fatal bleeding.
Assuntos
Transplante de Fígado , Miopatias Congênitas Estruturais , Peliose Hepática , Humanos , Lactente , Doadores Vivos , Masculino , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/cirurgiaRESUMO
Epithelial cell transforming sequence 2 (ECT2), a guanine nucleotide exchange factor, is predominantly localized in the nucleus of non-transformed cells and functions to regulate cytokinesis. ECT2 is also localized in the cytoplasm of cancer cells. Aberrant cytoplasmic expression of ECT2 is thought to drive tumor growth and invasion. In this study, we investigated the cytoplasmic expression of ECT2 and its prognostic and biological significance in lung adenocarcinoma. Western blotting of cellular fractions from the nucleus and cytoplasm was performed to determine the subcellular localization of ECT2 in lung adenocarcinoma cell lines. The cytoplasmic expression of ECT2 in 167 lung adenocarcinomas was evaluated by immunohistochemistry and its clinical significance was examined using Kaplan-Meier curves and Cox regression analysis. Scraping cytology specimens of 13 fresh lung adenocarcinomas were used to assess the subcellular localization of ECT2 and its phosphorylation at Thr790 (P-ECT2(T790)). We found that ECT2 was localized in both the nucleus and cytoplasm of lung adenocarcinoma cell lines and tumor tissues. Cytoplasmic expression of ECT2 was detected by immunohistochemistry in 83 (50%) of the lung adenocarcinomas, and was found to increase during cancer progression. It was expressed in 30 (29%) small adenocarcinomas ( ≤ 2 cm in diameter) and 53 (82%) advanced adenocarcinomas ( > 2 cm in diameter). Cytoplasmic positivity for ECT2 was associated with a poor outcome in terms of both disease-free and overall survival (both P < 0.001), and was an independent prognostic factor for overall survival (P = 0.025). Immunocytochemical staining for P-ECT2(T790) demonstrated cytoplasmic and membrane positivity in Calu-3 cells and scraping cytology specimens. Positive P-ECT2(T790) staining was correlated with cytoplasmic ECT2 expression in 6 of 13 scraped cytology specimens tested. In conclusion, our findings indicate that cytoplasmic ECT2 expression could promote the malignant progression of lung adenocarcinoma and may represent a potent therapeutic target for patients with lung adenocarcinoma.
Assuntos
Adenocarcinoma de Pulmão/metabolismo , Citoplasma/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Citoplasma/química , Progressão da Doença , Intervalo Livre de Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas/genéticaRESUMO
Dickkopf-related protein 3 (DKK3) is one of the DKK family (DKK1-4), an evolutionally conserved group of secreted glycoproteins characterized by two distinct cysteine-rich domains. DKK3 is considered to be a tumor suppressor gene. However, it has been shown that 30-50% of various cancers are DKK3-positive, suggesting that DKK3 may have an additional function other than tumor suppression. In this study, we focused on lung adenocarcinoma, which is the major histological type of lung cancer. We analyzed the relationship between DKK3 expression and clinicopathological features by immunohistochemistry, using 200 lung adenocarcinoma specimens. We found that 40.5% and 59.5% of cases were DKK3-positive and -negative, respectively, and that positive cases had a greater tendency for progression than negative cases (P < 0.05). Furthermore, in vitro analyses demonstrated that DKK3 suppression affected cell adhesion in three DKK3-expressing lung adenocarcinoma cell lines and that DKK3-knockdown cells were less invasive in comparison to control cells. These results suggest that DKK3 plays a role in the progression of lung adenocarcinoma by promoting cell adhesion and invasion. DKK3 might be a new extracellular cancer therapeutic target, and it seems important to clarify molecular mechanisms underlying the DKK3 functions depending on cell context.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma de Pulmão/metabolismo , Adesão Celular/genética , Neoplasias Pulmonares/metabolismo , Invasividade Neoplásica/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologiaRESUMO
The clinicopathological implications of ovarian cancer immunoreactive antigen domain containing 2 (OCIAD2) in lung adenocarcinoma were investigated. The expression of OCIAD2 in 191 surgically resected lung adenocarcinomas was examined using immunohistochemistry. OCIAD2 expression was quantified using the H-score and dichotomized as high or low. High OCIAD2 protein expression was significantly correlated with vascular invasion (P = 0.0018), lymphatic permeation (P = 0.049), T factor (P = 0.0024), and pathological stage (P = 0.0003). High OCIAD2 expression was significantly associated with poorer overall survival (OS) (n = 191, P = 0.0325). In peripheral-type lung adenocarcinomas (n = 161), high OCIAD2 expression was significantly associated with both poorer OS (P = 0.0214) and poorer disease-free survival (P = 0.0496). Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) showed weaker OCIAD2 expression than invasive adenocarcinoma. Among small adenocarcinomas measuring 2 cm or less in greatest dimension classified according to the Noguchi's classification (n = 79), invasive adenocarcinomas showed significantly higher OCIAD2 expression than non-invasive adenocarcinomas (P = 0.0007). Interestingly, OCIAD2 was expressed heterogeneously even within a tumor, and its expression was higher in areas of invasion than in areas of in situ spread. Our results suggest that OCIAD2 could be a useful prognostic biomarker of lung adenocarcinoma.
