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1.
Gastric Cancer ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32189226

RESUMO

NTRK gene rearrangements occur in a wide spectrum of tumors and are actionable events predictive of response to TRK inhibitor. We report the first case of gastric carcinoma harboring a NTRK fusion in a 79-year-old man. The tumor was composed predominantly of poorly cohesive carcinoma with focal tubular differentiation. Solid sheet-like or nested pattern of large oxyphilic cells was also noted in 10% of tumor. Pan-Trk immunohistochemistry demonstrated Trk expression with a diffuse cytoplasmic and dot-like staining only in the solid component. Extensive lymphatic invasion and multiple nodal metastases were noted and were predominated by Trk-positive component. A novel ATP1B1-NTRK1 fusion was detected by RNA-seq using fresh frozen sample. The patient died of the disease, despite surgery and chemotherapy. Although extremely rare, NTRK rearrangement does occur in gastric carcinoma and might be associated with aggressive phenotype as well as histologic features like solid growth with extensive lymphatic invasion.

2.
Intern Med ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051379

RESUMO

An 80-year-old man with a history of cutaneous squamous cell carcinoma (SCC) was referred to our department for a solitary lung nodule. The nodule was surgically resected and diagnosed as SCC. Because the lung lesion and a previous skin lesion showed similar histological findings, the origin of the lung tumor was uncertain. Next-generation sequencing using a targeted driver oncogene panel was applied for the further examination. The lung lesion was diagnosed as primary lung SCC, as the two tumors possessed distinct somatic mutations in TP53. Recent advances in clinical sequencing have enabled us to obtain an accurate diagnosis in pathologically challenging cases.

4.
Mod Pathol ; 33(2): 206-216, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31375767

RESUMO

Gastric neoplasms exhibiting oxyntic gland differentiation typically are composed of cells with mild cytonuclear atypia differentiating to chief cells and to a lesser extent, parietal cells. Such tumors with atypical features have been reported also and terminology for this entity remains a matter of considerable debate. We analyzed and classified 26 tumors as oxyntic gland neoplasms within mucosa (group A, eight tumors) and with submucosal invasion. The latter was divided further into those with typical histologic features (group B, 14 tumors) and atypical features, including high-grade nuclear or architectural abnormality and presence of atypical cellular differentiation (group C, four tumors). Groups A and B tumors shared similar histologic features displaying either a chief cell predominant pattern characterized by monotonous chief cell proliferation, or a well-differentiated mixed cell pattern showing admixture of chief and parietal cells resembling fundic gland. In addition, group C tumors displayed atypical cellular differentiation, including mucous neck cell and foveolar epithelium. Moderate or even marked cytological atypia was noted in group C, whereas it was usually mild in the other groups except for three group B tumors with focal moderate atypia. More than 1000 µm submucosal invasion and lymphovascular invasions were recognized only in group C. Mutation analyses identified KRAS mutation in one group C tumor as well as GNAS mutation in in one group A and group B tumors. Intramucosal tumors appear to behave biologically benign and should be classified as "oxyntic gland adenoma". Those with submucosal invasion also have low malignant potential; however, a subset will have atypical features associated with aggressive histologic features and should be designated as "adenocarcinoma of fundic gland type". Especially, we suggest "adenocarcinoma of fundic gland mucosa type" for tumors with submucosal invasion exhibiting atypical cellular differentiation, because the feature is likely to be a sign of aggressive phenotype.

5.
Virchows Arch ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836926

RESUMO

Thirty years have passed since a possible association of Epstein-Barr virus (EBV) with gastric carcinoma was reported. We now know EBV-associated gastric carcinoma to be a specific subtype of gastric carcinoma. Global epigenetic methylation and counteraction of the antitumour microenvironment are two major characteristics of this subtype of gastric carcinoma. Recent development of therapeutic modalities for gastric carcinoma, such as endoscopic mucosal dissection and immune checkpoint inhibitor therapy, has made the presence of EBV infection a biomarker for the treatment of gastric carcinoma. This review presents a portrait of EBV-associated gastric carcinoma from initiation to maturity that we define as the 'gastritis-infection-cancer sequence', followed by its molecular abnormalities and interactions with immune checkpoint molecules and the microenvironment. EBV non-coding RNAs (microRNA and circular RNA) and exosomes derived from EBV-infected cells that were previously behind the scenes are now recognized for their roles in EBV-associated gastric carcinoma. The virus utilizes cellular machinery skilfully to control infected cells and their microenvironment. We should thus strive to understand virus-host interactions more fully in the following years to overcome this virus-driven subtype of gastric carcinoma.

