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Hepatic metachronous oligometastatic nasopharyngeal carcinoma (hmoNPC) exhibits distinct clinical characteristics compared to other types of metastatic NPC. We investigated the optimal therapy for hmoNPC. 160 patients with hmoNPC treated in Sun Yat-sen University Cancer Center between 2010 and 2021 were retrospectively recruited. A total of 56 patients were classified into the local therapy (LT) cohort, 23 into the systemic therapy (ST) cohort and 81 into the combination therapy (LT + ST) cohort. The median PFS was 7.9 months (95% confidence interval [CI]: 4.1-11.9 months) in the LT cohort, 15.5 months (95% CI: 10.5-32.3 months) in the ST cohort, and 31.3 months (95% CI: 20.3 to NA months) in the LT + ST cohort. The median OS was 41.1 months (95% CI: 30.0-54.0 months) in the LT cohort, 50.4 months (95% CI: 41.5 to NA months) in the ST cohort and not reached (NR) (95% CI: 77.3 to NA months) in the LT + ST cohort. Cox analysis was used to construct nomograms to predict patient outcomes. Among patients with no evidence of disease status after LT, the prognosis was significantly better in the LT + ST cohort than LT cohort (median PFS: NR [95% CI: 29.0 to NA months] vs. 20.0 months [95% CI: 10.4 to NA months]). More survival benefits were achieved with platinum-based chemotherapy than oral monotherapy (median PFS: NR [95% CI: 21.7 to NA months] vs. 17.2 months [95% CI: 10.2 to NA months]). Fewer postoperative early progression events were observed in neoadjuvant chemotherapy cohort than in adjuvant chemotherapy cohort (2.78% vs. 18.81%, P = .013). In conclusion, combining neoadjuvant platinum-based chemotherapy and local therapy was the best strategy for patients with hmoNPC.
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Neoplasias Hepáticas , Carcinoma Nasofaríngeo , Humanos , Masculino , Feminino , Estudos Retrospectivos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Adulto , Idoso , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Segunda Neoplasia Primária/terapia , Segunda Neoplasia Primária/patologia , Adulto JovemRESUMO
Pure primary gastric squamous cell carcinoma (PGSCC) is a notably rare gastric malignancy. We present the case of a 51-year-old woman with advanced gastric squamous cell carcinoma characterized by a 7.6 cm necrotic mass invading the proximal stomach, liver metastasis, and lymphadenopathy at diagnosis. Despite the lack of standardized treatment protocols, we review tumor markers and potential management strategies, including surgical and chemotherapeutic interventions. The rarity and aggressive nature of PGSCC necessitates further research to develop effective detection and treatment methods to improve patient prognosis and survival outcomes.
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BACKGROUND: Spontaneous hepatic hemorrhage is a rare condition, most commonly diagnosed in patients with hepatocellular carcinoma or hepatic adenomas, and is seldom caused by metastatic disease. In this case report, we present a patient with spontaneous hepatic hemorrhage due to hepatic metastasis of papillary thyroid carcinoma, an exceptionally rare occurrence. CASE PRESENTATION: The patient was a 77-year-old white male with a history of atrial fibrillation treated with apixaban. He presented at a local hospital with abdominal pain and nausea. A CT scan revealed a hepatic lesion in segment 3 with an adjacent hematoma. He was referred to our tertiary center and treated conservatively. Further evaluation revealed an intrathoracic goiter containing a tumorous process diagnosed as a papillary thyroid carcinoma (PTC), and the patient subsequently underwent thyroidectomy. A biopsy of the hepatic lesion confirmed it as a PTC metastasis. Due to worsening abdominal pain and anorexia, the patient underwent subacute hepatic segmental resection. Postoperatively, he developed iodine-refractory disease with disseminated metastasis and passed away 22 months after the initial admission. CONCLUSIONS: To our knowledge, this is the first recorded case of metastasized papillary thyroid carcinoma presenting with spontaneous hepatic hemorrhage-adding to the list of rare causes for this condition.
