RESUMO
Unknown interactions between drugs remain the limiting factor for clinical application of drugs, and the induction and inhibition of drug-metabolizing CYP enzymes are considered the key to examining the drug-drug interaction (DDI). In this study, using human HepaRG cells as an in vitro model system, we analyzed the potential DDI based on the expression levels of CYP3A4 and CYP1A2. Rifampicin and omeprazole, the potent inducers for CYP3A4 and CYP1A2, respectively, induce expression of the corresponding CYP enzymes at both the mRNA and protein levels. We noticed that, in addition to inducing CYP1A2, omeprazole induced CYP3A4 mRNA expression in HepaRG cells. However, unexpectedly, CYP3A4 protein expression levels were not increased after omeprazole treatment. Concurrent administration of rifampicin and omeprazole showed an inhibitory effect of omeprazole on the CYP3A4 protein expression induced by rifampicin, while its mRNA induction remained intact. Cycloheximide chase assay revealed increased CYP3A4 protein degradation in the cells exposed to omeprazole. The data presented here suggest the potential importance of broadening the current DDI examination beyond conventional transcriptional induction and enzyme-activity inhibition tests to include post-translational regulation analysis of CYP enzyme expression.
Assuntos
Citocromo P-450 CYP3A , Interações Medicamentosas , Omeprazol , RNA Mensageiro , Rifampina , Omeprazol/farmacologia , Humanos , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP3A/genética , Rifampina/farmacologia , RNA Mensageiro/metabolismo , Indutores do Citocromo P-450 CYP3A/farmacologia , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP1A2/biossíntese , Linhagem CelularRESUMO
Laparoscopic surgery is performed worldwide and has clear economic and social benefits in terms of patient recovery time. It is used for most gastrointestinal surgical procedures, but laparoscopic surgery for more complex procedures in the esophageal, hepatobiliary, and pancreatic regions remains challenging. Minimally invasive surgery that results in accurate tumor dissection is vital in surgical oncology, and development of surgical systems and instruments plays a key role in assisting surgeons to achieve this. A notable advance in the latter half of the 1990s was the da Vinci Surgical System, which involves master-slave surgical support robots. Featuring high-resolution three-dimensional (3D) imaging with magnification capabilities and forceps with multi-joint function, anti-shake function, and motion scaling, the system compensates for the drawbacks of conventional laparoscopic surgery. It is expected to be particularly useful in the field of hepato-biliary-pancreatic surgery, which requires delicate reconstruction involving complex liver anatomy with diverse vascular and biliary systems and anastomosis of the biliary tract, pancreas, and intestines. The learning curve is said to be short, and it is hoped that robotic surgery will be standardized in the near future. There is also a need for a standardized robotic surgery training system for young surgeons that can later be adapted to a wider range of surgeries. This systematic review describes trends and future prospects for robotic surgery in the hepatobiliary-pancreatic region.
Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/tendências , Laparoscopia/métodos , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Pâncreas/cirurgia , Fígado/cirurgia , Imageamento Tridimensional/métodos , Curva de Aprendizado , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/tendênciasRESUMO
Acute cholecystitis, a very common disease, is usually caused by gallstone obstruction of the cystic duct. Meanwhile, strangulated cholecystitis is extremely rare, and it develops when the gallbladder is strangled by a band. It is very similar to gallbladder torsion in terms of imaging findings and obstruction of blood and biliary flow, and it requires emergency surgery. We herein report a case of a 90-year-old woman with gallbladder strangulation caused by a fibrotic band due to a chlamydia infection, and we also reviewed some literature on strangulated cholecystitis.
