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BACKGROUND AND AIMS: EUS-guided fine-needle biopsy (EUS-FNB) performed with a Franseen needle or Fork-tip needle enables greater tissue acquisition. However, it is unknown whether EUS-FNB could contribute to lymphadenopathy genomic profiling. The aim of this study was to determine the efficacy of EUS-FNB using a Franseen or Fork-tip needle for tissue acquisition and genomic profiling in patients with lymphadenopathy. PATIENTS AND METHODS: Patients with abdominal lymphadenopathy who underwent EUS-guided fine needle aspiration (FNA)/EUS-FNB were included in this study. The amount of acquired tissue and its suitability for genomic profiling were compared between FNA and FNB. Specimen quality was evaluated by a widely used pathologic adequacy scoring system (0: insufficient; 1 to 2: cytologic; 3: limited histologic; 4 to 5: sufficient histologic). The criteria of FoundationOne CDx (F1CDx) and NCC Oncopanel (NOP) were used to assess the suitability for genomic profiling. RESULTS: In total, 72 patients underwent EUS-FNA, and the other 20 patients underwent EUS-FNB. The pathologic adequacy score and suitability for genomic profiling based on the criteria were significantly higher for FNB than for FNA [histologic adequacy score: 5 (4 to 5) versus 3 (0 to 5), P<0.01; F1CDx: 16.7% vs. 0%, P=0.01; NOP: 66.7% vs. 7.5%, P<0.01]. In multivariate analysis, EUS-FNB was identified as the only factor that influenced the suitability for genomic profiling based on the above-mentioned criteria (odds ratio 19.5, 95% CI: 3.74-102, P<0.01). CONCLUSIONS: EUS-FNB performed using Franseen or Fork-tip needles may result in greater lymphadenopathy tissue acquisition and thus enhanced suitability for genomic profiling compared with EUS-FNA.
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Convergence provides clues to unveil the non-random nature of evolution. Intermediate paths toward convergence inform us of the stochasticity and the constraint of evolutionary processes. Although previous studies have suggested that substantial constraints exist in microevolutionary paths, it remains unclear whether macroevolutionary convergence follows stochastic or constrained paths. Here, we performed comparative genomics for hundreds of lactic acid bacteria (LAB) species, including clades showing a convergent gene repertoire and sharing fructose-rich habitats. By adopting phylogenetic comparative methods we showed that the genomic convergence of distinct fructophilic LAB (FLAB) lineages was caused by parallel losses of more than a hundred orthologs and the gene losses followed significantly similar orders. Our results further suggested that the loss of adhE, a key gene for phenotypic convergence to FLAB, follows a specific evolutionary path of domain architecture decay and amino acid substitutions in multiple LAB lineages sharing fructose-rich habitats. These findings unveiled the constrained evolutionary paths toward the convergence of free-living bacterial clades at the genomic and molecular levels.
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Fructosa , Lactobacillales , Filogenia , Fructosa/metabolismo , Lactobacillales/genética , Lactobacillales/metabolismo , Lactobacillales/clasificación , Evolución Molecular , Genoma Bacteriano , Evolución Biológica , Ecosistema , GenómicaRESUMEN
BACKGROUND AND AIMS: When endoscopic retrograde cholangiopancreatography-guided biliary drainage is challenging, endoscopic ultrasound-guided biliary drainage (EUS-BD) can be used as an alternate treatment; however, this method requires operator expertise. Therefore, this study aimed to clarify the factors that are associated with a difficult EUS-BD. PATIENTS AND METHODS: Patients who successfully underwent EUS-BD were enrolled in this study. The patients were divided into the easy group and difficult group depending on whether the procedural time was more than 60 minutes, which was the cutoff value elicited from past reports. Patient characteristics and procedural factors were compared between the two groups. The factors associated with difficult procedures were also investigated. RESULTS: The patient characteristics were not significantly different between the easy group (n=22) and the difficult group (n=19). The diameter of the punctured bile duct was significantly different between the two groups. In the multivariate analysis, the diameter of the punctured bile duct was the only factor associated with a difficult EUS-BD (odds ratio 0.65, 95% confidence interval 0.46-0.91, P value=0.012). The cutoff value for the diameter of the punctured bile duct in predicting a difficult EUS-BD was 7.0 mm (area under the curve: 0.83, sensitivity 84.2%, specificity 86.4%). CONCLUSIONS: A nondilated bile duct might be a predictive factor for a difficult EUS-BD. For beginners of EUS-BD, the cutoff value for the punctured bile duct diameter found in this study, 7.0 mm, might become a barometer for puncture point selection.