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Hemorragia , Neoplasias Hepáticas , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Masculino , Idoso , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/secundário , Câncer Papilífero da Tireoide/secundário , Câncer Papilífero da Tireoide/complicações , Câncer Papilífero da Tireoide/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/complicações , Hemorragia/etiologia , Tomografia Computadorizada por Raios X , Evolução Fatal , Tireoidectomia , Carcinoma Papilar/secundário , Carcinoma Papilar/patologia , Carcinoma Papilar/complicaçõesRESUMO
PURPOSE: Outcomes of unresectable biliary tract cancer (BTC) with varying extents of liver involvement remain unclear. We evaluated characteristics and outcomes of BTC patients with liver metastases who underwent chemotherapy. METHODS: We retrospectively reviewed consecutive BTC patients with synchronous or metachronous intrahepatic metastases who started first-line chemotherapy at our institution between January 2016 and December 2021. RESULTS: Ninety-six patients were included, of which 57 only had liver metastases and 39 had multiorgan involvement. The liver only group had longer median overall survival (OS) (11.8 vs. 7.4 months, P = 0.006) and median progression-free survival (PFS) (4.1 vs. 2.7 months, P = 0.035) than the multiorgan group. Patients with oligometastases (defined as no more than three liver metastases) achieved longer OS than those with polymetastases (four or more liver metastases) in the entire cohort. Within the liver only group, there were no significant differences in OS or PFS between the oligometastasis and polymetastasis groups. Patients who underwent subsequent surgery had significantly longer median OS than those who did not (44.4 vs. 7.7 months, P < 0.001). Age ≥ 75 years, liver-only metastasis, modified Glasgow prognostic score ≥ 1 carcinoembryonic antigen ≥ 5 µg/L, and subsequent surgery were independent predictors of OS. Liver oligometastasis was only a significant predictor of longer OS in univariate Cox analysis. CONCLUSIONS: Outcomes in BTC patients with metastases limited to the liver, particularly those with oligometastasis, were more favorable than those with multiorgan metastases. Selected cases, generally with liver oligometastases, may achieve prolonged OS through subsequent surgery.
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Neoplasias do Sistema Biliar , Neoplasias Hepáticas , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Humanos , Masculino , Feminino , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Taxa de Sobrevida , Colangiocarcinoma , Metástase NeoplásicaRESUMO
We present a rare case of focal F-18-2-fluoro-2-deoxyglucose (FDG) uptake in the liver observed during a modified dual-time-point F-18 FDG positron emission tomography (PET)/computed tomography (CT), so-called early delayed scanning, in a 53-year-old woman diagnosed with breast cancer. This metastatic lesion was revealed in 80 min delayed images after FDG injection, but not in the usual one-hour images after injection. Modified dual-time-point F-18 FDG PET/CT is convenient because compared to the 2 h delayed images of dual-time-point PET/CT, it has a shorter scanning time and avoids additional radiation exposure.
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Hepatoid adenocarcinoma of the stomach (HAS) represents a rare malignant neoplasm sharing morphological and immunophenotypic similarities with hepatocellular carcinoma (HCC). Pathological morphology serves as the cornerstone for diagnosis, often accompanied by elevated alpha-fetoprotein (AFP) levels, nonspecific clinical symptoms, and imaging features reminiscent of gastric adenocarcinoma (GA). Liver metastases from HAS can mimic the enhancement patterns of HCC, posing challenges in differentiation from high-risk HCC cases. Conversely, HAS typically exhibits poorer prognostic outcomes compared to HCC and GA. This report presents a case of HAS with liver metastasis alongside a comprehensive literature review covering its pathology, molecular mechanisms, clinical presentations, and treatment modalities. Special focus is given to imaging characteristics and the utilization of radiomics for early-stage detection. The integration of imaging findings with laboratory results aids in HAS diagnosis, while radiomics provides novel insights for precise discrimination. In conclusion, the identification of distinct imaging markers distinguishing HAS from HCC and GA shows promise in facilitating optimal treatment strategies and improving patient outcomes.
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This study aimed to establish a machine learning (ML) model for predicting hepatic metastasis in esophageal cancer. We retrospectively analyzed patients with esophageal cancer recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2020. We identified 11 indicators associated with the risk of liver metastasis through univariate and multivariate logistic regression. Subsequently, these indicators were incorporated into six ML classifiers to build corresponding predictive models. The performance of these models was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. A total of 17,800 patients diagnosed with esophageal cancer were included in this study. Age, primary site, histology, tumor grade, T stage, N stage, surgical intervention, radiotherapy, chemotherapy, bone metastasis, and lung metastasis were independent risk factors for hepatic metastasis in esophageal cancer patients. Among the six models developed, the ML model constructed using the GBM algorithm exhibited the highest performance during internal validation of the dataset, with AUC, accuracy, sensitivity, and specificity of 0.885, 0.868, 0.667, and 0.888, respectively. Based on the GBM algorithm, we developed an accessible web-based prediction tool (accessible at https://project2-dngisws9d7xkygjcvnue8u.streamlit.app/ ) for predicting the risk of hepatic metastasis in esophageal cancer.
