[Surgical resection of a pulmonary pleomorphic carcinoma involving the azygos vein].

We report a case of surgical treatment of pulmonary pleomorphic carcinoma invading the azygos vein. Chest computed tomography (CT) revealed a mass of 6 cm in size, in the upper lobe of the right lung. He underwent the right upper lobectomy and lymph node dissection with combined resection of the involved azygos vein. Histological examination revealed pleomorphic carcinoma (pT3N0M0, stage IIB). The postoperative course was uneventful, and he was alive without recurrence 26 months after the operation. Six cases of pleomorphic carcinoma have been surgically treated between June 2008 and August 2009 in our institute. Early diagnose with complete resection is suggested to be essential in the improvement of survival for this disease based on review of our experience.

[Multiple myeloma presenting as a solitary tumor of the rib; report of a case].

A 78-year-old man complained of right lateral chest pain. Chest X-ray showed an abnormal shadow in the right upper lung field and chest computed tomography (CT) scan showed a lateral chest wall tumor sorrouding the right 4th rib. Bone scintigraphy revealed only one lesion in the right 4th rib. Chest wall tumor resection was done. Histological analysis of the tumor specimen showed plasmacytoma. After the operation, the diagnosis of multiple myeloma was established by demonstration of myeloma by a bone marrow biopsy. Multiple myeloma should be taken into account as one of causes of a chest wall tumor even if it is a solitary tumor of the rib.

Therapeutic effect of a new immunosuppressive agent, everolimus, on interleukin-10 gene-deficient mice with colitis.

A limited number of therapeutic strategies are currently available for patients with inflammatory bowel disease (IBD). In particular, the maintenance therapy after remission in Crohn's disease (CD) is not satisfactory and new approaches are needed. Interleukin-10 gene-deficient (IL-10-/-) mice, a well-characterized experimental model of CD, develop severe chronic colitis due to an aberrant Th1 immune response. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), a new immunosuppressive reagent, has been used successfully in animal models for heart, liver, lung and kidney transplantation. In the present study, we examined the efficacy of everolimus in the treatment of chronic colitis in an IL-10-/- mouse model. Everolimus was administered orally for a period of 4 weeks to IL-10-/- mice with clinical signs of colitis. The gross and histological appearances of the colon and the numbers, phenotype and cytokine production of lymphocytes were compared with these characteristics in a control group. The 4-week administration of everolimus resulted in a significant decrease in the severity of colitis, together with a significant reduction in the number of CD4+ T cells in the colonic lamina propria as well as IFN-gamma production in colonic lymphocytes. Everolimus treatment of established colitis in IL-10-/- mice ameliorated the colitis, probably as a result of decreasing the number of CD4+ T cells in the colonic mucosa and an associated reduction in IFN-gamma production.

[Therapeutic strategy for spontaneous pneumothorax].

This study assesed the treatment of spontaneous pneumothorax from April 1998 to October 2004. Chest computed tomography (CT) was conducted on admission to judge the presence or absence of bulla and/or bleb. A total of 168 cases (112 patients) were treated. There were 93 men and 19 women with a mean age of 40.6 (range, 15 to 98) years. Of the total cases, 119 were the first pneumothorax, and 49 cases were recurrence. Video-assisted thoracoscopic surgery (VATS) was the first-choice surgical procedure. We compared a retrospective series of 168 cases treated by observation with chest tube drainage in 94 cases and bed rest in 3 cases (57.7%), VATS in 62 cases (36.9%), or limited thoracotomy (LT) conventionally in 9 cases (5.4%). The recurrence rate by observation, VATS, or LT was 42, 13, and 0%, respectively. The rate of recurrence in the observation group was higher than in the VATS group, and the rate of recurrence in the presence of bulla and/or bleb was 48% and that of recurrence in their absence was 20%. These results suggest that VATS or LT should be recommended for patients with bulla and/or bleb indicated by chest CT. In VATS, an auto-sutured line with a polyglycolic acid (PGA) sheet and the use of fibrin glue spray were thought to be effective in preventing the recurrence of pneumothorax. Futhermore, LT with primary suturing was thought to be useful in cases of skip and multiple, in consideration of the numbers, patterns, and properties of the bulla and/or bleb from the intraoperative findings through the thoracoscope.

[Evaluation of the proximal stenosis of native coronary vessels after coronary artery bypass grafting].

