Dikkopf-1 as a novel serologic and prognostic biomarker for lung and esophageal carcinomas

Gene expression profile analysis of lung and esophageal carcinomas revealed that Dikkopf-1 (DKK1) was highly transactivated in the great majority of lung cancers and esophageal squamous cell carcinomas (ESCC). Immunohistochemical staining using tumor tissue microarrays consisting of 279 archived non-small cell lung cancers (NSCLC) and 280 ESCC specimens showed that a high level of DKK1 expression was associated with poor prognosis of patients with NSCLC as well as ESCC, and multivariate analysis confirmed its independent prognostic value for NSCLC. In addition, we identified that exogenous expression of DKK1 increased the migratory activity of mammalian cells, suggesting that DKK1 may play a significant role in progression of human cancer. We established an ELISA system to measure serum levels of DKK1 and found that serum DKK1 levels were significantly higher in lung and esophageal cancer patients than in healthy controls. The proportion of the DKK1-positive cases was 126 of 180 (70.0%) NSCLC, 59 of 85 (69.4%) SCLC, and 51 of 81 (63.0%) ESCC patients, whereas only 10 of 207 (4.8%) healthy volunteers were falsely diagnosed as positive. A combined ELISA assays for both DKK1 and carcinoembryonic antigen increased sensitivity and classified 82.2% of the NSCLC patients as positive whereas only 7.7% of healthy volunteers were falsely diagnosed to be positive. The use of both DKK1 and ProGRP increased sensitivity to detect SCLCs up to 89.4%, whereas false-positive rate in healthy donors was only 6.3%. Our data imply that DKK1 should be useful as a novel diagnostic/prognostic biomarker in clinic and probably as a therapeutic target for lung and esophageal cancer.     

Activation of an oncogenic TBC1D7 (TBC1 domain family,member 7) protein in pulmonary carcinogenesis

To develop novel biomarkers and therapeutic agents for lung cancers, we screened molecules that were highly expressed in lung cancers by means of cDNA microarray analysis and found an elevated expression of TBC1 domain family, member 7 (TBC1D7) in the majority of lung cancers. Northern‐blot analysis using mRNAs from 16 normal tissues detected its expression only in testis. Immunohistochemical staining using tumor tissue microarrays consisting of 261 archived non‐small cell lung cancer (NSCLC) specimens suggested an association of TBC1D7 expression with poor prognosis for NSCLC patients (P = 0.0063). Treatment of lung cancer cells using siRNA against TBC1D7, suppressed its expression and resulted in inhibition of the cell growth. Furthermore, the induction of exogenous expression of TBC1D7 conferred growth‐promoting activity at in vitro and in vivo conditions. We also identified TBC1D7 to interact with TSC1 protein in lung cancer cells. TSC1 introduction into cells increased the level of TBC1D7 protein, whereas knockdown of TSC1 expression decreased the level of TBC1D7 protein, suggesting that TBC1D7 is stabilized probably through interaction with TSC1. In addition, inhibition of the binding between TBC1D7 and TSC1 by a TBC1D7‐derived 20‐amino acid cell‐permeable peptide (11R‐TBC1D7_152‐171), which corresponded to the binding domain to TSC1, effectively suppressed growth of lung cancer cells. Selective suppression of TBC1D7 and/or inhibition of the TBC1D7‐TSC1 complex formation could be promising therapeutic strategies for lung cancer therapy. © 2010 Wiley‐Liss, Inc.     

Surgical treatment of acute ascending dissection--a simplified operative method

Primary anastomosis for acute ascending aortic dissection was performed in 8 patients. Primary anastomosis included resection of the intimal tear where applicable, a circumferential suture line in the ascending aorta at the site of the tear, and wrapping of the anastomosis of the ascending aorta with Dacron vascular prosthesis. The aortic valve was resuspended in 1 of 6 patients associated with aortic regurgitation. In 4 patients, aortic regurgitation disappeared postoperatively. Two patients show minor non-progressive valve regurgitation. Two of 8 patients died early postoperatively. There was no late death and dilatation of the aortic root in the follow-up period of mean 27 months. On the basis of these results, we believe that primary anastomosis is a simpler and safer operative method for acute dissection of the ascending aorta.     

