Search

Purpose: The mechanism underlying the immunomodulation caused by blood transfusion has yet to be elucidated. The aim of the present study was to determine whether the transfusion of a soluble or insoluble factor present in stored blood can induce immunomodulation, which would thereby promote solid tumor growth., Methods: C57Bl/6J mice were subcutaneously inoculated with B16-CG melanoma cells, which secrete beta-human chorionic gonadotropin (beta-hCG). Following inoculation, each of three different products of allogeneic and syngeneic blood were transfused on days 0 and 1: fresh whole blood, stored whole blood, and supernatants from the stored blood. Tumor growth was then monitored by measuring urinary beta-hCG. All mice were killed on day 15, and the tumor weight and volume were measured., Results: Transfusion of all allogeneic blood products enhanced tumor growth, as did the stored syngeneic whole blood. Neither fresh syngeneic blood nor the supernatant from stored syngeneic blood promoted tumor growth. Although the tumors were not visually detectable until day 10 after inoculation, by day 7 the levels of urinary beta-hCG were significantly higher in the mice that received allogeneic blood supernatant than in the mice that received saline., Conclusions: A soluble alloantigen enhances solid tumor growth, as does an insoluble factor present in stored syngeneic whole blood. The immunomodulation associated with this factor begins to enhance tumor growth within 7 days after transfusion.

Laminin-5 is an essential component of epithelial basal membranes. Matrix metalloproteinase-2 (MMP-2) changes laminin-5 from static to migratory substrate by cleaving the short arm of the gamma2 subunit of the laminin-5. Recently, the expression of laminin-5 gamma2 chain has been reported to be a marker of invasiveness of epithelial malignant tumors. We investigated the expression of laminin-5 gamma2 chain and MMP-2 in the neoplastic changes of uterine cervical squamous epithelium. Tissue samples of normal uterine cervix, cervical intraepithelial neoplasia-1, -3 (CIN-1, -3) and squamous cell carcinoma keratinizing (SCC-K) and non-keratinizing (SCC-NK) were analyzed for expression of the laminin-5 gamma2 chain and MMP-2 by immunohistochemistry. In normal uterine cervix and CIN-1, laminin-5 gamma2 chain was immunolocalized only in the basal membrane. In CIN-3, expression of laminin-5 gamma2 chain and MMP-2 became apparent at the epithelial-stromal interface of epithelial cells. In SCC-K and SCC-NK, laminin-5 gamma2 chain and MMP-2 expression were abundant at the epithelial-stromal interface of tumor clusters. These results suggest that the expression of laminin-5 gamma2 chain and MMP-2 may be involved in the process of neoplastic changes of uterine cervical squamous epithelium.

Research exploring the E6-p53 and E7-pRb model has resulted in the identity of the viral gene's actions on numerous cellular proteins and processes normally involved in cell growth and proliferation. Specially, several findings have established the various ways by which the HPV-infected cell may escape controls governing cell growth and proliferation, including the fidelity of the host cell's genome and apoptosis. A large body of knowledge already generated in this area supports the view that high-risk HPV types have the ability to transform cells into a malignant phenotype. Such ability, however, is not sufficient to actually and inevitably produce cervical carcinoma, as indicated by the frequent spontaneous clearance of HPV infection and the long delay between the onset of persistent infection and emergence of the malignancy. Delay in the participation of cofactors has been suggested as explanation in this regard. However, it remains unclear how and when cofactors or factors that are innate in the HPV-infected cells launch the host cells into an irreversible progression to carcinoma.

We successfully performed off-pump coronary artery bypass grafting (OPCAB) with concomitant esophagectomy in a 77-year-old man with esophageal cancer and severe stenosis of the anterior descending branch of the left coronary artery. Off-pump coronary artery bypass grafting was performed via median sternotomy and esophagectomy was done via the left thoracoabdominal approach. The patient was discharged with a patent graft 8 weeks after surgery. The benefits of OPCAB include that it is less invasive and heparinization can be avoided. This case report demonstrates that simultaneous OPCAB and esophagectomy is advantageous for a selected population with surgically correctable coronary artery disease and resectable esophageal cancer.

