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Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is essential for the development of new organ systems, but transcriptional control of angiogenesis remains incompletely understood. Here we show that FOXC1 is essential for retinal angiogenesis. Endothelial cell (EC)-specific loss of Foxc1 impairs retinal vascular growth and expression of Slc3a2 and Slc7a5, which encode the heterodimeric CD98 (LAT1/4F2hc) amino acid transporter and regulate the intracellular transport of essential amino acids and activation of the mammalian target of rapamycin (mTOR). EC-Foxc1 deficiency diminishes mTOR activity, while administration of the mTOR agonist MHY-1485 rescues perturbed retinal angiogenesis. EC-Foxc1 expression is required for retinal revascularization and resolution of neovascular tufts in a model of oxygen-induced retinopathy. Foxc1 is also indispensable for pericytes, a critical component of the blood-retina barrier during retinal angiogenesis. Our findings establish FOXC1 as a crucial regulator of retinal vessels and identify therapeutic targets for treating retinal vascular disease.
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Barreira Hematorretiniana , Células Endoteliais , Fatores de Transcrição Forkhead , Neovascularização Retiniana , Animais , Masculino , Camundongos , Angiogênese , Barreira Hematorretiniana/metabolismo , Células Endoteliais/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Cadeia Pesada da Proteína-1 Reguladora de Fusão/metabolismo , Cadeia Pesada da Proteína-1 Reguladora de Fusão/genética , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pericitos/metabolismo , Retina/metabolismo , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/genética , Neovascularização Retiniana/patologia , Vasos Retinianos/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Esophageal intramural pseudodiverticulosis (EIPD) is a rare disease. A 78-year-old man with dysphagia presented to our hospital. The presence of diffuse esophageal spasm was suspected by his primary-care doctor. High-resolution manometry (HRM) showed no abnormal findings. The patient was diagnosed with EIPD and Candida esophagitis, by esophagogastroduodenoscopy (EGD) and esophagography. His symptoms improved after symptomatic treatment for Candida esophagitis with oral administration of an antifungal drug. EIPD should be considered in patients with dysphagia; EGD and esophagography should be performed when diagnosing EIPD.
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Transtornos de Deglutição , Divertículo Esofágico , Estenose Esofágica , Esofagite , Masculino , Humanos , Idoso , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Divertículo Esofágico/diagnóstico por imagem , Estenose Esofágica/terapia , Endoscopia do Sistema Digestório , ManometriaRESUMO
Geriatric patients with existing studies on the safety and efficacy of peroral endoscopic myotomy (POEM) for achalasia involve small sample sizes and single institutions. However, multi-center, large-scale data analyses are lacking. The study aimed to clarify the characteristics of geriatric patients with esophageal motility disorders (EMDs) and determine the procedure-related outcomes and clinical course following POEM. This cohort study included 2,735 patients with EMDs who were treated at seven Japanese facilities between 2010 and 2019. The patients' characteristics and post-POEM clinical courses were compared between the geriatric (age ≥ 75 years; n = 321) and non-geriatric (age < 75 years; n = 2,414) groups. Compared with the non-geriatric group, the geriatric group had higher American Society of Anesthesiologists physical status scores; more recurrent cases; lower incidence of chest pain; and higher incidence of type III achalasia, distal esophageal spasm, and Jackhammer esophagus. Furthermore, the incidence of sigmoid esophagus was higher, although esophageal dilation was not severe in this group. POEM was safe and effective for geriatric patients with treatment-naïve and recurrent EMDs. Furthermore, compared with the non-geriatric group, the geriatric group had lower post-POEM Eckardt scores, fewer complaints of refractory chest pain, and a lower incidence rate of post-POEM reflux esophagitis. Geriatric patients are characterized by worse clinical conditions, more spastic disorders, and greater disease progression of EMDs, which are also the indications for minimally invasive POEM. POEM is more beneficial in geriatric patients as it has lowering symptom scores and incidence rates of reflux esophagitis.