Assuntos
Infecções por Chlamydia , Colecistite Aguda , Colecistite , Doenças da Vesícula Biliar , Feminino , Humanos , Idoso de 80 Anos ou mais , Vesícula Biliar/cirurgia , Colecistite/cirurgia , Doenças da Vesícula Biliar/complicações , Doenças da Vesícula Biliar/cirurgia , Infecções por Chlamydia/complicações , Infecções por Chlamydia/diagnósticoRESUMO
INTRODUCTION: The spleen is a lymphatic organ that manages immune surveillance of the blood, produces blood cells, and helps filter the blood, remove old blood cells, and fight infection. The normal splenic weight is approximately 65-265 g. This study evaluated spleen volume and segmental volume. METHODS: 121 patients who underwent enhanced CT at our center were analyzed. The spleen was divided into upper, middle, and lower segments according to arterial flow area, and the volume of each segment was measured. Patients were classified into two groups as those with and without liver cirrhosis, and differences in the distribution of the segments in these groups was evaluated. RESULTS: The mean upper, middle, and lower spleen segmental volume ratios were 35.4%, 37.0%, and 27.6%, respectively. In the liver cirrhosis group, the segmental splenic volume ratios for the upper, middle, and lower segments were 34.5%, 38.5%, and 28.0%, respectively, indicating that these ratios remain similar regardless of liver cirrhosis status. CONCLUSION: The present findings on segmental spleen volume are useful for estimating infarction volume in cases of partial splenic arterial embolization.
Assuntos
Embolização Terapêutica , Baço , Humanos , Baço/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/terapia , Procedimentos Cirúrgicos VascularesRESUMO
OBJECTIVE: The spleen is part of the lymphatic system and is one of the least understood organs of the human body. It is involved in the production of blood cells and helps filter the blood, remove old blood cells, and fight infection. Partial splenic artery embolization (PSE) is widely used to treat pancytopenia and portal hypertension. The efficacy of PSE for improving thrombocytopenia has been well demonstrated. In this study, we evaluated the splenic infarction ratio and platelet increase ratio after PSE. METHODS: Forty-five consecutive patients underwent PSE from January 2014 to August 2022. We retrospectively evaluated the splenic infarction volume and ratio after PSE and analyzed the relationship between the splenic infarction ratio and platelet increase ratio after PSE. RESULTS: The platelet increase ratio was correlated with the splenic infarction ratio after PSE. The cutoff value for the splenic infarction ratio with a two-fold platelet increase was 63.0%. CONCLUSION: We suggest performance of PSE in patients with a splenic infarction ratio of 63% to double the expected platelet count.
Assuntos
Hiperesplenismo , Infarto do Baço , Humanos , Infarto do Baço/diagnóstico por imagem , Infarto do Baço/terapia , Hiperesplenismo/terapia , Estudos Retrospectivos , Artéria EsplênicaRESUMO
Body temperature in homeothermic animals does not remain constant but displays a regular circadian fluctuation within a physiological range (e.g., 35°C-38.5°C in mice), constituting a fundamental systemic signal to harmonize circadian clock-regulated physiology. Here, we find the minimal upstream open reading frame (uORF) encoded by the 5' UTR of the mammalian core clock gene Per2 and reveal its role as a regulatory module for temperature-dependent circadian clock entrainment. A temperature shift within the physiological range does not affect transcription but instead increases translation of Per2 through its minimal uORF. Genetic ablation of the Per2 minimal uORF and inhibition of phosphoinositide-3-kinase, lying upstream of temperature-dependent Per2 protein synthesis, perturb the entrainment of cells to simulated body temperature cycles. At the organismal level, Per2 minimal uORF mutant skin shows delayed wound healing, indicating that uORF-mediated Per2 modulation is crucial for optimal tissue homeostasis. Combined with transcriptional regulation, Per2 minimal uORF-mediated translation may enhance the fitness of circadian physiology.