This study was designed to evaluate proximal native coronary stenosis (PNCS) after coronary artery bypass grafting (CABG). In 36 patients undergoing postoperative coronary arteriography, the PNCS bypassed with internal thoracic artery (ITA), saphenous vein graft (SVG) and right gastroepiploic artery (RGEA) progressed in 9 of 23 vessels (39%), in 15 of 28 vessels (53%), in 4 of 11 vessels (36%), respectively. Stenosis of no grafted coronary vessels progressed in 3 of 26 vessels (11%). Twelve native coronary vessels (9: 99% and 3: 90% stenosis vessels) bypassed with grafts were obstructed. This study confirms that the PNCS progresses significantly by CABG just after the operation and that it tends to progress highly with SVG in comparison with arterial grafts such as ITA or RGEA. Because operative mortality for repeated CABG is approximately twice as high as that for primary CABG, it is important to decide whether early postoperative percutaneous transluminal angioplasty is needed or not, in considering of future graft failure and stenosis progression of the native coronary vessels by CABG.

Suppression of PI3K/mTOR pathway rescues LLC cells from cell death induced by hypoxia.

Cancer cells in solid tumors are challenged by various microenvironmental stresses, including hypoxia, and cancer cells in hypoxic regions are resistant to current cancer therapies. To investigate the mechanism of resistance to hypoxia in cancer cells, we examined mouse Lewis lung carcinoma (LLC) cells, which died due to necrosis at high density under hypoxic but not under normoxic conditions. Levels of mammalian target of rapamycin (mTOR), a central regulator of cellular energy, are reported to be suppressed in hypoxia. We found that phosphorylation of two molecules downstream to it, ribosomal p70 S6 kinase (S6K) and ribosomal protein S6, was markedly suppressed by hypoxia. Overexpression of the active form of S6K increased the sensitivity of LLC cells to hypoxia. On the other hand, inhibition of PI3K or mTOR dramatically reduced hypoxia-induced cell death under hypoxic conditions. Under hypoxic conditions, blockade of the PI3K or mTOR pathway increased levels of intracellular ATP and delayed decreases in pH and glucose level in culture medium, without affecting the cell cycle.

[Clinical evaluation of risk factors for respiratory failure after coronary artery bypass grafting with cardiopulmonary bypass].

The relationship between the duration of postoperative mechanical ventilation and pre-, intra- and just post-operative factors was studied in 48 patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. The patients were divided into 2 groups on the basis of the duration of mechanical ventilation: group A with less than 24 hours (n=35) and group B with more than 24 hours (n=13). Investigation of the perioperative parameters which significantly correlated with the duration of mechanical ventilation revealed that emergency case, cardiac dysfunction, high dose administration of cathecolamine, high left atrial pressure (LAP), low serum albmin, and renal dysfunction after transfer to intensive care unit (ICU) were found to be increased risks of postoperative respiratory failure.

[Prospective study of systemic inflammatory response syndrome after cardiac surgery as a effective indicator].

This prospective study was designed to elucidate the meaning of systemic inflammatory response syndrome (SIRS), the mechanisms that lead to the protraction of SIRS, and whether SIRS is potentially a simple and effective postoperative indicator or not in patients who are operated on with cardiopulmonary bypass (CPB). We studied the duration of SIRS in 90 patients. Our data showed that 83 (92%) of the 90 patients met 2 or more criteria for SIRS and that significant relationship between the protraction of SIRS and the duration of aortic clamping time, CPB time, operation time, and the risk of postoperative organ damage and complication. Those results suggest that SIRS after cardiac surgery with CPB can be regarded as right criteria and highly valuable indexes of preparatory state of organ dysfunction.

Video-assisted thoracic lobectomy by the substernal hand-assisted method for a metastatic lung tumor.

In lobectomy by video-assisted thoracic surgery (VATS), the surgeon is required to have experience and a high degree of skill in performing the operation. We applied substernal hand-assisted thoracoscopic lobectomy to remove a metastatic lung tumor that originated from colon cancer in one patient and obtained satisfactory results. This method compensates for a current limitation of VATS lobectomy, namely, the fact that the surgeon cannot touch the lesion. The reported method is safe and useful for thoracoscopic surgery. It can be performed easily, even if the surgeon is not experienced in performing VATS lobectomy.

Hand-assisted thoracoscopic resection for anterior mediastinal masses.