Assuntos
Acalasia Esofágica , Transtornos da Motilidade Esofágica , Esofagite Péptica , Miotomia , Cirurgia Endoscópica por Orifício Natural , Idoso , Dor no Peito/etiologia , Estudos de Coortes , Acalasia Esofágica/etiologia , Acalasia Esofágica/cirurgia , Transtornos da Motilidade Esofágica/etiologia , Transtornos da Motilidade Esofágica/cirurgia , Esfíncter Esofágico Inferior/cirurgia , Esofagite Péptica/etiologia , Humanos , Japão/epidemiologia , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Esophageal achalasia causes dysphagia following impaired relaxation of the lower esophageal sphincter due to the degeneration of Auerbach's plexus in the esophageal smooth muscle. Recently, peroral endoscopic myotomy (POEM) has become one of the preferred treatment options for esophageal achalasia. However, pathomorphological changes after POEM have not been well examined. CASE PRESENTATION: A 65-year-old man with a history of POEM for esophageal achalasia was diagnosed with clinical stage II (cT2-N0-M0) thoracic esophageal squamous cell carcinoma and was consequently treated with neoadjuvant chemotherapy followed by thoracoscopic esophagectomy. Intraoperatively, the esophagus appeared dilated, reflecting esophageal achalasia; however, fairly slight fibrous adhesions were observed between the esophagus and the pericardial surface despite previously performed POEM via an anterior incision. Histopathological examination revealed esophageal wall thickening, edema, and fibrosis extending from the lamina propria to the submucosa. Besides, the majority of the inner layer and some proportion of the outer layer of the muscularis propria were found to be missing or atrophic at the esophagogastric junction (EGJ). No ganglion cells could be detected at the Auerbach's plexus. CONCLUSIONS: The previous history of POEM did not affect circumferential mediastinal periesophageal dissection during thoracoscopic esophagectomy. Nevertheless, a large proportion of the inner layer of the muscularis propria at the EGJ level seemed to have become lost or atrophic because of the POEM procedure.
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AIM: As the population ages, the proportion aged ≥75 years is expected to increase. Many studies on peroral endoscopic myotomy (POEM) as treatment for esophageal achalasia have already been reported; however, few studies have been designed on patients aged ≥75 years. The purpose of this study is to describe the characteristics of esophageal achalasia in patients >75 years and to evaluate the outcomes of POEM. METHODS: This study included 121 patients who underwent POEM for esophageal achalasia, which was divided into the geriatric (n = 18) group aged ≥75 and the young (n = 103) group ≤74 years. The characteristics of esophageal achalasia and the short-term outcomes after POEM in the geriatric group compared with the young group were retrospectively investigated. RESULTS: The median age of the geriatric group was 78 years, and two patients were initially diagnosed with refractory pneumonia, and esophageal achalasia was initially overlooked. The preoperative Eckardt score of the geriatric group was significantly lower than that of the young group (4 vs. 6, P = 0.007), particularly in the regurgitation score. The Eckardt score and integrated relaxation pressure of both groups were significantly improved after POEM (P < 0.001). There were no cases of perioperative complications in the geriatric group. CONCLUSIONS: POEM for esophageal achalasia is a safe and effective treatment even in geriatric patients >75 years of age. In geriatric patients with recurrent or intractable pneumonia, it is important to rule out esophageal achalasia. Geriatr Gerontol Int 2021; 21: 788-793.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Acalasia Esofágica , Miotomia , Cirurgia Endoscópica por Orifício Natural , Idoso , Acalasia Esofágica/diagnóstico , Acalasia Esofágica/cirurgia , Esofagoscopia , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: The synchronous incidence of multiple myeloma (MM) and other primary malignant solid tumor is rare. No detailed studies have been published regarding the perioperative management of patients with concurrent MM and malignant solid tumor. We report a patient with concurrent MM and gastric cancer who experienced rapid progression of liver metastasis after lenalidomide was discontinued. PRESENTATION OF CASE: An 82-year-old woman with MM was diagnosed with clinical T3N2M0 gastric cancer, and MM had been maintained in remission with lenalidomide. Preoperatively, pancytopenia was found, and lenalidomide was discontinued and lenograstim was administered. Blood transfusions were also administered preoperatively due to anemia caused by tumor bleeding. Surgery was performed after her pancytopenia improved. Intraoperatively, several nodules were found on the liver, which were diagnosed as adenocarcinoma metastases. On postoperative day 13, a low density mass in the liver that was not observed before surgery was shown. The patient received best supportive care because she did not desire adjuvant chemotherapy for gastric cancer or resumption of treatment for MM. She died of progressive gastric cancer on postoperative day 80. DISCUSSION: Discontinuation of lenalidomide in our case may have promoted tumor angiogenesis and lowered antitumor immunity, causing rapid tumor growth and liver metastasis. Continuation of the MM agent may be preferable in patients who do not have marked myelosuppression. CONCLUSION: Surgeons should be familiar with the risks associated with discontinuation of MM drugs when operating on patients with MM and concurrent malignant solid tumor.