Assuntos
Relógios Circadianos , Camundongos , Animais , Relógios Circadianos/genética , Ritmo Circadiano/fisiologia , Fases de Leitura Aberta/genética , Temperatura Corporal , Regulação da Expressão Gênica , Mamíferos/metabolismo , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismoRESUMO
Liver cancer, including hepatocellular carcinoma (HCC), is the fifth most common cause of cancer deaths in Japan. The main treatment options for HCC are surgical resection, liver transplantation, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and systemic chemotherapy. Here, recent medical treatments for HCC, including surgery, percutaneous ablation, transcatheter arterial chemoembolization/transcatheter arterial embolization, and drug therapy, are reviewed with a focus on Japan.
Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Terapia Combinada , Humanos , Japão , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Simple hepatic cysts are typically saccular, thin-walled masses with fluid-filled epithelial lined cavities. They arise from aberrant bile duct cells that develop during embryonic development. With the development of diagnostic modalities such as ultrasonography (US), CT, and MRI, simple hepatic cysts are frequently detected in clinical examinations. US is the most useful and noninvasive tool for diagnosis of simple hepatic cysts and can usually differentiate simple hepatic cysts from abscesses, hemangiomas, and malignancies. Cysts with irregular walls, septations, calcifications, or daughter cysts on US should be evaluated with enhanced CT or MRI, to differentiate simple hepatic cysts from cystic neoplasms or hydatid cysts. Growth and compression of hepatic cysts cause abdominal discomfort, pain, distension, and dietary symptoms such as nausea, vomiting, a feeling of fullness, and early satiety. Complications of simple hepatic cysts include infection, spontaneous hemorrhage, rupture, and external compression of biliary tree or major vessels. Asymptomatic simple hepatic cysts do not require treatment. Treatment for symptomatic simple hepatic cysts includes percutaneous aspiration, aspiration followed by sclerotherapy, and surgery. The American College of Gastroenterology clinical guidelines recommend laparoscopic fenestration because of its high success rate and low invasiveness. Percutaneous procedures for treatment of simple hepatic cysts are particularly effective for immediate palliation of patient symptoms; however, they are not generally recommended because of the high rate of recurrence. Management of simple hepatic cysts requires correct differentiation from neoplasms and infections, and selection of a reliable treatment.
Assuntos
Cistos , Hepatopatias , Cistos/complicações , Cistos/diagnóstico , Cistos/terapia , Humanos , Hepatopatias/complicações , Hepatopatias/diagnóstico , Hepatopatias/terapia , Imageamento por Ressonância Magnética , UltrassonografiaRESUMO
BACKGROUND: The number of patients with hemodialysis is increasing increased yearly. Few reports are available on hepatobiliary and gastrointestinal surgery in these patients. PATIENTS AND METHODS: A total of 222 patients who underwent partial liver resection or segmentectomy in our hospital between January 2015 and September 2019 were included in this study. Patients were divided into the hemodialysis group (n=9) and non-hemodialysis group (n=213). RESULTS: No significant difference was observed in postoperative complications between the hemodialysis and non-hemodialysis group. The hemodialysis group had a significantly higher infectious complication rates than the non-hemodialysis group (33.3% vs. 8.0%, p=0.009). In logistic regression analysis, hemodialysis was only a significant risk factor for postoperative infectious complications (OR=5.61, 95% CI=1.12-28.20, p=0.036). CONCLUSION: Liver resections, at least segmentectomy or smaller, is acceptable in patients on hemodialysis. However, these patients may have a higher risk of postoperative infectious complications than other patients.
Assuntos
Hepatectomia , Neoplasias Hepáticas , Hepatectomia/efeitos adversos , Humanos , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Diálise Renal , Estudos RetrospectivosRESUMO
Follicular pancreatitis (FP) is characterized by nodular mass composed of lymphoid hyperplasia and fibrosis. We here present radiological and pathological features of three cases of FP. The three patients were middle- or old-aged men, and nodular mass was pointed out at health examination. Computed tomography failed to demonstrate a mass. Magnetic resonance imaging demonstrated a mass in each case. 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) demonstrated two nodular masses with high standardized uptake value (SUV) in two cases and single mass in one case. The pathological examination disclosed two lesions with fibrosis and hyperplastic lymphoid follicles in two cases and one lesion in one case. Masses with high SUV appeared to correspond with the lesions of FP. Compared with the features of FDG-PET images of pancreatic ductal carcinoma, multiple lesions with high SUV favor a diagnosis of FP rather than pancreatic cancer. FDG-PET is useful for the diagnosis of FP.
