Junichi Okamoto

Decreased expression of haemoglobin beta (HBB) gene in anaplastic thyroid cancer and recovory of its expression inhibits cell growth

Anaplastic thyroid cancer (ATC) is one of the most fulminant and foetal diseases in human malignancies. However, the genetic alterations and carcinogenic mechanisms of ATC are still unclear. Recently, we investigated the gene expression profile of 11 anaplastic thyroid cancer cell lines (ACL) and significant decreased expression of haemoglobin beta (HBB) gene in ACL. Haemoglobin beta is located at 11p15.5, where loss of heterozygosity (LOH) was reported in various kinds of cancers, including ATC, and it has been suggested that novel tumour suppressor genes might exist in this region. In order to clarify the meaning of decreased expression of HBB in ATC, the expression status of HBB was investigated with ACL, ATC, papillary thyroid cancer (PTC) and normal human tissues. Haemoglobin beta showed significant decreased expression in ACLs and ATCs; however, in PTC, HBB expressed equal to the normal thyroid gland. In addition, HBB expressed in normal human tissues ubiquitously. To validate the tumour-suppressor function of HBB, cell growth assay was performed. Forced expression of HBB in KTA2 cell, which is a kind of ACL, significantly suppressed KTA2 growth. The mechanism of downregulation of HBB in ATC is still unclear; however, our results suggested the possibility of HBB as a novel tumour-suppressor gene.

Down-regulation of an inhibitor of cell growth, transmembrane protein 34 (TMEM34), in anaplastic thyroid cancer

PurposeAnsaplastic thyroid cancer (ATC) is one of the most lethal malignancies, but the carcinogenic mechanism of ATC has not been clarified. Recently, we performed a cDNA microarray analysis and identified transmembrane protein 34 (TMEM34) that down-regulated in anaplastic thyroid cancer cell lines (ACL)s as compared to normal thyroid tissues.MethodsTo investigate the role of TMEM34 in ATC carcinogenesis, we examined expression levels of TMEM34 in ACLs as well as differentiated thyroid cancers (DTC)s and normal human tissues. To explore the effect of TMEM34 in ATC development, cell-growth assays with KTA2 cells were performed.ResultsExpression of TMEM34 was down-regulated in all 11 ACLs, as compared to either normal thyroid tissues or cell lines derived from papillary or follicular thyroid cancers. TMEM34 was expressed ubiquitously in normal human tissues tested. Transfection of TMEM34 into KTA2 cells led to inhibition of cell growth.ConclusionsOur findings suggest that TMEM34 might be a tumor suppressor gene, associated with the development of ATC from DTC.

Down-regulation of transcription elogation factor A (SII) like 4 (TCEAL4) in anaplastic thyroid cancer

BackgroundAnaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies and appears to arise mainly from transformation of pre-existing differentiated thyroid cancer (DTC). However, the carcinogenic mechanism of anaplastic transformation remains unclear. Previously, we investigated specific genes related to ATC based on gene expression profiling using cDNA microarray analysis. One of these genes, transcription elongation factor A (SII)-like 4 (TCEAL4), encodes a member of the transcription elongation factor A (SII)-like gene family. The detailed function of TCEAL4 has not been described nor has any association between this gene and human cancers been reported previously.MethodsTo investigate the role of TCEAL4 in ATC carcinogenesis, we examined expression levels of TCEAL4 in ACLs as well as in other types of thyroid cancers and normal human tissue.ResultsExpression of TCEAL4 was down-regulated in all 11 ACLs as compared to either normal thyroid tissues or papillary and follicular thyroid cancerous tissues. TCEAL4 was expressed ubiquitously in all normal human tissues tested.ConclusionTo our knowledge, this is the first report of altered TCEAL4 expression in human cancers. We suggest that loss of TCEAL4 expression might be associated with development of ATC from DTC. Further functional studies are required.

