To develop a gene therapy for osteopathies, this study was conducted to establish a method of transferring the BMP gene, a bone formation factor, to cells and administering the cells with BMP expression to patients with osteopathies. Although virus vectors are frequently used for gene transfer, there has been reported a death case of gene therapy using the adenovirus vector. Therefore, various efforts have been made to prevent such complications. In the present study, we used electroporation by which gene transfer can be efficiently performed without inducing severe complications after electric perforation of the cell membrane. Human bone tissues were initially collected intraoperatively, and BMP-2 and Smad4 genes were cloned and integrated into GFP and DsRed plasmid vectors. Using in vitro electroporation, these plasmid vectors were transferred to the cultured chondrocytes (KTN-1) derived from human herniated intervertebral disk. Confocal laser microscopy revealed that the BMP gene was successfully transferred to the nucleus of chondrocytes in the presence of Smad. Since electroporation facilitated human gene transfer to the target cells, gene therapy using electroporation may facilitate individualized treatment for patients.

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Currently, extracellular matrix MMP has been discussed in relation to the extrusion and spontaneous regression of the herniated mass observed in lumbar disc herniation. However, the question remains as to whether degenerated protein is really the cause of this condition's pathogenesis. We confirmed immunologically by means of electron microscopy that extrusion is caused by the AGEs (advanced glycation end products)-induced cross-linking of collagen, and that spontaneous regression is due to AGE receptors on macrophages. Further, AGEs were found to be already exposed during histogenesis, suggesting a relation to apoptosis. In lumbar disc herniation and aging, glucose-derived AGEs cross-link proteins and cause vascular tissue damage.

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The effect of fluid percussion injury (FPI) on the propagation of neuronal activity in the rat hippocampus was investigated by using optical and extracellular recording techniques. Under anesthesia with pentobarbital sodium, a moderate impact (1.5-2.0 atm) was applied to the parietal cerebral cortex of the left hemisphere at -3 mm (i.e. caudal) from bregma, 3.5 mm lateral from the sagittal suture. Systemic oxygenation remained normal during the anesthesia. The rats recovered fully from anesthesia within 30-60 min, and their subsequent behavior, such as feeding and grooming, was normal. After a survival period of 1 week from the FPI or sham-operation, neuronal activities were recorded from the hippocampal CA1 region and the dentate gyrus (DG) in either coronal or horizontal brain slice preparations. In sham-operated rats, there was no significant difference in the neuronal activity between contralateral and ipsilateral hippocampal CA1 areas and DG. In coronal slices (-5.6--6.4 mm from bregma), moderate impact (1.5-2.0 atm) markedly depressed the neuronal activity of the ipsilateral (impact side) CA1 region and of the DG directly under the cerebral cortex that received the impact. In horizontal slices, on the other hand, the neuronal activity was markedly enhanced in the ipsilateral hippocampal CA1 region and the DG adjacent the temporal lobe of the cerebral cortex. Field potentials were recorded from the dentate granule cell layer and the hippocampal CA1 pyramidal cell layer in either coronal or horizontal slice. Moderate impact strongly depressed the field potential in the ipsilateral CA1 region and DG directly under the injured cerebral cortex. In horizontal slices, the field potential was followed by multiple population spikes in ipsilateral hippocampal CA1 and the DG neurons. Bicuculline (15 μM) increased the number of spikes of the field potential even after the brain injury. These results suggest that FPI depresses the neuronal activity in the ipsilateral hippocampus directly under the injured parietal cortex, while it enhances the neuronal activity of the ipsilateral hippocampus adjacent to the temporal cortex. The facilitation of neuronal activity following FPI is not due to disinhibition resulting from depression of GABAergic interneuron activity.

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We investigated the effects of combination therapy with N-(4-hydroxyphenyl)retinamide (4-HPR) and tamoxifen (TAM) on estrogen receptor (ER) negative breast cancer, for which no effective supplementary therapy has been established, using the human breast cancer cell line MDA-MB-231. TAM or 4-HPR alone had little antitumor effect, but the combined use of TAM and 4-HPR had a strong cell growth inhibitory effect. Cell cycle analysis by flow cytometry showed an increased frequency of the G2/M phases in the 4-HPR-TAM combination group. Measurement of ³H-TAM incorporation into the cell showed that, compared with the TAM group, the 4-HPR-TAM combination group incorporated about 1.45 times more TAM into the cell. Thin-layer chromatographic analysis of changes in the cell membrane ganglioside GM₃ showed a marked increase in GM₃ in the 4-HPR-TAM combination group. We speculate that the administration of TAM in the presence of 4-HPR changes the membrane glycolipid GM₃, increasing intracellular TAM concentrations, thus exerting antitumor activity. Presumably, during this process, antitumor effects do not induce cell death but arrest the cell cycle in the G2 phase. Thus, the combined use of TAM and 4-HPR inhibited the growth of the ER-negative breast cancer cell line MDA-MB-231. These results suggest that combination therapy with TAM and 4-HPR can be a potent supplementary therapy also for ER-negative patients in clinical practice.