RESUMO
BACKGROUND: The Pringle maneuver is often used in liver surgery to minimize bleeding during liver transection. Many authors have demonstrated that intermittent use of the Pringle maneuver is safe and effective when performed appropriately. However, some studies have reported that the Pringle maneuver is a significant risk factor for portal vein thrombosis. In this study, we evaluated the effectiveness of portal vein flow after the Pringle maneuver and the impact that massaging the hepatoduodenal ligament after the Pringle maneuver has on portal vein flow. MATERIALS AND METHODS: Patients treated with the Pringle maneuver for hepatectomies performed to treat hepatic disease at our hospital between August 2014 and March 2019 were included in the study (N = 101). We divided these patients into two groups, a massage group and nonmassage group. We measured portal vein blood flow with ultrasonography before and after clamping of the hepatoduodenal ligament. We also evaluated laboratory data after the hepatectomy. RESULTS: Portal vein flow was significantly lower after the Pringle maneuver than before clamping of the hepatoduodenal ligament. The portal vein flow after the Pringle maneuver was improved following massage of the hepatoduodenal ligament. After hepatectomy, serum prothrombin time was significantly higher and serum C-reactive protein was significantly lower in the massage group than in the nonmassage group. CONCLUSION: Massaging the hepatoduodenal ligament after the Pringle maneuver is recommended in order to quickly recover portal vein flow during hepatectomy and to improve coagulability.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Hepatectomia/métodos , Ligamentos/fisiopatologia , Neoplasias Hepáticas/cirurgia , Massagem/métodos , Veia Porta/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Idoso , Feminino , Humanos , Fígado/irrigação sanguínea , Fígado/cirurgia , Neoplasias Hepáticas/diagnóstico , MasculinoRESUMO
BACKGROUND: Patients with recurrent hepatocellular carcinoma or metastatic liver cancer from colorectal cancer after surgical resection have traditionally been treated with conventional open surgery. However, recent technical advances have facilitated laparoscopic repeat hepatectomy (LapRH), which has advantages over open laparotomy. We describe the results of LapRH at our institution and retrospectively compare short-term outcomes after LapRH and initial laparoscopic partial liver resection (LapPLR). METHODS: From April 2010 through December 2017, 24 patients (16 men, 8 women; median age, 69 years) underwent LRH for cancer recurrence or metastasis after initial partial hepatectomy at our institution. LapRH involved partial hepatectomy in 21 patients and lateral segmentectomy in 3 patients. Short-term outcomes (operative time, intraoperative blood loss, and postoperative hospital stay) for these 24 patients were compared with those for 117 patients who underwent initial LapPLR during the same period. RESULTS: There were no significant differences between the LapPLR and LapRH groups in baseline characteristics, including patient age and underlying disease. No LapRH procedure required conversion to open surgery. There were no statistically significant differences between the groups in median operation time (268 min for LapPLR, 294 min for LapRH; p = 0.55), blood loss (224.0 mL for LapPLR, 77.5 mL for LapRH; p = 0.76), or length of hospital stay (11.0 days for LapPLR, 10.2 days for LapRH; p = 0.83). CONCLUSIONS: LapRH for recurrent liver cancer yielded satisfactory outcomes when compared with those of initial hepatectomy. Further studies are needed, however, to confirm the present results.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Reoperação , Fatores de Tempo , Resultado do TratamentoRESUMO
The indocyanine green (ICG) fluorescence method is reportedly useful for intraoperative visualization of hepatocellular carcinoma and metastatic liver cancer. Herein, we report the use of an ICG fluorescence navigation system for laparoscopic hepatectomy. The patient was a 73-year-old man with a surgical history of two laparotomies for hepatocellular carcinoma resection. During follow-up at our hospital, abdominal computed tomography revealed recurrence of hepatocellular carcinoma in the lateral area of the liver, after which the patient was hospitalized for surgery. His surgical history indicated that adhesions in the abdominal cavity were likely. We scheduled laparoscopic repeat hepatectomy (LRH) with an ICG fluorescence method in which ICG dye was injected intravenously 2 days before surgery. ICG fluorescence was easily detected intraoperatively. The advantages of the present approach are that it induces pneumoperitoneum and, with laparoscopic magnification, enables good visualization of the surgical field for LRH and clear intraoperative identification of the tumor, thus facilitating LRH. Laparoscopic partial resection of the liver (S3) was successfully performed; the operation time was 197 minutes and bleeding volume was 30 mL. Postoperative course was uneventful and he was discharged on postoperative day 10.
