Immunobead and Density Gradient Purification of Paget Cells: In vitro Studies of Proliferation

Previous studies using primary monolayer cultures of epithelial cells from the involved epidermis of patients with mammary and extramammary Paget's disease investigated whether Paget cells proliferate as other malignant cells do. Although epithelial monolayers from the involved skin were maintained for approximately 45 days, no permanent cell lines were established. The proportion of carcinoembryonic antigen (CEA)-positive cells did not increase in the long-term cultures. Herein, we report studies of whether there is a real reduction of Paget cell numbers or if this is merely a decrease in the expression of CEA by the cells. Furthermore, we investigated whether Paget cells survive longer when cultured free from any potential inhibitory keratinocytes or other epidermal cells. Skin samples were obtained from one patient with mammary Paget's disease and three with extramammary Paget's disease; epidermal cells were cultured in vitro. An enrichment of Paget cells was carried out from the cultured epidermal cells by combining an anti-epithelial membrane antigen monoclonal antibody, binding to immunobeads, and density gradient centrifugation in Nycodenz. The separated cells were re-cultured in Keratinocyte-SFM serum-free media. The proportion of CEA-positive cells did not increase in the cultures, and the purified cells did not show any increase in survival times compared to the non-purified cultured cells. These results suggest that the decrease of CEA-positive cells noted during culture results from a decline in expression of CEA in the Paget cells. Paget cells in the involved epidermis do not proliferate significantly and thus differ from many other malignant cells.     

Chemo-endocrine therapy in patients with stage D2 prostate cancer

There have only been a few studies of chemo-endocrine therapy compared with endocrine therapy alone in newly diagnosed prostate cancer patients. We assessed the effects of these two therapies by comparing long-term survival rates. One hundred and twenty-nine patients were entered in this study between November 1977 and March 1992. Seventy-seven patients were treated with endocrine therapy alone. Other 52 patients received chemo-endocrine therapy, which included orchiectomy and/or diethylstilbestrol diphosphate (DES-DP) plus Cisplatin, with or without other cytotoxic agents. All patients had bone metastasis at the beginning of the study. There was a significant difference in survival between patients who received endocrine therapy and chemo-endocrine therapy (P = 0.0078). That is, survival rate was superior for the chemoendocrine therapy patients throughout the entire follow-up period. These data suggest that early chemo-endocrine therapy containing Cisplatin, with or without maintenance chemotherapy, is a potentially effective treatment for newly diagnosed metastatic prostate cancer and is worth further investigation via a randomized trial.     

A CASE OF METASTATIC YOLK SAC TUMOR OF TESTIS IN A CHILD

We report a case of testicular yolk sac tumor in a child aged 3 years and 6 months with multiple bulky metastases to lung and retroperitoneum (stage 11182). After three courses of chemotherapy with a PV 8 regimen (cisplatin, vinblastine and bleomycin). complete and partial responses were obtained for lung and retroperitoneal lymph node metastases, respectively. The patient was followed-up closely. However, on the basis of a re-elevated alpha-letoprotein (AFP) after 4 months' follow-up, he was treated with three courses of salvage chemotherapy with a modified VAB-6 regimen (cyclophosphamide. etoposide. actinomycin D, bleomycin and cisplatin), lollowed by retroperitoneal lymph node dissection. Histologically, only necrotic tissue was found. There is no evidence of recurrence 24 months after lymphadenectomy. There is very little information in the literature on the appropriate management of postchemotherapy residual mass in pediatric testicular tumors.     

Primary leiomyosarcoma of the thyroid gland

Primary leiomyosarcoma of the thyroid gland is extremely rare, and to the best of our knowledge only five well-documented cases have been reported in the world literature. We herein report a 58-year-old female patient with primary leiomyosarcoma of the thyroid who was successfully treated by total thyroidectomy with a modified neck dissection. Immunohistochemically, the tumor cells showed positive reactivity to α-smooth muscle actin and vimentin. Radical surgery was thus considered to be essential in the treatment of this rare but rather aggressive malignancy.     

Primary malignant melanoma of the rectum: Report of a case

We describe herein a rare case of primary malignant melanoma of the rectum in an 85-year-old woman. The patient presented with intermittent rectal bleeding, and a colonoscopy revealed an ulcerated polypoid mass in the rectum, located 5 cm from the anal verge. The lesion was histologically characterized by solid growths of small round cells with scanty cytoplasm and prominent nucleoli. Although no melanin pigment was found in the tumor cells, they were immunohistochemically positive for HMB-45, a monoclonal antibody highly specific for malignant melanoma. Thus, HMB-45 proved very useful to establish a diagnosis of amelanotic malignant melanoma of the rectum.     

