<Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> mutations in a population-based study of male breast cancer

Background

The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC) in the United Kingdom is not known, and the importance of these genes in the increased risk of female breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear.

Methods

We have carried out a population-based study of 94 MBC cases collected in the UK. We screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these cases to calculate the risk of breast cancer to female relatives of MBC cases. We also estimated the contribution of BRCA1 and BRCA2 to this risk.

Results

Nineteen cases (20%) reported a first-degree relative with breast cancer, of whom seven also had an affected second-degree relative. The breast cancer risk in female first-degree relatives was 2.4 times (95% confidence interval [CI] = 1.4–4.0) the risk in the general population. No BRCA1 mutation carriers were identified and five cases were found to carry a mutation in BRCA2. Allowing for a mutation detection sensitivity frequency of 70%, the carrier frequency for BRCA2 mutations was 8% (95% CI = 3–19). All the mutation carriers had a family history of breast, ovarian, prostate or pancreatic cancer. However, BRCA2 accounted for only 15% of the excess familial risk of breast cancer in female first-degree relatives.

Conclusion

These data suggest that other genes that confer an increased risk for both female and male breast cancer have yet to be found.

     

A comparison of coplanar four-field techniques for conformal radiotherapy of the prostate.

BACKGROUND AND PURPOSE: Conformal radiotherapy of the prostate is an increasingly common technique, but the optimal choice of beam configuration remains unclear. This study systematically compares a number of coplanar treatment plans for four-field irradiation of two different clinical treatment volumes: prostate only (PO) and the prostate plus seminal vesicles (PSV). MATERIALS AND METHODS: A variety of four-field coplanar treatment plans were created for PO and PSV volumes in each of ten patients. Plans included a four-field 'box' plan, a symmetric plan having bilateral anterior and posterior oblique fields, a plan with anterior oblique and lateral fields, a series of asymmetric plans, and a three-field plan having anterior and bilateral fields for comparison. Doses of 64 and 74 Gy were prescribed to the isocentre. Plans were compared using the volume of rectum irradiated to greater than 50% (V50), 80% (V80) and 90% (V90) of the prescribed dose. Tumour control probabilities (TCP) and normal tissue complication probabilities (NTCP) for the rectum, bladder and femoral heads were also evaluated. Femoral head dose was limited such that less than 10% of each femoral head received 70% of the prescribed dose. RESULTS: For the PO group, the optimal plan consisted of anterior oblique and lateral fields (Rectal V80 = 23.8+/-5.0% (1 SD)), while the box technique (V80 = 26.0+/-5.8%) was less advantageous in terms of rectal sparing (P = 0.001). Similar results were obtained for the PSV group (Rectal V80 = 43.9+/-5.0% and 47.3+/-5.5% for the two plan types, respectively, P = 0.001). The three-field plan was comparable to the optimal four-field plan but gave higher superficial body dose. With dose escalation from 64 to 74 Gy, the mean TCP for the optimal plan rose from 52.0+/-2.8% to 74.1+/-2.0%. Meanwhile, rectal NTCP for the optimal plan rose by 3.5% (PO) or 8.4% (PSV), compared to 4.7% (PO) or 10.1% (PSV) for the box plan. CONCLUSIONS: For PO volumes, a plan with gantry angles of 35 degrees, 90 degrees, 270 degrees and 325 degrees offers a high level of rectal sparing and acceptable dose to the femoral heads for all patients, while for PSV volumes, the corresponding plan has gantry angles of 20 degrees, 90 degrees , 270 degrees and 340 degrees. Using these plans, the gain in TCP resulting from dose escalation can be achieved with a smaller increase in anticipated rectal NTCP.     

Prolonged QT interval and cardiac arrhythmias in two neonates: sudden infant death syndrome in one case

Two neonates with arrhythmias and the long QT syndrome are described. The arrhythmias were detected in utero and both infants were apparently well after birth. The first infant, although well, had a bradycardia for the first 9 days of life. A normal heart rate was documented at 10 days but a prolonged QT interval was not appreciated on the ECG. He was discharged from hospital but died suddenly and unexpectedly 3 days later. A post-mortem examination failed to find a cause for his death which therefore fell into the category of the sudden infant death syndrome (SIDS). A retrospective analysis of the perinatal electrocardiogram showed a probable junctional rhythm with 2:1 conduction to the ventricle; the QT interval was prolonged at 0.52 seconds (QTC = 0.63). The second infant had a QT interval of 0.52 seconds (QTC = 0.54) and frequent ventricular premature beats on a 24-hour electrocardiogram. She was treated with propranolol and remains well 2 years later. Sudden infant death has often been described in the siblings of children with the long QT syndrome and one other report described a case of SIDS which was said to have had a prolonged QT interval on the perinatal ECG. This report, however, provides unquestionable evidence, in one case, of an association between the long QT syndrome and SIDS.     

An analysis of eccentric photo refraction

The optics of eccentric photo refraction are analysed. The variation of photo refractive lunula area with refractive error, pupil size, flash eccentricity and camera aperture were calculated using a model eye. Measurements from photographs of paraxial (eccentric) photo refraction of model eyes show that a good agreement exists between theory and experiment over a range of refractive errors from — 10 D to +10 D. Calculations were also made for a standard reduced eye. The optimal set-up for measuring refractive error accurately over a wide range of refractive states is discussed, as are the problems which arise from non-central fixation.     

