A structured course teaching junior doctors invasive medical procedures results in sustained improvements in self-reported confidence.

Pressure on working hours has led to a decrease in opportunities for training in invasive medical procedures for junior doctors. The effect of a structured course on immediate and medium-term changes in self-reported confidence was investigated. A one-day model-based practical course was run on two separate occasions teaching central venous line placement, lumbar puncture, Seldinger-technique chest drain insertion and knee joint aspiration. Attendees were asked to indicate their confidence in each procedure on a 10-point Likert scale before, immediately after and three months after the course. Significant improvements in self-reported confidence were seen for all procedures which were sustained at three months. Feedback was universally positive. Practical preclinical training may be a useful adjunct to patient-based training in invasive procedures. The course was particularly popular with foundation year trainees: ideally this training should be available before trainees' first exposure in the clinical setting.

Localised Ewing sarcoma/PNET of bone--prognostic factors and international data comparison.

BACKGROUND: To determine if the distribution of prognostic factors accounted for the differences when the outcome for localised Ewing Sarcoma/PNET bone in Saudi Arabia was compared with results from countries with well developed health care systems. PROCEDURE: Retrospective analysis was undertaken of 163 consecutive patients of all ages, treated with radical intent at KFSHRC from 1975 to 1998. Standard chemotherapy was commenced in all patients. The local treatment modality was resection +/- radiation in 30% and radiation treatment alone in 67%. Size data were available for 51 patients treated from 1994 to 1998, inclusive. One third of these patients had tumors with volume >500 ml. RESULTS: Three year survival significantly increased with the year of diagnosis, 1975-1988 45%; 1989-1993 55%; and 1993-1998 63% (P = 0.006). Favorable prognostic factors were age < or =14 (P = 0.07); site, distal extremity, and skull (P = 0.08); and volume < or = 200 ml (P = 0.06). Secondary prognostic factors were response to induction chemotherapy, both histological, 100% necrosis, (P = 0.04) and clinical CR+PR, (P = 0.02). From 1994 to 1998, 3 year survival for tumors in the distal extremity and skull was 80% and for small tumors, < 200 ml, at any site was 82%. In comparison, the 3 year survival for patients with tumors at any other sites was 60%, and for tumors >200 ml, 55%. CONCLUSIONS: Overall survival progressively improved. From 1994 to 1998 the survival of patients with small tumors and/or favorable sites was similar to the best reported results. It was not possible to compare results by tumor size for large tumors, > 500 ml, due to the absence of data from elsewhere. A better staging system is required for the international comparison of results.

Metastatic Ewing sarcoma/PNET of bone at diagnosis: prognostic factors--a report from Saudi Arabia.

BACKGROUND: To evaluate outcome and prognostic factors in Saudi Arabian patients with metastatic Ewing sarcoma and PNET of bone (PMES) at diagnosis. PROCEDURE: Ninety-nine of 304 (33%) consecutive patients with Ewing sarcoma and PNET of bone registered at our centre from 1975 to 1998, had metastatic disease at registration and 93 were available for analysis. The maximum x-axis diameter of the primary tumor was used as the measure of primary tumor size. Usually a trial of systemic treatment was undertaken before a decision was made on local treatment. Standard chemotherapy regimens were used in all treated patients. Forty-one (44%) patients did not receive radical local treatment due to an inadequate response to chemotherapy, or a decision not to undertake more than palliative treatment. Radical treatment of the primary site was radiation alone 41 (79%), resection alone 7 (13%), and resection and radiation 4 (8%). RESULTS: The 5-year survival rates were 9% for all 93 evaluable patients, 16% for 52 patients who received chemotherapy and radical local treatment, 0% for 41 patients who received lesser treatment, 19% for 43 patients with lung metastases alone, and 0% (P = 0.002) for 50 patients with other sites involved. For 60 patients with imaging data, 5-year survivals were 34 and 0% when the maximum transverse diameter of the primary tumor was < 10 cm (N = 20) and > or = 10 cm (N = 40), respectively. CONCLUSIONS: Small primary tumor size and the presence of lung metastases alone were the only significant favorable prognostic factors. Earlier diagnosis will be the basis for better results.

Extramedullary myeloid tumors in children: the limited value of local treatment.