Two Autopsied Cases of Familial Sudanophilic Leukodystrophy

Abstract: Two autopsied female sibling cases of sudanophilic leukodystrophy are reported. Case A and case B were the second and third of seven siblings, and a sister and a brother died from severe progressive neurological disease with similar symptoms. Consanguineous marriages were noted in the family of both cases through the past three generations. Case A gradually developed intellectual deterioration and tetraplegia at the age of 29, progressed to akinetic mutism within one year and thereafter survived for 14 years. Neuropathologically, a severe atrophy and degeneration were noted in the white matter of the whole cerebrum, sparing the subcortical U-fibers. Myelin and axons were severely damaged with peripheral astrocytic gliosis. Case B developed similar clinical symptoms at the age of 20 and survived for 7 years in the state of akinetic mutism. Similar postmortem findings as those of case A were found in the white matter of the cerebrum with formation of sudanophilic breakdown products and with thick fibrillary gliosis. The pyramidal tract was completely degenerated. There was no accumulation of abnormal lipid in the brains of both cases.     

Bacterial superantigen enhances cytokine production by T-helper lymphocyte subset-2 cells and modifies glomerular lesions in experimental immunoglobulin a nephropathy

Background The purpose of this study was to examine the effects of bacterial suporantigens, which can derange the immune response and contribute to the renal lesions of immunoglobulin A (lgA) nephropathy. Methods Twenty-five micrograms of a bacterial superantigen, staphylococcal enterotoxin B (SEB), was injected into IgA nephropathy-prone ddY mice intrathymically when they reached 6 weeks of age. Evaluation included measurement of albumin excretion in urine, immunoglobulin concentration, and lymphokine production in vitro, as well as analysis of T-cell receptor expression in splenic T-cell subsets and examination of renal histology by light and fluorescence microscopy. Results At 40 weeks of age, the serum level of IgA in these mice was substantially increased and the number of Vβ8⁺ CD4⁺splenic T-cells was significantly decreased compared with measurements in untreated controls. Both control and SEB-treated mice excreted less than 30 μg/mL of urinary albumin. In mice given SEB, the amount of interleukin 2 (IL-2) and tumor necrosis factor-α (T helper 1 [Th1]-type cytokines) produced by the in vitro-stimulated lymphocytes significantly decreased. whereas that of interleukin 4 (IL-4) and interleukin 6 (IL-6) (Th2-type cytokines) markedly increased compared with measurements in control mice. At 40 weeks of age, mice given SEB showed marked glomerular hypercellularity and enhanced glomerular C3 deposition by renal histology, compared with control mice. Conclusion These results suggest that bacterial superantigen SEB may modify glomerular lesions through activating Th2 cells, while inducing deletion of Th1 cells in this experimental model.     

Congenital esophageal atresia successfully treated by early ligation of a tracheoesophageal fistula and delayed repair of the esophagus in a premature infant: Report of a case

We report herein the case of a premature infant with esophageal atresia (EA) and a tracheoesophageal fistula (TEF) associated with cardiac anomalies who was successfully treated by an early ligation of the TEF following gastrostomy, and delayed repair of the esophagus. A 1212-g male was born prematurely at 31 gestational weeks, at which time he was diagnosed as having EA with TEF and patent ductus arteriosus (PDA), ventricular septal defect (VSD), and atrial septal defect (ASD). A gastrostomy was initially performed but following extubation he gradually became tachypneic. A chest roentogenogram revealed atelectasis and ground-glass appearance, and reintubation was required. Ligation of the TEF was performed 53h after his birth. Following the improvement of his respiratory condition through ventilatory support and the intratracheal administration of pulmonary surfactant, he underwent repair of the esophagus on the 6th day of life. Postoperatively, he suffered from heart failure, but was treated with peritoneal dialysis and pharmacological closure of the PDA. Weaning the infant from the ventilator proved difficult, but it was finally achieved when he had reached a weight of 2268g at 3 months of age by enteral feeding. Our experience of this case demonstrates that early ligation of TEF should be performed for a premature infant with EA and TEF before respiratory distress syndrome (RDS) has developed. If a gastrostomy is required to prevent gastric distention, it should be followed by simultaneous or immediate ligation of the TEF.