Assuntos
Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/análise , Proteínas de Neoplasias/biossíntese , Adenocarcinoma de Pulmão/mortalidade , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
It has been reported that N-myc downstream regulated gene 1 (NDRG1) is related to the prognosis of non-small cell lung cancer (NSCLC), and associated with c-Myc degradation in NSCLC cell lines. However, the relationship of NDRG1 to prognosis or c-Myc expression in lung adenocarcinoma has not been well clarified. The present study was designed to investigate the prognostic significance of NDRG1 and/or c-Myc expression in lung adenocarcinoma using immunohistochemistry with a tissue microarray. We examined 184 lung adenocarcinomas and observed low expression of NDRG1 in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), whereas high expression of NDRG1 was seen in invasive adenocarcinoma. Each of the clinicopathological features except age was significantly correlated with NDRG1 expression. Kaplan-Meier curves indicated that high expression of NDRG1 was significantly correlated with poor prognosis in comparison with low expression (log-rank, P < 0.001). Univariate and multivariate analyses indicated that vascular invasion (P = 0.012), lymphatic permeation (P = 0.038), and NDRG1 expression (P = 0.026) were independent prognostic factors. Expression of NDRG1 and positivity for c-Myc were significantly correlated (P = 0.005). These findings indicate that NDRG1 expression is associated with both prognosis and c-Myc expression in lung adenocarcinoma.
Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Proteínas de Ciclo Celular/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Neoplasias Pulmonares/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma de Pulmão , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-myc/biossínteseRESUMO
Although several non-alcoholic steatohepatitis (NASH) models have been reported to date, few of these models fully reflect the histopathology and pathophysiology of human NASH. The aim of this study was to establish a novel NASH model by feeding a high-fat (HF) diet and administering both carbon tetrachloride (CCl4 ) and the Liver X receptor agonist T0901317. Male C57BL/6J mice were divided into four groups (each n = 5): HF, HF + CCl4 , HF + T0901317, and the novel NASH model (HF + CCl4 + T0901317). CCl4 (0.1 mL/kg) and T0901317 (2.5 mg/kg) were intraperitoneally administered four times and five times, respectively. The livers of the novel NASH model group presented a whitish colour. The serum levels of TNF-α and IL-6 were significantly increased in the novel NASH model group, and mice in this group exhibited histopathological features and insulin resistance reflective of NASH, i.e., macrovesicular hepatic steatosis, ballooning hepatocytes, Mallory-Denk bodies, lobular inflammation and fibrosis. The novel NASH model group presented significantly upregulated expression levels of mRNAs related to lipogenesis, oxidative stress, fibrosis and steatosis and significantly downregulated expression levels of mRNAs related to triglyceride export. We successfully established a novel experimental NASH model that exhibits similar histopathology and pathophysiology to human NASH.
