This study was carried out to determine whether locoregional control of nasopharyngeal carcinoma in the young by irradiation has improved since 1975. Fifty-seven consecutive, previously untreated, patients, less than 30 years old, were diagnosed and treated at University of Toronto Hospitals between 1958 and 1990; 21 patients were treated before and 36 after 1975. Staging was as follows: M0, n = 54; M1, n = 3; T1 + T2, n = 26; T3 + T4, n = 31; N0, n = 10; N1 + N2a, n = 10; N2b + N2c, n = 24; N3, n = 13. All patients were irradiated. The primary tumour dose was 3500-7000 cGy (median 5450). Adjuvant chemotherapy was introduced in 1977. Subsequently, 10/26 (38%) M0 patients received this treatment. For all 57 patients, 10-year survival was 56%. For 52 M0 patients with complete follow-up data, 10-year survival was 63%; 10-year relapse free survival (RFS) was 61%. Age, sex, race, and histology were not significant variables. Ten-year RFS results were: T1 + T2, M0 (n = 24) 70%, T3 + T4, M0 (n = 27) 52%, (P = 0.25); N0-N2c (n = 41) 64%, N3 (n = 11) 54% (P = 0.31). Relapse occurred in 20/52 (38%) patients. Survival from the date of first relapse was 10% at 10 years. No patient with systemic relapse survived. Only 1/32 (3%) patients treated after 1975 developed an isolated locoregional relapse, giving a 10-year isolated locoregional relapse free rate (LR RFS) of 96%, compared with 5/20 (25%) prior to 1975, which gave a 10-year LR RFS of 75% (P = 0.05). Two of the five patients who relapsed before 1975 were salvaged by re-irradiation. Systemic relapse, either alone or combined with locoregional relapse, accounted for 6/11 (55%) relapses before 1975 and 8/9 (89%) after 1975. Ten-year systemic RFS was 90% for patients who received adjuvant chemotherapy (n = 10) and 72% for patients treated since 1977 by irradiation alone (n = 16) (P = 0.41). Isolated local relapse was exceptional in patients treated after 1975 (1/32).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Embryo viability associated with microassisted fertilization.

Embryo morphology and cleavage rates represent useful, but not absolute, measures of embryo viability. Oocyte and embryo chromosomal abnormalities affect embryo viability and are reflected to some degree in the morphology of oocytes and embryos. Microassisted fertilization techniques have been successfully used to treat severe male-factor infertility. Zona drilling using acidified Tyrode's solution is detrimental to oocyte and embryo viability and should not be used. Partial zona dissection (PZD) produces viable embryos that have developmental competence no different from that of routine IVF embryos, but the oocytes should be shrunken in hypertonic sucrose prior to PZD to avoid distortion and mechanical damage. The size of the cut in the zona pellucida is also critical and should be kept to a minimum to avoid loss of blastomeres during transfer. It appears from data on embryo quality, pregnancy rates and implantation rates that SUZI embryos have viability comparable to that of routine IVF embryos. Astonishingly, the passage of an injection needle directly into the ooplasm during ICSI has no effect on fertilization or developmental competence, as demonstrated by the excellent clinical pregnancy rates.

Embryo, Mammalian↗

PubMed1994

Local experience with zona drilling, zona cutting and sperm microinjection.

Clinical trials were performed between 1987 and 1992 on the use of zona drilling (ZD), zona cutting (ZC) and subzonal sperm microinjection (SZI) for the treatment of severe male infertility. ZD significantly improved the fertilization rate, but embryo morphology was poor and no pregnancies were achieved, so it was abandoned in favour of ZC. The fertilization rate was acceptable in the first trial of ZC but embryo morphology was still poor and no pregnancies were achieved, so a number of protocol changes were instigated. Shrinkage of oocytes in hypertonic sucrose prior to ZC markedly improved embryo quality, whereas transfer of embryos on Day 3 after oocyte retrieval enhanced the pregnancy rate. However, despite these improvements, the overall pregnancy rate in the third ZC trial was still low (16.6% per transfer), so a trial of SZI was initiated in 1992. The overall fertilization rate in 82 SZI cycles was 34.4% and, although the polyspermy rate was high, a clinical pregnancy rate of 30.8% per transfer and an implantation rate of 18.4% per embryo were achieved. These trials demonstrate that SZI is a successful treatment for severe male infertility; under the trial conditions, at least, it was superior to ZD or ZC.

Embryonic and Fetal Development↗

PubMed1994

The contribution of embryo cryopreservation to in-vitro fertilization/gamete intra-fallopian transfer: 8 years experience.