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Colestasis , Endosonografía , Humanos , Endosonografía/métodos , Colestasis/diagnóstico por imagen , Colestasis/cirugía , Colangiopancreatografia Retrógrada Endoscópica , Conductos Biliares/diagnóstico por imagen , Conductos Biliares/cirugía , Drenaje/métodos , Ultrasonografía Intervencional , StentsRESUMEN
OBJECTIVE: The optimal management strategy for patients with accessory renal arteries undergoing endovascular aortic repair is unclear. This study aimed to investigate the impact of accessory renal artery (aRA) embolization on postoperative renal deterioration and to identify the predictors of postoperative renal deterioration in patients who underwent endovascular aortic repair (EVAR). METHODS: A retrospective single-centre observational study was conducted at our hospital. Of 331 consecutive patients who underwent endovascular aortic repair between April 2011 and February 2021, 29 patients with an aRA were included in this study. Spearman's rank correlation coefficients of decrease in estimated glomerular filtration rate (eGFR), renal volume reduction rate, infarcted renal volume, and quantity of contrast use for postoperative renal deterioration were analyzed. The correlation coefficients of the correlations between infarcted renal volume, renal volume reduction rate, and decrease in eGFR and the rate of aRA diameter were also analyzed. Multivariable nominal logistic regression analyses were conducted to evaluate the odds of postoperative renal deterioration. RESULTS: The renal volume reduction rate and infarcted renal volume had a significant positive correlation with the decrease in eGFR. Body surface area and preoperative renal volume were significantly but negatively correlated with the decrease in eGFR. The infarcted renal volume, renal volume reduction rate, and decrease in eGFR were significantly and positively correlated with the aRA diameter. The odds ratio for decreased eGFR rate in preoperative renal volume was .96 (95% CI 0.930â.996, P = .009). CONCLUSIONS: EVAR with aRA embolization impacts postoperative renal deterioration in patients with preoperative low renal volume, and the diameter of the embolized aRA might be a predictor of postoperative renal deterioration.
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Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Enfermedades Renales , Humanos , Reparación Endovascular de Aneurismas , Arteria Renal/diagnóstico por imagen , Arteria Renal/cirugía , Estudios Retrospectivos , Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/efectos adversos , Resultado del Tratamiento , Procedimientos Endovasculares/efectos adversos , Factores de RiesgoRESUMEN
An 85-year-old woman underwent aortic arch replacement and thoracic endovascular aortic repair (TEVAR) 5 years ago. She suffered from chest and back pain. Computed tomography (CT) demonstrated enlargement of the aortic aneurysm by a type â ¢b endoleak. TEVAR was performed to close a type â ¢b endoleak with a relining technique uneventfully. Intraoperative completion aortography and postoperative CT confirmed the disappearance of a type â ¢b endoleak. She was discharged 27 days after the treatment.
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Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Femenino , Humanos , Anciano de 80 o más Años , Prótesis Vascular , Endofuga/diagnóstico por imagen , Endofuga/etiología , Endofuga/cirugía , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/métodos , Reparación Endovascular de Aneurismas , Stents , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Resultado del Tratamiento , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Estudios RetrospectivosRESUMEN
A 53-year-old man presented to the emergency department with chest and back pain. Contrast-enhanced computed tomography( CT) revealed a Stanford type A acute aortic dissection with a pseudo-lumen occlusion. On the same day, the patient underwent emergent aortic arch replacement with frozen elephant trunk. When introducing cardiopulmonary bypass, arterial cannula was inserted into the right femoral artery. The day after surgery, swelling of the right lower leg appeared with CK and intramuscular compartment pressure elevation. Thus, the patient was diagnosed with compartment syndrome and decompressive fasciotomy was performed. Although there was no preoperative blood flow disturbance in the lower extremities on preoperative CT, lower limbs ischemia happened. Necrotic muscles in his right leg required debridement, but amputation was not needed. The patient was discharged unaided utilising orthotics on the day 120. In muscular, young male patients, care should be taken in the method of blood delivery.