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Neoplasias Esofágicas , Neoplasias Hepáticas , Aprendizado de Máquina , Humanos , Neoplasias Esofágicas/patologia , Neoplasias Hepáticas/secundário , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Fatores de Risco , Curva ROC , Programa de SEERRESUMO
Colorectal cancer (CRCa) is the most frequent gastrointestinal (GI) malignancy, while the liver is the most common site of distant metastases from CRCa, arising from hematogenous spread mainly via the portal venous system. The multiform nature of tumor presentation necessitates a comprehensive approach to diagnosis, perioperative care, and oncological treatment strategy. Herein, we present a case of a 76-year-old male patient diagnosed with obstructive bowel ileus due to a sigmoid tumor with synchronous, suspicious for metastasis, liver lesion who underwent Hartmann's sigmoidectomy in conjunction with left lateral hepatic resection at the same time. Intraoperatively significant blood loss occurred, while the postoperative course of the patient included pulmonary embolism (PE) six days after the procedure, being discharged on postoperative day (POD) 21. After oncological consensus, the patient underwent adjuvant chemotherapy and his reevaluation nine months after surgery confirmed that he is free of active disease. It is evident, however, that the number of existing studies concerning synchronous metastasectomy alongside CRCa resection in an emergency setting is limited and the literature gaps on this matter emphasize the need for further research.
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Adesão Celular , Neoplasias do Colo , Neoplasias Hepáticas , Proteínas Associadas a Pancreatite , Humanos , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Linhagem Celular Tumoral , Proteínas Associadas a Pancreatite/metabolismo , Proteínas Associadas a Pancreatite/genética , Animais , Regulação Neoplásica da Expressão Gênica , CamundongosRESUMO
Hepatoid adenocarcinoma (HAC) is a rare form of adenocarcinoma that is diagnosed based on immuno-histochemical findings reminiscent of hepatocellular carcinoma (HCC). The clinical characteristics of HAC include increased levels of serum alpha-fetoprotein and a poor prognosis due to early liver metastasis. In particular, diagnosing liver metastasis of HAC can be challenging owing to radiological findings similar to those of HCC. Although HAC can occur in various organs, the stomach is the most common site. We present the case of a 64-year-old femalewho presented with multiple tumors in the liver. During subsequent examination, rectal cancer was identified and diagnosed as HAC through a biopsy. Herein, we report this case along with a literature review.
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OBJECTIVES: This study aimed to evaluate the prognostic significance of postoperative Creatine Kinase type M and B (CK-MB) to total Creatine Kinase (CK) ratio (CK-MB/CK) in colorectal cancer (CRC) patients after radical resection. METHODS: This was a single-center retrospective cohort analysis. Subjects were stage I-III CRC patients hospitalized in Sichuan Cancer Hospital from January 2017 to May 2021. Patients were divided into abnormal group and normal group according to whether the CK-MB/CK ratio was abnormal after surgery. Through a comparative analysis of clinical data, laboratory test results, and prognosis differences between the two groups, we aimed to uncover the potential relationship between abnormal CK-MB > CK results and CRC patients. To gauge the impact of CK-MB/CK on overall survival (OS) and disease-free survival (DFS), we employed the multivariable COX regression and LASSO regression analysis. Additionally, Spearman correlation analysis, logistic regression, and receiver-operating characteristic (ROC) curve analysis were conducted to assess the predictive value of the CK-MB/CK ratio for postoperative liver metastasis. RESULTS: Cox regression analysis revealed that the CK-MB/CK ratio was a stable risk factors for OS (HR = 3.82, p < 0.001) and DFS (HR = 2.31, p < 0.001). To distinguish hepatic metastases after surgery, the ROC area under the curve of CK-MB/CK was 0.697 (p < 0.001), and the optimal cut-off value determined by the Youden index was 0.347. CONCLUSIONS: Postoperative abnormal CK-MB/CK ratio predicts worse prognosis in CRC patients after radical resection and serves as a useful biomarker for detecting postoperative liver metastasis.
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Neoplasias Colorretais , Humanos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Idoso , Biomarcadores Tumorais/sangue , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Creatina Quinase/sangue , Creatina Quinase Forma MB/sangue , Curva ROC , Adulto , Intervalo Livre de DoençaAssuntos
Carcinoma Adenoide Cístico , Neoplasias Hepáticas , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/secundário , Carcinoma Adenoide Cístico/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Colorectal cancer, a leading cause of cancer-related deaths, often results in liver metastases, with about half of patients affected. For those ineligibles for surgery, percutaneous microwave ablation (MWA) offers a viable alternative. Conventionally, visualizing liver lesions prior to MWA demands significant IV contrast, often needing repeated sessions. We introduce a technique using minimal IV contrast to treat multiple metastatic lesions simultaneously. A case of a 47-year-old male with stage 4 colorectal adenocarcinoma and multiple liver metastases is presented. Instead of the typical 100-150 cc of IV contrast, our method used just 25 cc, successfully ablating 6 hepatic metastases in 1 session. This approach not only reduces contrast volume but also optimizes treatment efficiency.