PURPOSE: To determine the incidence of extramedullary tumors (EMT) in Saudi Arabian children with acute myeloid leukemia, the factors associated with these tumors and the impact of local treatment on local tumor control, complete remission and survival rates. PATIENTS AND METHODS: One hundred children, median age 6 years, who received their primary treatment for acute myeloid leukemia at King Faisal Specialist Hospital and Research Center, from 1983 to 1997 were studied. EMT at diagnosis occurred in 18 (18%) patients at 25 sites. Meningeal leukemia, hepatosplenomegaly, lymph node enlargement, gingival hypertrophy, and cutaneous infiltration were not included in the definition of EMT. With these exclusions, children with EMT were younger than those without EMT (median age, 3.5 v. 7.5 years) and were more likely to have meningeal leukemia at diagnosis (33% v. 10%). The t(8;21) translocation was associated with a 47% EMT incidence compared with 23% without the translocation. Local radiation treatment was given to 16 of 25 (64%) EMT sites. RESULTS: The overall 5-year survival rate for all patients was 28%, and this was not significantly influenced by the drug regimen used, meningeal leukemia at diagnosis, the presence of the (8;21) translocation, M4 and M5 morphology combined, or EMT at diagnosis. Significant differences were observed in the 5-year survival rates for patients who underwent allogeneic bone marrow transplantation (52%; N = 37) and those who attained complete remission (CR) but did not undergo transplantation (21%; N = 44) and those who did not achieve complete remission with initial therapy (5%; N = 19). Systemic and local EMT CR was achieved in 17 of 18 patients with EMT, including 12 patients who underwent radiation treatment and 5 of 6 of those who did not. Isolated relapse was not seen at an EMT site and was not noted at any later stage of the disease. CONCLUSIONS: Permanent local control at sites of EMT was achieved in all patients who attained a bone marrow CR, whether or not the site was irradiated. Local radiation treatment of an EMT site did not appear to contribute to overall CR and survival rates. The use of radiation treatment should be conservative and limited to patients in whom there is a real and immediate threat to vision or renal function or when the spinal cord is compromised.

Ovarian irradiation and prednisone following surgery and radiotherapy for carcinoma of the breast.

Following mastectomy, patients aged 35 to 76 years with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy (NT), ovarian irradiation (R) 2000 rads in 5 days, or ovarian irradiation in the same dosage plus prednisone (R + P) 7.5 mg daily for up to five years. A total of 703 eligible patients received the randomly assigned treatment. The median follow up was 21 years with a range of 14 to 25 years. Overall, there was a delay in recurrence (p = 0.03) and survival was prolonged (p = 0.19) for patients who received R, but in neither case was the difference significant after adjusting for the multiplicity in our data. Overall, patients who received R + P experienced a significant delay in recurrence (p = 0.0003) and a significantly prolonged survival (p = 0.005), even after adjusting for multiple comparisons. In premenopausal patients who received R, the recurrence of breast cancer was delayed and survival prolonged, but not significantly. In premenopausal women aged 45 years or more, R + P therapy significantly prolonged survival (p = 0.0004), while the delay in recurrence although significant (p = 0.02) was only marginally so after allowance for multiple comparisons. No value was demonstrated for ovarian irradiation with or without prednisone therapy in postmenopausal patients. A new finding in this review was that contralateral breast cancer as the first failure was reduced by R + P compared to NT in the overall group.

Childhood medulloblastoma in Ontario, 1977-1987: population-based results.

A retrospective review was carried out to study children, not more than 16 years old, with a confirmed diagnosis of medulloblastoma, who were residents of the Province of Ontario at the time of diagnosis between 1977 and 1987 inclusive. The provincial tumour registry provided the population database. One hundred and eight children with medulloblastoma were identified of whom 72 (67%) were initially treated at University of Toronto Centres and 36 (33%) at other Health Science Centres, hospitals, and Regional Cancer Centres (RCC) in Ontario. The hospital/Cancer Centre records were reviewed. The 5-year relapse-free survival (RFS) for all patients treated in Ontario was 58% (SE = 5%). Those treated in Toronto had a 5-year RFS of 65% (SE = 6%) compared to 44% (SE = 8%) for those treated in other RCCs in the province (P = 0.02). Relapse-free survival for the RCCs ranged from 25 to 60%, with a trend for improved survival with increasing centre size. Univariate analysis of determinants of relapse-free survival for all 108 patients showed the following variables to be significant: T-stage (Tx + T1 + T2 vs. T3A + T3B) P = 0.0004, M-stage (M0 + Mx vs. M1-4) P = 0.0006, extent of resection (total vs. less than total) P = 0.002, radiotherapy (craniospinal irradiation and posterior fossa boost vs. other) P = 0.02, and treatment centre (Toronto centres vs. RCC) P = 0.02. Cases treated at centres outside metropolitan Toronto had a nearly two-fold (relative risk = 1.93; 95% confidence interval = 1.07, 3.47) greater risk of recurrence or death than those seen in Toronto. However, in multivariate analysis this difference was not quite significant (P = 0.07) after controlling for stage (T and M), extent of resection, meningitis, and gender. These data suggest that patients with medulloblastoma should be referred for treatment to large centres with major pediatric neurosurgical and oncology resources.