Descending necrotizing mediastinitis associated with Lactobacillus plantarum

BackgroundDescending necrotizing mediastinitis (DNM), a severe infection with a high fatality rate, develops in mediastinal spaces due mainly to deep cervical abscesses. The majority of causative microbes of DNM are Streptococci and oral anaerobes. DNM associated with Lactobacillus-infection is rather rare.Case presentationA 69-year-old male with an unremarkable past medical history was referred to our hospital for surgical resection of advanced laryngeal cancer. Full examination revealed a neck abscess and DNM with a background of untreated diabetes mellitus. Initially, he was treated with meropenem. However, Lactobacillus plantarum was isolated from surgical drainage of a mediastinal abscess. Despite using antibiotics capable of eradicating all isolates with susceptibilities not differing significantly from those of the neck and mediastinal abscesses, we attributed DNM to the L. plantarum detected only in the mediastinal abscess. After DNM treatment, he underwent total pharyngolaryngectomy with bilateral neck dissection followed by reconstruction using free jejunum. He was discharged fully recovered.ConclusionWe concluded that L. plantarum as the sole cause of the mediastinal abscess in the present case cannot be ruled out. As the number of immunocompromised patients increases, we should be cautious regarding this “familiar” microbe.

Factors Determining the Choice of Surgical Procedure in Elderly Patients with Non-Small Cell Lung Cancer

BACKGROUND In the elderly patients, optimal surgical treatment can be difficult to achieve, because of comorbidity. Therefore, we aimed to clarify the preferred surgical management in this patient group. METHODS A retrospective study was conducted between April 2008 and March 2015 that included patients with non-small cell lung cancer (NSCLC) aged ≥ 75 years. RESULTS We included 44 patients who underwent partial resection (n = 20) or lobectomy (n = 24). There were no significant differences between the two groups on most variables, except for some character. Survival analysis revealed a significant difference in overall survival (OS) between the two groups; however, no significant differences existed in the disease-free survival or in the OS for stage I disease. Postoperative complications led to poor prognoses. Cox regression analysis revealed statistical significance for the Brinkman Index, the ratio of the pulmonary artery diameter to the ascending aorta diameter (PA:A), and the alveolar-arterial oxygen gradient. Only the PA:A ratio remained significant after multivariate analysis, with a higher ratio associated with better survival. CONCLUSION In elderly patients with NSCLC, surgical resection should not be denied because of age alone. However, partial resection should be favored to lobectomy when possible.

Dissimilarity in gene expression profiles of lung adenocarcinoma in Japanese men and women.

BACKGROUND Although clinical differences in lung cancer between men and women have been noted, few studies have examined the sex dissimilarity using gene expression analysis. OBJECTIVE The purpose of this study was to determine the different molecular carcinogenic mechanisms involved in lung cancers in Japanese men and women. METHODS Patients who received surgery for stage I lung adenocarcinoma were included. RNA was extracted from cancerous and normal tissue, and gene expression was then examined with oligonucleotide microarray analysis. A quantitative polymerase chain reaction assay was performed. RESULTS In a microarray analysis of tissue from 13 men and 6 women, 12 genes were under-expressed and 24 genes were overexpressed in lung adenocarcinoma in women compared with men. Genes related to cell cycle were present in underexpressed genes, and genes related to apoptosis, ubiquitination, and metabolism were observed in overexpressed genes. Of interest among the selected genes were WAP four-disulfide core domain 2 (WFDC2) and major histocompatibility complex, class II, DM alpha (HLA-DMA); these genes were classified into 2 groups by hierarchical clustering analysis. Expression of WFDC2 in nonsmokers was significantly higher than that in smokers (P=0.023). However, there was no significant difference in HLA-DMA expression between smokers and nonsmokers. CONCLUSION Thirty-six genes that characterize lung adenocarcinoma by sex were selected. This information may contribute to the development of novel diagnostic techniques and treatment modalities that consider sex differences in lung adenocarcinoma.

