Tumor necrosis factor inhibitor gene transfer ameliorates lung graft ischemia-reperfusion injury

OBJECTIVE: Tumor necrosis factor is an important mediator of lung transplant ischemia-reperfusion injury, and soluble type I tumor necrosis factor receptor binds to tumor necrosis factor and works as a tumor necrosis factor inhibitor. The objectives of this study were to demonstrate that gene transfer of type I tumor necrosis factor receptor-IgG fusion protein reduces lung isograft ischemia-reperfusion injury and to compare donor endobronchial versus recipient intramuscular transfection strategies. METHODS: Three donor groups of Fischer rats (n = 6/group) underwent endobronchial transfection with either saline, 2 x 10(7) plaque-forming units of control adenovirus encoding beta-galactosidase, or 2 x 10(7) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein. Left lungs were harvested 24 hours later. Two recipient groups (n = 6/group) underwent intramuscular transfection with 2 x 10(7) plaque-forming units or 1 x 10(10) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein 24 hours before transplantation. All donor lung grafts were stored for 18 hours before orthotopic lung transplantation. Graft function was assessed 24 hours after reperfusion. Transgene expression was evaluated by means of enzyme-linked immunosorbent assay and immunohistochemistry of type I tumor necrosis factor receptor. RESULTS: Endobronchial transfection of donor lung grafts with 2 x 10(7) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein significantly improved arterial oxygenation compared with the saline and beta-galactosidase donor groups (366.6 +/- 137.9 vs 138.8 +/- 159.9 and 140.6 +/- 131.4 mm Hg, P =.009 and.010, respectively). Recipient intramuscular transfection with 1 x 10(10) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein improved lung graft oxygenation compared with that seen in the low-dose intramuscular group (2 x 10(7); 320.3 +/- 188.6 vs 143.6 +/- 20.2 mm Hg, P =.038). Type I tumor necrosis factor receptor-IgG fusion protein was expressed in endobronchial transfected grafts. In addition, intramuscular type I tumor necrosis factor receptor-IgG fusion protein expression was dose dependent. CONCLUSIONS: Donor endobronchial and recipient intramuscular adenovirus-mediated gene transfer of type I tumor necrosis factor receptor-IgG fusion protein improved experimental lung graft oxygenation after prolonged ischemia. However, donor endobronchial transfection required 500-fold less vector. Furthermore, at low vector doses, it does not create significant graft inflammation.     

Malignant fibrous histiocytoma of perirenal tissue: a case report

A 75-year-old woman was admitted to our hospital with an extremely large retroperitoneal tumor that had been detected with ultrasound on a routine health check. She had no complaint except lumbar pain. Computed tomography revealed a heterogenous tumor located outside the right kidney which was enhanced gradually. Doppler ultrasound showed mild vascularity in the tumor. We performed tumorectomy and right nephrectomy because the tumor was adherent to the right kidney. The tumor was 16 x 11 x 7 cm in size and weighed 621 g. The histopathological diagnosis was malignant fibrous histiocytoma. The tumor was considered to have arisen from perirenal tissue.     

Elastofibroma dorsi as differential diagnosis in tumors of the thoracic wall

We report the case of a 73-year-old woman who presented with a soft tissue tumor located between the scapula and the rib cage. Magnetic resonance imaging showed an inhomogeneous tumor on the right dorsolateral thoracic wall that measured 7 x 4 x 7 cm with contrast enhancement. The findings were suggestive of partial infiltration of intercostal muscles and were suspicious of a malignant tumor. After local excision at a district hospital had failed to render definitive diagnosis, the patient underwent complete resection of the tumor at our institution. Histology from the specimen was consistent with elastofibroma dorsi with free resection margins.     

Laparoscopic resection of large adrenal ganglioneuroma

We report on a 23-year-old woman with a right adrenal tumor 13 cm in diameter who was treated by laparoscopy. The patient was asymptomatic, and the tumor was incidentally diagnosed on abdominal ultrasonography. A subsequent computed tomography (CT) of the abdomen confirmed a 12 x 7 x 8-cm homogenous mass of the right adrenal. Magnetic resonance imaging (MRI) showed a solid mass measuring 13 x 7 x 7.5 cm arising from the right adrenal. Laparoscopic complete excision of the mass was accomplished through a transabdominal lateral approach. The postoperative period was uneventful, and the patient was discharged on the second postoperative day. Histology was consistent with an adrenal ganglioneuroma. Two years later, there is no evidence of recurrence on abdominal CT scan.     