Spinal cord tumors in children: long-term results of combined surgical and radiation treatment.

The authors report a series of 31 children under 17 years of age with primary spinal cord tumors who underwent radiation treatment following decompression laminectomy with or without tumor resection between 1959 and 1990. The tumors consisted of 15 astrocytomas, 11 ependymomas, one mixed glioma, one gangliolioma, and three of unknown histology. Ten- and 20-year survival rates and 10- and 20-year relapse-free survival rates for the 28 patients with known histology were 80% and 53%, and 73% and 67%, respectively. Eleven patients (35%) had no resection, 14 (45%) had a partial resection, and six (19%) had a grossly complete resection. Eight patients (26%) are dead: five due to recurrent tumor, two due to a second malignant tumor, and one due to intercurrent disease. primary tumor relapse or progression occurred in nine patients (29%), four of whom were salvaged. A second malignant tumor developed in four patients (13%), two of whom died. Local control of the tumor was finally achieved in 26 cases (84%), despite either grossly incomplete or no resection in 25 of these cases (81%). These statistics suggest that radiation treatment without resection may achieve long-term control in children with astrocytoma or ependymoma of the spinal cord.

Long-term follow-up of patients treated with COMP or LSA2L2 therapy for childhood non-Hodgkin's lymphoma: a report of CCG-551 from the Childrens Cancer Group.

PURPOSE: We analyzed the long-term results of a Childrens Cancer Group (CCG) randomized study comparing cyclophosphamide, vincristine, methotrexate, and prednisone (COMP) versus LSA2L2 as treatment for childhood non-Hodgkin's lymphoma. The initial results were previously reported (N Engl J Med 308:559, 1983). PATIENTS AND METHODS: A total of 429 patients are reported here, 68 with localized disease and 361 with disseminated disease. The distribution of disseminated-disease patients by histologic type was 164 lymphoblastic, 60 large-cell, and 137 undifferentiated lymphomas. Median follow-up duration of surviving patients is 8 years. RESULTS: Event-free survival (EFS) of patients with localized disease was 84% at 5 years. No differences were seen between the two treatment regimens. Results for patients with disseminated disease was dependent on histologic subtype: patients with lymphoblastic lymphoma did better when treated with LSA2L2 (5-year EFS of 64% v 35% for COMP); COMP produced better results for patients with undifferentiated lymphoma (5-year EFS of 50% v 29% for LSA2L2). Results for large-cell lymphoma patients were similar (5-year EFS of 52% for COMP v 43% for LSA2L2). Five percent of patients died of treatment-related complications while on therapy (primarily infections). Only four deaths without progression have been observed off-therapy (two from restrictive lung disease, one from an acute asthma attack, one from colon cancer). Patient survival rates after recurrence were poor. CONCLUSION: Treatment success can be expected in 84% of pediatric patients with localized non-Hodgkin's lymphoma. For patients with disseminated disease, treatment success can be expected in 64% of those with lymphoblastic and 50% of those with undifferentiated or large-cell disease. To date, late adverse events are rare.

Differences between rat and guinea pig aorta in postreceptor mechanisms of alpha 1-adrenoceptors.