6.
Auris Nasus Larynx ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31879078

RESUMO

A solitary fibrous tumor (SFT) is a rare neoplasm with recurrent NAB2-STAT6 gene fusion. An SFT may develop almost anywhere throughout the body, including the head and neck region, and is characterized by a broad spectrum of malignancy. Here we present a case involving a 57-year-old male with a dumbbell-shaped SFT in the cervical spine that mimicked schwannoma. Repeated fine-needle aspiration cytology failed to establish a definitive diagnosis. Given that the tumor size increased significantly over a 10-month period, open biopsy was then performed. Though the biopsy result was inconclusive, a nonepithelial tumor, including sclerosing epithelioid fibrosarcoma or ossifying fibromyxoid tumor, was suspected. The tumor was then completely removed together with adjacent parts of C2 and C3 vertebrae and left vertebral artery via combined anterior and posterior approaches. Histologically, the tumor consisted of round cells with prominent stromal hyalinization and was immunohistochemically positive for STAT6, CD34, and cytokeratin. Finally, Todai OncoPanel, a next-generation sequencing-based molecular profiling system using formalin-fixed paraffin-embedded samples, demonstrated fusion transcript in which NAB2 exon 6 was fused to STAT6 exon 16 supporting the diagnosis of SFT, while whole-exome sequencing analysis detected no somatic mutations which were known to be oncogenic.

7.
Case Rep Dent ; 2019: 6245808, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565444

RESUMO

Background: A radicular cyst is the most common odontogenic cyst of inflammatory origin. Radiographically, it commonly demonstrates clear unilocular radiolucency; radicular cysts with multilocular radiolucency are quite rare. Case Presentation: A 64-year-old Japanese man who presented with a bilocular radiolucent lesion in his left mandible was referred by a dental clinic to our oral and maxillofacial surgery department. He had no particular subjective symptoms. Orthopantomography and computed tomography (CT) revealed an 18 mm × 15 mm lesion with well-defined bilocular radiolucency in the left mandible expanding from the distal side of a canine tooth to the bottom of the 2nd premolar. The lesion included the roots of the 1st and 2nd premolars. The root of the 2nd premolar showed knife-edge resorption. Although the 1st premolar was nonvital, the 2nd premolar was a vital tooth. As differential diagnoses, a radicular cyst, ameloblastoma, odontogenic keratocyst, pseudocyst, and others might be considered. We performed a total resection of the bilocular lesion and diagnosed the lesion as a radicular cyst with tooth structure components inside. The tooth structure components represented lamellar structures of cementum; they were located only in the proximal part (under the 1st premolar) of the lesion. The distal part of the lesion presented distinctive inflammation without tooth structure components. Conclusion: We encountered a rare case of a bilocular radicular cyst with tooth structure components inside.

9.
Drug Discov Ther ; 13(3): 164-167, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31257354

RESUMO

Immune checkpoint inhibitors are associated with a wide spectrum of immune-related adverse events (irAEs) that are typically transient but are sometimes severe or even fatal. No consensus exists for the treatment of severe immune-mediated pneumonitis that is refractory to corticosteroids. Here, we report an autopsy case of pembrolizumab-induced pneumonitis that was transiently improved using infliximab. A 67-year-old male with advanced lung adenocarcinoma developed pneumonitis two weeks after a single dose of first-line pembrolizumab. The pneumonitis was refractory to corticosteroids, and the patient required mechanical ventilation. Addition of a single dose of infliximab rapidly improved the respiratory status and chest CT showed resolution of ground-glass opacities in the right upper and middle lobes. However, the patient died from re-exacerbation of pneumonitis 17 days after infliximab administration. The autopsy confirmed organizing phase diffuse alveolar damage in the right lower lobe, while the right upper lobe remained almost intact consistent with the CT findings, which is suggestive of the therapeutic effect of infliximab. The half-life of infliximab is 7-12 days, and a second dose of infliximab two weeks after the first dose is sometimes required for the treatment of gastrointestinal toxicity induced by anti-CTLA4 antibodies. Although the current guidelines do not recommend repeated administration of infliximab for immune-mediated pneumonitis, the present case suggests that repeated infliximab therapy may be beneficial in the treatment of immune-mediated pneumonitis.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Infliximab/administração & dosagem , Pneumonia/tratamento farmacológico , Adenocarcinoma de Pulmão/tratamento farmacológico , Idoso , Autopsia , Evolução Fatal , Humanos , Infliximab/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pneumonia/induzido quimicamente , Pneumonia/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
10.
Case Rep Oncol Med ; 2019: 9141870, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316849