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To clarify the management and treatment for the refractory cases of secondary spontaneous pneumothorax (SSP), we analyzed the clinical features in SSP complicating three cases of advanced silicosis, and discussed the available treatment. All three cases were males of age ranging from 60 to 70 years, and had silicosis with massive progressive fibrosis (PMF), classified as type 4 (PR4) according to the ILO guidelines. There was no correlation between the onset of SSP and the smoking habit, or the duration of the occupational exposure to silica. In a total of ten episodes of SSP, a refractory episode occurred in each of the three patients. No surgical treatment was possible because of some complications. Therefore, we administered conservative treatments under mechanical ventilation. The conservative treatments used were tube drainage with suction in each episode and pleurodesis by the combination of minocycline and OK-432 in one case. Approximately one month was the average time required for the air leak cessation. A significant decline in arterial oxygen tension (PaO₂) was observed after the treatment of one case, suggesting further respiratory deterioration. These results imply that the more aggressive treatments for refractory SSP should be limited because of the patient status and progression. More information might be required before performing these options safely and effectively.

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Between 1978 and 1999, 86 patients with chronic pancreatitis were surgically treated at the Surgical Department of Kurume University Hospital. Of these patients, 30 were treated by pancreatic duct drainage operation (drainage operation), while 40 were treated by pancreatic resection, and the results were compared between the two groups. In patients who underwent drainage operation, pain disappeared in 85.7%, slightly relieved in 10.7%, and not relieved in 3.6%. In patients who underwent pancreatic resection, pain disappeared in 73.4%, slightly relieved in 13.3%, and not relieved in 13.3%. Therefore, there was no significant difference in the pain-relieving effect between the two groups. However, the pain-relieving effect was poorer in patients who underwent pancreatic resection than in those who underwent drainage operation. In addition, all patients who showed poor results for pain relief had alcoholic pancreatitis. Endocrine and exocrine functions of the pancreas were improved in 6, maintained in 2, and exacerbated in 4 patients who underwent drainage operation. In patients who underwent pancreatic resection, endocrine and exocrine function of the pancreas were improved in 3, maintained in 3, and exacerbated in 13. Therefore, endocrine and exocrine function of the pancreas were poorer in patients who underwent pancreatic resection than in those who underwent drainage operation. Distant results in patients who underwent drainage operation were good in 75.0%, fair in 15.0%, and poor in 10.0%. In patients who underwent pancreatic resection, distant results were good in 80.0%, fair in 13.3%, and poor in 6.7%. Therefore, favorable distant results were obtained in both groups. These findings suggest that surgical techniques that preserve functions of the pancreas should be selected during surgical treatment for chronic pancreatitis. We consider that the presence or absence of main pancreatic duct dilation and the site of pancreatic lesions are important indices for selecting surgical techniques. Therefore, drainage operation consisting of pancreaticojejunostomy should be indicated for patients with main pancreatic duct dilation, while pancreatic resection should be indicated for those without main pancreatic duct dilation, those with localized pancreatic lesions, and those with suspected pancreatic cancer.

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The purpose of this study was to determine the feasibility of virtual endoscopy, named as “virtual CT laparoscopy”, in the hepatobiliary system prior to laparoscopic cholecystectomy. We applied this technique to 28 patients suspected of having biliary disease. These images were compared and analyzed qualitatively based on visualization of the structures critical to operative cholangiography and surgical findings. Twenty-four patients, who underwent laparoscopic cholecystectomy, were evaluated as follows: the common bile duct and the hepatic duct were adequately visualized in 23 (96%) of the 24 patients, the cystic duct in 21 (88%), the gallbladder opacification in 20 (83%), the liver inferior surface in 20 (83%). Four patients had anatomic variations detected virtual CT laparoscopy and were proven by operative cholangiography and surgical findings. We emphasize that our new technique may contribute to the laparoscopy during surgery as the aid of understanding of anatomical structures in these organs.

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We have reported a successful case of curative partial liver resection of metachronous liver metastasis from advanced gastric cancer. The patient was 56 years old and has undergone total gastrectomy with D₂ lymph node dissection (2 type, well-differentiated adenocarcinoma, H₀P₀n₀se, Stage 2). At 18 months later, follow-up ultrasound detected liver metastasis in the right posterior segment. Together with other imaging modalities, it was diagnosed as a solitary lesion without any other recurrence, and we performed partial resection of the right posterior segment. During the operation, there was no sign of any other recurrence (no peritoneal dissemination, no lymph node metastasis, and no other liver metastasis). Two Mitomycin-C (MMC) intravenous injections were given as postoperative chemotherapy. Usually, surgery for liver metastasis from gastric cancer is very rare as a curative therapy, because it is difficult to predict the effectiveness of the operation. In the present case, we decided on the operation since there was no sign of any other recurrence. It has now been 13 years to date since the partial liver resection and the patient remains free from recurrence.