Pineal germinoma: MR imaging

Magnetic resonance (MR) imaging characteristics of pineal germinomas are described in seven patients imaged with MR and computed tomography (CT). In patients with symptoms of an enlarging process in the quadrigeminal plate cistern, MR imaging was as sensitive as CT scanning in detecting the mass. MR imaging did not detect a normal-sized, calcified neoplastic gland. Germinoma, germinoma with embryonal cell carcinoma elements, and pineoblastoma demonstrated different MR signal characteristics. Although direct coronal and sagittal MR images were useful in defining the relationship of the tumor to the posterior third ventricle, Sylvian aqueduct, and vein of Galen, the ease, rapidity, and sensitivity of CT scanning suggest that CT should remain the modality of choice for initial evaluation and screening of the pineal region, especially in the younger pediatric population, in whom detection of calcification may provide the only clue of an abnormality.     

Pineal and CNS germ cell tumors: Royal Marsden Hospital experience 1962-1987

A retrospective analysis has been made of all patients with pineal and CNS germ cell tumors who were treated at The Royal Marsden Hospital between 1962-1987. A total of 67 new cases were seen: 17 had initial histological verification of tumor type and the remainder were tested for radiosensitivity with a dose of 20 Gy following a shunting procedure. Patients with germ cell or radiosensitive tumors were treated with a uniform policy of whole neuraxis radiotherapy giving 50 Gy to the local tumor and 30 Gy to the remaining brain and spinal cord. Nonresponding lesions continued with local fields to a dose of 50 Gy. Patients were divided into three groups (a) germinoma and radiosensitive tumours, 34 cases; (b) malignant teratoma, 12 cases; (c) non-germ cell, 21 cases. Median follow-up is 83 months (range 2-246 months). Overall and cause specific actuarial 5/10 year survival were for group 1, 81.7%/69.4% and 86.5%;/86.5%; group 2, 18.2%/18.2% and 18.2%/18.2%, and group 3, 64.3%/46.8% and 64.3%/52.6%, respectively. No patient in group 1 treated during the last 12 years has recurred. Univariate analysis of factors at presentation, showed that neurological performance status (p less than .001) as well as tumor type (p less than .001) correlated with outcome. Recurrence was confined to the primary site in only 1 of 4 patients in group 1 compared to 6 of 9 patients in group 2 and 9 of 10 patients in group 3. No isolated spinal recurrence occurred in group 1 patients. A total of eight patients have received platinum containing chemotherapy for recurrence (6 cases) or adjuvant therapy (4 cases). Germinomas appear to respond better than teratomas, all of which have recurred rapidly following initial partial response. Shunting and radiosensitivity testing remains the treatment of choice for tumors compatible with germinoma. Craniospinal irradiation is associated with low morbidity providing spinal growth is complete and is recommended in older patients as salvage following spinal recurrence is unsatisfactory. Aggressive combined modality approaches with surgery, radiotherapy and chemotherapy need to be investigated to improve results in CNS teratoma.     

Adhesion of Pseudomonas aeruginosa ocular isolates to mucin

The purpose of this study was to compare the adhesion of Pseudomonas aeruginosa ocular isolates to mucin. An adhesion assay was developed using biotin‐labelled P. aeruginosa strains (two corneal ulcer, two acute red eye, one asymptomatic and one standard strains) incubated with porcine gastric mucin immobilized on a nitrocellulose membrane. The adhesion was semiquantified using densitometry. The results showed that all P. aeruginosa strains tested were able to adhere to mucin to various extents with three strains (one corneal ulcer, one acute red eye, one asymptomatic) binding significantly greater than the negative control (P < 0.1). Results suggest that ocular strains of P. aeruginosa strains differ in their adhesion to mucin but this did not correlate with the pathogenic origin of the strain. It is concluded that the adhesion of P. aeruginosa strains to mucin alone may not be a principal determinant of pathogenesis but may be a contributing factor along with other bacterial virulence traits.     

Orchidectomy alone for stage I seminoma of the testis

Between 1983 and 1988, 113 patients with Stage I seminoma were managed after orchidectomy by surveillance rather than adjuvant radiotherapy. The actuarial risk of relapse at 3 years was 15.8% (95% confidence interval, 7.8% to 23.8%). All 13 patients who experienced a relapse are currently in remission (4 to 45 months after salvage therapy), although 5 suffered second relapses requiring further treatment. Close surveillance is a safe alternative to adjuvant radiotherapy in Stage I seminoma. However, the policy requires prolonged observation of patients with intensive use of resources. Therefore, adjuvant radiotherapy should be considered the treatment of choice.     

Pulmonary histiocytosis X: comparison of radiographic and CT findings

The authors retrospectively evaluated radiographs, computed tomographic (CT) scans, and results of pulmonary function tests (when available) for 17 patients with biopsy-proved pulmonary histiocytosis X. In 11 patients, high-resolution CT was used. In 12 patients, CT demonstrated cystic air spaces, usually less than 10 mm in diameter. In three of these 12, cysts were the only abnormality, but in six others, nodules (usually less than 5 mm in diameter) were also present. Two patients had only nodules and one, only emphysema. CT showed that many lesions that appeared reticular on plain radiographs were actually cysts. CT showed no central or peripheral concentration of lesions, but it did reveal that many small nodules were distributed in the centers of secondary lobules around small airways. CT findings correlated better with the diffusing capacity (rho = -0.71) than did the plain radiographic findings (rho = -0.57). Thus, CT was better than radiography at showing the morphology and distribution of lung abnormalities.