Hisashi Iwata

The importance of intraoperative fluid balance for the prevention of postoperative acute exacerbation of idiopathic pulmonary fibrosis after pulmonary resection for primary lung cancer.

OBJECTIVES Postoperative acute exacerbation (PAE) of idiopathic pulmonary fibrosis (IPF) is a serious complication that is hard to treat. Therefore, it is important to manage IPF patients in such a way as to avoid PAE. Conversely, the relationship between postoperative acute lung injury and perioperative fluid administration has been reported. Herein, we analyse the perioperative risk factors of PAE of IPF, including fluid management. METHODS Fifty-two patients diagnosed as having clinical IPF who underwent pulmonary resection (segmentectomy, lobectomy or bilobectomy) for primary lung cancer were analysed retrospectively. Preoperative predictive factors and perioperative management items, especially fluid management, were evaluated. RESULTS The incidence of PAE of IPF was 13.5% (7 of 52 patients). Six patients (85.7%) died of respiratory failure induced by uncontrollable PAE of IPF. Upon univariate analysis, the amount of the intraoperative fluid infused (ml/kg/h), the intraoperative fluid balance (ml/kg/h) and the preoperative C-reactive protein (CRP) level were found to be significantly higher in IPF patients who developed PAE than in those who did not. A multivariate logistic regression analysis showed that the intraoperative fluid balance and the preoperative CRP were prognostic factors for PAE of IPF [P = 0.026, odds ratio (OR) = 1.312 and P = 0.048, OR = 1.280, respectively]. CONCLUSIONS To prevent PAE of IPF, intraoperative management that minimizes intravenous fluid administration is essential. Moreover, caution is particularly important in patients with preoperative evidence of inflammation.

Hepatocyte growth factor gene transfer into the liver via the portal vein using electroporation attenuates rat liver cirrhosis

Although a variety of gene transfer methods to the liver have been designed, there are some problems such as the transfection efficiency and safety. In the present study, we developed a modified method of gene transfer into the liver by infusion of plasmid DNA via the portal vein followed by electroporation. After green fluorescence protein gene transfer, transgene expressions were detected in 24 h, and then maximally at 3 days, and persisted for 3 weeks. Histological analysis revealed that very mild tissue damage was induced in the liver to which electroporation was applied. In the second study, human hepatocyte growth factor (HGF) was more detected in the liver injected with 500 μg of human HGF gene than 100 μg of human HGF gene. However, serum HGF did not increase with 100 or 500 μg of human HGF gene. Moreover, 500 μg of HGF gene transfer into the liver by using this method could achieve the long survival of all dimethylnitrosamine-treated rats and attenuate the fibrous regions in the liver. These results suggest that HGF gene transfer into the liver via the portal vein using electroporation might be one of the useful methods for the treatment of various liver diseases.

Skeletal muscle targeting in vivo electroporation-mediated HGF gene therapy of bleomycin-induced pulmonary fibrosis in mice

Lung fibrosis is a common feature of interstitial lung diseases, and apoptosis and fibrinogenesis play critical roles in its formation and progression. Hepatocyte growth factor (HGF) is one of the ideal therapeutic agents for prevention of lung fibrosis because of its antiapoptotic and fibrinolytic effects. The aim of this study is to establish nonviral HGF gene therapy of bleomycin-induced lung fibrosis avoiding the viral vector-related side effects. C57BL/6 mice were injected with 3.0 mg/kg body weight of bleomycin intratracheally. Following bleomycin injection, 50 μl of pUC-HGF (1 mg/ml) was injected into each of the quadriceps muscle. Immediately after plasmid injection, in vivo electroporation was performed with pulse generator. Skeletal muscle-targeting electroporation induced transgene expression on day 1 and persisted for 4 weeks, and human HGF was also detected in the lung. In mice transferred with HGF, pathological score (1.0±0.3 vs 3.2±0.6), TUNEL-positive cell index (4.5±1.1 vs 14.2±3.1), and hydroxyproline content (9.0±1.3 vs 14.4±5.1 μmol/g) were significantly reduced compared with the control. Furthermore, survival rate of HGF mice was significantly improved compared with the control. Our data indicate that HGF gene therapy with a single skeletal muscle-targeting electroporation has a therapeutic potential for bleomycin-induced lung fibrosis and this strategy can be applied as a practical gene therapy protocol for various organs.