Epidermoid cyst of the scrotum: report of a case

A 61-year-old male visited our hospital with the chief complaint of a mass in the right scrotum on October 4, 1985. Under the diagnosis of intrascrotal tumor, the mass was resected surgically. It was a subcutaneous tumor, and had no relation to any intrascrotal organ, such as testis, epididymis or spermatic cord. The mass was 7 x 6 x 5 cm. Pathological diagnosis was epidermoid cyst of the scrotum. Epidermoid cyst of the scrotum is a rare disease and only 7 cases have been reported in Japan.     

A case of giant prostatic cystadenoma

An 80-year-old man was admitted to our hospital with the chief complaint of urinary retention. On physical examination, a large tumor was recognized in pelvic cavity. Serum levels of prostatic acid phosphatase and gamma-seminoprotein were elevated. Anterior pelvic exenteration was performed because the tumor was huge and malignancy could not be ruled out preoperatively. The tumor weight was 660 g (11 x 8 x 7 cm) and had a multicystic structure macroscopically. Immunohistochemical study by the prostatic specific antigen stain showed positive staining in the epithelial cells of the tumor, which suggest that the tumor was of prostatic origin.     

A surgical case of T-cell non-Hodgkin's lymphoma originating in the wall affected by chronic tuberculous empyema following artificial pneumothorax]

A 63-year-old male patient underwent artificial pneumothorax for right pulmonary tuberculosis 39 years ago, and thereafter suffered from chronic empyema, though asymptomatic. In December, 1989, he was found to have a 5 cm tumor in his right chest wall. The tumor grew to 15 cm in 2 weeks and was associated with severe pain. A chest CT revealed that the tumor of the chest wall corresponded to the area of the wall affected by empyema. The patient underwent full thickness resection of the chest wall including the tumor and the empyematous wall (20 x 20 cm) on March 7, 1990. The tumor was 11 x 8 x 7 cm large and had developed from the empyematous wall to the lateral side of chest wall. There was no invasion of the thoracic cavity by the empyema. The lesion was pathologically diagnosed as diffuse, large to intermediate T-cell non-Hodgkin's lymphoma. Postoperatively the patient was treated with radiotherapy and VEPA therapy, but the tumor metastasized to both lungs, and the patient died 161 days after surgery. The majority of cases of malignant lymphoma reported to have originated in empyematous chest walls have been of the B-cell type. The T-cell type is rare, and the present case is only the second case reported. Chest CT was an effective method of diagnostic imaging in this disease.     

Unusually large stromal tumor of the rectum causing obstruction

A male, 74 years old patient with perineal, sacral pain and with defecation disorders attended the outpatient clinic of HIETE. The origine of the complains was a retrorectal, fist like, rectum narrowing tumor. The tumor was covered by normal mucosa from rectal side. Preoperative examinations--endoscopy, CT, MRI transrectal US--detected a tumor with size 7 x 6 x 5 cm, growing from the muscular wall of the rectum, with no connection with the surrounding tissues. Deep biopsy revealed malignant mesenchymal tumor. After preoperative irradiation abdominoperineal rectum amputation was performed. The recovery was uneventful. The definitive hystological examination proved a gastrointestinal stromal tumor (GIST). This type of tumor rarely occurs in the large intestine or in the rectum, that why the publishing can be interesting.     

Pancreatoblastoma treated by delayed operation after effective chemotherapy

A case of pancreatoblastoma in a 4-year-old girl is presented. She was admitted with an abdominal mass and vomiting in August 1994. Computed tomography scan showed a 10- x 8- x 7-cm mass occupying both the head and body of the pancreas. Serum alpha-fetoprotein (AFP) level was 9,600 ng/mL (normal, <8.3 ng/mL). Results of open biopsy of the tumor showed pancreatoblastoma. Chemotherapy was administered using the new A-1 regimen consisting of cyclophosphamide, etoposide, pirarubicin, and cisplatin. After 3 cycles of chemotherapy, the size of the tumor was reduced to 5 x 4 x 3 cm, the portal vein became patent, and the AFP value decreased to 98.1 ng/mL. Total removal of the tumor was performed leaving the head and tail of the pancreas. Postoperative chemotherapy continued for 2 years. The patient has been disease free for 5 years, and her serum AFP remained within normal levels.     

A case of ectopic pheochromocytoma of pulmonary origin

A 55-year-old woman with pulmonary tumor was scheduled for tumor resection. Preoperatively, her episode of paroxysmal hypertension suggested the existence of pheochromocytoma, but MIBG (metaiodo-benzylguanidine) scintigraphy revealed no local accumulation. Therefore, physicians and surgeons denied the possibility of pheochromocytoma. During epidural catheterization, hypertension occurred, which was controlled by diltiazem 2 mg. Anesthesia was induced with midazolam 10 mg, propofol 70 mg and fentanyl 300 microg and maintained with propofol 4-7 mg x kg(-1) x hr(-1), epidural block with 1% mepivacaine and nitrous oxide 66% in oxygen. Manipulation of the tumor induced hypertension. Diltiazem 1-2 microg x kg(-1) x min(-1) and nicardipine 0.4-4 microg x kg(-1) x min(-1) were administered. After tumor resection, blood pressure decreased to 82/42 mmHg and norepinephrine 0.05-0.25 microg x kg(-1) x min(-1) was infused. Norepinephrine infusion was continued for 24 hours after surgery. She was discharged from the recovery room on the third postoperative day without any complications. A case of ectopic pheochromocytoma of pulmonary origin was managed with midazolam, propofol, fentanyl and continuous epidural block. Diltiazem, nicardipine and norepinephrine were administered to control blood pressure.     

