Combination immunotherapy using autologous tumor-stimulated lymphocytes and trastuzumab (Herceptin) for the patients with recurrent breast cancer

PURPOSE: We report two patients with refractory recurrent breast cancer (HER2/neu: +) postoperatively, who had failed response to the available conventional chemotherapy of CAF (cyclophosphamide, adriamycin, 5-fluorouracil) and docetaxel, etc. They markedly responded to the combination immunotherapy using intraperitumoral injections of autologous tumor cell-stimulated T lymphocyte (AuTL) and trastuzumab (Herceptin), an anti-HER2 monoclonal antibody. METHODS: AuTLs were administrated directly into the recurrent tumor by intraperitumoral injections biweekly and trastuzumab was infused systemically every week. The treatments were repeated for 6 and 11 injections in the patients, respectively. The total administered T cells had reached to 3.8 x 10(9) and 6.4 x 10(9), respectively. The dosage of trastuzumab was 2 mg/kg in each patient. RESULTS: The carcinomatous pleural effusion had disappeared and was well controlled in patient 1 and a marked regression in injected fields in comparison to the size of the recurrent tumor before treatment was observed in patient 2. The tumor marker proteins (CEA, CA15-3, TPA) had also decreased significantly. The adverse effects of the immunotherapy were tolerable with grades 1-2 infusion reaction of fever, tachycardia and hypotension, but no cardiac dysfunction was observed. CONCLUSIONS: Clinical responses of recurrent breast cancer were observed in two patients after receiving the intra-peritumoral AuTL injection plus trastuzumab immunotherapy. These results showed that refractory recurrent breast cancer may be controlled effectively and safely by repeating the cellular immunotherapy combined with trastuzumab and suggested utility of combining these agents in clinical trial.     

Docosahexaenoic acid enhances cyclooxygenase-2 induction by facilitating p44/42, but not p38, mitogen-activated protein kinase activation in rat vascular smooth muscle cells

The effect of docosahexaenoic acid (DHA) on cyclooxygenase expression induced by interleukin (IL)-1beta and phorbol 12-myristate 13-acetate (PMA) in rat vascular smooth muscle cells (VSMCs) was investigated in order to clarify the cellular mechanism of cardiovascular protective effects. DHA and eicosapentaenoic acid slightly enhanced IL-1beta-induced cyclooxygenase (COX)-2, but not COX-1, expression, whereas arachidonic acid had no effect. DHA also slightly enhanced PMA-induced COX-2 expression. DHA stimulated both rapid and prolonged activation of p44/42, but not p38, mitogen-activated protein kinase (MAPK) induced by IL-1beta and PMA. These results suggest that DHA enhances the COX-2 expression by selectively facilitating p44/42 MAPK activation in VSMCs.     

Urachal anomalies and tumor: clinical investigation of 14 cases

Diseases associated with persistent urachus are relatively rare. During the past 9-year period, there have been 14 patients with urachal disease consisting of 10 with urachal abscess and 4 with urachal cancer. The 10 patients with urachal abscess consisted of 7 males and 3 females aged 19-77 years (mean, 46 years). The 4 patients with urachal cancer consisted of 2 males and 2 females aged 48-81 years (mean, 57 years). As symptoms, lower abdominal pain was frequently observed in the patients with persistent urachus with abscess and gross hematuria in those with urachal cancer. Echo and magnetic resonance imaging (MRI) were useful for visualizing the lesion. Computed tomogtaphic (CT) scanning could not visualize the lesion in 2 patients. Nine patients underwent MRI, which visualized the lesion in all of them. As urachal abscess, an umbilical fistula was observed in 3 patients, urachal cyst in 4, and urachal diverticulum in 1. The preoperative diagnosis was urachal cancer in 6 patients, and pathological examination showed 4 patients with adenocarcinoma, 1 with inflammatory granuloma, and 1 with pseudosarcoma. Urachal abscess was treated by resection of the abscess in 6 patients, transurethral resection in 1, and resection of the umbilicus and urachus and total cystectomy in the other. Of the patients with urachal cancer, 1 underwent total cystectomy and the other 3 underwent total urachal resection and partial cystectomy. In 2 patients with persistent urachus with abscess, the differentiation between abscess and malignant tumor was difficult.     