We report three cases of anterior mediastinal disease (pericardial cyst, thymoma, and myasthenia gravis) in which we used a hand-assisted method in combination with thoracoscopic resection via an infrasternal approach in order to improve the maneuverability and safety of the operation. This technique combines the advantages of both thoracoscopic and incisional resection. It shows promise of becoming a less invasive operation that can be used to treat certain mediastinal tumors, both malignant and benign.

Expression of human beta-defensin 2 (hBD-2) in Helicobacter pylori induced gastritis: antibacterial effect of hBD-2 against Helicobacter pylori.

BACKGROUND: Human beta-defensin 2 (hBD-2) plays a role in the innate defence system at mucosal surfaces. Colonisation of Helicobacter pylori in the stomach is an important pathological factor in gastrointestinal illnesses, including gastritis, peptic ulcer, and gastric adenocarcinoma. AIMS: To evaluate the antibacterial role of hBD-2 against H pylori infection in the gastric mucosa. SUBJECTS: Biopsied gastric mucosa specimens from H pylori positive (n=6) and H pylori negative (n=6) individuals were used. H pylori was determined by the presence of urease activity and microscopic examination. METHODS: The specimens were examined for hBD-2 expression by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and in situ hybridisation. The antibacterial effect of hBD-2 against H pylori was evaluated by the number of colony forming units of H pylori after incubation with 0, 10(-9), 10(-8), 10(-7), 10(-6), or 10(-5) M of hBD-2 peptide. RESULTS: All six H pylori positive specimens expressed a high level of hBD-2 mRNA while hBD-2 mRNA was not detected in the H pylori negative specimens by RT-PCR. Immunohistochemistry using anti-hBD-2 antiserum revealed that hBD-2 was expressed in the surface epithelium of H pylori infected specimens. In gastric specimens obtained after H pylori eradication, hBD-2 immunoreactivity had dramatically decreased. In situ hybridisation confirmed that hBD-2 transcripts were localised in the epithelium of H pylori infected gastric specimens. Incubation with hBD-2 reduced the growth rate of cultured H pylori in a dose dependent manner, and incubation with 10(-5) M hBD-2 completely inhibited the proliferation of H pylori. CONCLUSIONS: H pylori infection induces hBD-2 expression in the human gastric epithelium. hBD-2 inhibited the growth of H pylori in vitro, suggesting that hBD-2 plays an antibacterial role in H pylori induced gastritis.

Thymic carcinoids in multiple endocrine neoplasia-type 1.

We report a case of a 45-year-old man with thymic carcinoids in multiple endocrine neoplasm-type 1. Extended total thymectomy was performed through a median sternotomy, and the mediastinal regional lymph nodes and fibroadipose tissue were dissected. Multiple endocrine neoplasm-type 1 related thymic carcinoids are rare and have a poor prognosis. The efficacy of radiotherapy and chemotherapy for prolonging survival is limited, and an aggressive surgical approach with complete excision of the tumor with resection of the peripheral tissues and dissection of the mediastinal lymph nodes seems to be the best available treatment today. We have found that this practice of thymectomy at an early stage in combination with genetic and effective radiological treatment can be effective for multiple endocrine neoplasm-type 1 patients.

Mitral valve plasty for mitral regurgitation after blunt chest trauma.

A 21 year-old woman was admitted to our hospital because of chest and back pain after blunt chest trauma. On admission, consciousness was clear and a physical examination showed labored breathing. Her vital signs were stable, but her breathing gradually worsened, and artificial respiration was started. The chest roentgenogram and a subsequent chest computed tomographic scans revealed contusions, hemothorax of the left lung and multiple rib fractures. A transthoracic echocardiography (TTE) revealed normal left ventricular wall motion and mild mitral regurgitation (MR). TTE was carried out repeatedly, and revealed gradually progressive MR and prolapse of the posterior medial leaflet, although there was no congestive heart failure. After her general condition had recovered, surgery was performed. Intraoperative transesophageal echocardiography (TEE) revealed torn chordae at the posterior medial leaflet. The leaflet where the chorda was torn was cut and plicated, and posterior mitral annuloplasty was performed using a prosthetic ring. One month later following discharge, the MR had disappeared on TTE.

High-output heart failure caused by a huge renal arteriovenous fistula after nephrectomy: report of a case.