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Disección Aórtica , Síndromes Compartimentales , Humanos , Masculino , Persona de Mediana Edad , Síndromes Compartimentales/diagnóstico por imagen , Síndromes Compartimentales/etiología , Síndromes Compartimentales/cirugía , Pierna , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Puente Cardiopulmonar , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/cirugíaRESUMEN
Endoscopic ultrasound-guided biliary drainage (EUS-BD) may prevent stent placement at the bile duct stricture. Therefore, whether a plastic stent (PS) or metallic stent (MS) should be used for EUS-BD remains to be undetermined. The present study aimed to clarify whether a PS or MS was more efficient for EUS-BD. Patients with malignant biliary obstruction who were successfully treated with EUS-BD were enrolled in the present study. The clinical characteristics, procedural outcomes and time to recurrent biliary obstruction (TRBO) were compared between patients treated with a PS (PS group) and patients treated with an MS (MS group). Consequently, 28 patients underwent PS placement and 11 patients underwent MS placement. In the PS group, 12 patients also underwent EUS-antegrade stenting (AGS) using an MS. The TRBO was not significantly different between the two groups (P=0.25). When the patients with AGS were excluded, the TRBO was significantly longer in the MS group than in the PS group (P=0.036). However, the TRBO was not significantly different between the patients in the MS group and those in the PS group who underwent AGS (P=0.61). In EUS-BD, MS is expected to be associated with a longer TRBO than PS. However, combining EUS-BD with AGS may help overcome the shorter TRBO associated with the use of PS.
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A 76-year-old man had been under observation for nephrotic syndrome. He suffered from hypotension and transient loss of consciousness. He was diagnosed with thoracic aortic aneurysm and severe aortic valve stenosis. Ascending aorta replacement concomitant with aortic valve replacement was performed uneventfully. He was diagnosed with light chain amyloidosis by pathological examination of the resected ascending aorta. He was received referral treatment for amyloidosis.
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Aneurisma de la Aorta Torácica , Aneurisma de la Aorta , Estenosis de la Válvula Aórtica , Masculino , Humanos , Anciano , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Aneurisma de la Aorta/cirugía , Aorta/cirugía , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/complicacionesRESUMEN
A 59-year-old woman was transferred to our hospital because of a sudden onset of chest and back pain. Computed tomography (CT) demonstrated Stanford type A acute aortic dissection with cardiac tamponade and right airway bleeding. Hemorrhage from ruptured false lumen extended along the pulmonary artery (PA), compression of the right PA were recognized due to hematoma surrounding the PA. An emergency operation was performed. The primary tear was located at the distal aortic arch, and total arch replacement with frozen elephant trunk was performed. During the operation, she had airway bleeding. The bleeding was thought to be due to the hematoma extending along the pulmonary artery. She was extubated 7th postopratively. She was discharged 44 days after the operation.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Femenino , Humanos , Persona de Mediana Edad , Aneurisma de la Aorta Torácica/complicaciones , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular/métodos , Disección Aórtica/complicaciones , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Aorta Torácica/cirugía , Hemorragia/diagnóstico por imagen , Hemorragia/etiología , Hemorragia/cirugía , Hematoma/cirugía , Pulmón/cirugíaRESUMEN
PURPOSE: Drug-induced interstitial lung disease (ILD) is not a rare adverse event in the current chemotherapy strategy for pancreatic ductal adenocarcinoma (PDAC). Thus, we aimed to find the optimal management for PDAC patients with a history of ILD induced by a gemcitabine-based regimen. METHODS: We conducted a multicenter retrospective study. The primary endpoint was the overall survival (OS) of patients who underwent either S-1 monotherapy or FOLFOX after the onset of ILD. Toxicity data was also analyzed in the 2 groups. RESULTS: Twenty-four patients were diagnosed with ILD and 17 patients who received subsequent chemotherapy were enrolled in the study. Among 17 patients who were managed with subsequent chemotherapy after recovering from ILD, we did not observe significant difference in OS between S-1 and FOLFOX (290.0 days vs. undefined, p = 0.39). Relapse of drug-induced ILD was not observed in all cases during the course. Overall, severe adverse events (CTCAE Grade 3 or 4) were observed in 3 patients (23.1%) in S-1 treatment group and 1 patient (25.0%) in FOLFOX treatment group (p = 0.93). CONCLUSIONS: S-1 monotherapy and FOLFOX are comparable as the subsequent chemotherapy after gemcitabine-based chemotherapy-induced ILD in unresectable PDAC.