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A 63-year-old man with protein C deficiency underwent thoracoscopic esophagectomy and digestive reconstruction using a gastric tube for thoracic esophageal cancer. On postoperative day 3, the gastric tube was removed because of anastomotic leakage and gastric tube necrosis. Digestive reconstruction using a free jejunal graft was attempted 140 days after the first surgery. However, thrombus formation in the artery and vein of the jejunal graft resulted in a failed reconstruction. Ten days after this surgery, digestive reconstruction using the colon was performed with intraoperative heparin administered for anticoagulation control. The surgery was successful, with no thrombus formation afterward. When performing digestive reconstruction in patients with conditions predisposing to thrombus formation, perioperative management should be completed with careful attention toward preventing thrombus formation. In particular, appropriate anticoagulation control, such as the administration of intraoperative heparin, is recommended in patients with protein C deficiency because necrosis of the reconstructed organ is likely.
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Neoplasias Esofágicas/cirurgia , Esofagectomia , Procedimentos de Cirurgia Plástica , Deficiência de Proteína C/complicações , Toracoscopia , Trombose/etiologia , Idoso , Anticoagulantes/uso terapêutico , Neoplasias Esofágicas/patologia , Humanos , Masculino , Deficiência de Proteína C/diagnóstico , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/instrumentação , Fatores de Risco , Trombose/diagnóstico por imagem , Trombose/cirurgia , Falha de TratamentoRESUMO
Low-energy extracorporeal shock waves (LESW) have been studied as a new treatment for angina pectoris and several ischemic diseases because of its effect on angiogenesis and inhibition of fibrosis of the heart. The effect of LESW on fibrosis in liver cirrhosis has not been studied. The aim of this study was to verify the amelioration of liver fibrosis by LESW and elucidate its mechanisms in a rat model of drug-induced liver cirrhosis. Male Wistar rats aged 7 weeks were injected with carbon tetrachloride intraperitoneally twice a week for 12 weeks. Eight rats underwent LESW therapy (0.25 mJ/mm2, 4 Hz, 1000 shots) under general anesthesia (shock wave group). Seven rats only underwent general anesthesia (control group). Quantitative analysis showed that the area of fibrosis in the shock wave group was significantly reduced compared with the control group (11,899.9 vs. 23,525.3 pixels per field, p < 0.001). In the shock wave group, the mRNA expression of transforming growth factor (TGF)-ß1 was significantly suppressed (0.40-fold, p = 0.018) and vascular endothelial growth factor-B was significantly increased (1.77-fold, p = 0.006) compared with the control group. Serum albumin was significantly higher in the shock wave group than in the control group (3.0 vs. 2.4 g/dl, p = 0.025). Aspartate aminotransferase/alanine aminotransferase ratio decreased by LESW compared with the control group (1.49 vs. 2.04, p = 0.013). These results suggest that LESW therapy ameliorates liver fibrosis by reducing the expression of TGF-ß1 and increasing the expression of angiogenic factors, and improves hepatic function.
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Tratamento por Ondas de Choque Extracorpóreas , Cirrose Hepática/patologia , Cirrose Hepática/terapia , Fígado/patologia , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica , Fígado/metabolismo , Cirrose Hepática/genética , Masculino , RNA Mensageiro/genética , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta1/genética , Fator B de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: Studies have shown a variety of nutritional indices to be prognostic predictors for esophageal cancer patients. However, which nutritional index should be used and when it should be measured during the perioperative period remain unclear. This study attempted to clarify the details surrounding predictive nutritional evaluation by assessing the longitudinal data of serologic indices in perioperative esophageal cancer patients. METHODS: The study included 141 esophageal cancer patients who underwent neoadjuvant chemotherapy after radical esophagectomy at Tohoku University Hospital from April 2008 to December 2017. The nutritional status was retrospectively assessed during the perioperative period, and the prognostic factors related to survival were analyzed. RESULTS: Use of the controlling nutritional status (CONUT) score showed that malnutrition occurred only from 14 days after surgery in most cases. Use of the prognostic nutritional index (PNI) showed that the ratio of malnutrition increased gradually from presurgery to 14 days after surgery. The timing of malnutrition that affected survival was 14 days after surgery with the CONUT score and presurgery and 4 months after surgery with the PNI. A multivariable analysis of independent prognostic factors predicting survival identified malnutrition 14 days after surgery with the CONUT score and a low PNI before surgery, invasion depth of the primary lesion, and node metastasis. CONCLUSIONS: Malnutrition occurring during the perioperative state of esophageal cancer was shown to be a survival prognostic factor. Development of an optimal nutritional intervention is recommended for esophageal cancer patients to prevent malnutrition both before and after surgery.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/mortalidade , Neoplasias Esofágicas/mortalidade , Terapia Neoadjuvante/mortalidade , Avaliação Nutricional , Estado Nutricional , Assistência Perioperatória , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