Postnephrectomy renal arteriovenous fistula (AVF) with an aneurysmal lesion is a rare clinical entity that may cause high-output heart failure. In this report, we describe the case of a 68-year-old man who had undergone nephrectomy for renal tuberculosis 43 years previously, in whom an acquired large renal AVF presenting as an aneurysm caused congestive cardiac failure. We also discuss the hemodynamic, hormonogenic (human arterial natriuretic polypeptide; hANP), and radiographic findings before and after surgery for the AVF. The AVF with an aneurysmal lesion was clearly visualized by three-dimensional-computerized tomographic (CT) scanning, and proximal ligation of the renal artery was followed by an uneventful recovery. This procedure can produce good results when a fistula is too large to allow safe embolization and when excision would be hazardous due to inflammation surrounding the fistula.

Expression of tyrosine kinase receptors Tie-1 and Tie-2 in giant cell tumor of the tendon sheath: a possible role in synovial proliferation.

We have recently demonstrated that Tie-1 and Tie-2 are expressed in synovial cells from rheumatoid arthritis (RA). To elucidate the possible involvement of Tie receptors in synovial proliferation, we analyzed their expression by immunostaining in five cases of giant cell tumor of tendon sheath (GCTTS), which represents a proliferating lesion of synovial cells. Strong immunoreactivity for both Tie-1 and Tie-2, regardless of the individual patient's profile, was observed in all cases of GCTTS. Six sets of double immunohistochemical stainings for Tie-1/Tie-2 and fibronectin, CD68, or CD34 were carried out to determine the phenotype of Tie-1 and Tie-2-positive tumor components. In these studies, both Tie-1 and Tie-2 immunoreactivity were widely observed in the fibronectin-positive fibroblastic and the CD68-positive histiocytic mononuclear cells, as well as in the osteoclast-like giant cells. In tumor vasculature, Tie receptors were expressed in the CD34-positive endothelial cells possessing proliferating cell nuclear antigen (PCNA) immunoreactivity. We also evaluated the correlation of Tie-1/Tie-2 expression and proliferating cells in GCTTS by using double staining of Tie-1/Tie-2 together with PCNA. Overexpression of PCNA immunoreactivity was frequently found in Tie receptors-positive cells with no obvious differences in the expression pattern of Tie-1 and Tie-2. These findings suggest the possible involvement of Tie receptors in the pathogenesis of GCTTS other than solely via their involvement in angiogenesis and subsequent vascularization. It was demonstrated that Tie-2 immunoreactivity was restricted to the fibroblastic, but not histiocytic, phenotype in RA synovium, suggesting different regulatory control of Tie-2 expression in GCTTS and RA synovium. Overexpression of Tie receptors in GCTTS may imply a biological role for these receptors in synovial proliferation.

The sympathetic nervous system promotes carbon tetrachloride-induced liver cirrhosis in rats by suppressing apoptosis and enhancing the growth kinetics of regenerating hepatocytes.

Norepinephrine is considered to possess potent anti-apoptotic action in regenerating hepatocytes. To clarify the role of the sympathetic nervous system in apoptosis that occurs in chronic liver damage and following the promotion of liver cirrhosis, we studied a carbon tetrachloride (CCl4)-induced liver injury model, using spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and chemically sympathectomized WKY. At 24 h after CCl4 administration. acute damage, characterized by vacuolated hepatocytes in the centrilobular zone, was greater in SHR than in WKY. This vacuolated change in WKY hepatocytes was significantly reduced by chemical sympathectomy with 6-hydroxydopamine (6-OHDA). After 48 h, the acute damage was dramatically improved in each animal, without significant differences between the three groups. In chronic damage after weekly repetition of CCl4 treatment for 4 weeks, fibrosis was evident in SHR, while in the other groups there was only scant fibrosis in the centrilobular zone. After 8 weeks' repetition of CCl4, liver cirrhosis was seen only in SHR. The incidence of apoptotic cells in areas of both acute and chronic damage in WKY, detected by terminal deoxynucleotidyl transferase-dUTP nick end labeling, was significantly increased in comparison with that in SHR, and was further increased by 6-OHDA pretreatment. In contrast, there was significantly greater enhancement of the growth of hepatocytes in SHR than in WKY in both acute and chronic damage. Moreover. hepatocyte growth kinetics in WKY was significantly inhibited after sympathectomy in acute injury, as evidenced by immunohistochemistry for proliferating cell nuclear antigen (PCNA). In vitro, the amount of hepatocellular apoptosis induced by transforming growth factor-beta1 was significantly decreased by incubation with norepinephrine. These findings suggest that the anti-apoptotic effect of the sympathetic nervous system increases cell growth kinetics and promotes liver cirrhosis in this animal model.