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Carcinoma Ductal Pancreático , Enfermedades Pulmonares Intersticiales , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Japón , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Paclitaxel , Albúminas , Neoplasias PancreáticasRESUMEN
A 73-year-old man underwent drug eluting stent (DES) implantation in the left anterior descending artery (LAD) 11 years ago and in the right coronary artery (RCA) 8 years ago. He suffered from chest tightness and was diagnosed with severe aortic valve stenosis. Perioperative coronary angiography revealed no significant stenosis and thrombotic occlusion of the DES. Five days before operation, antiplatelet therapy was discontinued. Aortic valve replacement was performed uneventfully. But he developed chest pain and transient loss of consciousness, electrocardiographic changes were observed on the 8th postoperative day. Emergency coronary angiography revealed thrombotic occlusion of the drug eluting stent in the RCA, despite the postoperative oral adoministration of warfarin and aspirin. Percutaneous catheter intervention (PCI) restored the stent patency. Dual antiplatelet therapy (DAPT) was initiated immediately after the PCI, and anticoagulation therapy with warfarin was continued. Clinical symptons of stent thrombosis disappeared immediately after the PCI. He was discharged 7 days after the PCI.
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Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Masculino , Humanos , Anciano , Válvula Aórtica/cirugía , Stents Liberadores de Fármacos/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Warfarina , Periodo PerioperatorioRESUMEN
An 86-year-old woman who suffered from cardiac tamponade due to acute Stanford type A aortic dissection was admitted to our hospital. An emergency operation was performed uneventfully. She suffered from abdominal pain 13 days after the operation. Computed tomography( CT) scan revealed pericholecystic fluid and unclear gallbladder wall, revealing acalculous necrotizing cholecystitis. We performed open cholecystectomy and abdominal cavity drainage. No gallstones were observed. She underwent intensive treatment. She was discharged without complications 44 days after the cholecystectomy.
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Disección Aórtica , Vesícula Biliar , Femenino , Humanos , Anciano , Anciano de 80 o más Años , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Tomografía Computarizada por Rayos X , NecrosisRESUMEN
BACKGROUND/AIMS: Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC. METHODS: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018-2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA. RESULTS: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. CONCLUSION: EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.
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Evolution prediction is a long-standing goal in evolutionary biology, with potential impacts on strategic pathogen control, genome engineering, and synthetic biology. While laboratory evolution studies have shown the predictability of short-term and sequence-level evolution, that of long-term and system-level evolution has not been systematically examined. Here, we show that the gene content evolution of metabolic systems is generally predictable by applying ancestral gene content reconstruction and machine learning techniques to ~3000 bacterial genomes. Our framework, Evodictor, successfully predicted gene gain and loss evolution at the branches of the reference phylogenetic tree, suggesting that evolutionary pressures and constraints on metabolic systems are universally shared. Investigation of pathway architectures and meta-analysis of metagenomic datasets confirmed that these evolutionary patterns have physiological and ecological bases as functional dependencies among metabolic reactions and bacterial habitat changes. Last, pan-genomic analysis of intraspecies gene content variations proved that even "ongoing" evolution in extant bacterial species is predictable in our framework.
