RESUMO
SUBJECTS: We first reviewed surgical outcomes and pathological findings of 32 patients(laparoscopic group: LDP n=11, open group: ODP n=21)who underwent distal pancreatectomy for pancreatic cancer from January 2018 to October 2022. Then we reviewed long-term outcomes, and recurrence type for 20 patients(LDP: n=5, ODP: n=15)from January 2018 to February 2021. RESULTS: LDP group had significantly longer operation time and less blood loss. There was no difference in length of hospital stay, postoperative complications, number of dissected lymph nodes, positive lymph node metastasis rate, and adjuvant chemotherapy rate. Because of high rate of pancreatic stump closure by hand sewing in ODP, postoperative pancreatic fistula rate was higher in ODP than in LDP. The 2-year relapse-free survival rate was 60% in LDP, 33% in ODP, and the 2-year overall survival rate was 60% in LDP, 71% in ODP, and there were no significant differences. As for the type of recurrence, in LDP group, 2 cases of distant metastases and no local recurrence was observed, and in ODP group, 6 cases each of local recurrences and distant metastases were observed. CONCLUSION: LDP was not inferior to ODP in short and long- term outcomes, safety, curability, and local control ability.
Assuntos
Laparoscopia , Pancreatectomia , Neoplasias Pancreáticas , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Recidiva Local de Neoplasia/cirurgia , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
Epidemiological studies have shown that cigarette smoking increases the risk of Alzheimer disease. However, inconsistent results have been reported regarding the effects of smoking or nicotine on brain amyloid ß (Aß) deposition. In this study, we found that stimulation of the nicotinic acetylcholine receptor (nAChR) increased Aß production in mouse brains and cultured neuronal cells. nAChR activation triggered the MEK/ERK pathway, which then phosphorylated and stabilized nuclear SP1. Upregulated SP1 acted on two recognition motifs in the BACE1 gene to induce its transcription, resulting in enhanced Aß production. Mouse brain microdialysis revealed that nAChR agonists increased Aß levels in the interstitial fluid of the cerebral cortex but caused no delay of Aß clearance. In vitro assays indicated that nicotine inhibited Aß aggregation. We also found that nicotine modified the immunoreactivity of anti-Aß antibodies, possibly through competitive inhibition and Aß conformation changes. Using anti-Aß antibody that was carefully selected to avoid these effects, we found that chronic nicotine treatment in Aß precursor protein knockin mice increased the Aß content but did not visibly change the aggregated Aß deposition in the brain. Thus, nicotine influences brain Aß deposition in the opposite direction, thereby increasing Aß production and inhibiting Aß aggregation.
Assuntos
Secretases da Proteína Precursora do Amiloide , Peptídeos beta-Amiloides , Ácido Aspártico Endopeptidases , Nicotina , Receptores Nicotínicos , Fator de Transcrição Sp1 , Animais , Humanos , Masculino , Camundongos , Peptídeos beta-Amiloides/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Fosforilação/efeitos dos fármacos , Receptores Nicotínicos/metabolismo , Fator de Transcrição Sp1/metabolismoRESUMO
Brain amyloid-ß (Aß) governs the pathogenic process of Alzheimer's disease. Clinical trials to assess the disease-modifying effects of inhibitors or modulators of ß- and γ-secretases have not shown clinical benefit and can cause serious adverse events. Previously, we found that the interleukin-like epithelial-to-mesenchymal transition inducer (ILEI, also known as FAM3C) negatively regulates the Aß production through a decrease in Aß immediate precursor, without the inhibition of ß- and γ-secretase activity. Herein, we found that MS-275, a benzamide derivative that is known to inhibit histone deacetylases (HDACs), exhibits ILEI-like activity to reduce Aß production independent of HDAC inhibition. Chronic MS-275 treatment decreased Aß deposition in the cerebral cortex and hippocampus in an Alzheimer's disease mouse model. Overall, our results indicate that MS-275 is a potential therapeutic candidate for efficiently reducing brain Aß accumulation.
Assuntos
Doença de Alzheimer , Piridinas , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide , Peptídeos beta-Amiloides , Benzamidas/farmacologia , Precursor de Proteína beta-AmiloideRESUMO
Endovascular treatment of aneurysmal subarachnoid hemorrhage during pregnancy involves a risk of intraoperative radiation exposure to the fetus. The transradial approach does not require fluoroscopy of the maternal abdominopelvic region, which reduces fetal radiation exposure. We report a case of a female at 21 gestation weeks who developed subarachnoid hemorrhage due to a ruptured right posterior communicating artery aneurysm. The patient underwent balloon-assisted coil embolization via the transradial approach, which achieved aneurysmal obliteration with minimal fetal radiation exposure and without puncture site complications. The patient was free from neurological sequelae. Further, the patient delivered a healthy newborn through an elective cesarean section at 37 gestation weeks without any complications. The transradial approach allows endovascular treatment of ruptured intracranial aneurysms during pregnancy, with minimal risks of fetal radiation exposure.