Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

Study on reoperation in cardiac disease]

Between January in 1988 and September in 1990, 65 patients underwent reoperation for acquired heart disease. Previous operations were closed mitral commissurotomy in 19, open mitral commissurotomy in 19, mitral valve replacement in 22, aortic valve replacement in one, and mitral repair in 4. After median sternotomy performed by hand-operated chisel and hammer, minimized dissection of the adhesive lesion was achieved. During the sternotomy, two patients required additional right thoracotomy because of marked median sternal adhesion and major cardiovascular injury occurred in three patients. Cardioplegic solution was introduced in normograde fashion except in two patients. In two patients with previous MVR by porcine prosthesis severe calcification was found in the left atrial wall and the prosthesis was not removed in one. Postoperative complications were low cardiac output syndrome requiring intra-aortic balloon pumping in two, re-thoracotomy due to hemorrhage in one, and mild air embolism without neurological damage in two. There was one early death (1.5%) but no late death. Although perioperative complication seemed to increase in reoperation, post-reoperative results was as good as those in the primary cardiac operation and reoperation on cardiac surgery should be performed before losing the indication for operation.     

Characterization of htAKR, a novel gene product in the aldo-keto reductase family specifically expressed in human testis

In human testis, expression of a novel member of the aldo-keto reductase family was identified. Based on its testis-specific expression, we termed this protein human testis aldo-keto reductase (htAKR). In addition to four major isoforms, the existence of multiple alternatively spliced products of htAKR was detected using RT-PCR followed by nested PCR. htAKR was a homologue of mouse liver keto-reductase, AKR1E1, with close similarity in their genomic organizations. htAKR4, the longest isoform, was expressed as a non-fused native form. It exhibited a limited activity toward 9,10-phenanthrenequinone, while no activity toward the steroids or prostaglandins was demonstrated. Using the laser capture microdissection technique and RT-PCR, expression of htAKR was detected in testicular germ cells as well as in interstitial cells. The levels of htAKR mRNA in the tissues obtained from seminoma were much lower than those in normal testes. A significant decline in the htAKR expression was observed when NEC8, a cell line originated from a human testicular germ cell tumour, was exposed to phorbol 12-myristate 13-acetate or 5alpha-dihydrotestosterone. These results indicate that the expression of htAKR, down-regulated in the testicular tumour, is possibly controlled by mitogenic and hormonal signals.     

Infrared Thermometry for Rapid, Noninvasive Detection of Reflux of Spermatic Vein in Varicocele

Purpose

We evaluated infrared thermometry for measurement of reflux of blood via the internal spermatic vein.

Materials and Methods

The change in scrotal temperature in patients with varicoceles and controls with different positions was measured with an infrared thermometer.

Results

Scrotal neck temperature in the patients increased during Valsalva's maneuver with upright position (mean plus or minus standard deviation 34.62 plus/minus 1.20 to 36.05 plus/minus 1.42C), while no statistically significant increase occurred in the controls (32.91 plus/minus 0.92 to 33.42 plus/minus 1.15C). Two weeks after high ligation of the internal spermatic vein the scrotal temperature in the patients decreased to the same level (0.59 plus/minus 0.84C) as in the controls. Using this method 2 subclinical varicoceles were also found on the right side in patients with a left varicocele.

Conclusions

Infrared thermometry is noninvasive, rapid and simple for documenting varicoceles, including subclinical disease.     

Effect of recombinant granulocyte colony-stimulating factor (rG-CSF) on chemotherapy-induced neutropenia in patients with urogenital cancer

Summary The effects of recombinant granulocyte colony-stimulating factor (rG-CSF) on the myelosuppression, especially neutropenia, induced by cancer chemotherapy in patients with urogenital cancer were investigated in a randomized, controlled clinical study. In this study, rG-CSF was given subcutaneously at a dose of 2 g/kg per day for 14 consecutive days. Changes in neutrophil counts were compared between the first (no rG-CSF) and second cycles (rG-CSF treatment period) of chemotherapy. rG-CSF administration was found to be effective in reducing the duration of neutropenia, in elevating the neutrophil nadir, and in reducing recovery time. Based on comparisons between the randomized rG-CSF treatment group (with rG-CSF) and the control group, treatment with rG-CSF resulted in the moderation or prevention of neutropenia and the acceleration of recovery. These results demonstrate that in chemotherapy of patients with urogenital cancer, in which neutropenia is a dose- or schedule-limiting factor, the concomitant use of rG-CSF may enable an increase in the dose (higher single dose or increased dose per unit of time) or shorten the chemotherapy period.     

