RESUMEN
Agarose-based cell block (CB) technique can be modified to be combined with the frozen section technique for the preparation of a high-quality frozen-embedded CB (F-CB) from an effusion or fine-needle aspiration (FNA) cytology sample. This combined technique can be effectively used for the immunocharacterization of the hematolymphoid cells on F-CB. To demonstrate the applicability of performing diagnostic ICC on F-CB, we have analyzed the immunophenotype of the hematolymphoid cells in a series of eight cases of effusions and eight cases of FNA cytology specimens by using CB-ICC on sections cut from frozen-embedded CBs. The SurePathTM residue or cytologic material scraped off from the FNA cytology smear that was diagnostic for or suspicious of hematolymphoid malignancy was pelleted and pre-embedded in agarose. Half of the agarose-embedded pellet was frozen-embedded in OCT compound for the preparation of F-CB, while the other half was processed for the preparation of paraffin-embedded CB. Sections cut from the F-CB and P-CB were used for CB-ICC. Panels of ICC on the F-CBs could enable the immunocytochemical differential diagnosis of large cell hematologic malignancies that encompass anaplastic large cell lymphoma and other forms of large-cell hematolymphoid malignancies such as large B-cell lymphomas, anaplastic plasma cell myeloma, myeloid sarcoma, and T-lymphoblastic lymphoma. It also appeared that the small B-cell lymphomas in the effusions or FNAs could be differentially diagnosed with the aid of CB-ICC on the F-CB. A modified agarose-based CB technique can be combined with the frozen-embedded CB method for the preparation of F-CB that can be directly used for the immunocytochemical differential diagnosis of hematolymphoid cytology samples.
Asunto(s)
Linfoma de Células B Grandes Difuso , Mieloma Múltiple , Humanos , Inmunohistoquímica , Sefarosa , Biopsia con Aguja Fina/métodos , Mieloma Múltiple/patología , Linfoma de Células B Grandes Difuso/patologíaRESUMEN
The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
RESUMEN
The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
RESUMEN
Autophagy, a mechanism that maintains cellular homeostasis, is involved in tumor cell growth and survival in cancer, and autophagy inhibitors have been tested clinical trials for anticancer therapy. To elucidate the clinical and prognostic implications of autophagy in small intestinal adenocarcinoma (SIAC), we assessed the expression of autophagy markers, LC3B and p62, in 171 surgically resected primary SIACs using automated quantitative analysis. Positive LC3B, p62 nuclear (p62Nu), and p62 cytoplasmic (p62Cy) expression was observed in 23 (13.5%), 52 (30.4%), and 43 (25.1%) carcinomas, respectively. LC3B+ expression was correlated with undifferentiated carcinoma (p < 0.001) and high histologic grade (p = 0.029). The combined expression of LC3B and p62Nu (LC3+/p62Nu+) was related to the older age of patients (p = 0.017), undifferentiated carcinoma (p < 0.001), and high grade (p = 0.031). LC3B+ (p = 0.006), p62Cy+ (p = 0.041), or p62Nu+ (p = 0.006) expression were associated with worse survival. In addition, SIAC patients with either LC3B+/p62Nu+ (p = 0.001) or LC3B+/p62Cy+ (p = 0.002) expression had shorter survival times. In multivariate analysis, LC3B expression remained an independent prognostic factor (p = 0.025) for overall survival. In conclusion, autophagy may play a role in the tumorigenesis of SIACs, and LC3B and p62 could be used as prognostic biomarkers and potential therapeutic targets for SIACs.
RESUMEN
Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the "Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm" to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.
RESUMEN
BACKGROUND AND AIMS: Endobiliary brushings are routinely used in the diagnosis, treatment, and prognostication of biliary strictures. However, standard Papanicolaou (Pap) staining has a low sensitivity in this setting, and the accuracy of brush cytology has not been established for indeterminate strictures. We therefore evaluated the diagnostic merit of methionyl-transfer RNA synthetase 1 (MARS1) immunofluorescence (IF) staining in such cytologic specimens. METHODS: During ERCP, endobiliary brushings were obtained from patients with extrahepatic biliary strictures prospectively enrolled at 6 tertiary hospitals. Using liquid-based cytologic preparations of these samples, we performed Pap and MARS1 IF staining. RESULTS: In total, 240 patients were eligible; of these, we compared the Pap and MARS1 IF staining results of 218 (malignant, 157; benign, 61). By conventional Pap staining, the diagnoses were distributed as follows: malignant, 55; suspicious of malignancy, 60; atypical, 45; negative for malignancy, 58. MARS1 IF staining was strongly positive in malignant biliary stricture but not so in specimens negative for malignancy. The diagnostic parameters (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) of the MARS1 IF (93.6%, 96.7%, 98.7%, 85.5%, and 94.5%, respectively) and conventional Pap (73.2%, 100%, 100%, 59.2%, and 80.7%, respectively) staining methods differed significantly (P < .0001). CONCLUSIONS: The high sensitivity and accuracy of MARS1 IF staining enabled the detection of malignancy in patients with biliary strictures. Further prospective studies are needed to validate our findings. (Clinical trial registration number: NCT03708445.).