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We present a case with an unusual fracture. A 28-year-old man presented a painful and swollen left elbow after falling down. Radiographs revealed combined fractures in the capitellum and the radial head associated with a medial capsular avulsion. Two osteochondral fragments from the capitellum were found at the operation. One was the free fragment revealed on radiographic examination. Another was not revealed before the operation and was found piercing the fracture line of the radial head. These two fragments were removed. The radial head fracture was reduced and was fixed using two Herbert screws. It is very difficult to detect a fragment of the capitellum that impaled the radial head on a plain radiogram before operation. Also, a capsular injury and/or ligamentous injury is often overlooked. This fact should be kept in mind whenever a non-operatively treated radial head fracture fails to respond as expected.

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We report a case of gallbladder cancer associated with pancreaticobiliary maljunction. The patient was a 60-year-old woman who consulted a local doctor because of discomfort in the right hypochondriac region. Abdominal ultrasonography (US) showed a gallbladder abnormality, and she was referred to Kurume University Hospital, where she was hospitalized for further study and surgery. Abdominal US revealed a sessile tumor with an irregular surface in the fundus of the gallbladder. The internal echo of the tumor was nonhomogeneous, and the structure of the gallbladder wall was partly torn. The common bile duct and the left intrahepatic bile duct were dilated. Abdominal computed tomography (CT) showed an elevated lesion with the same degree of imaging effect as that of the liver on the peritoneal side of the fundus of the gallbladder. The structure of the gallbladder was preserved, and the gallbladder was well demarcated from the surrounding tissue. No hepatic or lymph node metastases were noted. Endoscopic retrograde cholangiopancreatography (ERCP) visualized the pancreaticobiliary maljunction where the pancreatic duct joined the bile duct, entering an approximately 2-cm-long common channel. Dilatation of the common bile duct and intrahepatic bile ducts was observed and diagnosed as the IV-A type according to the Toya classification. Abdominal angiography in the arterial phase showed dilatation of the cystic artery and hyperplasia of vessels but no apparent encasement. In the venous phase, a deep-staining tumor was observed. From the above findings, we made a diagnosis of gallbladder cancer complicating pancreaticobiliary maljunction, and performed an operation. Since intraoperative US showed that the outermost layer of the gallbladder was in part ill-demarcated, we diagnosed the depth of penetration as ss, and performed cholecystectomy and bile duct resection and hepatic resection (S4a and S5), and lymphnode dissection (D₂; dissection of groups 1 and 2 lymphnodes). The resected specimen grossly showed a papillomatous lesion with a cauliflower-like surface. The histopathologic diagnosis was papillary adenocarcinoma, depth ss, stage II. Tumor cells proliferated in a papillomatous pattern and were mostly confined to the muscular coat but partly infiltrated into the subserosal coat. In the diagnosis of pancreaticobiliary maljunction, it is crucial to consider complicating gallbladder cancer.

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We report a case of minute lung carcinoma that developed in a focal honeycombed lesion in the right lung. A 70-year-old man presented hemosputum, and a cytological examination result was at class IV. A right lower lobectomy of the lung was performed. Microscopically, the thickened alveolar wall revealed tumor cells indicating a minute carcinoma, and showed squamous hyperplasia, metaplasia, and dysplasia, with the carcinoma in the distal airway epithelium. This peripheral lung carcinoma in a focal honeycombed lesion demonstrated the various stages of multistep carcinogenesis, which is recognized in hilar type squamous cell carcinoma. To date, the association between a honeycombed lesion and lung cancer has been poorly described. Here we have presented clear evidence of the association of this carcinoma with the honeycombed lesion.

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We report a case of disseminated recurrence of inferior bile duct carcinoma growing in the fistula where the percutaneous transhepatic cholangiodrainage (PTCD) catheter was instituted. The recurrent tumor seemed to be implanted by dissemination of the original tumor during the first surgery. We could successfully remove this recurring tumor with lateral segmentectomy of the liver plus peritoneal dissection. This patient had been followed after the first surgery (pancreaticoduodenectomy) for inferior bile duct carcinoma causing obstructive jaundice. CEA and CA19-9 raised and CT scan confirmed the recurrent tumor in the lateral segment of the liver. This patient has been in good condition for 2 years following the second surgery.

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A 77-year-old man with a history of cerebral infarction was admitted to our hospital with chest oppression. Coronary angiography revealed 2-vessel disease involving left main trunk. Coronary artery bypass grafting to left anterior descending artery and obtuse marginal branch was scheduled, but the patient developed hemiparesis and the scheduled coronary artery bypass grafting was postponed by at least one month. Unfortunately, the patient complained of severe chest pain at midnight of the second day from the onset of the neurological deficits and went into cardiogenic shock. We performed off-pump coronary artery bypass grafting to left anterior descending artery on the 5th day from the onset of the neurological deficits. His postoperative course was uneventful. Off-pump coronary artery bypass grafting is appropriate as an alternative procedure for high-risk patients with recent neurological deficits.

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