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BACKGROUND/AIM: The aim of this study was to describe and evaluate the patterns, perioperative outcomes, and survival rates of patients subjected to hepatic resections for ovarian-derived liver metastasis as part of cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Furthermore, we investigated two subgroups of tumor patterns: hematogenous liver metastasis and infiltrative liver metastatic spread. PATIENTS AND METHODS: A retrospective study was conducted. Patients from a University Tertiary Hepatic and Peritoneal Surface Malignancy Center with primary or recurrent ovarian cancer, who underwent liver resection as part of cytoreductive surgery between January 1992 and December 2022, were included. RESULTS: Data from 35 patients were analyzed. Both median overall survival (OS) and disease-specific survival (DSS) were 24.97 months. In a multivariate setting, the combined effect of age, peritoneal carcinomatosis index, body mass index, hematogenous liver metastasis vs. infiltrative spread types, and HIPEC (HR=0.2372; 95%CI=0.0719-0.7823; p=0.0181) over OS was tested. Survival analysis revealed no differences between the two metastatic spread types (OS: p=0.9720; DSS: p=0.9610). Younger age (p=0.0301), splenectomy (p=0.0320), lesser omentectomy (p=0.0178), and right upper quadrant peritonectomy (p=0.0373) were more characteristic for those patients with infiltrative liver metastatic spread. CONCLUSION: Complete cytoreductive surgery, including hepatic resection is a feasible approach with or without additional HIPEC, which may provide survival benefit for patients with advanced and/or recurrent ovarian cancer. If metastatic and infiltrative liver involvement is suspected, liver-specific imaging is recommended.
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Hipertermia Induzida , Neoplasias Hepáticas , Neoplasias Ovarianas , Neoplasias Peritoneais , Humanos , Feminino , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Hipertermia Induzida/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Procedimentos Cirúrgicos de Citorredução/métodos , Resultado do Tratamento , Neoplasias Hepáticas/tratamento farmacológico , Taxa de Sobrevida , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Solid pseudopapillary neoplasm (SPN) is a rare tumor mostly occurring in the pancreas. They are low-grade malignant tumors of the exocrine pancreas that occasionally metastasize, usually to the liver or peritoneum. Additionally, multiple metastases of extrapancreatic SPN to the liver are extremely rare and have been reported before. This study presents a case of a 13-year-old male patient with retroperitoneal SPN and multiple hepatic metastases. The patient presented with abdominal trauma and underwent enhanced CT, which revealed upper pancreatic occupancy and three hypodense foci in the right lobe of the liver. Moreover, increased spleen size was noted. The patient's serum tumor marker CA125 was increased to 39.00 U/mL (N < 35.0 U/mL), and circulating tumor cells were elevated to 10.2 FU/3 mL (N < 8.7 FU/3 mL). The patient underwent retroperitoneal occupancy resection and splenectomy, followed by resection of liver metastases 7 months after the surgery. Furthermore, multiple liver metastases from retroperitoneal SPN were confirmed postoperatively. The patient recovered for 1 year without tumor recurrence. This case emphasizes the importance of evaluating serum tumor markers and medical imaging in young patients as well as the fact that surgery appears to be the preferred treatment option for multiple metastases in SPN.
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PURPOSE: To assess the inter-reader reproducibility of radiomics features on multiple MRI sequences after segmentations of colorectal liver metastases (CRLM). METHOD: 30 CRLM (in 23 patients) were manually delineated by three readers on MRI before the start of chemotherapy on the contrast enhanced T1-weighted images (CE-T1W) in the portal venous phase, T2-weighted images (T2W) and b800 diffusion weighted images (DWI). DWI delineations were copied to the ADC-maps. 107 radiomics features were extracted per sequence. The intraclass correlation coefficient (ICC) was calculated per feature. Features were considered reproducible if ICC > 0.9. RESULTS: 90% of CE-T1W features were reproducible with a median ICC of 0.98 (range 0.76-1.00). 81% of DWI features were robust with median ICC = 0.97 (range 0.38-1.00). The T2W features had a median ICC of 0.96 (range 0.55-0.99) and were reproducible in 80%. ADC showed the lowest number of reproducible features with 58% and median ICC = 0.91 (range 0.38-0.99) When considering the lower bound of the ICC 95% confidence intervals, 58%, 66%, 54% and 29% reached 0.9 for the CE-T1W, DWI, T2W and ADC features, respectively. The feature class with the best reproducibility differed per sequence. CONCLUSIONS: The majority of MRI radiomics features from CE-T1W, T2W, DWI and ADC in colorectal liver metastases were robust for segmentation variability between readers. The CE-T1W yielded slightly better reproducibility results compared to DWI and T2W. The ADC features seem more susceptible to reader differences compared to the other three sequences.