Background: Recent advances in the treatment of thoracic esophageal cancer have afforded it a better prognosis. As a consequence, increasing attention is being paid to the outcomes with postoperative monitoring for second primary malignancies after esophagectomy, but no recent study has focused on the longterm followup and outcomes in these patients., Study Design: In 1989, we began intensive prospective screening and surveillance designed to detect cancers of the head and neck, lung, stomach, residual esophagus, and colon/rectum after esophagectomy. Between 1989 and 2001, 365 patients underwent esophagectomy for thoracic squamous cell esophageal carcinoma in our department. Of those, 200 were followed up as part of this program. Excluded were patients in whom esophageal cancer recurred, patients with other prior or simultaneous malignancies, and patients who died within a year of operation. Clinicopathologic profiles and treatment outcomes were determined for 33 patients who developed a second primary malignancy after esophagectomy., Results: The interval between the primary esophageal cancer and the secondary carcinoma was 49 +/- 40 months (median, 48 months). The second primary malignancies were located in the stomach (30%), head and neck (24%), lung (24%), colon/rectum (9%), liver (6%), pancreas (3%), and blood (6%). Twenty-one patients (64%) were classified as stage 0, I, or II; 10 (30%) were stage III or IV. Overall, the 2-year, 3-year, and 5-year survival rates following diagnosis of a second primary malignancy were 58.0%, 58.0%, and 48.6%, respectively. Of the 19 patients (58%) in whom second primary malignancies were detected before symptoms developed, the 5-year survival rate was 70.7%, which was significantly greater than that among patients whose secondary malignancies were discovered after symptoms developed (17.1%)., Conclusions: Good outcomes in the treatment of second primary malignancies after esophagectomy for thoracic squamous cell esophageal carcinoma can be obtained with longterm, intensive followup and active surgical intervention for detected malignancies.

Background/aims: To determine whether the clinical presentation of pulmonary edema following esophagectomy can be objectively determined by changes in X-ray density in the lung field on chest radiography., Methodology: Sixteen patients who underwent esophagectomy for thoracic esophageal cancer and five patients who underwent less radical surgery at Akita University Hospital between July 2000 and March 2001 were recruited to the thoracic esophageal cancer and control groups, respectively. Chest radiography was carried out using five aluminum disks (15, 20, 25, 30 and 35 mm thickness) placed in upper right corner of the film and X-ray density for the disks and chest lung field was measured using a densitometer until POD 7., Results: In the thoracic esophageal cancer group, X-ray density in the lung field, body weight, and respiratory index increased significantly in the immediate postoperative period. The X-ray density in the lung field peaked on POD 2, and remained constant to POD 6. Correlations were found among changes in X-ray density in the lung field, body weight, and respiratory index., Conclusions: The measurement of X-ray density on a chest radiograph is useful for prediction as well as early management of patients with pulmonary edema following esophagectomy for thoracic esophageal cancer.

Background/aims: Recent advances in the treatment of esophageal cancer have afforded better prognosis for patients. Despite the increased need to monitor the progress of patients with reconstructed digestive tracts over the long-term, no reliable prospective studies have yet been conducted. This prospective study determined secondary disease of the reconstructed gastric tube after esophagectomy for esophageal cancer., Methodology: One hundred and fourteen patients who underwent esophagectomy and reconstructed gastric tube via the posterior mediastinal route between April 1992 and March 1999 at Akita University Hospital, were followed up. Follow-up endoscopy was carried out once a year to determine the incidence and characteristics of secondary disease of the reconstructed gastric tube., Results: Fifty-four (47%) patients were found to have secondary gastric abnormalities. Of these, 4 patients (3.5%) had carcinoma of the gastric tube, 12 patients (10.5%) had benign gastric tumor, 7 patients (6.1%) had gastric ulcers, and 40 patients (35.1%) had erosive or hemorrhagic gastritis. Three patients found to have early gastric cancer upon periodic follow-up endoscopy underwent successful complete resections., Conclusions: Annual follow-up endoscopy is vital to the detection of early, curative secondary gastric cancer and ulceration in patients following esophagectomy for esophageal cancer.

Objective: The purpose of this study was to present our experiences of an innovative surgical approach for vaginal agenesis with the use of Interceed absorbable adhesion barrier (Ethicon) to achieve a satisfactory neovagina., Study Design: The current study involved 10 subjects who were diagnosed with vaginal agenesis. After the creation of a vaginal tunnel, a mold that had been wrapped with Interceed was placed in the neovagina., Results: No operative and postoperative complications were encountered. The duration of the operation was < or =30 minutes, and blood loss was minimal. The postoperative hospital stay was only 2 days. Epithelialization of the neovagina was achieved 1 to 4 months after the operation, and all patients were satisfied with the outcome. The neovagina that was created with this procedure was not much different from the normal adult vagina as far as histologic and physiologic conditions are concerned., Conclusion: This innovative surgical procedure may be a potential alternative approach for the therapy of vaginal agenesis with the use of the absorbable adhesion barrier Interceed with excellent results.