Cryopreservation of human adipose tissue-derived stem/progenitor cells using the silk protein sericin.

Adipose tissue-derived stem/progenitor cells (ASCs) have attracted attention as a cell source that replaces marrow stromal cells (MSCs); ASCs may thus have applications in both regenerative medicine and cell transplantation. These medical treatments, however, require a high-quality supply of human ASCs. Therefore, the cryopreservation methods have been improved by changing a component of a cryopreservation medium. Sericin, a protein hydrolysate (with an average molecular weight of 30 kDa) is very rich in serine. The viability and the adipogenic/osteogenic potential of human ASCs were tested after freezing in a cryopreservation medium containing sericin. After thawing, the viability of the human ASCs frozen in the cryopreservation medium was found to be more than 95%. The proliferation rate of human ASCs frozen in CELLBANKER 2, and DMEM/Hams F-12 medium (serum free) + 10% DMSO, 0.1 mol/L maltose, and 1% sericin was higher than that of the cells frozen in the maintenance medium + 10% DMSO. The adipogenic/osteogenic differentiation capabilities of frozen human ASCs were examined by Oil Red O staining/Von Kossas method. The human ASCs were frozen using CELLBANKER 2, and DMEM/Hams F-12 medium (serum free) + 10% DMSO, 0.1 mol/L maltose, and 1% sericin were positive. In conclusion, the cryopreservation medium containing sericin is therefore considered to have a beneficial effect on freezing human ASCs. This serum-free cryopreservation medium should be widely used in regenerative medicine, cell transplantation, and biological research.

Neurogenic tumors of the mediastinum and chest wall: MR imaging appearance.

Various histologic types of neurogenic tumors may originate in the mediastinum and chest wall. It is possible to make accurate diagnosis of these tumors by using the multiplanar capability and high contrast resolution of MR imaging because of these characteristic imaging findings. MR and histologic features of these tumors are illustrated and described in this essay.

Improvement of the survival rate after rat massive hepatectomy due to the reduction of apoptosis by caspase inhibitor

Background and Aim:  Acute liver failure after massive hepatectomy is caused by both necrosis and apoptosis in the remnant liver. We investigate the protective effect of the caspase inhibitor on apoptosis after massive hepatectomy in rats.

Primary peritonitis associated with streptococcal toxic shock-like syndrome: report of a case.

Several reports over the past 15 years describe severe group A streptococcal infections causing septic shock, soft-tissue necrosis, and multiple organ failure; a phenomenon known as streptococcal toxic shock-like syndrome (TSLS). However, primary peritonitis associated with TSLS is rare. We report the case of a 40-year-old man admitted with pain in both thighs, hypotension, and severe abdominal pain. His daughter had been diagnosed with streptococcal pharyngitis 3 days earlier. We performed an emergency laparotomy for peritonitis, and culture of the ascites was positive for group A β-hemolytic streptococcus (GAS). Further serotyping of the isolated GAS strain revealed the T-type 22 and the pyrogenic exotoxin gene, spe-C. The criteria for TSLS were clearly met, including the isolation of GAS from ascites, hypotension, liver failure, renal failure, coagulopathy, myositis, and a generalized erythematous macular rash with desquamation.

Antegradely insertable aortic balloon occlusion catheter for aortic arch repair.

Abstract We have developed an antegradely insertable aortic balloon occlusion catheter for aortic arch repair, and review our experiences of using it. The purpose of the present study was to examine the usefulness of the balloon for surgical treatment of aortic arch aneurysm. In 30 patients with aortic arch aneurysm, including 22 with a non-ruptured and 8 with a ruptured aneurysm, the catheter was antegradely inserted into the descending thoracic aorta through the aortic arch or the aneurysm without opening the pleural space after establishing antegrade selective cerebral perfusion and obtaining cardiac arrest. During distal anastomosis, the catheter occluded the aorta with continuous perfusion of the lower half of the body through an arterial cannula inserted into the femoral artery. Among the patients with a nonruptured aneurysm, two deaths (9.1%) occurred because of aorto-broncho-esophageal fistulae or cardiac arrest due to severe asthma attack within 30 days, and the other three hospital deaths were due to aspiration pneumonia, multiple organ failure with preoperative renal dysfunction, or low cardiac output syndrome due to perioperative myocardial infarction. Among the patients with a ruptured aneurysm, three deaths (37.5%) were due to acute myocardial infarction, respiratory failure, or intractable arrhythmia within 30 days, and another hospital death was caused by mediastinitis. No paraplegia was caused in any patient excluding one of the patients with a ruptured aneurysm who could not be weaned from the extracorporeal circulation due to perioperative myocardial infarction. There was no early postoperative serious visceral organ dysfunction except for two patients with postoperative low cardiac output syndrome or preoperative severe renal dysfunction. This catheter was effective in protecting the visceral organs and the spinal cord in the repair of an aortic arch aneurysm.