Assuntos
Hepatectomia , Verde de Indocianina/química , Laparoscopia , Reoperação , Idoso , Fluorescência , Humanos , Cuidados Intraoperatórios , MasculinoRESUMO
Ravuconazole is a fourth generation azole exerting strong antifungal activity, with low drug-drug interaction and hepatic dysfunction risks. Fosravuconazole l-lysine ethanolate (fosravuconazole; NAILIN® Capsules 100â mg) was developed as a ravuconazole prodrug. Ravuconazole exerts strong antifungal activity against various pathogenic fungi including dermatophytes and Candida. Through prodrug formation, pharmacokinetic improvement was achieved, and bioavailability after oral administration reached 100%. The plasma ravuconazole concentration became 10-35 times higher than with current oral anti-onychomycosis drugs, and showed good skin and nail tissue transition plus tissue retention. This improvement obtained with fosravuconazole reflects its superior pharmacokinetic properties. We conducted a clinical trial with fosravuconazole orally administered once a day (100â mg ravuconazole) for 12 weeks in Japanese onychomycosis patients. The ravuconazole concentration in nail tissues exceeded the MIC90 against dermatophytes, even after treatment completion. Furthermore, the placebo-controlled, double-blind, comparative trial showed significantly superior effects (at 48 weeks after starting treatment, with a complete cure rate of 59.4%, a marked clinical improvement rate of 83.1%, and a mycological cure rate by direct microscopy of 82.0%). The major adverse reactions were laboratory abnormalities and gastrointestinal disorders with no severe symptoms, suggesting good tolerability. Fosravuconazole has fewer drug-drug interactions, is not affected by food, and is also expected to improve medication adherence since the administration period is only 12 weeks and there is no drug-free period as required with pulse therapy. Thus, fosravuconazole has many favorable pharmacological properties and can reasonably be expected to become a new oral treatment option for onychomycosis.
Assuntos
Antifúngicos/uso terapêutico , Lisina/uso terapêutico , Onicomicose/tratamento farmacológico , Triazóis/uso terapêutico , Administração Oral , Antifúngicos/farmacocinética , Cápsulas , Método Duplo-Cego , Humanos , Lisina/análogos & derivados , Lisina/farmacologia , Pró-Fármacos/farmacocinética , Pró-Fármacos/uso terapêutico , Tiazóis/farmacocinética , Tiazóis/uso terapêutico , Triazóis/farmacocinéticaRESUMO
BACKGROUND: Relatively high mortality and morbidity rates are reported after liver resection (LR). However, the early predictors of complications after LR are not clear. This study was performed to clarify the usefulness of procalcitonin (PCT) for the early prediction of complications after elective LR. METHODS: This observational study included 72 consecutive patients who underwent elective LR from December 2015 to March 2017. Patients were categorized into two groups: those with and without postoperative complications (Clavien-Dindo grade ≥II). The values of postoperative inflammatory markers (white blood cell [WBC] count, C-reactive protein [CRP] and PCT) were compared between the two groups. RESULTS: CRP and PCT were significantly higher in patients with than without complications; however, the WBC count showed no difference within 5 days postoperatively. The maximum area under the receiver operating characteristic curves within 2 days after LR using the WBC count, CRP and PCT were 0.608, 0.697 and 0.860, respectively, PCT had the best predictive ability in the early postoperative period. The PCT level peaked within 2 days postoperatively in 61 patients (85%). The maximum PCT level within 2 days postoperatively (PCT1-2) was significantly higher in patients with than without complications (0.52 vs. 0.19 ng/mL, p<0.001). A cutoff PCT1-2 level of 0.35 ng/mL achieved 80% sensitivity and 83% specificity. In patients without complications, there was no difference in PCT1-2 even when the surgical procedure differed (p=0.935). CONCLUSIONS: PCT1-2 is an early predictive marker after LR and can be similarly used regardless of the LR procedure.