Lectin histochemistry of foamy cells in non-nervous tissues of feline sphingomyelinosis.

Foamy cells in non-nervous tissues from a female Siamese cat with sphingomyelinosis were examined by lectin histochemistry. Many foamy cells, so-called Niemann-Pick cells, were found in the non-nervous tissues, such as liver, spleen, lung, kidney, adrenal gland, lymph node and tonsil. These cells were positive for Concanavalia ensiformis agglutinin, Ricinus communis agglutinin-I and wheat germ agglutinin. Storage materials in the foamy cells were different from those in affected cells of the nervous tissues. This study suggests that lectin histochemistry might be helpful in the diagnosis of sphingomyelinosis.     

Factors affecting leakage following esophageal anastomosis

Esophageal anastomotic leaks remain the most serious problem following extirpative procedures for esophageal carcinoma. We conducted a retrospective analysis of 352 patients with carcinoma in the thoracic esophagus who had undergone esophageal anastomosis following esophagectomy at the Kurume University Hospital between 1981 and 1990. Of these, 94 patients (27%) developed anastomotic leaks, and out of this subgroup, 21 (6%) died as a direct result of the leak. A further 20 patients (6%) underwent repair of the leak, after which they were able to tolerate oral intake. The anastomotic leak healed spontaneously in the other 53 patients (15%). The risk factors predisposing to leaks from esophageal anastomoses were determined as: (1) the anastomosis being performed via a retrosternal or subcutaneous route as opposed to an intrathoracic route, (2) the use of colonic interposition as opposed to a gastric pedicle, (3) performing a manual anastomosis as opposed to a mechanical anastomosis, and (4) employing an end-to-end anastomosis, as opposed to an end-to-side anastomosis, using a mechanical method. By introducing an anastomotic stapling device, a microvascular technique, a staged operation based on the preoperative risk analysis, and improvement in pre- and postoperative management, the incidence of anastomotic leakage could be decreased from 35% to 14%, and that of consequent hospital mortality, from 9% to 2%.     

Surgical management of the coronary artery to pulmonary artery fistulas; a case of a large ruptured aneurysm

Three patients were treated for coronary artery-pulmonary artery fistula. Each was asymptomatic due to a coronary artery fistula. There was one instance each of myocardial infarction, mitral stenosis and a large closed ruptured aneurysm including a thrombus. All the fistulas were comprised of several small plexiform arranged vessels. The left to right shunt ratio was approximately 8 per cent or less. A surgical operation was performed to close the drainage orifice of the fistulas through pulmonary arteriotomy under cardiopulmonary bypass in two patients while one patient underwent a ligation of a large abnormal vessel to the aneurysm followed by a resection of the aneurysm without cardiopulmonary bypass. A large saccular aneurysm of such fistulas is rare and a rupture of such an aneurysm is even more rare. The surgical management of coronary artery fistulas is also discussed herein.     

Gold-induced severe cholestatic jaundice in rheumatoid arthritis patient and effect of repeated steroid pulse therapy]

A 32-year-old female with early stage of rheumatoid arthritis (RA) developed anorexia, pruritus, dark urine, pale stool and jaundice 3 weeks after initiation of chrysotherapy. She was administered a total of 35mg of gold sodium thiomalate (GST) intramuscularly and auranofin 6mg per day orally. Liver function tests and biopsy specimens showed severe cholestatic jaundice. Prednisolone 30mg per day and plasma exchange were started. No response however was obtained and the total bilirubin level gradually increased. Steroid pulse therapy, 1000mg methylprednisolone for successive 3 days as one therapy unit, was repeated 4 times. Liver functions were then gradually improved. Gold induced hepatotoxicity is a rare complication. We concluded that the hepatotoxicity in this case was caused by allergic reaction against GST and repeated steroid pulse therapy was very effective to these conditions.     

Gastropericardial and gastrobrachiocephalic vein fistulae caused by penetrating ulcers in a gastric pedicle following esophageal cancer resection: A case report

The gastric pedicle is commonly used for reconstruction following resection of esophageal cancer. However, we recently experienced a case in which two gastric tube ulcers occurred three months postoperatively; one penetrating into the pericardial cavity and the other into the left brachiocephalic vein. To our knowledge, no other such a case has ever been reported and we therefore report and discuss its etiology and management.