Safe transection of aberrant arteries associated with pulmonary sequestrations

BackgroundVideo-assisted thoracoscopic surgery (VATS) lobectomy is increasingly used for pulmonary sequestration; however, there are few descriptions of safe handling of the aberrant artery. Here we clarify the safe handling of an aberrant artery using a clinical review and an experimental model.MethodsWe retrospectively reviewed the records of patients who underwent lobectomy for pulmonary sequestration with aberrant arteries at the Nippon Medical School between January 2008 and December 2010. This was supplemented by an experimental pressure test using vessels obtained from pigs.ResultsWe identified four patients with aberrant arteries that were successfully occluded via either stapling. In the experimental model, we divided pig vessels into small-diameter (S) and large-diameter (L) groups. The 1.0-mm-high staples were stronger in the S group than in the L group (p = 0.028). In the L group, the 2.0-mm-high staples were stronger than the 1.0-mm staples (p = 0.015). Leakage from the staple line was associated with a poorer B-shape of inserted staples.ConclusionsThe techniques described in this report are useful in successful minimally invasive transection of an aberrant artery (other than very thin vessels) when resecting a pulmonary sequestration by stapler only. A detailed investigation should be performed to determine the most appropriate stapler or cartridge.

Prognostic effect of incompletely lobulated fissures in p-Stage I non-small-cell lung cancer

OBJECTIVES Division of incompletely lobulated fissures is often performed during surgical resection of non-small-cell lung cancer (NSCLC); however, the effect of lobulation on tumour recurrence is unclear. This study aimed to assess the prognostic effect of lobulation in patients with NSCLC according to their preoperative and operative findings. METHODS A retrospective study of patients with p-stage I NSCLC who underwent lobectomy was conducted between April 2008 and April 2016. A receiver operating characteristic curve of the number of stapling cartridges was constructed to determine the optimal cut-off value. Patients who underwent division of the interlobar fissure using 2 or more stapling cartridges (H group) were compared with those who did not undergo division of the interlobar fissure or who underwent division of the interlobar fissure using only 1 cartridge (L group). RESULTS The study included 85 patients, and of these patients, 46 were included in the L group and 39 in the H group. Survival analysis showed better disease-specific survival (P = 0.0135) and disease-free survival (P = 0.0412) in the L group. Cox regression analysis showed better disease-specific survival in patients who underwent division of the interlobar fissure with few stapler cartridges than in those who underwent division with more stapler cartridges (P = 0.021). CONCLUSIONS The extent and status of incompletely lobulated fissures are significant risk factors for disease-specific survival in patients with resected p-stage I NSCLC.

Communication Site Ligation and Polyglycolic Acid Sheet Use for the Treatment of Hydrothorax in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

Introduction: Hydrothorax due to pleuroperitoneal communication (PPC) can occur in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). We report our experiences of the safety and efficacy of the treatment of four patients with a novel video- assisted thoracoscopy method. Methods: Single-port video-assisted thoracoscopic surgery (VATS) was performed with a mini-thoracotomy of 5 cm in length. The PPC site was identified on the diaphragm and ligated using an endoscopic loop. The diaphragm was then covered using a polyglycolic acid (PGA) sheet, over which adhesive chemicals (OK432 and tetracycline) were sprayed. Results: We assessed the efficacy of our approach in four patients (one female and three males) aged 42–74 years (mean: 62.0 years). The hydrothoraxes were right sided in all the patients. The mean operation and postoperative drainage times were 92.5 min and 3.0 days, respectively. The hydrothoraxes did not recur in any patient during follow-up periods of 8–46 months. Conclusion: Our suture- and staple-free technique is not only easy to perform but also appears to be safe and effective for the management of hydrothorax in patients receiving CAPD. Larger scale studies are now indicated.

Mediastinal Neurofibroma Originating from the Pulmonary Branch of the Right Vagus Nerve in a Patient without von Recklinghausen Disease

Intrathoracic neurofibromas originating from the vagus nerve in patients without von Recklinghausen disease is rare and poses a problem in etiological diagnosis. Surgical resection is usually necessary for precise diagnosis of such tumors. We report the first case of a neurofibroma originating from the right pulmonary branch of the vagus nerve in a 34-year-old male without von Recklinghausen disease. The diagnosis was suggested by the radiological features and was confirmed histologically after resection.