Asunto(s)
Neoplasias de los Conductos Biliares , Colestasis , Metionina-ARNt Ligasa , Colangiopancreatografia Retrógrada Endoscópica , Constricción Patológica , Humanos , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
Endoscopic management of benign biliary stricture (BBS) remains challenging. Stenting is currently used for BBS management, but refractory BBS remains problematic. The aim of this study was to assess the safety and feasibility of a dilation balloon-equipped cylindrical light diffuser for BBS in a large animal model. A total of seven mini-pigs were used in the current study. Laser settings were chosen based on the findings of a previous animal study. Five animals were used in a preliminary study to establish process conditions. BBSs were created in the common bile ducts of the other two animals by intraductal radiofrequency ablation (RFA) via endoscopic retrograde cholangiography (ERC). At 4 weeks post-RFA, laser ablation was performed using a customized balloon-equipped cylindrical diffuser at 10 W for 10 s while maintaining balloon inflation for 10 s at 5 atm. A follow-up ERC was performed at 4 weeks post-laser ablation and the animals were sacrificed for histologic evaluation. BBS was observed in all animals by ERC at 4 weeks post-RFA. The mean bile duct stricture diameter in the two animals as determined by ERC was 0.8 mm. Laser ablations were performed without technical difficulty and no adverse event was encountered. At 4 weeks post-laser ablation, mean biliary stricture diameter had dilated to 1.6 mm on cholangiographic finding. On histologic examination, inflammatory cell infiltration in lamina propria and dense collagen deposition were observed, but there was no evidence of bile duct perforation. The devised balloon-equipped cylindrical laser light diffuser appears to be safe and feasible for the treatment of BBS. However, further studies and modifications are required before it can be applied clinically as a monotherapy.
Asunto(s)
Enfermedades de los Conductos Biliares/cirugía , Terapia por Láser/instrumentación , Animales , Enfermedades de los Conductos Biliares/diagnóstico por imagen , Conductos Biliares/diagnóstico por imagen , Conductos Biliares/patología , Colangiografía , Constricción Patológica/etiología , Constricción Patológica/patología , Constricción Patológica/cirugía , Modelos Animales de Enfermedad , Femenino , Terapia por Láser/efectos adversos , Proyectos Piloto , Porcinos , Porcinos EnanosRESUMEN
BACKGROUND: Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis. METHODS: Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses ('not-NASH,' 'borderline,' and 'NASH') of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system. RESULTS: Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52-0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH. CONCLUSIONS: A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.
RESUMEN
The first edition of the 'Standardized Pathology Report for Colorectal Cancer,' which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of "standard data elements" and "conditional data elements." Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as "standard data elements," while other prognostic factors and factors related to adjuvant therapy are classified as "conditional data elements" so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.
RESUMEN
PURPOSE: The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice. MATERIALS AND METHODS: Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs. RESULTS: Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity. CONCLUSION: Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.
Asunto(s)
Tumores Neuroendocrinos/epidemiología , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Niño , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Tumores Neuroendocrinos/etiología , Tumores Neuroendocrinos/terapia , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/terapia , Vigilancia de la Población , Pronóstico , República de Corea , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Liquid-based cytology (LBC) testing induces morphologic changes due to the use of specific fixatives and preparation techniques, and the cytologies of effusions determined in this manner differ morphologically from those of conventional cytopreparation (CCP) smear methods. We compared the cytologic features of pulmonary small cell carcinoma in effusion fluid using CCP and LBC preparations. METHODS: Fifty-three malignant effusion specimens from 36 patients with small cell carcinoma were examined, including 41 LBCs from 27 patients and 12 CCPs from 9 patients. RESULTS: LBC and CCP preparations preserved the typical features of small cell carcinoma, that is, nuclear molding, very high nuclear to cytoplasmic ratio and granular chromatin. The architectural patterns involved small cohesive clusters and chains with nuclear molding, tight three-dimensional clusters, or single cell dispersion were preserved in both preparations. Oval nuclei (83.3% vs 26.8%, P < .001) and a discernable rim of cytoplasm (66.7% vs 26.8%, P = .043) were more frequently identified in CCPs, whereas cellular degeneration and dry artifact were more frequent in LBC preparations (73.2% vs 8.3%, P < .001). LBC had a tendency to show frequent nuclear size variation (51.2% vs 25.0%) than CCP. CONCLUSION: LBC tends to show more degeneration and dry artifact with exaggerated irregular nuclear shape and nuclear size variation and scanty cytoplasm than CCP. Cytopathologists should be familiar with the cytomorphologic spectrum of this tumor in CCP and LBC prepared effusions.