The relative importance of different postreceptor mechanisms associated with alpha 1-adrenoceptor activation in guinea pig aorta and rat aorta was compared. In both tissues, a concentration-dependent correlation was observed between contractile responses produced by high concentrations of norepinephrine (NE) and inositol-1-phosphate (IP1) accumulation. Blockade of Ca2+ entry through voltage-dependent membrane channels by nifedipine had no inhibitory action on NE-induced contractile responses in guinea pig aorta, but significantly inhibited NE-induced contractile responses in rat aorta. Nifedipine had no major effect on NE-induced IP1 accumulation in either tissue. A medium with no Ca2+ inhibited NE-induced contractile responses and IP1 accumulation in guinea pig aorta, but had a more marked effect on contractile responses and IP1 accumulation in rat aorta. The combination of a high concentration of nifedipine and a medium with no Ca2+ almost completely inhibited NE-induced contractile responses and IP1 accumulation in both tissues. Exposure to EGTA also virtually completely inhibited NE-induced contractile response and IP1 accumulation in both tissues. Significant 45Ca2+ entry was stimulated in rat aorta by NE, and this entry was completely blocked by nifedipine. No significant 45Ca2+ entry was stimulated by NE in guinea pig aorta. We conclude that the most important postreceptor event linked to alpha 1-adrenoceptor stimulation in guinea pig aorta is activation of the phosphatidylinositol pathway, whereas in rat aorta Ca2+ entry through voltage-dependent membrane channels is as important as activation of the phosphatidylinositol pathway. We also conclude that activation of the phosphatidylinositol pathway in both tissues is critically dependent on the presence of a small amount of Ca2+, which may enter from the external medium.

Therapeutic radiation at a young age is linked to secondary thyroid cancer. The Late Effects Study Group.

We estimated the risk of thyroid cancer among 9170 patients who had survived 2 or more years after the diagnosis of a cancer in childhood. As compared with the general population, patients had a 53-fold increased risk (95% confidence interval, 34-80). Risk increased significantly with time since treatment for the initial cancer (P = 0.03). Detailed treatment data were obtained for 23 cases and 89 matched controls from the childhood cancer cohort. Sixty-eight % of the thyroid cancers arose within the field of radiation. Radiation doses to the thyroid of greater than 200 cGy were associated with a 13-fold increased risk (95% confidence interval, 1.7-104). The risk of thyroid cancer rose with increasing dose (P less than 0.001), but this was derived almost entirely from the increase from less than 200 to greater than 200 cGy. The risk of thyroid cancer did not decrease, however, at radiation doses as high as 6000 cGy.

The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone.

In a prospective randomized trial designed to study the effectiveness of adjuvant chemotherapy following standard surgical treatment and radiation therapy, 233 eligible patients with medulloblastoma were treated by members of the Children's Cancer Study Group and the Radiation Therapy Oncology Group. Eligible patients were randomly assigned to receive radiation therapy with or without adjuvant chemotherapy consisting of 1-(2-chloroethyl)-3-cyclohexyl-nitrosourea (CCNU), vincristine, and prednisone. The estimated 5-year event-free survival probability was 59% for patients treated with radiation therapy and chemotherapy and 50% for patients treated with radiation therapy alone, a difference which is not statistically significant. The 5-year survival probability was 65% for both groups. Although the treatment difference was not statistically significant when all patients were combined, in the small number of patients with more extensive tumors, event-free survival was better in the group receiving chemotherapy (48% vs. 0%, p = 0.006). In these latter patients the survival time is also significantly prolonged. Extent of disease (as measured by the M staging criteria described by Chang) and age at diagnosis were significantly associated with outcome; advanced disease and young age had a worse prognosis. The extent of tumor resection was not an independent prognostic factor. It is concluded that chemotherapy does not benefit patients with low-stage medulloblastoma, but may benefit those with more advanced stages of disease.

The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Childrens Cancer Study Group.

Fifty-eight patients with high-grade astrocytoma were treated by members of the Childrens Cancer Study Group in a prospective randomized trial designed to study the effectiveness of chemotherapy as an adjuvant to standard surgical treatment and radiotherapy. Following surgical therapy, patients were assigned randomly to radiotherapy with or without chemotherapy consisting of chloroethyl-cyclohexyl nitrosourea, vincristine, and prednisone. Treatment with chemotherapy prolonged survival and event-free survival. Five-year event-free survival was 46% for patients in the radiotherapy and chemotherapy group, and 18% for patients in the radiotherapy-alone group. Five-year survival was similarly improved. The differences in outcome due to treatment were statistically significant after correcting for imbalances in important prognostic factors (event-free survival, p = 0.026; survival, p = 0.067). The presence of mitoses or necrosis in the tumor specimen was associated with poorer outcome. Patients whose initial surgery was limited to biopsy, and patients with basal ganglia lesions, also had significantly worse outcome. Chemotherapy administered at the time of recurrence in a small number of patients did not produce any long-term survivors. This study is to our knowledge the only randomized trial to investigate effectiveness of chemotherapy in the treatment of high-grade astrocytoma in children.

Similar efficacy of 6 and 18 months of therapy with four drugs (COMP) for localized non-Hodgkin's lymphoma of children: a report from the Childrens Cancer Study Group.