RESUMO

Brain metastasis frequently develops in non-small-cell lung cancer (NSCLC). Here, we report a patient who developed brain metastasis from ALK-positive NSCLC which mimicked brain abscess. He was admitted for suspected obstructive pneumonia nine months after curative lung resection. Head magnetic resonance imaging revealed a cavitary lesion, which was compatible with brain abscess but rare in brain metastasis. However, after treatment with antibiotics, the brain lesion increased in size. Aspiration of the liquid content of the brain lesion revealed cancer cells. When a brain lesion suggestive of abscess develops in a patient with ALK-positive NSCLC, aspiration may be necessary to differentiate metastasis from abscess.

11.
Cancer Sci ; 110(8): 2652-2657, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31222846

RESUMO

Next-generation sequencing (NGS) has been implemented in clinical oncology to analyze multiple genes and to guide therapy. In patients with advanced lung cancer, small biopsies such as computed tomography-guided needle biopsy (CTNB), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and transbronchial biopsy (TBB) are less invasive and are preferable to resection to make a pathological diagnosis. However, the quality of DNA/RNA and NGS from small lung tumor biopsy samples is unknown. Between April 2017 and March 2018, 107 consecutive samples were obtained from thoracic tumors or metastatic sites for targeted NGS analysis. Fifteen samples were obtained through CTNB, 11 through EBUS-TBNA, 11 through TBB and 70 through surgical resection. All samples were formalin-fixed and paraffin-embedded. DNA and RNA quality was measured using the ddCq method and the percentage of RNA fragments above 200 nucleotides (DV200), respectively. Our custommade probes were designed to capture exon sequences of 464 cancer-related genes and transcripts of 463 genes. DNA and RNA yield from the 3 biopsy methods were similar, and less than the yield obtained from resected samples. The quality of DNA and RNA was similar across all methods. Overall, 12 of 15 CTNB samples (80%), all 11 EBUS-TBNA samples, and 9 of 11 TBB samples (82%) underwent successful NGS assays from DNA. NGS analysis from RNA was successful in all 12 CTNB samples, 9 of 11 EBUS-TBNA samples (82%), and 8 of 11 TBB samples (73%). CTNB, EBUS-TBNA and TBB mostly resulted in adequate DNA and RNA quality and enabled high-quality targeted NGS analysis.


Assuntos
Neoplasias Pulmonares/genética , Biópsia/métodos , DNA/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , RNA/genética
12.
Int J Hematol ; 110(3): 381-384, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31093933

RESUMO

Obstructive jaundice is an initial symptom in 1-2% of diffuse large B cell lymphoma (DLBCL) cases. The major cause of bile duct obstruction in patients with DLBCL is extrinsic compression by enlarged lymph nodes. In such cases, the existence of bile duct invasion of lymphoma is rarely mentioned or observed pathologically, so the ratio of bile duct invasion to the total cases of obstructive jaundice, and its significance remains unknown. We report two cases of DLBCL presenting as an obstructive jaundice, in which we demonstrated bile duct invasion pathologically by biopsy from the wall of common bile duct with endoscopic retrograde cholangiopancreatography (ERCP). Endoscopic stent placement is a minimally invasive procedure to relieve cholestasis and is effective for diagnosing bile duct invasion. This procedure should thus be performed in all cases of obstructive jaundice caused by lymphoma to evaluate for bile duct invasion. Our cases suggest that ERCP may be useful as a diagnostic procedure for bile duct invasion.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Colestase , Icterícia Obstrutiva , Linfoma Difuso de Grandes Células B , Idoso , Colestase/diagnóstico por imagem , Colestase/patologia , Colestase/fisiopatologia , Humanos , Icterícia Obstrutiva/diagnóstico por imagem , Icterícia Obstrutiva/patologia , Icterícia Obstrutiva/fisiopatologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/fisiopatologia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/fisiopatologia , Masculino , Invasividade Neoplásica
13.
Interact Cardiovasc Thorac Surg ; 29(3): 442-448, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31106332