Asunto(s)
Citodiagnóstico , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Anciano , Anciano de 80 o más Años , Cromatina/metabolismo , Cromatina/patología , Citoplasma/metabolismo , Citoplasma/patología , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Carcinoma Pulmonar de Células Pequeñas/patologíaRESUMEN
Background and Aim: Post endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis is not an uncommon adverse event but may not be avoidable. Various pharmacological and endoscopic techniques have been used to prevent post-ERCP pancreatitis (PEP), but most have been ineffective. The aim of this study was to evaluate the preventative effect of an intrapancreatic duct injection of nafamostat mesilate (NM) on PEP. Methods: This experimental study was conducted on 8 mini pigs. Animals were randomly allocated to a control group (n = 4) and or a NM group (n = 4). Pancreatitis was induced by infusing contrast medium into the main pancreatic duct by ERCP in all animals. After contrast medium injection, NM (50 mg/5 cc) was infused in the NM group and the same amount of 5% dextrose solution was infused in the control group. Twenty-four hours after endoscopic procedures, pancreatic inflammation, edema, vacuolization, necrosis and hemorrhage were evaluated histologically. Results: All animals survived until the end of the experiment. No peri-procedural technical difficulty or adverse event was encountered. Histologic examinations confirmed acute pancreatitis in all animals. In histologic acute pancreatitis scoring, no significant intergroup differences were observed between edema (P = 0.134), leukocyte infiltration (P = 0.356), vacuolization (P = 1.000), or hemorrhage (P = 0.071) scores. However, mean necrosis score was significantly lower in the NM group (1.0) than in controls (1.75, P = 0.024). Conclusion: NM injection into the intrapancreatic duct produced promising results with respect to the prevention of PEP development, especially regarding the prevention of necrosis.
Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Guanidinas/administración & dosificación , Conductos Pancreáticos/efectos de los fármacos , Pancreatitis/prevención & control , Inhibidores de Proteasas/administración & dosificación , Animales , Benzamidinas , Modelos Animales de Enfermedad , Humanos , Infusiones Parenterales/métodos , Necrosis/etiología , Necrosis/prevención & control , Conductos Pancreáticos/patología , Pancreatitis/etiología , Pancreatitis/patología , Proyectos Piloto , Porcinos , Porcinos EnanosRESUMEN
Background and study aims Intraductal radiofrequency ablation (ID-RFA) is a recently developed method widely used for treatment of malignant extrahepatic biliary tract obstructions. However, its safety in hilar application has yet to be clearly demonstrated. The aim of this study was to evaluate the safety of ID-RFA in the treatment of malignant hilar obstruction. Patients and methods Endoscopic retrograde cholangiography followed by temperature-controlled ID-RFA at the hilar area using different probe lengths (11, 18, and 22âmm) and settings (7 or 10âW for 60â-â120âs) was performed in six mini-pigs. In addition, patients with malignant hilar obstruction who underwent palliative ID-RFA were retrospectively evaluated. Results In the animal study using different ID-RFA settings , post-ID-RFA fluoroscopic radiocontrast leakage and microscopic bile duct perforation with hepatic abscess were observed in four of the six mini-pigs. Only two of the them, in which an 11-mm ID-RFA probe at a target temperature of 80â°C, power of 7âW, and duration of 60âs was used, underwent successful ID-RFA without any immediate adverse events (AEs). Clinically, ID-RFA was performed using the 11-mm probe with the setting of 80â°C, 7âW, and 60â-â120âs for malignant hilar obstruction, and total of 11 patients underwent successful ID-RFA without AEs. Conclusions Our study suggests that ID-RFA performed using a short-length probe with settings of 80â°C, 7âW and 60â-â120âs is a safe and feasible palliative treatment for malignant hilar obstruction.