In this paper, the authors summarized their experience with embryo cryopreservation over an 8-year period. The results, therefore, reflect the long-term benefit of embryo cryopreservation to the overall in-vitro fertilization/gamete intra-Fallopian transfer (IVF/GIFT) programme and to the women who had embryos cryopreserved. The stable survival rate of thawed embryos and pregnancy rate, especially over the past 4 years, suggests that the results can reliably be used to evaluate the efficacy of the embryo cryopreservation programme. The ongoing pregnancy rate of frozen/thawed embryo transfer is 10.9%, comparable with the ongoing pregnancy rate of fresh IVF/embryo transfer in our unit over the same period. In addition to those factors known to affect the pregnancy rate in fresh IVF/GIFT cycles, such as age of the recipients and number of embryos transferred, the major factor affecting the efficacy of the cryopreservation programme is the number of oocytes retrieved in the initial stimulation cycle, and the number of embryos available for cryopreservation. The storage time of cryopreserved embryos will also have a significant effect on the realization of the total potential of embryo cryopreservation. Overall the contribution of cryopreservation to our IVF/GIFT programme is substantial, increasing pregnancy rate by 4%, while the greater net benefit, of course, is for the women who had embryos cryopreserved (pregnancy rate increased by 7%), especially for those who returned for frozen/thawed embryo transfer cycles (pregnancy rate increased by 11%).

Adult↗

PubMed1994

Successful treatment of severe male factor infertility in 100 consecutive cycles using intracytoplasmic sperm injection.

In this report, we present the results of our first 100 consecutive cycles of intracytoplasmic sperm injection (ICSI). Overall, fertilization occurred in 98% of cycles and embryos were transferred in 94% (2.6 embryos per cycle). About 50% of patients had embryos frozen. The overall fertilization rate was 71%, of which 4% were abnormally fertilized (three pronuclei). A total of 30 clinical pregnancies were established (32% per transfer), resulting in 18 singleton, six twin and one triplet ongoing pregnancies. The implantation rate per embryo was 15%. There were no significant differences in the fertilization or pregnancy rates between patients who had only occasional motile spermatozoa in the ejaculate, semen that was too poor for routine in-vitro fertilization (IVF), or who had failed routine IVF and/or subzonal sperm injection (SUZI). A group of 18 patients were treated with both ICSI and routine IVF on their first cycle because of the high likelihood of failed fertilization due to poor sperm morphology < 20% normal). In this group, ICSI oocytes had a fertilization rate of 76% compared to only 15% for the routine IVF (control) oocytes, and six patients conceived after transfer of ICSI embryos (33%), indicating that ICSI can be used successfully on 50% of the oocytes if fertilization failure is expected. Similarly, patients who had failed to become pregnant with SUZI achieved excellent results after ICSI. There were no significant differences between ICSI and routine IVF in the proportions of grade 1, 2 or 3 embryos on day 3 post-oocyte recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

The influence of sperm morphology and the acrosome reaction on fertilization outcome after sub-zonal injection (SZI) of human spermatozoa.

The usefulness of sub-zonal injection (SZI) for the treatment of severe male factor infertility has been restricted by low and unpredictable fertilization rates and the high risk of polyspermy after the injection of multiple spermatozoa. In this prospective study, we have evaluated whether sperm morphology and the percentage of acrosome-reacted spermatozoa at the time of injection can be used to predict SZI fertilization outcomes. Populations of motile spermatozoa equivalent to those injected were collected from the medium/oil interface immediately after SZI of each cohort of oocytes. Morphology was assessed using the World Health Organization 1987 criteria and the acrosomal status of spermatozoa was determined after staining with rhodamine-conjugated Pisum sativum agglutinin. A fertilization index (FI) was calculated to express the actual fertilizing potential of the spermatozoa injected. In all, 67 patients underwent 72 SZI cycles. The overall fertilization and polyspermy rates were 36 and 47% respectively, and a clinical pregnancy rate per transfer of 22% was achieved. Linear regression analysis demonstrated a statistically significant relationship between morphology and the FI (r = 0.506, P < 0.0001). Patients with < or = 10% normal morphology always had a FI < or = 10%, and this was reflected by low fertilization and polyspermy rates and the high number (32%) of cycles with complete failure of fertilization in this group. In patients with > 10% normal morphology, there were two patterns: low (< or = 10% FI) or high (> or = 10% FI) fertility. This was evident in the fertilization (23 and 85%, respectively), and polyspermy (25 and 68%, respectively) rates of these two patient sub-groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗

PubMed1994

Chemical and glass thermometers for axillary temperatures: how do they compare?