Surgical outcome of abdominal aortic aneurysm repair in patients undergoing chronic hemodialysis

Abstract. Abdominal aortic aneurysm repair in patients undergoing chronic hemodialysis presents several surgical difficulties due to tissue fragility, accelerated atherosclerosis, and calcification of the aorta. In addition to these surgical procedure-related problems, anemia, electrolyte abnormalities, bleeding tendency, and susceptibility to infection were also critical issues in perioperative management. The aim of this study was to examine the surgical outcome of abdominal aortic aneurysm repair in patients undergoing chronic hemodialysis. Between January 1988 and August 2001, six patients undergoing chronic hemodialysis underwent repair of an abdominal aortic aneurysm. There were five males and one female, and the mean age was 65 years. Two of the six patients had bilateral common iliac artery aneurysms in addition to the abdominal aortic aneurysm. At the time of abdominal aortic aneurysm repair, the duration of hemodialysis had ranged from 3 to 109 months, with a mean of 34 months. All patients underwent hemodialysis on the day prior to the abdominal aortic aneurysm repair operation. The first postoperative hemodialysis was scheduled to be performed on the day after operation or later. The mean duration of operation was 291 min. Blood transfusion was required in all patients. The first postoperative hemodialysis was performed between the first and third postoperative days. Postoperative complications were: ileus in one, and atrial fibrillation and blue toe syndrome just after operation in one. There was no hospital death. The follow-up period was 56 months. One patient died of lingual cancer at 102 months after operation. Five patients are alive. Abdominal aortic aneurysm repair can be done in patients on chronic hemodialysis with an acceptable early and long-term outcome.

Abdominal aortic aneurysm related to Takayasu arteritis during pregnancy

Y. Umeda (*) · Y. Mori · H. Takagi · H. Iwata · Y. Fukumoto · H. Hirose First Department of Surgery, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8705, Japan Tel. 81-58-267-2619; Fax 81-58-267-2955 e-mail: umeda@cc.gifu-u.ac.jp A cystic lesion in a 34-year-old woman was found incidentally at the dorsal side of the uterus during her pregnancy on ultrasound examination and magnetic resonance (MR) imaging (Fig. 1). Computed tomography (CT) was not performed at that time because of her pregnancy. An ovarian cyst was suspected and followed up by the obstetrician. After a natural delivery, a pulsatile mass was found in the left upper abdomen and she was then referred to our hospital. An infrarenal fusiform abdominal aortic aneurysm with a maximum diameter of 6cm was revealed on a CT scan (Fig. 2). She had no history of hypertension or abdominal trauma. The abdominal aortic aneurysm was repaired with a tube graft via a midline laparotomy. She recovered uneventfully after the operation and was discharged from the hospital. Histological examination revealed fibrous thickening of the intima, diffuse lymphohistiocytic infiltration and marked destruction of elastic fibers especially on the adventitial side of the media, and proliferation of the vasa vasorum with perivascular infiltration of lymphocytes in the adventitia. These changes corresponded with the pathologic finding of Takayasu arteritis. Takayasu arteritis is an idiopathic inflammatory arteriopathic disease that leads to stenotic or occlusive changes in the aorta and its main branches. However, aneurysmal formation has also been reported in 2%–30% of Takayasu arteritis patients. Therefore, even in young people, aortic aneurysm related to Takayasu arteritis should not be excluded from the diagnosis of abnormality in an aortic lesion.