New epitope peptides derived from parathyroid hormone-related protein which have the capacity to induce prostate cancer-reactive cytotoxic T lymphocytes in HLA-A2+ prostate cancer patients

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is produced by cancer cells and has been suggested to be responsible for malignancy-associated hypercalcemia and osteolysis after bone metatsases. Therefore, PTHrP is a promising target in the treatment of metastatic prostate cancer. METHODS: Seven PTHrP-derived peptides were prepared based on the HLA-A2 binding motif. These peptide candidates were screened by their ability to induce peptide-specific cytotoxic T lymphocytes (CTLs), and their ability to be recognized by immunoglobulin G (IgG). RESULTS: Both the PTHrP59-67 and PTHrP42-51 peptides were found to efficiently induce peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A2+ prostate cancer patients with several HLA-A2 subtypes. These CTLs showed HLA-A2-restricted cytotoxicity toward prostate cancer cells. IgG reactive to the PTHrP42-51 peptide was frequently detected in prostate cancer patients. CONCLUSIONS: These results indicate that these two new PTHrP peptides will be useful in the peptide-based immunotherapy of HLA-A2+ prostate cancer patients, especially those with bone metastases.     

Extended transsphenoidal surgery for suprasellar craniopharyngiomas: infrachiasmatic radical resection combined with or without a suprachiasmatic trans-lamina terminalis approach

BACKGROUND: An extended transsphenoidal approach allowed for direct midline exposure of the parasellar structures such as the hypothalamic-pituitary axis and the third ventricle. To evaluate the capability of this approach for removal of suprasellar craniopharyngiomas, surgical outcomes were retrospectively analyzed. METHODS: During a 9-year period, 20 consecutive patients with suprasellar craniopharyngioma underwent transsphenoidal tumor resection. The average follow-up period was 55 months. No patient had a purely intrasellar tumor, 9 had prechiasmatic tumors, 9 had retrochiasmatic tumors, and 2 had purely intraventricular tumors. RESULTS: Total resection was achieved in 86% of operations. Even in mostly intraventricular cases, a transsphenoidal trans-lamina terminalis approach afforded complete resection. Visual improvement and preservation of the pituitary stalk were achieved in 84% and 95% of cases, respectively. New postoperative deterioration of pituitary function occurred in about 65% of cases, and no patient resolved their preoperative hormonal disturbance after surgery. The overall percentage of patients with diabetes insipidus increased to 61% postoperatively from 11% preoperatively. Nonendocrinologic surgical complications were observed: worsening of vision in 3 patients, hyperphagia in 3 patients, short-term memory loss in 2 patients, and cerebrospinal fluid leakage in 3 patients. Recurrence after total resection occurred in 2 (11%) patients with retrochiasmatic tumors. CONCLUSIONS: Reasonable surgical results in this study suggest that the extended transsphenoidal approach is safe and effective for removal of craniopharyngiomas. Although preservation of the pituitary stalk can be achieved in a high percentage of patients, postoperative endocrinopathy still remains as a significant problem after radical removal of the craniopharyngioma.     

Use of the airway scope for difficult airway

The Airway Scope (AWS) is a new videolaryngoscope which consists of an optical system and a single-use blade. The blade of the device is designed according with the pharyngeal anatomy, and thus the AWS is expected to have a role in the management of difficult airway. We here report 15 patients with difficult airway in whom the AWS provided in successful intubation. The AWS provides a view of the glottis with Cormack-Lehane grade 1 and resulted in successful intubation in the 15 patients. The AWS is useful for the management of difficult airway.     

Recombinant sendai virus-mediated gene transfer to adipose tissue-derived stem cells (ASCs)

Adipose tissue-derived stem cells (ASCs) are expected to have clinical applications as well as other stem cells, because ASCs can be obtained safely from adult donors and used in autologous therapies without concern about rejection and the need for immunosuppression. However, the use of gene transfer with Sendai virus (SeV) vectors, which can efficiently introduce foreign genes without toxicity into several cells, with ASCs has not yet been investigated. This study documents on the use of SeV vectors for gene transfer to ASCs. The dose-dependent GFP expression of ASCs transfected with SeV vectors after 48 h of culture at 37 degrees C was first evaluated. Next, the cellular toxicity of ASCs transfected with SeV vectors was verified. In addition, SeV vectors were compared with adenovirus (AdV) vectors. Finally, the time-dependent GFP expression of ASCs transfected with SeV vectors was evaluated. The results showed that transfection of ASCs with SeV vectors results in more efficient expression of transgene (GFP expression) in the ASCs than with AdV vectors after 48 h of culture at 37 degrees C. Moreover, while the transfection of ASCs with AdV vectors at high MOIs was cytotoxic (a lot of transfected cells died) that of ASCs with SeV vectors at high MOIs was not necessarily cytotoxic. In addition, the preservation of multilineage ASCs transfected with SeV was observed. In conclusion, this is the first report describing the successful use of SeV-mediated gene transfer in ASCs, and the results indicate that SeV may thus provide advantages with respect to safety issues in gene therapy.     