Assuntos
Modelos Animais de Doenças , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Tetracloreto de Carbono/toxicidade , Dieta Hiperlipídica/efeitos adversos , Hidrocarbonetos Fluorados/toxicidade , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sulfonamidas/toxicidadeRESUMO
Cyclophilin A (CypA) has been reported to be upregulated in malignant tumors. CypA expression is thought to be associated with acquisition of tumor growth and anti-apoptotic function. Although upregulation of CypA has been reported in lung adenocarcinoma, its clinicopathological significance and roles in malignant progression remain unclear. Here we investigated the implications of CypA expression for outcome in patients with lung adenocarcinoma. Lung adenocarcinoma specimens from 198 cases were selected and reclassified according to the World Health Organization classification (4th edition) and the Noguchi classification. CypA expression was assessed by immunohistochemistry, and the H-score was calculated on the basis of intensity and proportion. The specificity of the antibody used was confirmed by Western blotting and the cut-off point was determined from the ROC curve. Sixty-seven cases (33.8%) had low CypA expression (CypA-L group) and 131 (66.2%) had high CypA expression (CypA-H group). Many cases of adenocarcinoma in situ were CypA-L, and advanced adenocarcinomas tended to be classified as CypA-H. Clinically, patients with CypA-H tumors showed a significantly poorer prognosis than those with CypA-L tumors. This is the first investigation of the implications of the CypA expression level in terms of the clinical characteristics of resected lung adenocarcinomas.
Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Ciclofilina A/biossíntese , Neoplasias Pulmonares/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma de Pulmão , Adulto , Idoso , Ciclofilina A/análise , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
A 54-year-old woman presented withtransient back pain. She was diagnosed withleiomyosarcoma of the inferior vena cava (IVC) by computed tomography (CT) and was referred to our hospital. Contrastenhanced CT revealed a mass (38×42 mm) located in the retroperitoneal space along the course of the right ovarian vein. The mass compressed the IVC into a crescent shape. A tumor thrombus was also found in the IVC. 18 F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) revealed high uptake at the caudal side of the tumor. These radiological findings strongly suggested the diagnosis of leiomyosarcoma arising from the right ovarian vein. She underwent tumor resection with right nephrectomy, IVC resection, and IVC patch reconstruction without any notable events after surgery. Histopathological diagnosis was leiomyosarcoma arising from the ovarian vein, not from the IVC. Two months after the surgery, CT revealed multiple pulmonary metastases and a single liver metastasis. The patient was referred to another hospital for further treatment. She was treated with chemotherapy and was alive with disease at 14 months after the surgery.
Assuntos
Leiomiossarcoma/irrigação sanguínea , Leiomiossarcoma/diagnóstico por imagem , Ovário/irrigação sanguínea , Neoplasias Vasculares/diagnóstico por imagem , Neoplasias Vasculares/patologia , Veias/diagnóstico por imagem , Veias/patologia , Feminino , Humanos , Leiomiossarcoma/cirurgia , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Neoplasias Vasculares/cirurgia , Veias/cirurgiaRESUMO
Hirschsprung disease (HSCR) is a congenital disease resulting from failure of neural crest-derived ganglion cells to colonize the colon. Conventional diagnostic methods are insufficient for evaluating the 'functional' prognosis of HSCR. In order to elucidate the maturation of ganglion cells, 17 immunohistochemical markers were examined. We examined the digestive tracts of 2 human early delivery patients, 2 miniature swine fetuses, 4 little infants, 3 infants, 3 children, 6 adults, and 3 aged individuals. With increasing age, the labeling index (LI) for both calretinin and tyrosine hydroxylase (TH) increased, whereas that for SOX10 decreased. We then examined the 'transitional zone' of HSCR in 21 affected patients and 18 controls for these three markers. The LI of calretinin and TH were significantly lower than in the controls (median: 3.7 in HSCR and 8.2 in controls, P < 0.001, median: 27.9 in HSCR and 44.4 in controls, P < 0.001, respectively). In contrast, the LI for SOX10 showed no significant difference (median: 33.7 in HSCR and 29.2 in controls, P = 0.666) however, hierarchical cluster analysis was able to divide HSCR patients into two groups. These results suggest that immature ganglion cells are present in the transitional zone of HSCR, and that HSCR may have two different pathophysiological processes.