Significant antitumoral activity of cationic multilamellar liposomes containing human IFN-beta gene against human renal cell carcinoma.

PURPOSE: Immunotherapy is the most effective treatment against metastatic renal cell carcinoma (RCC). However, the response rate is approximately 15%. More effective therapy is, therefore, needed for patients with metastatic RCC. We then examined the antitumor effect of cationic multilamellar liposome containing human IFN-beta (huIFN-beta) gene (IAB-1) against RCC. EXPERIMENTAL DESIGN: Concentrations of huIFN-beta protein were measured by ELISA. The cytotoxicity of IAB-1 against human RCC (NC65, ACHN, and freshly isolated RCC cells), prostate and bladder cancer cell lines, and renal proximal tubule endothelial cells (RPTEC5899) was examined by the colorimetric method using tetrazolium salt. Apoptosis was assessed by the acridine-orange staining. For in vivo study, we used NC65 cells inoculated into severe combined immunodeficiency mouse. RESULTS: The RCC cells treated with IAB-1 secreted significant amounts of huIFN-beta protein continuously. Drastic in vitro cytotoxic effect of IAB-1 against RCC was observed. In contrast, treatment with 1000 IU/ml recombinant huIFN-beta protein resulted in weak cytotoxicity. The cytotoxic effect against prostate and bladder cancer cell lines was less than that against RCC. Furthermore, no significant cytotoxicity was observed in RPTEC5899 cells. Apoptosis was observed in the cells treated with IAB-1, but recombinant huIFN-beta failed to induce apoptosis. The size of NC65 tumors transfected with IAB-1 in mice was significantly smaller than that receiving injection of empty liposome or recombinant huIFN-beta protein. CONCLUSION: These findings indicate that IAB-1 may have an antitumor activity against human RCC by inducing apoptosis, suggesting its potential clinical application for gene therapy against RCC.     

Coronary artery bypass surgery in a patient with myasthenia gravis

A 73-year-old man with myasthenia gravis required quadruple coronary artery bypass grafting due to triple-vessel disease. Anesthetic management was performed with general anesthesia using a reduced dose of muscle relaxant with the aid of a neuromuscular transmission monitor. He was extubated 14 hrs after surgery without difficulty under this monitor. His postoperative course was uneventful. A patient with myasthenia gravis who required coronary artery bypass surgery was successfully performed by the deliberate preoperative evaluation of patient's myasthenic and cardiac status, and by the careful perioperative management.     

Effects of idursulfase enzyme replacement therapy for Mucopolysaccharidosis type II when started in early infancy: Comparison in two siblings

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder that is progressive and involves multiple organs and tissues. While enzyme replacement therapy (ERT) with idursulfase has been shown to improve many somatic features of the disease, some such as dysostosis multiplex and cardiac valve disease appear irreversible once established, and little is known about the preventative effects of ERT in pre-symptomatic patients. We report on two siblings with severe MPS II caused by an inversion mutation with recombination breakpoints located within the IDS gene and its adjacent pseudogene, IDS-2. The siblings initiated treatment with idursulfase at 3.0 years (older brother) and 4 months (younger brother) of age, and we compared their outcomes following 2 years of treatment. At the start of treatment, the older brother showed typical features of MPS II, including intellectual disability. After 34 months of ERT, his somatic disease was stable or improved, but he continued to decline cognitively. By comparison, after 32 months of ERT his younger brother remained free from most of the somatic features that had already appeared in his brother at the same age, manifesting only exudative otitis media. Skeletal X-rays revealed characteristic signs of dysostosis multiplex in the older brother at the initiation of treatment that were unchanged two years later, whereas the younger brother showed only slight findings of dysostosis multiplex throughout the treatment period. The younger brother's developmental quotient trended downward over time to just below the normal range. These findings suggest that pre-symptomatic initiation of ERT may prevent or attenuate progression of the somatic features of MPS II. Follow-up in a larger number of patients is required to confirm the additive long-term benefits of ERT in pre-symptomatic patients.