Complicated anesthetic management for esophageal atresia repair in a baby with total anomalous pulmonary venous connection diagnosed after esophageal surgery

A male newborn infant born at 38 weeks of gestation and weighing 2,660 g, was diagnosed as esophageal atresia. Although there was mild cyanosis at birth, his initial ultrasonographic examination performed by neonatologist showed normal anatomy of the heart. He underwent a surgical repair of esophageal atresia under general anesthesia. Anesthesia was induced with fentanyl and pancuronium, and maintained with sevoflurane and 60% oxygen. Frequent desaturation occurred during the procedure, requiring manual hyperventilation with 100% oxygen. Since blood pressure during the operation was unstable, volume loading with albumin was attempted. Further echocardiography was performed by pediatric cardiologist after going back to NICU. This revealed total anomalous pulmonary venous connection (TAPVC). He underwent cardiac surgery for repair of TAPVC on the next day. Although TAPVC was not preoperatively diagnosed regardless of results of echocardiogram, cyanosis and unstable blood pressure should be considered as signs of potential cardiac disease. Fluid restriction, higher hemoglobin, lower inspired oxygen and slightly higher carbon dioxide rather than albumin administration and hyperventilation should have been attempted during the esophageal repair.     

Beneficial effects of suplatast tosilate (IPD-1151T) in a rat cystitis model induced by intravesical hydrochloric acid

OBJECTIVE: To examine the effects of suplatast tosilate (IPD-1151T), a Th2 cytokine inhibitor recently recognized to improve the symptoms in patients with interstitial cystitis (IC), in a rat model of HCl-induced chronic cystitis, to elucidate the possible mechanisms by which the drug improves the symptoms of IC. MATERIALS AND METHODS: Chronic cystitis was induced by intravesical instillation of 0.2 mL of 0.4 m HCl in female adult rats. After a once-daily oral administration of IPD-1151T (0.1-100 mg/kg) or prednisolone (5 mg/kg) for 7 days, cystometry was performed under urethane anaesthesia. The bladder from HCl-induced cystitis rats was also assessed histopathologically. RESULTS: On cystometrography there was frequent voiding in cystitis rats. Administration of IPD-1151T for 7 days after intravesical HCl instillation dose-dependently increased the micturition volume and intercontraction intervals. Treatment with prednisolone had similar therapeutic effects. Histological analyses in the bladder from cystitis rats revealed oedema and infiltration of inflammatory cells such as mast cells and eosinophils in the lamina propria and the transitional epithelial thickening. These histological changes and the number of mast cells and eosinophils were reduced by administration of IPD-1151T or prednisolone. CONCLUSION: The present results indicate that IPD-1151T improves bladder function and pathological changes in HCl-induced cystitis rats, as previously observed in patients with IC. The rat cystitis model induced by HCl could provide useful information for studying proposed therapies for IC which might involve T cell-dependent inflammatory responses as one of its potential pathophysiologies.     

Breast-conserving surgery: quadrantectomy

The surgical techniques and clinical results of quadrantectomy as a form of breast-conserving surgery are described. A quadrantectomy is a breast-conserving technique including wide resection and tumorectomy. A quadrantectomy is designed to remove an anatomic segment of breast tissue (duct-lobular system). It has the advantage of greater surgical curability than other conserving techniques in cases with ductal spread, because breast cancer arising in the terminal duct often spreads in the duct-lobular system. However, quadrantectomy poses some cosmetic problems due to the large volume of breast tissue excised. Additionally, quadrantectomy has failed to show better results in local recurrence rates compared with wide resection. Therefore quadrantectomy should be limited to breast cancer with segmental and wide ductal spread. It is important to determine the surgical technique that compromises between local curability and cosmetic results for each patient with breast cancer.     

Metastases to the penis from carcinoma of the prostate

A 58-year-old man presented with dysuria at the Osaka Medical College Hospital in November 1996. Laboratory examination revealed elevated serum prostate-specific antigen (PSA) to > 100 ng/mL. Adenocarcinoma of the prostate with metastasis to the bone was diagnosed after a biopsy of the prostate and bone scintigraphy; hormonal therapy was administered. Although bone metastasis was well controlled and the serum PSA level declined to within normal levels (2.0 ng/mL), several painless nodules were found on the penile glans. Biopsy of the nodules showed that the penile tumor was a metastasis from the prostate cancer. The patient underwent partial penectomy for relief from penile pain. The serum PSA level showed no elevation 3 months after the partial penectomy, suggesting that careful observation of prostate cancer patients is necessary, even when oseous metastasis is well controlled and serum PSA levels are kept within normal ranges by hormonal therapy. The case also indicates that urologists should consider the possibility of metastasis to the penis from prostate cancer.     

Appendiceal carcinoma invading the urinary bladder

A case is reported of a 78-year-old woman with appendiceal carcinoma invading the bladder causing irritative symptoms. Although several imaging studies suggested that the secondary bladder tumor was of cecal or appendiceal origin, such as abscess or mucocele, histologic findings on transurethral and transvaginal biopsy were inconclusive. However, following laparotomy, pathologic examination of the frozen sections revealed a mucinous cystadenocarcinoma originating in the appendix and a right hemicolectomy and en bloc partial cystectomy were performed. One year after the operation, the patient was well with no evidence of recurrent cancer.