Assuntos
Calbindina 2/metabolismo , Sistema Nervoso Entérico/patologia , Gânglios Autônomos/patologia , Doença de Hirschsprung/metabolismo , Fatores de Transcrição SOXE/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Adolescente , Adulto , Idoso , Anticorpos , Biomarcadores/metabolismo , Calbindina 2/imunologia , Criança , Pré-Escolar , Sistema Nervoso Entérico/metabolismo , Feminino , Gânglios Autônomos/metabolismo , Trato Gastrointestinal/patologia , Doença de Hirschsprung/patologia , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Fatores de Transcrição SOXE/imunologia , Coloração e Rotulagem , Tirosina 3-Mono-Oxigenase/imunologiaRESUMO
A 45-year-old man presented with severe abdominal distention with massive ascites due to a diffusely disseminated peritoneal tumor. A core needle biopsy specimen was obtained from the peritoneal lesion. Histological diagnosis was epithelioid type mesothelioma. He did not choose to receive chemotherapy. For 2.5 years, he went without medical intervention, and his disease gradually progressed, leading to a worsening of his symptoms. The patient then chose to be treated with combination chemotherapy of cisplatin and pemetrexed, followed by pemetrexed alone. There was remarkable tumor shrinkage and his symptoms improved. These effects have been sustained for two years after the initial chemotherapy. Chemotherapy appears to have contributed to survival prolongation for this patient. This case exemplifies the fact that malignant peritoneal mesothelioma may progress slowly when fits with some good prognostic factors, and it is important to consider the prognostic factors.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Ascite/etiologia , Cisplatino/administração & dosagem , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Neoplasias Pulmonares/complicações , Masculino , Mesotelioma/complicações , Mesotelioma Maligno , Pessoa de Meia-Idade , Pemetrexede , Neoplasias Peritoneais/complicações , Neoplasias Peritoneais/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Myxofibrosarcoma is a myxoid soft tissue sarcoma showing T2 high intensity on magnetic resonance imaging. However, myxofibrosarcoma is a heterogeneous sarcoma with both myxoid and cellular portions. Magnetic resonance imaging findings were obtained MRI findings for comparison with histological and Ki-67 immunohistochemical features, in different portions of one myxofibrosarcoma. CASE PRESENTATION: Magnetic resonance imaging observations were compared with gross pathological and microscopic findings of a myxofibrosarcoma from a 50-year-old Japanese female. The Ki-67 labeling indices of different portions of the tumor, that is, the myxoid, cellular, and histologically confirmed infiltrative margin portions (pathological tail sign), were compared. The T2 low intensity area was more cellular than the T2 high intensity area, while the cellular portion had a significantly higher Ki-67 index than the myxoid portion (p = 0.0313). The portions with the pathological tail sign had a significantly higher Ki-67 labeling index than those without this sign (p = 0.0313). CONCLUSIONS: More cellular portions of a myxofibrosarcoma correspond to more areas of the tumor showing aggressive features. Furthermore, our data also support the hypothesis of high aggressiveness being associated with the pathological tail sign in myxofibrosarcoma. To our knowledge, this is the first case report to describe comparisons among the imaging findings, histological features, and Ki-67 immunohistochemistry results for different portions of one myxofibrosarcoma.
Assuntos
Fibrossarcoma , Antígeno Ki-67 , Imageamento por Ressonância Magnética , Humanos , Feminino , Pessoa de Meia-Idade , Antígeno Ki-67/metabolismo , Fibrossarcoma/patologia , Fibrossarcoma/diagnóstico por imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologiaRESUMO
INTRODUCTION: Lung adenocarcinoma progresses stepwise from atypical adenomatous hyperplasia to adenocarcinoma in situ (AIS), followed by minimally invasive adenocarcinoma (MIA), and then obvious invasive adenocarcinoma. In this study, we examined the protein expression profiles of early and epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinomas. METHODS: Fifteen cases of small and EGFR mutation-positive adenocarcinomas were collected, including AIS, MIA, and small invasive adenocarcinoma (SIA). We examined their protein expression profiles by tandem mass tag (TMT)-labeling liquid chromatography-mass spectrometry (LC-MS/MS) and compared the results between AIS and MIA versus SIA. The differentially expressed proteins were then verified by Western blot analysis and immunohistochemistry (IHC). The clinicopathological implications of the proteins were also examined by IHC. RESULTS: A total of 4220 proteins were identified by LC-MS/MS analysis. Pathway analysis of the differentially expressed proteins revealed that pathways related to interferon α/ß signaling, glutamate and glutamine metabolism, and gluconeogenesis were upregulated in SIA relative to AIS. Among the 13 differentially expressed proteins, cellular retinoic acid binding protein 2 (CRABP2), delta(24)-sterol reductase (DHCR24), and adenylate kinase 4 (AK4) were expressed significantly more strongly in SIA than in AIS. Patients with high expression of CRABP2, DHCR24, and AK4 showed a significantly poorer outcome than those with low expression. CONCLUSION: In comparison with AIS, SIA shows differences in several different protein expression pathways. Furthermore, CRABP2, DHCR24, and AK4 are useful IHC markers for diagnosis of lung adenocarcinoma invasiveness and may be associated with malignant progression of AIS.