Axillary temperatures recorded with a disposable chemical thermometer (DCT) measured a mean 0.29 degrees C higher than a mercury in glass thermometer (MGT) but differences could be wide. Differences between the same methods were however also wide. The DCT is safe and easy to use. Provided the higher readings are taken into consideration it is a suitable alternative to the MGT.

Adolescent↗

PubMed1994

A prospective randomized trial to determine the benefit of surgical resection of residual disease following response of small cell lung cancer to combination chemotherapy.

Three hundred twenty-eight patients with limited stage small cell lung cancer were enrolled in a trial to evaluate surgical treatment for such patients responding to chemotherapy. Cyclophosphamide, doxorubicin, and vincristine were administered every 21 days for five cycles. Patients achieving at least partial response who had confirmation of pure small cell histologic features by pathology review and who were fit enough for thoracotomy were randomized to undergo or not to undergo pulmonary resection. All randomized patients received radiotherapy to the chest and brain. Two hundred seventeen (66%) of the patients achieved objective response (90 complete response; 127 partial response). One hundred forty-six patients were randomized (66% of responders, 44% of all patients): 70 to surgery and 76 to no surgery. Results of surgery were 83% resection rate, 19% pathologic complete remission rate, and 9% with residual non-small cell histologic features only, for a total of 28% eradication of small cell lung cancer. The survival curves for the two arms are not different (log rank p = 0.78). Median survivals were 12 months for all enrolled patients and 16 months for those who were randomized. Actuarial 2-year survival is 20%. The results of this trial do not support the addition of pulmonary resection to the multimodality treatment of small cell lung cancer.

Adult↗

PubMed1994

Time course of nitric oxide production and epithelial dysfunction during ischemia/reperfusion of the feline small intestine.

The objective of this study was to correlate nitric oxide production with time of reperfusion of the post-ischemic feline small intestine. Epithelial permeability, quantitated as blood-to-lumen clearance of 51Cr-EDTA, following 1 hr of ischemia and 4 hr of reperfusion of the small intestine, increased approximately 10-fold. This increase was further augmented by L-NAME infusion between 60 and 120 min but not at 240 min. Ca(2+)-dependent nitric oxide synthase activity was reduced by approximately 50% at 3 and 4 hr of reperfusion, whereas Ca(2+)-independent nitric oxide synthase activity was undetectable throughout the experiment. Administration of L-arginine at the start of reperfusion attenuated the reperfusion-induced epithelial barrier dysfunction for the first 120 min but not at 180 or 240 min. Continuous infusion of a nitric oxide donor (CAS 754) following 1 hr of reperfusion reduced epithelial permeability at 4 hr of reperfusion. In conclusion, a reduction in nitric oxide production was observed with time of reperfusion, possibly due to reduced nitric oxide synthase levels.

Animals↗

PubMed1994

A study of K88-mediated haemagglutination by enterotoxigenic Escherichia coli (ETEC).

The K88 fimbrial adhesin is a major virulence determinant of certain strains of enterotoxigenic Escherichia coli (ETEC) that infect and colonise neonatal pigs. This study investigates the haemagglutination properties of all three serotypes (ab, ac and ad) with eleven erythrocyte species. Wide variation in the haemagglutination properties indicated differences in both the K88 receptor and adhesin structure. In particular, the receptor binding properties of E. coli serotype K88ad were significantly different from both K88ab and K88ac. K88-mediated haemagglutination was inhibited strongly by a range of glucosides, glucosamine, chondrosine and pig gastric mucin but only weakly by mamman and heparin. The most effective inhibitor was n-dodecyl-beta-D-glucopyranoside which prevented haemagglutination at a concentration of 0.72 mM. It is hypothesised that the potent inhibition observed with glucosides may be due to interference with hydrophobic interactions and is not necessarily specific.

Animals↗

PubMed1993

Spinal cord ependymomas: a retrospective analysis of 59 cases.