Assuntos
Neoplasias Hepáticas/cirurgia , Pró-Calcitonina/sangue , Idoso , Procedimentos Cirúrgicos Eletivos , Feminino , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Curva ROC , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The vein that runs between ventral and dorsal Segment 8 is called the anterior fissure vein (AFV). AFV is sometimes needed as a boundary for Subsegmentectomy in Segment 8. The aim of the present study was to investigate the AFV to determine whether the AFV can be used a landmark for subsegmentectomy of the liver at Segment 8. METHODS: We analyzed data from 151 patients who had undergone abdominal computed tomographic (CT) examinations. The position of the AFV is identified by determining whether the AFV drains flows into the proximal, medial, or distal portion of the middle hepatic vein (MHV) or right hepatic vein (RHV). Furthermore, the proximal region is divided into 2 halves; the proximal portion is designated as P1 and the distal portion is designated as P2. RESULTS: The AFV could be identified in 78.8% (119/151) of the patients. The AFV flowed into the MHV in 84.9% of the patients and into the RHV in 15.1%. Among the former, the AFV flowed into the proximal MHV in 69.7% of the patients. CONCLUSIONS: Although the AFV might not be easily identifiable, the AVF can be used to determine the border between the ventral and dorsal portions of Segment 8. The AFV should thus be used as a landmark for Subsegmentectomy.
Assuntos
Pontos de Referência Anatômicos , Hepatectomia/métodos , Veias Hepáticas/diagnóstico por imagem , Fígado/diagnóstico por imagem , Veia Porta/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fígado/irrigação sanguínea , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Adulto JovemRESUMO
In the original publication of this article, Fig. 5 was published with incorrect color of the approximate lines of CBD and Control.
RESUMO
BACKGROUND: Congenital biliary dilatation (CBD) is a congenital malformation involving both dilatation of the extrahepatic bile duct and pancreaticobiliary maljunction. Persistent reflux of pancreatic juice injures the biliary tract mucosa, resulting in chronic inflammation and higher rates of carcinogenesis in the biliary tract, including the gallbladder. Telomeres are repetitive DNA sequences located at the ends of chromosomes. Chromosomal instability due to telomere dysfunction plays an important role in the carcinogenesis of many organs. This study was performed to determine whether excessive shortening of telomeres occurs in the gallbladder mucosa of patients with CBD. METHODS: Resected gallbladders were obtained from 17 patients with CBD, ten patients with cholecystolithiasis without pancreatic juice reflux, and 17 patients with normal gallbladders (controls) (median age of each group of patients: 37, 50, and 53 years, respectively). The telomere lengths of the gallbladder epithelium were measured by quantitative fluorescence in situ hybridization using tissue sections, and the normalized telomere-to-centromere ratio (NTCR) was calculated. RESULTS: The NTCRs in the CBD, cholecystolithiasis, and control groups were 1.24 [interquartile range (IQR) 1.125-1.52], 1.96 (IQR 1.56-2.295), and 1.77 (IQR 1.48-2.53), respectively. The NTCR in the CBD group was significantly smaller than that in the cholecystolithiasis and control groups (p = 0.003 and 0.004, respectively), even in young patients. CONCLUSIONS: Our findings indicate that telomere shortening in the gallbladder mucosa plays an important role in the process of carcinogenesis in patients with CBD. These results support the recommendation of established guidelines for prophylactic surgery in patients with CBD because CBD is a premalignant condition with excessive telomere shortening.