INTRODUCTION: Most transitional cell carcinomas (TCCs) occur in the urinary tract. There are no reports of TCC originating in the colon. This report presents a very rare case of TCC that primarily occurred in the colon. PRESENTATION OF CASE: A 78-year-old female presented with adenocarcinoma of the rectum and TCC of the ascending colon. She was screened for urologic and gynecologic carcinomas because the TCC was considered a metastatic lesion; however, cytodiagnosis of urine, the cervix and corpus uteri revealed no abnormal findings. An operation was performed, and histological examination revealed adenocarcinoma of the rectum and TCC of the ascending colon. Immunohistochemical stained specimens of the ascending colon revealed tumor cells of cytokeratin (CK) 7-/CK20+ pattern. Eleven months post-operation, a metastatic TCC was found in the liver. The patient was treated with chemotherapy; however, she died 19 months after the operation. DISCUSSION: Our case was clinically considered that the TCC primarily occurred in the colon after analyzing the results of several examinations. Immunohistochemical staining of CK7 and CK20 expression pattern also suggested that the TCC of the ascending colon originated in the colon. CONCLUSION: To the best of our knowledge, this is the first literature report of TCC that originated in the colon. TCC that primarily occurs in the colon may rapidly progress, as in the case presented. Therefore, it is necessary to establish more appropriate treatment for similar cases.
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INTRODUCTION: Situs inversus totalis (SIT) is a rare congenital condition characterized by a complete transposition of thoracic and abdominal organs. Here, we present two successful cases of left thoracoscopic esophagectomy in the prone position for SIT-associated esophageal cancer. PRESENTATION OF CASE: Our first case was of an 82-year-old man who underwent a left thoracoscopic esophagectomy in the prone position, followed by hand-assisted laparoscopic gastric mobilization. Surgical duration and blood loss were 661min and 165g, respectively. His postoperative course was uneventful. The second case was of a 66-year-old man who underwent a left thoracoscopic esophagectomy in the prone position, followed by gastric mobilization via laparotomy owing to a concomitant intestinal malrotation and polysplenia. Surgical duration and blood loss were 637min and 220g, respectively. We trained for the surgical procedures preoperatively using left-inverted and right-inverted thoracoscopic surgical videos of patients with normal anatomy. DISCUSSION: Surgical procedures in SIT patients are challenging owing to their mirrored anatomy. Recognitionãof theirãvariationsãisãthus important toãavoidãintraoperative accidental injuries. Left-inverted and right-inverted thoracoscopic surgical videos of patients with normal anatomy were found to be useful for image training prior to the actual surgery. CONCLUSION: Thoracoscopic surgical treatment for esophageal cancer associated with SIT in the prone position can be performed safely, similar to the manner performed for thoracoscopic surgery in the right decubitus position, or surgery via an open thoracotomy. Gastric mobilization via laparotomy should be considered in patients associated other anatomic variations.
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A 63-year-old male visited our hospital, complaining of discomfort when swallowing. Upper gastrointestinal endoscopy revealed a type 2 tumor in the middle thoracic esophagus, which was diagnosed as squamous cell carcinoma by endoscopic biopsy. Computed tomography revealed situs inversus totalis (SIT). We assessed the relationship of the esophagus with neighboring organs using preoperative three-dimensional imaging. We performed thoracoscopic esophagectomy with radical lymph node dissection in the right decubitus position and hand-assisted laparoscopic gastric mobilization in the supine position. The definitive diagnosis was squamous cell carcinoma, pT2N1M0, pStage IIB according to the Union for International Cancer Control. The patient's postoperative course was uneventful, and 5 years post-operation, he is alive without recurrence. In SIT patients, surgical procedures are difficult because of anatomic transposition. Three-dimensional imaging effectively assesses the anatomical structure and contributes to safer thoracoscopic esophagectomy for esophageal cancer patients with SIT. Relevant literature is also discussed and reviewed.