RESUMEN
The increasing prevalence of cholesterol gallstone disease places an economic burden on the healthcare system. To identify novel therapeutics, we assessed the effects of n-3 polyunsaturated fatty acids (PUFA) in combination with UDCA in a mouse model of cholesterol gallstones. Gallstone dissolution, gallbladder wall thickness, mucin gene expression in the gallbladder, and levels of phospholipids, cholesterol, and bile acids in bile and serum were analysed. RNA was extracted from the liver for mRNA sequencing and gene expression profiling. Combination treatment resulted in greater gallstone dissolution compared with the control group, and PUFA and combination treatments reduced the thickness of the gallbladder wall. Expression levels of mucin genes were significantly lower in the UDCA, PUFA, and combination groups. Transcriptome analyses revealed that combination treatment modulated hepatic lipid metabolism. The PUFA and combination groups showed elevated bile phospholipid and bile acid levels and a lower cholesterol saturation index. Combination treatment with PUFA and UDCA dissolves cholesterol gallstones in mice by decreasing mucin production, increasing levels of phospholipids and bile acids in bile, and decreasing cholesterol saturation. Further studies of the therapeutic effects of combination PUFA and UDCA treatment in patients with cholesterol gallstones are warranted.
Asunto(s)
Colesterol/metabolismo , Ácidos Grasos Omega-3/administración & dosificación , Cálculos Biliares/tratamiento farmacológico , Ácido Ursodesoxicólico/administración & dosificación , Animales , Ácidos y Sales Biliares/metabolismo , Quimioterapia Combinada , Vesícula Biliar/efectos de los fármacos , Vesícula Biliar/metabolismo , Cálculos Biliares/metabolismo , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Fosfolípidos/metabolismoRESUMEN
PURPOSE: The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. MATERIALS AND METHODS: We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. RESULTS: The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. CONCLUSION: The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.
Asunto(s)
Carcinoma in Situ/diagnóstico , Resección Endoscópica de la Mucosa/métodos , Neoplasias Gástricas/diagnóstico , Carcinoma in Situ/patología , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Gástricas/patologíaRESUMEN
Substantial alterations at the multi-omics level of pancreatic cancer (PC) impede the possibility to diagnose and treat patients in early stages. Herein, we conducted an integrative omics-based translational analysis, utilizing next-generation sequencing, transcriptome meta-analysis, and immunohistochemistry, combined with statistical learning, to validate multiplex biomarker candidates for the diagnosis, prognosis, and management of PC. Experiment-based validation was conducted and supportive evidence for the essentiality of the candidates in PC were found at gene expression or protein level by practical biochemical methods. Remarkably, the random forests (RF) model exhibited an excellent diagnostic performance and LAMC2, ANXA2, ADAM9, and APLP2 greatly influenced its decisions. An explanation approach for the RF model was successfully constructed. Moreover, protein expression of LAMC2, ANXA2, ADAM9, and APLP2 was found correlated and significantly higher in PC patients in independent cohorts. Survival analysis revealed that patients with high expression of ADAM9 (Hazard ratio (HR)OS = 2.2, p-value < 0.001), ANXA2 (HROS = 2.1, p-value < 0.001), and LAMC2 (HRDFS = 1.8, p-value = 0.012) exhibited poorer survival rates. In conclusion, we successfully explore hidden biological insights from large-scale omics data and suggest that LAMC2, ANXA2, ADAM9, and APLP2 are robust biomarkers for early diagnosis, prognosis, and management for PC.
Asunto(s)
Coagulación con Plasma de Argón , Neoplasias de los Conductos Biliares/terapia , Endoscopía del Sistema Digestivo , Neoplasias Quísticas, Mucinosas y Serosas/terapia , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/patología , Biopsia , Humanos , Masculino , Neoplasias Quísticas, Mucinosas y Serosas/diagnóstico por imagen , Neoplasias Quísticas, Mucinosas y Serosas/patología , Valor Predictivo de las Pruebas , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: A reproducible, endoscope-based, large animal model, of acute pancreatitis was developed to meet the need for a suitable means of preclinically testing treatments. The aim of this study was to develop an endoscope-based animal model of acute pancreatitis. METHODS: This experimental study was conducted on six mini-pigs. The pancreatitis model was induced by infusing contrast medium (CM) or sodium taurocholate (TCA) under high pressure (100 mmHg) into the main pancreatic duct by endoscopic retrograde pancreatography. Animals were randomly allocated to three groups: a CM group, a 10% TCA group, and a 20% TCA group. Pancreatic injuries were evaluated histologically, and serum amylase and lipase levels were measured. RESULTS: Acute pancreatitis was observed in all animals during hematologic and histologic examinations. Serum amylase and lipase levels were significantly higher (> 10 times baseline), and pancreatic edema, vacuolization of acinar cells, and hemorrhagic necrosis were observed. Severity of pancreatitis tended to be greater in the TCA groups than in the CM group as assessed using histologic scores, and degrees of pancreatitis were found to be dose-dependently related to TCA concentration. CONCLUSION: The two endoscopic procedures described are effective and safe for creating a swine model of acute pancreatitis. The authors hope the described endoscopic methods will assist in the development of a suitable treatment strategy.