High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

BACKGROUND: The aim of this study was to investigate the efficacy and safety of high-dose chemotherapy (HDCT) for the treatment of patients with advanced testicular cancer. METHODS: Fourteen patients were treated with high-dose carboplatin, etoposide and cyclophosphamide (with or without THP-adriamycin) followed by peripheral blood stem cell transplantation. The treatment was used for two refractory cases, a second relapse, and for consolidation after the first relapse in one case each. It was also used for nine cases as part of the first-line treatment following primary conventional-dose chemotherapy, and for one case as the first salvage for a late recurrent tumor of teratoma with malignant transformation. RESULTS: The first two patients who received intensive pretreatment with cisplatin-based chemotherapy did not respond to HDCT. The two patients who were treated with HDCT as the first or second salvage therapy achieved successful outcomes. The results for the subsequent nine patients (consisting of two with stage IIIC, five with IIIB2, one with IIB, and one extragonadal seminoma) were two progressive disease, three no change and four partial remission. Only three are alive with NED following salvage surgery. Finally, a case of teratoma with malignant transformation did not respond well to two cycles of HDCT. There were no marked adverse reactions except one episode of severe neutropenic colitis. CONCLUSIONS: The results demonstrated the limited efficacy of HDCT even in cases with a good to intermediate risk rating according to classification by the International Germ Cell Cancer Collaborative Group. Because treatment for relapse after HDCT is extremely difficult, new HDCT regimens consisting of drugs that are not used in induction chemotherapy need to be established.     

Health related quality of life in Japanese men after radical prostatectomy or radiation therapy for localized prostate cancer

BACKGROUND: We performed a retrospective survey of general and disease specific health-related quality of life (HRQOL) after radical prostatectomy (RP) and external beam radiotherapy (XRT) in Japanese men. METHODS: A total of 186 patients underwent RP and 78 underwent XRT for clinically localized prostate cancer between 2000 and 2002. We measured the general and disease specific HRQOL with the MOS 36-Item Health Survey and the University of California, Los Angeles Prostate Cancer Index, respectively. Each treatment group was further divided into four subgroups according to the time scale. RESULTS: Patients from the RP group were significantly younger than those from the XRT group. The tumor characteristics differed significantly in their distributions among the treatment groups. Patients undergoing XRT had low scores in most of the general measures of HRQOL just after treatment, but after 6 months there were no differences between the treatment groups, except for the physical domains. The RP group was associated with worse urinary function, whereas the XRT group had worse bowel function and bother during the first 6 months after treatment. Thereafter, however, urinary and bowel domain did not differ between the groups. Both groups reported poor sexual function, although the RP group scored lower sexual bother. CONCLUSION: The patients who underwent RP had significantly worse urinary and better bowel function than those treated with XRT. Both treatment groups had decrements in sexual function throughout the post-treatment period; careful attention should be paid to this side-effect in preoperative counselling, especially in younger patients, regardless of the primary treatments.     

Impact of hormonal therapy prior to radical prostatectomy on the recovery of quality of life

BACKGROUND: We investigated the changes in health-related quality of life (HRQOL) in patients who underwent prostatectomy (RP) with or without neoadjuvant hormonal therapy (NHT). METHODS: A total of 72 patients undergoing direct RP (DRP group) and 26 patients receiving neoadjuvant hormonal therapy (NHT group) were enrolled in the present study. The baseline interview was conducted before RP (not initiation of therapy). Follow-up interviews were conducted in person at scheduled study visits of 3, 6, and 12 months after surgery. We measured general and disease specific HRQOL with the Medical Outcomes Study 36-Item Short Form and University of California, Los Angeles Prostate Cancer Index, respectively. RESULTS: At baseline, the NHT group scored statistically lower for not only sexual function (P < 0.001), but also the general HRQOL, such as role limitations due to physical problems (P = 0.007), social function (P = 0.045) and mental health (P = 0.034), than the DRP group. The NHT group reported lower scores in social function and mental health at 3 months (P = 0.040 and 0.006, respectively). Patients who received NHT for more than 3 months continued to show significantly lower scores for some HRQOL domains 12 months later. CONCLUSION: Neoadjuvant hormonal therapy may decrease not only sexual function, but also general HRQOL before surgery. The recovery of HRQOL appeared to be further prolonged in patients who received long-term NHT.     