Successful treatment of localized non-Hodgkin's lymphoma (NHL) in childhood with 18 months of cyclophosphamide, vincristine, methotrexate (MTX), and prednisone (COMP) prompted a randomized clinical trial to determine whether a 6-month course of the same therapy was as effective as an 18-month course when combined with local irradiation. Two successive Childrens Cancer Study Group (CCSG) protocols (CCG 551 and CCG 501) entered 232 eligible patients from October 1979 until April 1986. Initially, all children with localized disease were considered eligible, but by a subsequent amendment, those with lymphoblastic (LB) histology were excluded. Hence, the study population consisted of 211 patients with nonlymphoblastic (NLB) and 21 with LB disease. Early relapses (before 6 months) occurred in 13 patients with NLB histology. Late relapses were seen in seven patients, three with LB histology. Among the 104 randomized patients who followed the prescribed therapy, there were four recurrences and no differences between 6-month and 18-month therapy. The overall survival for NLB disease was 91% on CCG 551 and 98% on CCG 501. We conclude that 6 months of COMP is excellent therapy for children with localized NLB NHL.

Guidelines for the surgical management of soft-tissue sarcoma. Report of the Canadian Sarcoma Group.

The Canadian Sarcoma Group was formed in 1985 by interested surgeons, oncologists and pathologists. In the evaluation of new protocols, standard surgical guidelines have been developed which incorporate the concepts of multimodality therapy, particularly radiotherapy and chemotherapy. Also defined are the procedures performed: biopsy, marginal resection, wide local excision, radical resection and the principles to be considered when doing a diagnostic biopsy and a curative resection, particularly with limb salvage in mind. To optimize local control of the disease, centres treating sarcomas should have access to computed tomography, radionuclide scanning, to radiation and medical oncologists, and members of other surgical specialties. This team approach increases survival by 10% and also provides the best circumstances in which to study adjuvant therapy. Surgical guidelines are also essential in order to compare the results of different clinical trials.

The cost of radiation treatment at an Ontario regional cancer centre.

The cost of radiation treatment in 1985 at an Ontario regional cancer centre accruing 2500 new patients annually was examined. The radiation treatment department was equipped with three high-energy treatment machines, a treatment simulator and a treatment planning computer and was appropriately staffed. The total average annual cost of operating one high-energy treatment machine was $668,963. Salaries and employee benefits accounted for 78% of the costs. An average of 5439 radiation treatments were given annually with each treatment machine, at a cost $123 per treatment. The cost of a curative course of radiation treatment (average of 21 treatments) was $2583, and the cost of a palliative course (average of 7 treatments) was $861.

The pathology of non-Hodgkin's lymphoma of childhood: II. Reproducibility and relevance of the histologic classification of "undifferentiated" lymphomas (Burkitt's versus non-Burkitt's).

The Children's Cancer Study Group conducted prospective clinical trials of 608 children with non-Hodgkin's lymphoma from 1977 to 1983. In 1980, significant differences in survival of children with disseminated disease correlated with histologic diagnosis and the randomized treatment employed. A pathology reproducibility review showed the lymphoblastic lymphoma cases to be virtually 100 per cent distinguishable histologically from the nonlymphoblastic lymphomas (Burkitt's, non-Burkitt's, and "histiocytic"). However, diagnostic reproducibility of the pathologist-of-record was 59 per cent in the Burkitt's and non-Burkitt's lymphoma group. Therefore, 159 cases, agreed on by the pathologist-of-record and the "lymphoma panel" as Burkitt's (77 cases) or non-Burkitt's lymphoma (82 cases) and designated as the "reference diagnosis," were blindly reviewed twice each by two hematopathologists to yield the "review diagnoses." Consensus agreement was achieved in 67 per cent of cases overall, 82 per cent of Burkitt's and 54 per cent of non-Burkitt's lymphoma. Using the "reference diagnoses," we found that the relative frequency of Burkitt's and non-Burkitt's lymphoma was associated with the extent of disease at diagnosis (P = 0.06) but not with other prognostic factors. Despite the difficulties in histologic classification, analyses that used either "reference diagnoses" or "consensus review diagnoses" and that were adjusted for extent of disease consistently demonstrated significantly shorter event-free survival for patients having Burkitt's lymphoma; their failure rate was four times that for patient's with non-Burkitt's lymphoma. Newer cell biologic techniques hopefully will enhance histopathologic distinctions that remain the basis for diagnosis.