Surgical treatment of lumbar ossification of the posterior longitudinal ligament. Report of two cases and description of surgical technique

The authors report two cases of patients with lumbar ossification of the posterior longitudinal ligament (OPLL). One patient underwent surgery via the single posterior approach, and the other patient underwent combined anterior-posterior surgery. The authors consider the anterior approach for excision of the ossified lesion to be the most reasonable for treatment of lumbar OPLL. It is extremely important, however, to select the surgical procedure according to the individual patient's condition.     

Clinical statistics on testicular tumors in the Japanese during the 1970's

A statistical analysis was made by computer on 511 cases of testicular tumor experienced at 14 facilities in Japan between 1970 and 1979. The age distribution of the patients had two peaks, one under 3 years (15%) and the other between 25 and 34 years (32%). Forty percent of the patients were office workers and 76% were college graduates. Fifty percent of the patients had 0 to 1 sibs. The blood type distribution was similar to that for the whole Japanese population. Six percent of the patients had a past history of trauma, and no relation with cell type was detected. Sixty nine percent of the patients were married and 31% were not married. Sixty seven percent of the patients over 30 had seminoma, and 78% of the patients under 29 years old had non-seminoma. Seminoma was rare in patients under 9 years old. Histologically, 75% were simple type, and 25% were mixed type. Forty three percent of the cases were seminoma and 57% were non-seminoma. Of the stage I cases, 78% and 57%, and of the stage III cases 7 and 28%, respectively, were seminoma and non-seminoma, many of the non-seminoma being at high stage. The 5-year survival rate for the 75 patients under 9 years old was 96%, and that for the 341 patients over 15 years was 70%, the survival rate for the patients under 9 years being significantly higher. The 5-year survival rate for stage I, II and III seminoma was 100, 65 and 0%, respectively, while that for non-seminoma was 93, 56 and 8%, respectively. The survival rate for stage I was higher for seminoma cases than for non-seminoma cases. No difference was detected between survival rate for stage II or III between seminoma and non-seminoma. The survival rate for seminoma did not differ with the time when the surgery was performed, but for the patients with non-seminomatous tumors, the survival rate was higher for the patients operated within one month than those operated later. The survival rate was not related to the weight of the extracted testicle. The 5-year survival rate for the patients with normal body temperature was 78% whereas that for the patients who had fevers was 32%. The 5-year survival rate for the patients not accompanied by abdominal tumors was about 80%, whereas that for the patients with palpated abdominal tumors was 42%.(ABSTRACT TRUNCATED AT 400 WORDS)     

The cost and yield of photoscreening: impact of photoscreening on overall pediatric ophthalmic costs

BACKGROUND: Approximately 5% of preschool-age children suffer from amblyopia. Many of them have high or unequal hyperopia. Amblyogenic risk factors frequently can be detected by photoscreening. METHODS: Free photoscreening was offered to Alaskan children ages 1 to 5 from urban and rural screening hubs. Screened images were mailed to the Alaska Blind Child Discovery coordinating center for physician photoscreen interpretation, specifically seeking latent or anisometropic hyperopia. Parents and screeners then were mailed results and information about amblyopia. Follow-up examination data were tallied, and a cost-consequence analysis was developed for various vision screening paradigms and eye care. RESULTS: From 1996 through 2003, a total of 13,255 screenings were performed with a positive interpretation rate of 4.7%. Penetrance of screening was 22% in urban and 44% in rural communities. Positive predictive value was estimated to be more than 90%. Average cost to screen and inform an Alaskan preschooler was approximately 10.67 dollars, and cost to detect amblyogenic risk factors by photoscreening in an Alaskan was approximately 206 dollars. Compared to American Academy of Pediatrics (AAP) 1995 guidelines, implementing photoscreening added 9%, while mandating complete prekindergarten examination added 49% to overall eye care. CONCLUSIONS: MTI photoscreening achieved high community penetrance and high positive predictive value for latent hyperopia and other amblyogenic factors. When follow-up costs are considered, adding photoscreening to current AAP guidelines may add 112 dollars per child over 10 years, but probably would assist in the reduction of amblyopia. Penetrance of urban photoscreening likely will remain low unless pediatric vision screening guidelines and reimbursement are revised.