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Bacterias , Evolución Molecular , Filogenia , Bacterias/genética , Genómica , Genoma BacterianoRESUMEN
A 78-years-old woman was referred to our institution for the treatment of right subclavian artery (SCA) aneurysm. She previously underwent total arch replacement via median sternotomy approach. Preoperative computed tomography revealed a 55 mm sized SCA aneurysm. Stent graft was inserted from brachiocephalic artery to right common carotid artery via the graft anastomosed. The orifice of the right SCA was covered with stent graft inserted into the right common carotid artery-brachiocephalic artery and the right SCA was occluded with coils distal to the aneurysm, carotid-SCA bypass was performed with 8 mm ePTFE graft. Postoperative examination conï¬rmed complete exclusion of the aneurysm and patency of the bypass graft. We thought that hybrid treatment for this patient was a less invasive alternative to conventional surgical procedure.
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Aneurisma , Implantación de Prótesis Vascular , Femenino , Humanos , Anciano , Arteria Subclavia/diagnóstico por imagen , Arteria Subclavia/cirugía , Aneurisma/diagnóstico por imagen , Aneurisma/cirugía , Arteria Carótida Común/diagnóstico por imagen , Arteria Carótida Común/cirugía , Stents , Tomografía Computarizada por Rayos X , Implantación de Prótesis Vascular/métodosRESUMEN
BACKGROUND: Clinically insignificant hemolytic anemia is occasionally a complication of prosthetic valve replacement. However, hemolysis related to kinked grafts is a very rare complication after central repair for acute aortic dissection. CASE PRESENTATION: A 42-year-old man had undergone replacement of the ascending aorta and a root repair for type A aortic dissection 6 months previously. Laboratory data showed mild hemolysis 5 months later, and he began to complain of fatigue on exertion. The serum hemoglobin level reduced to 8.6 g/dL, and lactate dehydrogenase levels increased to 3071 IU/L with gross change in urine color, indicating hemoglobinuria. We diagnosed mechanical hemolytic anemia caused by a kinked graft and planned a repeat operation. The kinked graft was resected and graft-graft anastomosis was performed. Postoperatively, the clinical course was uneventful, and the hemolytic anemia completely resolved. CONCLUSION: We herein report a case of hemolytic anemia caused by kinking of the graft 6 months after acute aortic dissection repair. The diagnosis was swiftly made, and the patient was successfully managed with redo surgery.
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Anemia Hemolítica , Disección Aórtica , Masculino , Humanos , Adulto , Hemólisis , Disección Aórtica/cirugía , Anemia Hemolítica/etiología , Anemia Hemolítica/cirugía , Aorta/cirugía , Reoperación , Prótesis Vascular/efectos adversosRESUMEN
BACKGROUND: The treatment for ampullary cancer is pancreatoduodenectomy or local ampullectomy. However, effective methods for the preoperative investigation of hilar biliary invasion in ampullary cancer patients have not yet been identified. AIM: To determine the necessity of and an appropriate method for investigating hilar biliary invasion of ampullary cancer. METHODS: Among 43 ampullary cancer patients, 34 underwent endoscopic treatment (n = 9) or surgery (n = 25). The use of imaging findings (thickening and enhancement of the bile duct wall on contrast-enhanced computed tomography, irregularity on endoscopic retrograde cholangiography, thickening of the entire bile duct wall on intraductal ultrasonography (IDUS), and partial thickening of the bile duct wall on IDUS) and biliary biopsy results for diagnosing hilar biliary invasion of ampullary cancer was compared. RESULTS: Hilar invasion was not observed in every patient. Among the patients who did not undergo biliary stent insertion, the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results showed the highest accuracy (100%) for diagnosing hilar biliary invasion. However, each imaging method and biliary biopsy yielded some false-positive results. CONCLUSION: Although some false-positive results were obtained with each method, the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results was useful for diagnosing hilar biliary invasion of ampullary cancer. However, hilar invasion of ampullary cancer is rare; therefore, the investigation of hilar biliary invasion of ampullary cancer might be unnecessary.