Assuntos
Adenocarcinoma in Situ , Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Proteômica , Cromatografia Líquida , Espectrometria de Massas em Tandem , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/patologia , Adenocarcinoma in Situ/genética , Adenocarcinoma in Situ/patologia , Receptores ErbB/genética , MutaçãoRESUMO
BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare locally aggressive vascular neoplasm that occurs mainly in the pediatric population. KHE usually originates just underneath the skin and affects deeper tissues through infiltrative growth; however, visceral tissue involvement is quite rare. CASE PRESENTATION: An 8-month-old girl with jaundice and acholic stool was referred to our hospital for further evaluation of a hepatoduodenal ligament tumor. A blood examination revealed high bilirubin and liver enzyme levels, but no signs of coagulopathy. The first attempt at a diagnostic surgical procedure did not provide sufficient diagnostic information. However, the histopathological diagnosis of the cystic duct excised in the second surgery indicated KHE. Therefore, in our case, KHE was considered a cause of obstructive jaundice. Sirolimus (rapamycin) was initiated, and the patient was discharged 7 months after admission. CONCLUSIONS: In cases of atypical hypervascular lesions in the abdominal cavity, especially in the pediatric population, it is important to consider the possibility of KHE, and surgical intervention with proper strategies is required for diagnosis, followed sequentially by promising treatments.
RESUMO
The management and outcome of ABO-incompatible (ABO-I) liver transplantation (LT) has been improving over the past few decades. Recently, the introduction of a pathological evaluation of acute antibody-mediated rejection (AMR) for liver allograft has provided a new recognition of allograft rejection in LT. Methods: One hundred and one pediatric ABO-I LTs performed in our institute were retrospectively analyzed. We assessed the clinical manifestations, diagnosis, and treatment of acute AMR, focusing on the recipient age and pathological findings. Results: Twelve cases (11.9%) of acute AMR related to ABO-I were observed. Nine cases developed mixed T cell-mediated rejection (TCMR)/AMR. These consisted of 6 patients in the younger age group for whom the preconditioning treatment was not indicated and 4 patients in the older age group to whom rituximab was administered as planned. Two patients in the older age group to whom preoperative rituximab was not administered as planned developed isolated AMR. Acute AMR in the older group required plasma exchange for treatment, regardless of the coexistence of TCMR. In contrast, those in the younger group were successfully treated by intravenous methylprednisolone pulse and intravenous immunoglobulin without plasma exchange, accounting for mild immune reaction. Conclusions: Acute ABO-I AMR can develop simultaneously with TCMR, even in young patients with a compromised humoral immune response following ABO-I LT. Establishing the accurate diagnosis of AMR with a pathological examination, including component 4d staining, is crucial for optimizing treatment.
RESUMO
Anaplastic large cell lymphoma (ALCL) accounts for 10-15% of childhood non-Hodgkin lymphoma cases; it is generally chemo-sensitive and is one of the most curable pediatric cancers. We report here a case of pediatric ALCL complicated with acute liver failure due to the aggravation of pre-existing biliary hepatopathy by lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). Although the initial treatment response against ALCL was very good, poor and irreversible liver function due to biliary cirrhosis worsening by lymphoma-associated HLH prevented the patient from receiving further consolidation chemotherapies. To make matters worse, his condition was accompanied with intrahepatic fungal pseudoaneurysm and invasive fungal infection. Thus, we decided to perform an urgent living-donor liver transplantation from his father to correct the patient's liver function and make it possible to proceed with further ALCL therapy. After the living-donor liver transplantation, the patient successfully received consolidation therapy with brentuximab vedotin. To our knowledge, this may be an early reported case of a pediatric patient undergoing liver transplantation during treatment for ALCL. In most patients with HLH-associated ALCL, liver function improves when ALCL is controlled. However, acute liver failure is occasionally observed in HLH cases with pre-existing liver dysfunction. In such cases, liver transplantation should be considered to correct liver dysfunctions if the disease control of HLH is satisfactory.