Coronary Artery Spasm Induced by Ergonovine in an Infarct Related Coronary Artery Late After Primary Angioplasty

We report two cases with induced coronary spasm of the culprit lesion in the infarct related coronary artery in the chronic phase after primary percutaneous transluminal coronary angioplasty (PTCA). To our knowledge, there are few data on the response of the angioplasty site to ergonovine in human coronary arteries after primary PTCA. It is important to note that chest pain recurring after successful primary PTCA is not automatically related to restenosis, and coronary spasm in patients with previous myocardial infarction, should also be considered . (J Interven Cardiol 2000;31–34)     

Endoscopic Scoring System for Experimental Colitis with Trinitrobenzene Sulfonic Acid in Rats

Abstract: Experimental colitis models require serial sacrifice of animals to confirm the evolution of the inflammatory process. Endoscopy may possibly enable us to detect sequential changes in the lesions throughout the inflammatory process without killing animals. Using rat colitis induced with trinitrobenzene sulfonic acid (TNBS) after the study by Morris et al. the accuracy of endoscopic examination was investigated by comparing endoscopic findings with histologic findings. A polyethylene catheter was rectally inserted into rats’(Fischer, 6W male) colon. After intraluminal administration of 25 mg TNBS dissolved in 0.5 ml of 50% ethanol, each animal was kept in the tail-up position for one minute. Colonic changes were examined weekly with an Olympus BF-3C20. It took about 3 min to complete the observation per rat. We offered a novel endoscopic and histologic scoring system. The endoscopic score mainly reflected the size of the ulcers occupying the lumen and the histologic score the sizel depth of the ulcers and the degree of acute inflammation in the colonic mucosa. A highly significant (r = 0.71, p<0.01) linear correlation was observed between the endoscopic and histologic scores. This system may allow us to detect potential therapeutic agents or to investigate the mechanism underlying colitis in the human counterpart, such as Crohn 's disease, without killing laboratory animals.     

Inflammatory Fibroid Polyp of the Ileum Which Could be Endoscopically Diagnosed —A Case Report and Review of the Literature—

Abstract: Inflammatory fibroid polyp (IFP) of the small intestine is a very rare disease. Our review of the literature revealed only 40 cases of small intestinal IFP were reported from July 1975 through August 1989 in Japan. It is extremely difficult to make a definite diagnosis of IFP prior to surgery; none of the cases reported were diagnosed preoperatively. We describe here the first case of small intestinal IFP in Japan whose diagnosis was strongly suspected from an endoscopic examination prior to surgery. A 62-year-old woman was admitted to our hospital with diarrhea, abdominal pain, nausea and vomiting. A plain abdominal x-ray revealed the presence of an ileus. The subsequent contrast x-ray performed via a long intestinal decompression tube and colonoscopic observation found an ileo-ileal intussusception caused by a spherical mass (about 30 mm in diameter) in the ileum. When pushed with forceps, the tumor demonstrated a rubber-like hardness, suggesting the presence of an IFP. Surgery was performed to treat the intestinal obstruction, and the ileo-ileal intussusception was confirmed at a site 30 cm proximal to the ileocecal valve. At the leading point of the intussusception there was a semipedunculated tumor of 30X30X25 mm in size. The intestinal tumor was histopathologically diagnosed as IFP.     

Adenosine and adenosine uptake inhibitors potentiate the neuromuscular blocking action of rocuronium mediated by adenosine A1 receptors in isolated rat diaphragms

Background: Adenosine, which pre‐junctionally modulates neuromuscular transmission, and adenosine uptake inhibitors, which increase extracellular adenosine, have been used clinically. We investigated the effects of adenosine, dipyridamole and midazolam on the neuromuscular blocking action of rocuronium. Methods: Isometric twitch tensions of rat nerve‐hemidiaphragm preparations elicited by indirect (phrenic nerve) supra‐maximal stimulation at 0.1 Hz were evaluated (n=6 in all data). Results: Pre‐treatments with adenosine (0.1 and 1 μM) and CCPA (1 μM, adenosine A₁ receptor agonist), but not that with CGS21680 (0.5 μM, A₂ receptor agonist), shifted the rocuronium concentration–twitch tension curves to the left and decreased the rocuronium concentration for 50% twitch depression (IC₅₀) compared with the control (P<0.01). The leftward shift induced by 1 μM adenosine was inhibited by pre‐treatments with theophylline (50 μM, non‐selective adenosine receptor antagonist) and DPCPX (0.2 μM, A₁ receptor antagonist) but not by that with DPMA (5 μM, A₂ receptor antagonist). Pre‐treatments with dipyridamole and midazolam, adenosine uptake inhibitors, shifted the curve to the left and decreased IC₅₀ at supra‐therapeutic concentrations (10 and 2.5 μM, respectively) but not at clinical concentrations (2 and 0.5 μM, respectively), and the leftward shifts were inhibited by pre‐treatment with DPCPX (0.2 μM). Conclusion: The results indicate that adenosine potentiates the neuromuscular blocking action of rocuronium mediated by adenosine A₁ receptors and that supra‐therapeutic concentrations of dipyridamole and midazolam also potentiate the action of rocuronium by increasing endogenous adenosine concentration.     