RESUMO

OBJECTIVES: Spread through air space (STAS) is recognized as a pattern of invasion in lung adenocarcinoma and has been reported to be a predictor of recurrence and survival in patients with early-stage lung adenocarcinoma. However, this parameter has not been studied well in stage III (N2) lung adenocarcinoma. In this study, we evaluated the association between STAS invasion patterns and recurrence and survival in stage III (N2) lung adenocarcinoma. METHODS: We retrospectively reviewed data from 76 patients at University of Tokyo with stage III (N2) lung adenocarcinoma who underwent surgery from August 1998 to December 2013. Statistical analysis was performed to determine the impact of STAS invasion clinicopathological features and clarify the relationship between this pattern of invasion and survival. RESULTS: Tumour STAS was observed in 46 of 76 patients (60.5%) and was significantly associated with the presence of lymphatic invasion (P < 0.001), papillary components (P < 0.001) and micropapillary components (P < 0.001). STAS was also significantly associated with recurrence (5-year recurrence-free probability: 19.0% vs 46.1%, P < 0.05). Univariate analyses showed that STAS was a significant risk factor for recurrence (hazard ratio 1.94, 95% confidence interval 1.07-3.51; P = 0.029). CONCLUSIONS: The presence of STAS invasion pattern is a significant risk factor for recurrence in stage III (N2) lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão/epidemiologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/mortalidade , Pneumonectomia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências
14.
Surg Today ; 49(10): 828-835, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30968225

RESUMO

PURPOSE: We compared three-dimensional (3D) and two-dimensional (2D) measurements of the solid component to determine radiological criteria for sublobar resection of lung adenocarcinoma ≤ 2 cm in size. METHODS: We included 233 surgical cases. The maximum size of the solid component for 3D measurement was calculated by delineating the solid component on successive axial images and reconstructing the 3D surface model. RESULTS: The predictive performance for adenocarcinoma in situ (n = 43) and minimally invasive adenocarcinoma (n = 77) were equivalent to areas under the curve of 0.871 and 0.857 for 2D and 3D measurements (p = 0.229), respectively. A solid component of 5 mm had a prognostic impact on both measurements ( ≤ 5 mm versus > 5 mm; p = 0.003 for 2D and p = 0.002 for 3D, log-rank test). Survival rates at 5 years were 94.7-96.9% following lobectomy and sublobar resection among patients with a solid component ≤ 5 mm in size. Sublobar resection resulted in worse survival rates, with declines at 5 years of 15.8% on 2D and 11.5% on 3D measurements, than lobectomy in patients with a solid component > 5 mm in size. CONCLUSIONS: A solid component ≤ 5 mm in size is an appropriate criterion for sublobar resection for both measurements. In addition, 2D measurement is justified because of its simple implementation.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Imagem Tridimensional , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Tomografia Computadorizada por Raios X , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glicosídeos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia/mortalidade , Pregnanos , Taxa de Sobrevida
15.
Cancer Sci ; 110(4): 1464-1479, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30737998

RESUMO

Tumor molecular profiling is becoming a standard of care for patients with cancer, but the optimal platform for cancer sequencing remains undetermined. We established a comprehensive assay, the Todai OncoPanel (TOP), which consists of DNA and RNA hybridization capture-based next-generation sequencing panels. A novel method for target enrichment, named the junction capture method, was developed for the RNA panel to accurately and cost-effectively detect 365 fusion genes as well as aberrantly spliced transcripts. The TOP RNA panel can also measure the expression profiles of an additional 109 genes. The TOP DNA panel was developed to detect single nucleotide variants and insertions/deletions for 464 genes, to calculate tumor mutation burden and microsatellite instability status, and to infer chromosomal copy number. Clinically relevant somatic mutations were identified in 32.2% (59/183) of patients by prospective TOP testing, signifying the clinical utility of TOP for providing personalized medicine to cancer patients.


Assuntos
Perfilação da Expressão Gênica , Neoplasias/genética , Transcriptoma , Processamento Alternativo , Biomarcadores Tumorais , Biópsia , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias/diagnóstico , Neoplasias/metabolismo , Proteínas de Fusão Oncogênica/genética , Sequenciamento Completo do Genoma
17.
J Dermatol ; 46(3): 263-266, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30628111

RESUMO

Many women experience some skin reaction or trouble in their monthly menstrual cycle, including the exacerbation of pre-existing diseases and skin eruptions directly associated with sex hormones. We herein report a Japanese woman who experienced repeated systemic urticaria in her premenstrual period, and was diagnosed as having estrogen dermatitis based on a positive result of intradermal estrogen skin test. Of note, the expression of estrogen receptor-ß was increased in small dermal vessels of this case as well as in those of patients with other inflammatory skin diseases. These results suggest that inflammation may induce estrogen receptor-ß expression in small dermal vessels, which potentially modifies the pathological skin inflammation during the menstrual period, leading to the development of estrogen dermatitis.