PURPOSE: To determine the outcome of patients with primary spinal ependymoma treated with postoperative radiotherapy and to identify clinical and treatment variables predictive of outcome. METHODS AND MATERIALS: A retrospective chart review was undertaken of 59 spinal ependymoma patients referred to the Princess Margaret Hospital between 1958 and 1987. All patients were treated with radiation therapy to either the site of the primary tumor or the craniospinal axis. There were 23 female and 36 male patients with a median age of 37 years (range: 8-66 years). Median follow-up was 130 months (range: 1-371 months). Clinical variables including age, sex, length of symptoms, functional status, tumor location, and grade as well as treatment variables including extent of surgery, radiation dose and treatment volume were analyzed for influence on outcome. RESULTS: Treatment was well-tolerated with no cases of radiation myelopathy identified. Overall actuarial survival at 5 and 10 years was 83% and 75%, respectively. Eleven patients had recurrent tumor with the 9/11 having a component of their recurrence within the treatment field. Median time to recurrence was 2 years with 9 of the 11 recurrences within the first 3 years. Tumor grade was the only independent variable identified as predictive of outcome. Patients with well differentiated tumors had a 5-year cause-specific survival of 97% compared to 71% for those with intermediate or poorly differentiated tumors (p = 0.005). CONCLUSION: We conclude that postoperative irradiation for patients with spinal ependymomas is associated with a favorable outcome and that tumor grade is a major prognostic factor. Based on results of this series and a review of the literature, specific management recommendations are made for this rare tumor.

Adolescent↗

PubMed1993

Ectopic corticotropin syndrome and small-cell carcinoma of the lung. Clinical features, outcome, and complications.

BACKGROUND: Ectopic corticotropin syndrome is a rare complication of small-cell lung cancer (SCLC). There is little information concerning this syndrome available in the literature. We therefore reviewed all cases of ectopic corticotropin syndrome seen at our institution during a 20-year period. METHODS: Cases were identified by searching a computerized database and reviewing the charts of all 840 patients with SCLC seen between 1971 and 1991. Patients were included if they met at least two of the following criteria: spontaneous hypokalemia (potassium level, < 3.2 mmol/L); plasma cortisol level greater than 600 nmol/L; 24-hour urinary free cortisol level greater than 400 nmol/d; and plasma corticotropin level greater than 22 pmol/L. Data were abstracted from the patients' medical records. RESULTS: Of 840 patients with SCLC, 14 (1.6%) had ectopic corticotropin production. This was diagnosed at the time of presentation with SCLC in seven patients and from 3 to 19 months later in the remainder. Five patients had limited disease and nine had extensive disease. One or more features of Cushing's syndrome were observed in 57% of patients, but the entire syndrome occurred rarely. Spontaneous hypokalemia was present in all patients, and 10 patients (71%) had hyperglycemia. There were two complete responses and one partial response to chemotherapy, giving an overall response rate of 21%, and the median survival was 5.5 months. Ten patients died of progressive growth of tumor, while three patients died of infections. In one other patient, infection probably contributed to death. A high rate of nonfatal infections was also seen. CONCLUSIONS: The occurrence of SCLC with ectopic corticotropin syndrome is associated with poor survival, and a high incidence of infective complications, in patients treated with chemotherapy.

ACTH Syndrome, Ectopic↗

PubMed1993

A randomized trial of radiation therapy compared to split course radiation therapy combined with mitomycin C and 5 fluorouracil as initial treatment for advanced laryngeal and hypopharyngeal squamous carcinoma.

Two hundred and twelve patients with previously untreated advanced squamous carcinoma of the larynx or hypopharynx were randomized to receive initial treatment with radiotherapy, 50 Gy in 20 fractions in 28 days or split course radiotherapy and concurrent chemotherapy, 25 Gy in 10 fractions in 14 days followed by a 4 week rest and a further 25 Gy in 10 fractions in 14 days starting on day 43; Mitomycin C was given on day 1 and day 43 and 5FU continuous infusions on days 1--4 and days 43--46. Surgery was reserved for persistent or recurrent disease. Two hundred and nine of the 212 patients randomized were included in the analyses. Outcome analyses were performed at a median follow-up interval of 4.4 years. No patients were lost to follow-up. No significant difference was found between the two arms for the end points of local relapse-free rate (p = 0.91), regional relapse-free rate (p = 0.17, adjusted) or overall survival (p = 0.86). Eight-eight patients had attempted surgical resection following radiotherapy failure. The contribution of salvage surgery to overall survival was similar for both arms of the study as was the surgical complication rate. Serious late radiation toxicity was minimal (3% in the RT group, 0% in the radiation therapy plus chemotherapy group). The result of the trial shows no advantage in terms of local control or survival for the experimental treatment arm of split course radiotherapy and concurrent chemotherapy with Mitomycin C and 5 Fluorouracil compared to radiotherapy alone.

Antineoplastic Combined Chemotherapy Protocols↗