Assuntos
Ductos Biliares Extra-Hepáticos/anormalidades , Vesícula Biliar/patologia , Ductos Pancreáticos/anormalidades , Encurtamento do Telômero , Adulto , Ductos Biliares Extra-Hepáticos/diagnóstico por imagem , Neoplasias do Sistema Biliar/diagnóstico por imagem , Neoplasias do Sistema Biliar/genética , Colangiopancreatografia Retrógrada Endoscópica , Colangiopancreatografia por Ressonância Magnética , Ducto Colédoco/anormalidades , Ducto Colédoco/diagnóstico por imagem , Dilatação Patológica/congênito , Dilatação Patológica/diagnóstico por imagem , Dilatação Patológica/genética , Epitélio/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos/diagnóstico por imagem , Lesões Pré-Cancerosas/diagnóstico por imagem , Lesões Pré-Cancerosas/genética , Tomografia Computadorizada por Raios XRESUMO
Brain metastases originating from esophageal or gastric cancer are rare, accounting for 2.1-3.3% of all brain tumors registered in Japan. There are no established therapeutic measures for brain metastases, which accordingly have a poor prognosis. We present here a patient who survived for 5 years after surgery and gamma knife treatment of a cerebellar metastasis from esophagogastric adenocarcinoma. The primary gastric cancer was treated by laparotomy with total gastrectomy, splenectomy, and D2 lymphadenectomy. It was diagnosed as a esophagogastric junction Siewert type II tumor, type 3, tub1-2, pT3 (SS), pN1, and stage IIB on histopathological examination of the surgical specimen. Five months postoperatively, a solitary cerebellar metastasis was identified and surgically removed, followed by 20 Gy administered by gamma knife stereotactic radiosurgery; the patient received no subsequent treatment such as chemotherapy. Five years after the primary surgery, there have been no recurrences and the patient has a good quality of life. There are very few case reports of long-term survival after surgical treatment of cerebellar metastases from esophagogastric junction cancer. We report our experience and review published case reports of surgical treatment of brain metastases from gastric cancer.
Assuntos
Neoplasias Cerebelares/cirurgia , Junção Esofagogástrica/cirurgia , Radiocirurgia , Neoplasias Gástricas/cirurgia , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/secundário , Intervalo Livre de Doença , Junção Esofagogástrica/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Gástricas/patologiaRESUMO
We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-d-aspartic acid (NMDA)-induced retinal damage in rats. Rapamycin inhibits mTOR activity, thereby preventing the phosphorylation of ribosomal protein S6, which is a downstream target of S6 kinase. Therefore, we aimed to determine whether PF-4708671, an inhibitor of S6 kinase, protects against NMDA-induced retinal injury. Intravitreal injection of NMDA (200 nmol/eye) caused cell loss in the ganglion cell layer and neuroinflammatory responses, such as an increase in the number of CD45-positive leukocytes and Iba1-positive microglia. Surprisingly, simultaneous injection of PF-4708671 (50 nmol/eye) with NMDA significantly attenuated these responses without affecting phosphorylated S6 levels. These results suggest that PF-4708671 and rapamycin likely protect against NMDA-induced retinal damage via distinct pathways. The neuroprotective effect of PF-4708671 is unlikely to be associated with inhibition of the S6 kinase, even though PF-4708671 is reported to be a S6 kinase inhibitor.