Changing patterns of intraocular inflammatory disease in Japan

Purpose: We investigated the frequencies and clinical characteristics of Japanese patients with uveitis. Methods: Records of 189 patients referred from April 1999 to March 2001 were retrospectively reviewed. Results: Fifty-six patients (29.6%) had anterior uveitis, 13 (6.9%) intermediate uveitis, 59 (31.2%) posterior uveitis, 58 (30.7%) panuveitis, and three (1.6%) papillitis. The most common diagnoses were Vogt-Koyanagi-Harada (VKH) disease (10.1%), biopsy-proven or presumed sarcoidosis (9.5%), acute anterior uveitis (7.9%), tuberculosis (6.9%), and Behçet’s disease (5.8%). Seventy-three patients (38.6%) were treated with local therapy alone, and 95 patients (50.3%) required systemic therapy. Ocular complications developed in 19.6% of patients, and systemic complications in 2.1%. Conclusions: These results confirm a continued high frequency of VKH disease and sarcoidosis, but suggest a decreased frequency of Behçet’s disease and an increased frequency of tuberculosis. Roughly one-half of the patients required systemic treatment in addition to local therapy, and ocular and/or systemic complications developed in one-fifth of the patients.     

Mutations in the 11-cis retinol dehydrogenase gene in Japanese patients with Fundus albipunctatus

PURPOSE: To detect mutations in the RDH5 gene encoding 11-cis retinol dehydrogenase in patients from Japan with fundus albipunctatus. METHODS: Polymerase chain reaction and direct genomic sequencing techniques were used to detect mutations of the RDH5 coding exons (exons 2-5) in two unrelated patients with fundus albipunctatus. Selected alleles that altered the coding region or intron splice sites were evaluated further through segregation analysis in the families of the index cases. RESULTS: Two novel RDH5 mutations were identified. One of these was a missense mutation Val264Gly in exon 5, and the other was an in-frame insertion of 3 bp in exon 5. CONCLUSIONS: The data indicate that mutations in RDH5 are the primary cause of fundus albipunctatus.     

Detection of p53 gene mutations in human esophageal squamous cell carcinomas using a p53 yeast functional assay: possible difference in esophageal carcinogenesis between the young and the elderly group.

A p53 yeast functional assay, which cannot only detect p53 gene mutations but also can assess p53 gene function, was used to screen for p53 gene dysfunction in human esophageal squamous cell carcinomas. Surgically resected frozen tissues of esophageal squamous cell carcinomas from 57 patients were examined for p53 gene mutation. Because the mean age of the patients diagnosed with esophageal squamous cell carcinoma was 64 years, we classified those who were <65 years of age as the Young Group and classified the others as the Elderly Group. The incidence of p53 gene mutations was 43 of 57 (75%). The incidence of p53 gene mutations observed in the Young Group was significantly higher than in the Elderly Group (P = 0.0007). Alcohol and smoking status did not relate to p53 gene mutation expression. Survival rate after surgery was not significantly associated with the presence of p53 gene mutation. However, in the Young Group with p53 gene mutation, those who had null mutations had a significantly shorter survival than those without null mutations (P = 0.0455). No other clinicopathological factors were associated with p53 gene mutations. Possibly, there may be a difference in esophageal carcinogenesis between the Young and the Elderly groups, because the incidence of p53 gene mutations is different between the two groups. In the Young Group, p53 gene mutation may cause esophageal carcinogenesis, and null mutation for p53 gene is a significant prognostic factor.     

Treatment outcomes of cervical esophageal cancer patients

Background

Although systemic therapy for esophageal carcinoma has advanced dramatically over the last several decades, the consensus of treatment for cervical esophageal carcinoma (CESCC) has yet remained controversial.

Patients and methods

We analyzed 56 CESCC patients who underwent various therapies in our hospital between January 2000 and December 2013.

Results

Thirteen cases underwent surgery without neo-adjuvant therapy (NAT), while 20 cases underwent surgery after NAT. Definitive chemo-radiotherapy (dCRT) was administered to 23 cases. Five cases underwent salvage surgery after dCRT. Three-year overall survival rates (3-year-OS) were similar between the NAT and dCRT groups (53.3 vs. 51.5 %). These cases were divided into clinical T2/T3 and T4 cases, and a differential analysis was performed. The 3-year-OS achieved by NAT in T2/T3 cases (90.9 %) tended to be better than that by dCRT (62.5 %). In contrast, the 3-year-OS achieved by NAT in T4 cases (12.5 %) tended to be worse than that by dCRT (34.2 %). The prognosis of CESCC patients undergoing salvage surgery after dCRT was very good, with 3-year-OS of 100 % in T2/T3 cases and 66.6 % in T4 cases. A comparative analysis of postoperative complications was performed between CESCC patients undergoing surgery after neo-adjuvant chemotherapy and chemo-radiotherapy to evaluate the operative risk for CESCC patients after CRT. The rates of postoperative complications were similar between these groups.

Conclusion

We analyzed the treatment outcomes of CESCC patients by dividing them according to the clinical tumor invasion depth. Salvage surgery may be an effective therapy for CESCC patients and needs to be considered.