A case of invasive thymoma which had grown in the SVC via left innominate vein through thymic vein]

A 66-year-old male was referred to our department with mediastinal tumor. The chest X-ray and the chest CT showed a large tumor adjacent to pulmonary artery and descending aorta. Cavogram revealed a filling defect of the SVC. He underwent complete resection of the tumor, resection of the SVC and reconstruction of the SVC with ringed PTFE. The main tumor was 12 x 7 cm in size and the tumor in the SVC was 20 x 15 mm in size. Histopathological findings showed a lymphocytic thymoma. Compact invaded nest of tumor cell was found in the innominate vein. The tumor in the SVC was invasive to the intima of the SVC, but its media and adventure were intact. This case is rare among patients with invasive thymoma as far as the growth is concerned.     

A case of renal metanephric adenoma: Histologic, immunohistochemical and cytogenetic analyses

BACKGROUND: A unique case of metanephric adenoma of the left kidney is reported in a 61-year-old woman presenting with an incidental renal mass on ultrasonography. METHODS/RESULTS: On radiographic examination, the presence of hypovascular renal cell carcinoma was suspected and left radical nephrectomy was performed. The resected tumor, measuring 4.9 x 4.7 x 4.5 cm, was well-circumscribed and solid and its cut surface was tan-pink with foci of focal hemorrhage and cystic change. Microscopically, the tumor was composed of uniformly small acini with hyperchromatic round nuclei. Some acini were dilated and occasionally contained glomeruloid-like bodies and psamoma bodies. Immunohistochemically, tumor cells showed positive immunoreaction for vimentin, cytokeratin and Leu 7. Cytogenetically, the tumor did not show numerical aberrations of chromosome 7 or 17 by fluorescence in situ hybridization. CONCLUSIONS: The patient is alive without recurrence or metastasis 4 years after surgery. Metanephric adenoma must be differentiated from other renal tumors, particularly Wilms' tumor or low-grade renal cell carcinoma. Immunohistochemical and cytogenetic analysis may be helpful in difficult cases.     

A resected case of thymolipoma]

We reported a resected case of thymolipoma, which has been hardly experienced. The patient was 21-year-old female and consulted a doctor for general fatigue. Chest roentgenogram revealed a mass-like shadow at the right lower mediastinum, which was suspected mediastinal tumor. The mass of right anteroinferior mediastinum, which was clearly shown by chest CT scan and MRI, was continued to the right lobe of the thymus. Under a diagnosis of anterior mediastinal tumor, operation was carried out. The tumor, which was 10 x 8 x 7 cm in diameter and 160 g in weight, was removed together with right lobe of the thymus. Histological diagnosis of thymolipoma was obtained from the resected specimen.     

A case of malignant fibrous histiocytoma arising from the renal capsule

A 62-year-old man was admitted with a chief complaint of general malaise. Computed tomography showed a large mass adjacent to the parenchyma of the left kidney. The mass was 17 x 13 x 12 cm in size. Preoperative diagnosis was left renal cell carcinoma and left radical nephrectomy was performed. Histopathologically, the tumor was diagnosed as malignant fibrous histiocytoma (MFH), and the tumor was considered to have arisen from the renal capsule. There has been no recurrence for 7 months postoperatively. We review 40 cases of MFH arising from the kidney or the renal capsule in the literature.     

Metanephric adenoma in a 59-year-old female: a case report

We report a case of metanephric adenoma in a 59-year-old female. The tumor was incidentally detected on computed tomography (CT) and ultrasound (US), and diagnosed as left renal cell carcinoma by radiological examination. Left nephrectomy was performed. The tumor measuring 4 x 3 x 3 cm had a clear margin and was encapslated with thick fibrous tissue. The cut surface was yellow-white and the boundary of renal parenchyma was clear. Histopathologically, the tumor showed a characteristic composition of small uniform cells with regular nuclei that formed a tubular pattern. Immunohistologically, they were positive for Leu-7 and vimentin. Pathological diagnosis was metanephric adenoma. We discuss the radiological findings of metanephric adenoma.     