Relevance of postcatheter removal incontinence to postoperative urinary function after radical prostatectomy

AIM: We examined whether postoperative urinary function after radical prostatectomy is associated with immediate incontinence just after catheter removal. PATIENTS AND METHODS: The current study included 80 patients with clinically localized prostate cancer, who underwent radical retropubic prostatectomy between January 2002 and May 2004. The amount of immediate incontinence was measured with a 24-h pad test just after catheter removal. The patients were categorized into the three groups based on the stratified grade of immediate urinary incontinence: groups I (0 g; 47 patients), II (1-99 g; 23 patients) and III (100 g and above; 10 patients), respectively. Urinary function and bother were assessed by a self-administered questionnaire using the University of California Los Angeles, Prostate Cancer Index at baseline, and at 3, 6 and 12 months postoperatively. The differences in scores of urinary function, bother and clinicopathological parameters were assessed in the three groups with one-way analysis of variance. RESULTS: No significant difference was observed in the clinicopathological parameters in the three groups. Preoperatively significant difference of urinary function scores was not evident and that of urinary bother scores was not observed in the three groups. Postoperatively urinary function scores were significantly different throughout the postoperative periods investigated, whereas difference in urinary bother scores observed at 3 months tended to disappear with time. CONCLUSION: Postcatheter removal incontinence might be related to postoperative urinary function after radical prostatectomy, although further investigation is necessary regarding the criteria for categorization because of a small number of the patients.     

Four year clinical statistics of iridium-192 high dose rate brachytherapy

BACKGROUND: We evaluated the efficacy and complications of high dose rate (HDR) brachytherapy using iridium-192 (192Ir) combined with external beam radiotherapy (EBRT) in patients with prostate cancer. METHODS: Ninety-seven patients underwent 192Ir HDR brachytherapy combined with EBRT at our institution between February 1999 and December 2003. Of these, 84 patients were analysed in the present study. 192Ir was delivered three times over a period of 2 days, 6 Gy per time, for a total dose of 18 Gy. Interstitial application was followed by EBRT at a dose of 44 Gy. Progression was defined as three consecutive prostate-specific antigen (PSA) rises after a nadir according to the American Society for Therapeutic Radiology and Oncology criteria. The results were classified into those for all patients and for patients who did not undergo adjuvant hormone therapy. RESULTS: The 4-year overall survival of all patients, the nonadjuvant hormone therapy group (NAHT) and the adjuvant hormone therapy group (AHT) was 87.2%, 100%, and 70.1%, respectively. The PSA progression-free survival rate of all patients, NAHT, and AHT was 82.6%, 92.0%, and 66.6%, respectively. Of all patients, the 4-year PSA progression-free survival rates of PSA<20 and PSA>or=20 groups were 100%, and 46.8%, respectively. According to the T stage classification, PSA progression-free survival rates of T1c, T2, T3, and T4 were 100%, 82.8%, 100%, and 12.1%, respectively. Prostate-specific antigen progression-free survival rates of groups with Gleason scores (GS)<7 and GS>or=7 were 92.8% and 60.1%, respectively. Of NAHT, PSA progression-free survival of PSA<20 was 100% vs 46.8% for PSA>or=20, that of T1c was 100% vs 75% for T2, and that of GS<7 was 100% vs 75% for GS>or=7. No significant intraoperative or postoperative complications requiring urgent treatment occurred except cerebellum infarction. CONCLUSIONS: 192Ir HDR brachytherapy combined with EBRT was as effective as radical prostatectomy and had few associated complications.     

Changes in hypothalamic-pituitary function following bone marrow transplantation in children

Patients who undergo bone marrow transplantation (BMT) frequently experience impaired pituitary function, but precise assessment using repeated provocative tests has not been described. We studied 32 children (16 boys) who had BMT after receiving preparative irradiation. Assessment of pituitary function was performed by infusing insulin, luteinizing hormone-releasing hormone (LHRH), and thyrotropin-releasing hormone (TRH) on several occasions at various intervals during the follow-up period. Serum free thyroxine (FT4) and thyrotropin (TSH) levels tended to be low during the early period following BMT. Serum FT4 concentrations reverted to the low-normal range 1 year after transplant, and eight of 29 patients had subnormal and delayed TSH response to TRH consecutively. No children showed overt hypothyroidism. Basal and peak serum gonadotropin levels in response to LHRH were elevated in the patients who had received transplant around the time of puberty. Leydig cell function assessed by human chorionic gonadotropin test was normal. Three girls experienced menarche, and one male patient fathered a normal boy 7 years after BMT. Pituitary-adrenal function and prolactin secretion were not affected. A high incidence of transient hypothyroidism which did not require replacement therapy and gonadal failure among pubertal children were observed. Shielding of gonads should be attempted, if possible, at the time of preparative irradiation to prevent resultant hypogonadism.