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Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Reprodutibilidade dos Testes , Radiômica , Imageamento por Ressonância Magnética/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagemRESUMO
Hepatic metastasis is a major cause of colorectal cancer (CRC)-related deaths. Presently, the role of long non-coding RNAs (lncRNAs) in hepatic metastases from CRC is elusive. We dissected possible interplay between LINC00858/miR-132-3p/IGF2BP1 via bioinformatics approaches. Subsequently we analyzed mRNA expression of LINC00858, miR-132-3p and IGF2BP1 through qRT-PCR. Western blot was used to detect protein expression of IGF2BP1. RNA immunoprecipitation chip and dual-luciferase assay validated interaction between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Cell viability, invasion, and migration were examined via CCK-8, colony formation, transwell and wound healing assays. Effect of LINC00858 on CRC hepatic metastases was validated via in vivo assay. Upregulated LINC00858 and IGF2BP1, and downregulated miR-132-3p were predicted in tumor tissues of patients with hepatic metastases from CRC. There were targeting relationships between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Besides, LINC00858 facilitated progression of CRC cells. Rescue assay suggested that silencing LINC00858 suppressed CRC cell progression, while further silencing miR-132-3p or overexpressing IGF2BP1 reversed such effects. LINC00858 could facilitate CRC tumor growth and hepatic metastases. LINC00858 induced CRC hepatic metastases via regulating miR-132-3p/ IGF2BP1, and this study may deliver a new diagnostic marker for the disease.
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Neoplasias Colorretais , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Colorectal cancer is one of the most common malignant tumors. At the advanced stage of colorectal cancer, cancer cells migrate with the blood to the liver from the hepatic portal vein, eventually resulting in a portal vein tumor thrombus (PVTT). To date, the progression of the early onset of PVTT [portal vein microthrombus (PVmT) induced by tumors] is unclear. Herein, we developed an on-chip PVmT model by loading the spheroid of colorectal cancer cells into the portal vein of a hepatic lobule chip (HLC). On the HLC, the progression of PVmT was presented, and early changes in metabolites of hepatic cells and in structures of hepatic plates and sinusoids induced by PVmT were analyzed. We replicated intrahepatic angiogenesis, thickened blood vessels, an increased number of hepatocytes, disordered hepatic plates, and decreased concentrations of biomarkers of hepatic cell functions in PVmT progression on a microfluidic chip for the first time. In addition, the combined therapy of thermo-ablation and chemo-drug for PVmT was preliminarily demonstrated. This study provides a promising method for understanding PVTT evolution and offers a valuable reference for PVTT therapy.
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Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) account for 80% of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). GEP-NETs are well-differentiated tumors, highly heterogeneous in biology and origin, and are often diagnosed at the metastatic stage. Diagnosis is commonly through clinical symptoms, histopathology, and PET-CT imaging, while molecular markers for metastasis and the primary site are unknown. Here, we report the identification of multi-gene signatures for hepatic metastasis and primary sites through analyses on RNA-SEQ datasets of pancreatic and small intestinal NETs tissue samples. Relevant gene features, identified from the normalized RNA-SEQ data using the mRMRe algorithm, were used to develop seven Machine Learning models (LDA, RF, CART, k-NN, SVM, XGBOOST, GBM). Two multi-gene random forest (RF) models classified primary and metastatic samples with 100% accuracy in training and test cohorts and >90% accuracy in an independent validation cohort. Similarly, three multi-gene RF models identified the pancreas or small intestine as the primary site with 100% accuracy in training and test cohorts, and >95% accuracy in an independent cohort. Multi-label models for concurrent prediction of hepatic metastasis and primary site returned >98.42% and >87.42% accuracies on training and test cohorts, respectively. A robust molecular signature to predict liver metastasis or the primary site for GEP-NETs is reported for the first time and could complement the clinical management of GEP-NETs.
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Neoplasias Intestinais , Neoplasias Hepáticas , Tumores Neuroendócrinos , Humanos , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Neoplasias Hepáticas/genéticaRESUMO
Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.