     

Expression of type 2 iodothyronine deiodinase in human osteoblast is stimulated by thyrotropin

Thyroid hormones play important roles in bone growth, development, and turnover. To exert its biological activity, T(4) needs to be converted to T(3) by iodothyronine deiodinase. In human thyroid gland as well as rat brown adipose tissue, type 2 iodothyronine deiodinase (D2) expression is regulated by a TSH receptor-cAMP-mediated mechanism. TSH receptor knockout mice demonstrated the direct effects of TSH on bone via TSH receptors found on osteoblast and osteoclast precursors. In the present study we investigated the possible expression and function of iodothyronine deiodinase and TSH receptors in human osteoblast-like osteosarcoma (SaOS-2) cells and normal human osteoblast (NHOst) cells. Iodothyronine deiodinase activity was detected in SaOS-2 cells and NHOst cells, and all of the characteristics of deiodinating activity were compatible with those of D2. Northern analysis demonstrated D2 mRNA expression in SaOS-2 cells and NHOst cells. D2 mRNA levels as well as D2 activities were rapidly increased by dibutyryl cAMP or forskolin in SaOS-2 cells and NHOst cells. TSH receptor mRNA was demonstrated in SaOS-2 cells and NHOst cells, and D2 mRNA and D2 activity were stimulated by TSH in both cells. In addition, all T(3) receptor isoforms were detected by RT-PCR in SaOS-2 cells and NHOst cells. The present results indicate the expression of functional TSH receptors and D2 in human osteoblasts and suggest previously unrecognized roles of TSH receptors and local T(3) production by D2 in the pathophysiology of human osteoblasts.     

Role of Albumin and High-Density Lipoprotein as Endotoxin-Binding Proteins in Rats with Acute and Chronic Alcohol Loading

In the present study, the role of albumin and high-density lipoprotein (HDL) as endotoxin (Et)-binding proteins in chronically alcohol-fed rats was studied. In acute ethanol-loaded rats, the Et clearance in the blood was slightly prolonged, and the amount of albumin and HDL-bound Et in the blood was markedly increased. In chronic ethanol-loaded rats, the Et clearance was significantly faster than that in the control, and HDL-bound Et was increased. In the chronic ethanol-fed rats with an additional 5 g/kg body weight of ethanol load, the Et clearance was much prolonged, and blood tumor necrosis factor and ALT was elevated, when HDL-bound Et was not further increased. Et-binding capacity of total proteins, albumin, and HDL in the hepatocyte culture medium were increased when the Kupffer cells were preincubated in the medium containing ethanol, and the resultant culture supernatant was added to the hepatocyte culture system. In the culture experiment in the chronic ethanol-loaded rats, such increases were not observed. These results suggest that the increase in Et-binding capacity of HDL and albumin may serve as a protective mechanism against Et in chronic ethanol-loaded rats. An addition of high-dose ethanol to these rats may lead to impaired Et binding and inactivation, which may finally result in increased endotoxicity.     

Laparoscopic transhiatal approach for resection of an adenocarcinoma in long-segment Barrett's esophagus

Barrett's esophagus(BE) is a precursor of esophageal adenocarcinoma and is associated with gastroesophageal reflux disease, which is often preceded by a hiatal hernia. We describe a case of esophageal adenocarcinoma arising in long-segment BE(LSBE) associated with a hiatal hernia that was successfully treated with a laparoscopic transhiatal approach(LTHA) without thoracotomy. The patient was a 42-year-old male who had previously undergone laryngectomy and tracheal separation to avoid repeated aspiration pneumonitis. An ulcerative lesion was found in a hiatal hernia by endoscopy and superficial esophageal cancer was also detected in the lower thoracic esophagus. The histopathological diagnosis of biopsy samples from both lesions was adenocarcinoma. There were difficulties with the thoracic approach because the patient had severe kyphosis and muscular contractures from cerebral palsy. Therefore, we performed subtotal esophagectomy by LTHA without thoracotomy. Using hand-assisted laparoscopic surgery, the esophageal hiatus was divided and carbon dioxide was introduced into the mediastinum. A hernial sac was identified on the cranial side of the right crus of the diaphragm and carefully separated from the surrounding tissues. Abruption of the thoracic esophagus was performed up to the level of thearch of the azygos vein via LTHA. A cervical incision was made in the left side of the permanent tracheal stoma, the cervical esophagus was divided, and gastric tube reconstruction was performed via a posterior mediastinal route. The operative time was 175 min, and there was 61 m L of intra-operative bleeding. A histopathological examination revealed superficial adenocarcinoma in LSBE. Our surgical procedure provided a good surgical view and can be safely applied to patients with a hiatal hernia and kyphosis.     

Evaluation of subcarinal lymph node dissection and metastasis in transmediastinal radical esophagectomy

Background

The aim of the present study was to evaluate subcarinal lymph node dissection in transmediastinal radical esophagectomy and subcarinal lymph node metastasis in patients with esophageal cancer.

Methods

Three hundred and twenty-three patients with primary esophageal cancer who underwent transmediastinal or transthoracic esophagectomy with radical two- or three-field lymph node dissection were retrospectively investigated. The clinicopathological characteristics of patients with subcarinal lymph node metastasis were analyzed in detail.

Results

The median of dissected subcarinal lymph nodes in transmediastinal and transthoracic esophagectomy groups was 6 and 7, respectively, and there was no significant difference between the two groups (p?=?0.12). Of all patients, 26 (8.0%) were pathologically diagnosed as positive for subcarinal lymph node metastasis, whereas only 7 (26.9%) of those with metastasis were preoperatively diagnosed as positive. In addition, all patients with subcarinal lymph node metastasis had other non-subcarinal lymph node metastasis. By univariate analysis, subcarinal lymph node metastasis was found in larger (≥?30 mm) and deeper (T3/T4a) primary lesions (p?=?0.02 and 0.02, respectively), but it was not found in 49 patients with the primary lesion located in the upper thoracic esophagus.

Conclusions

Subcarinal lymph nodes can be dissected in transmediastinal esophagectomy, almost equivalent to transthoracic esophagectomy. The tumor size, depth, and location may be predictive factors for subcarinal lymph node metastasis.