Objective: To investigate the mechanism by which methylprednisolone protects the liver from hypoxia-induced injury., Design: Prospective control study using the isolated rat liver., Setting: Animal research facility., Subjects: Male, fasted, pathogen-free Sprague-Dawley rats., Interventions: Low-flow hypoxia was produced by reducing afferent perfusate pressure from 10 to 2.5 cm H(2)O; isolated livers were portally perfused for 2 hrs., Measurements and Main Results: We measured mitochondrial membrane potential and hydrogen peroxide production by imaging rhodamine 123 and 2'-7'-dichlorofluorescein fluorescence, respectively. Leakage of mitochondrial enzymes was also monitored by assaying mitochondrial aspartate aminotransferase activity in the outflow perfusate, and the radical-scavenging effect of methylprednisolone was assessed by measuring luminol-dependent hydrogen peroxide chemiluminescence. Apoptosis in liver cells was determined by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling. Rhodamine 123 fluorescence was significantly diminished in the hypoxic liver, especially in the region of the terminal hepatic venules, which is indicative of membrane depolarization in the mitochondria in those areas. Hypoxia-induced mitochondrial dysfunction was indicated by leakage of aspartate aminotransferase into the outflow perfusate, and increased 2'-7'-dichlorofluorescein fluorescence indicated increased hydrogen peroxide levels, particularly in the midzone. Pretreatment with 30, 10, or 3 mg/kg of methylprednisolone inhibited the hypoxia-induced mitochondrial membrane depolarization and enzyme leakage, although hydrogen peroxide levels and apoptosis in sinusoidal endothelial cells were unaffected., Conclusions: Methylprednisolone does not protect the liver from hypoxia-induced injury by suppressing hydrogen peroxide production. Instead, the beneficial effect of methylprednisolone seems to be related to its ability to protect against mitochondrial membrane depolarization under hypoxic conditions.

Background: Low-flow hypoxia induces xanthine oxidase-dependent hydrogen peroxide production by hepatocytes in the midzone of blood-perfused rat livers and apoptosis in sinusoidal endothelial cells (SECs). As Bcl-2 is a potent inhibitor of apoptotic cell death and is localized mainly in the inner mitochondrial membrane and crista, the purpose of this study was to determine whether cell-specific changes in mitochondrial Bcl-2 levels could account for the hypoxia-induced apoptosis in SECs., Materials and Methods: A low-flow hypoxia model was generated in isolated rat livers by reducing perfusate inflow pressure from 10 to 2.5 cmH2O for 2 h. Apoptosis was then evaluated using the TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. Mitochondrial Bcl-2 protein levels were determined in hepatocytes and SECs using cryosectioning immunogold labeling electron microscopy.Results. TUNEL-positive nonparenchymal cells, identified as SECs, were observed predominantly in the midzone of low-flow hypoxic rat livers, whereas few parenchymal cells were stained. Mitochondrial Bcl-2 levels were higher in SECs than in hepatocytes under control conditions, but they declined significantly during hypoxia, though no morphological signs of apoptosis were apparent. In hepatocytes, by contrast, Bcl-2 levels were unaffected by hypoxia. Pretreatment with a specific xanthine oxidase inhibitor, sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo [1,5-a]-1,3,5-triazine-4-olate monohydrate, which blocks production of hydrogen peroxide, also blocked both the hypoxia-induced apoptosis and the decline in mitochondrial Bcl-2 in SECs., Conclusion: Hydrogen peroxide-dependent declines in Bcl-2 induce apoptosis in SECs in the hypoxic rat liver.

We report a case of gastrobronchial fistula that developed after esophagectomy for esophageal cancer. The fistula was repaired successfully by transposing a pectoralis major muscle flap. Complete healing was confirmed histologically by epithelialization of the fistula site and at autopsy 12 months after surgery. Muscle flap transposition effectively repairs gastrobronchial fistula.

Purpose: There is evidence that blood transfusion is associated with an increased rate of tumor recurrence. This study was conducted to assess the survival advantage of giving autologous blood instead of allogeneic blood during surgery for esophageal cancer., Methods: We retrospectively analyzed 62 patients who underwent esophagectomy for thoracic esophageal cancer between January 1991 and February 1995 and received allogeneic blood transfusion, and 61 patients operated on between March 1995 and February 1998, who received autologous blood transfusion. The clinicopathological factors and survival rates were compared between the two groups., Results: The clinicopathological factors that influenced prognosis were similar in the two groups; however, a definite survival advantage was evident in the autologous blood transfusion group. According to multivariate analyses, the transfusion of allogeneic blood was an independent prognostic factor ( P = 0.0222), as was the presence of metastatic lymph nodes. Patients who received allogeneic blood transfusions perioperatively had more than a twofold greater risk (Hazard ration 2.406) of death over patients who received autologous blood transfusions., Conclusion: Autologous blood transfusion appears to be an independent prognostic factor for the survival of patients with esophageal cancer.