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A 76-year-old man with thoracic aortic aneurysm was admitted to our hospital. Aortic arch replacement was performed uneventfully. He suffered from abdominal pain 17 days after the operation. Computed tomography (CT) scan revealed a strangulated bowel obstruction, and we performed emergent open abdominal surgery. During the operation, we found an adhesion between the greater omentum and the retroperitoneum. The small intestine was intussuscepted into this site, and strangulated with necrosis of a 35-cm length. We performed a partial resection of the small intestine. We encountered rare strangulated bowel obstruction after open heart surgery due to adhesion of the great omentum in a patient without a history of abdominal surgery.
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Aorta Torácica , Obstrucción Intestinal , Masculino , Humanos , Anciano , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Hernia Interna , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/cirugía , Intestino Delgado/patología , Adherencias Tisulares , Necrosis/etiologíaRESUMEN
A 84-year-old man was diagnosed with complete atrioventricular block and underwent pacemaker implantation( PMI). Two days after the PMI, chest X-ray revealed left pneumothorax, and a chest tube was inserted. The pneumothorax did not improve, and computed tomography revealed left lung injury by the right ventricular lead. Surgical procedure through median sternotomy was performed, and the penetrated lead was removed. The injured right ventricle and left lung were repaired. Ten days after the surgical procedure, intravenous implantation of new right ventricular lead was performed. He was discharged 38 days after the surgical procedure.
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Lesiones Cardíacas , Lesión Pulmonar , Marcapaso Artificial , Neumotórax , Anciano de 80 o más Años , Lesiones Cardíacas/diagnóstico por imagen , Lesiones Cardíacas/etiología , Lesiones Cardíacas/cirugía , Humanos , Pulmón , Lesión Pulmonar/diagnóstico por imagen , Lesión Pulmonar/etiología , Lesión Pulmonar/cirugía , MasculinoRESUMEN
BACKGROUND: Biliary tract cancer (BTC) has a poor prognosis; therefore, useful biomarkers and treatments are needed. Serum levels of macrophage inhibitory cytokine-1 (MIC-1), a member of the TGF-ß superfamily, are elevated in patients with pancreaticobiliary cancers. However, the effect of MIC-1 on BTC is unknown. Therefore, we investigated the effect of MIC-1 on BTC and assessed whether MIC-1 is a biomarker of or therapeutic target for BTC. METHODS: MIC-1 expression in BTC cells was determined by performing histological immunostaining, tissue microarray (TMA), western blotting, and reverse transcription PCR (RT-PCR). Cell culture experiments were performed to investigate the effect of MIC-1 on BTC cell lines (HuCCT-1 and TFK-1). The relationships between serum MIC-1 levels and either the disease state or the serum level of the apoptosis marker M30 were retrospectively verified in 118 patients with pancreaticobiliary disease (individuals with benign disease served as a control group, n = 62; BTC, n = 56). The most efficient diagnostic marker for BTC was also investigated. RESULTS: MIC-1 expression was confirmed in BTC tissue specimens and was higher in BTC cells than in normal bile duct epithelial cells, as determined using TMA, western blotting and RT-PCR. In cell culture experiments, MIC-1 increased BTC cell proliferation and invasion by preventing apoptosis and inhibited the effect of gemcitabine. In serum analyses, serum MIC-1 levels showed a positive correlation with BTC progression and serum M30 levels. The ability to diagnose BTC at an early stage or at all stages was improved using the combination of MIC-1 and M30. The overall survival was significantly longer in BTC patients with serum MIC-1 < the median than in BTC patients with serum MIC-1 ≥ the median. CONCLUSIONS: MIC-1 is a useful diagnostic and prognostic biomarker and might be a potential therapeutic target for BTC.