Assuntos
Dermatite/imunologia , Receptor beta de Estrogênio/metabolismo , Estrogênios/imunologia , Ciclo Menstrual/imunologia , Urticária/imunologia , Dermatite/diagnóstico , Dermatite/patologia , Receptor beta de Estrogênio/análise , Estrogênios/metabolismo , Feminino , Humanos , Testes Intradérmicos/métodos , Pessoa de Meia-Idade , Pele/patologia , Urticária/diagnóstico , Urticária/patologia
18.
BMC Cancer ; 19(1): 52, 2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-30634950

RESUMO

BACKGROUND: Cancers of unknown primary origin (CUPs) are reported to be the 3-4th most common causes of cancer death. Recent years have seen advances in mutational analysis and genomics profiling. These advances could improve accuracy of diagnosis of CUPs and might improve the prognosis of patients with CUPs. CASE PRESENTATION: A 76-year old male with an adenocarcinoma of unknown primary origin in the lung presented with another tumor of the palate mucosa. The tumor cells in the pleural effusion were all negative for immunohistochemical markers (TTF-1 and Napsin A) and lung-specific oncogenic driver alterations (EGFR mutation and ALK translocation). The tumor of the palate mucosa was likewise identified as an adenocarcinoma, and the cells showed cytological similarities with the tumor cells in the pleural effusion; TTF-1, Napsin A, EGFR mutation and ALK translocation were all negative. This result suggested that origins of the tumors of the palate mucosa and in the lung were the same, even though the origin had not yet been determined. Next, we addressed whether the tumor of the palate mucosa was a primary tumor or not. Secretory carcinoma (SC), which is a common type of minor salivary gland tumor (MSGT), was suspected; however, mammaglobin was negative and ETV6-NTRK3 (EN) fusion was not observed. Other MSGTs were excluded based on histological and immunohistochemical findings. Furthermore, an additional examination demonstrated an oncogenic KRAS mutation at codon 12 (p.G12D) in both palate tumor and in pleural effusion. KRAS mutation is known to exist in one-third of lung adenocarcinomas (LUADs), but quite rare in MSGTs. The possibility of metastasis from other organs was considered unlikely from the results of endoscopic and imaging studies. This result indicated that the primary site of the CUP was indeed the lung, and that the tumor of the palate mucosa was a metastasis of the LUAD. CONCLUSIONS: A tumor of the palate mucosa that showed diagnostic difficulties was determined to be a metastatic LUAD by genomic alterations and histopathological findings.


Assuntos
Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Mucosa Bucal/patologia , Palato/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Idoso , Quinase do Linfoma Anaplásico/genética , Biomarcadores Tumorais , Análise Mutacional de DNA , Receptores ErbB/genética , Testes Genéticos , Humanos , Imuno-Histoquímica , Queratina-7/metabolismo , Masculino , Mucosa Bucal/metabolismo , Mutação , Palato/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Tomografia Computadorizada por Raios X
20.
Hepatol Res ; 49(3): 304-313, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30182424

RESUMO

AIM: Liver fibrosis caused by congestive hepatopathy has emerged as an important complication after Fontan procedure. We evaluated the utility of the hepatic vein (HV) waveform using Doppler ultrasound for identification of liver fibrosis in Fontan patients. METHODS: We investigated the HV waveforms in 41 Fontan patients and assessed correlations with clinical parameters, liver fibrosis markers, and hemodynamic data. RESULTS: Based on our preliminary analysis of 64 adult patients with chronic liver disease who underwent liver biopsy, we classified HV waveforms into five types with reference to the degree of flattening (from type 1, normal triphasic waveform; to type 5, a monophasic waveform indicating cirrhosis), and confirmed a significant correlation between waveform pattern and fibrosis stage. Notably, we detected HV waveforms in all of the Fontan patients and classified them into five types. The HV waveform pattern positively correlated with γ-glutamyl transferase and hyaluronic acid levels, and negatively correlated with albumin level and platelet count, but did not correlate with central venous pressure or brain natriuretic peptide level, suggesting that HV waveform could reflect pathophysiological changes in the liver without being affected by hepatic congestion. The highest area under the receiver operating characteristic curve of the HV waveform for detecting advanced liver fibrosis, as defined by ultrasonic findings and clinical features, was 0.829 (81.8% sensitivity, 73.3% specificity), which was higher than that of other non-invasive fibrosis markers. CONCLUSIONS: Hepatic vein waveforms change in accordance with liver fibrosis progression in Fontan patients, and can be a useful indicator of liver fibrosis after the Fontan procedure.

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