A case of retroperitoneal tumor presenting with gross hematuria

A case of retroperitoneal tumor presenting with gross hematuria is reported. A 62-year-old female consulted our clinic with the chief complaint of gross hematuria. On physical examination, a goose-egg sized tumor was palpable in the left flank region. Drip infusion pyelography and computerized tomographic scan showed left retroperitoneal tumor which deviated the left kidney upwards. Percutaneous needle biopsy of the tumor revealed no malignancy. Total resection of the tumor was performed subsequently. A yellowish solid tumor was macroscopically encapsulated by fibrous tissue, weighed 230 g and 6 x 7 x 10 cm. Histopathological diagnosis was malignant schwannoma. After operation, the hematuria stopped without any treatment and deviation of the left kidney was improved. Soft tissue tumor should be treated by adjuvant chemotherapy with irradiation because of its high frequency of recurrence and metastasis. Combined chemotherapy with VCR, ADR, CPM and DTIC (CYVADIC) was performed and she is in good health at 1 year after operation.     

The retroperitoneal rhabdomyosarcoma: a case report

A case of rhabdomyosarcoma in the retroperitoneal space is reported. The patient, a 71-year-old man, visited us with a complaint of left flank pain. The tumor measuring 13 x 10 x 7 cm and weighing 700 g, was removed operatively. The patient had no evidence of recurrence in 12 months following surgery.     

Complex role of tumor cell transforming growth factor (TGF)-βs on breast carcinoma progression

Growth inhibition by the TGF-s has been extensively studied in both normal and transformed mammary epithelial cells. It has been proposed that loss of autocrine TGF- mediated growth regulation is a critical event in breast tumorigenesis and several lines ofin vitro andin vivo data support this hypothesis. However, a positive association between the expression of TGF-s by tumor cells and the progression or maintenance of breast cancinoma cells has been observed in many studies inin vivo tumor models. Possible mechanisms for these growth enhancing effects of TGF- include immunosuppression mediated by tumor TGF-s, enhanced angiogenesis, increased peritumoral stroma formation, and cell adhesion. The net effect of tumor cell TGF- on the biology of breast carcinogenesis would depend on the balance between autocrine growth inhibition of mammary epithelial cells and these growth enhancing effects.     

Combination chemotherapy of human renal cell carcinoma in athymic nude mice with human lymphoblastoid interferon (HLBI) and UFT, 5-Fu

The effectiveness of interferon alpha (HLBI) for nude mouse transplantable human renal cell carcinoma 72nd general meeting, in combination with UFT and 5-Fu, was examined using, 1 x 10(7) IU/kg, 2 x 10(7) IU/kg HLBI; 25 mg/kg 5-Fu; and 10 mg/kg, 20 mg/kg UFT, administered for 10 consecutive days. The ratio of relative mean tumor weight of treated group to control group was under 42% for the combination of 25 mg/kg (I.P.) 5-Fu, 20 mg/kg UFT, and HLBI and the effect was particularly clear for the combination with 2 x 10(7) IU/kg which indicated a grade IIA histologic classification. In comparison with the control groups only UFT (20 mg/kg) and HLBI (2 x 10(7) IU/kg) showed significant inhibition when administered alone. Although none of the drugs had an inhibitory effect when administered alone, in combined use they showed a strong antitumor effect which was more than synergistic. Orally administered 5-Fu showed a statistically significant difference only in the combination with 2 x 10(7) IU/kg HLBI. Furthermore, the concentration of 5-Fu in the tumor tissue was not affected by the route of administration or drug combination, whereas that in the serum was below the limit of detection in the intraperitoneally administered cases, 0.0096 +/- 0.0079 microgram/ml, lower than the value for orally administered cases. The 5-Fu concentration was 0.026 +/- 0.012 microgram/ml for orally administered UFT which was significantly higher than the value obtained for orally administered 5-Fu. Thus, combination therapy of HLBI and UFT for renal cell carcinoma is expected to be clinically useful.     

A case report of primary cardiac leiomyosarcoma]

A 26-year-old woman presenting symptoms of rapid progressive heart failure consulted with our hospital. Two-dimensional echocardiography showed a large mass in the left atrium (LA) and severe pulmonary hypertension. Emergent operation was performed because of hemodynamic reason and the risk of embolism. The tumor (7 x 6 x 3 cm) which was lobulated and had a smooth surface was arising from posterior wall of LA extending into the ostium of right lower pulmonary vein. The portion of tumor located was excised. The defect was reconstructed by bovine pericardium. Postoperative histopathological diagnosis was leiomyosarcoma. Hemodynamics recovered after surgical treatment and there were no problems for 5 months. However, tumor recurrence in LA and pulmonary metastasis was found 5.5 months after surgery. The patient died two weeks later by progressive heart failure. Primary cardiac leiomyosarcoma is extremely rare. The current world literature is reviewed with respect to this rare tumor.