Acute visual loss induced by dexamethasone during neoadjuvant docetaxol.

We present a case of a female patient who developed acute onset of visual loss due to central serous retinopathy as a consequence of steroid premedication for docetaxol given as second line neoadjuvant chemotherapy for breast cancer. Central serous retinopathy is a recognised association with steroids but has not been previously reported in association with the management of solid tumours. Reduction in steroid dose and duration permitted recovery of her visual acuity while allowing completion of the prescribed chemotherapy regimen. An overview of the presentation, pathogenesis, aetiologies and management of central serous retinopathy is given.

The use of bone markers in a 6-week study to assess the efficacy of oral clodronate in patients with metastatic bone disease.

Biochemical markers of bone metabolism are strongly associated with skeletal complications in metastatic bone disease. The bisphosphonate clodronate reduces skeletal morbidity by inhibiting bone resorption. This study investigated the use of bone markers to assess the efficacy of oral clodronate across a range of clinically relevant doses. There were 125 patients with metastatic bone disease randomized to daily oral clodronate (800, 1,600, 2,400 and 3,200 mg) or placebo in a double-blind, multicenter study. Urinary N-terminal telopeptide of type I collagen (U-NTX), serum C-terminal telopeptide of type I collagen (S-CTX), urinary calcium (U-Ca), and bone alkaline phosphatase were measured weekly for a 6-week treatment period. Doses of >or=1,600 mg clodronate produced mean reductions of >40% in U-NTX, S-CTX and U-Ca, all significantly different from placebo (P=0.0015, 0.001, 0.0036, respectively), after 6 weeks. Evaluation of least significant changes in markers suggested that the commonly used 1,600 mg dose was most appropriate for breast cancer patients. However, this dose was suboptimal for other (mainly prostate cancer) patients, who showed better response to 2,400 mg. The number of adverse events in the treatment arms was not significantly different from that in placebo, but a higher number of patients had diarrhea in the 3,200 mg arm and withdrew from the study. This trial is the first to explore the dose-response relationship of clodronate in oncology using specific markers of bone turnover. It has confirmed that the 1,600 mg dose is safe and effective for breast cancer patients but may be suboptimal for the other tumors studied.

Screening for ophthalmic involvement in asymptomatic patients with metastatic breast carcinoma.

BACKGROUND: Breast carcinoma metastasises to the eye more frequently than is clinically recognised. The incidence is perhaps not appreciated, either because of the more common involvement and consequences of spread to major organs (such as lung, liver, or bone) or because a number of eye lesions are small and asymptomatic. Over a 6-month period, all patients with locally advanced or metastatic breast cancer were screened for ocular involvement and as a result management recommendations made. MATERIALS AND METHODS: Between January 2001 and June 2001, 68 patients with known locally advanced or metastatic breast carcinoma were referred for a screening ophthalmic examination. The aim of the study was to assess the frequency of asymptomatic ocular metastases by breast carcinoma in visually asymptomatic patients. The recognition and early treatment of both ocular metastases and ocular manifestations of metastatic breast carcinoma are important in maximising the quality of life in this group of palliative patients. These patients were all referred and recruited from the Beatson Oncology Centre and Breast Unit at the Western Infirmary, Glasgow by the oncologist (ANH). Examination included visual acuity assessment, slit-lamp examination, tonometry, and indirect ophthalmoscopy. RESULTS: The median time from diagnosis of breast carcinoma to ophthalmic screening was 5 years (range 6 months-23 years). No patient had any evidence of choroidal metastases on ophthalmic examination. Four patients (5.8%) had ophthalmic manifestations of metastatic breast carcinoma and a further two had ocular complications of treatment. One patient had a restrictive motility problem from a metastatic deposit to her lateral rectus muscle and another had corneal punctate epitheliopathy secondary to a seventh nerve palsy. A further patient had coarse nystagmus from cerebellar metastases and the final patient of the four had a Horner's syndrome from metastases in the neck. In addition, two patients had symptomatic dry eyes whose onset coincided with commencement of chemotherapy. CONCLUSION: Ophthalmic manifestations of metastatic breast carcinoma occurred in 5.8% of asymptomatic patients. Orbital metastases were documented in one patient. No case of choroidal metastases was observed in this group with advanced or metastatic disease. Therefore, patients do not need to be routinely screened particularly for choroidal metastases.

Preoperative topical and intraoperative local mitomycin C adjuvant therapy in the management of ocular surface neoplasias.

AIMS: To demonstrate the efficacy of mitomycin C as adjuvant therapy preoperatively and intraoperatively in the management of recurrent or diffuse ocular surface neoplasias. METHODS: The case notes of 11 patients receiving mitomycin C adjuvant therapy as 0.04% eye drops four times a day in two weekly courses preoperatively and/or a single intraoperative application of 0.4 mg/ml of mitomycin C were reviewed. The histopathology included conjunctival primary acquired melanosis, conjunctival melanomas, sebaceous cell carcinomas with conjunctival intraepithelial spread, and conjunctival intraepithelial squamous neoplasias. Seven patients had additional limited local excision of the residual tumour mass and one had cryotherapy. RESULTS: All cases showed a favourable response to mitomycin C adjuvant therapy with regression in size or retardation of a rapid growth pattern and no serious sequelae. Postoperative follow up of 6-36 months following excision of the lesion with or without intraoperative mitomycin C showed no clinical recurrence in any of the cases. CONCLUSION: In this series, mitomycin C adjuvant therapy of recurrent or diffuse ocular surface neoplasias was well tolerated and showed favourable clinical results.

Methods of ovarian suppression used in the UK.

Ovarian suppression in the management of breast cancer has had a resurgence in the 1990s. In view of the development of luteinizing hormone-releasing hormone (LHRH) analogues and advances in laparoscopic surgery, we wished to determine whether more consultants are considering these methods for achieving ovarian suppression than radiotherapy. A questionnaire was designed to determine the current practice of consultants in the UK and to discover who is involved in making this decision. It was distributed via the Adjuvant Breast Cancer (ABC) trials office to consultants who enter patients into the ABC premenopausal trial. Seventy-four (72%) questionnaires were analysed. The preferred method of treatment was radiotherapy in 60%, surgery in 30% and LHRH analogues in 9%. Seventy-three per cent of consultants were using more than one technique but did not always involve the patient in the decision-making process to determine which treatment modality to use. Radiotherapy techniques used included using bony landmarks for field borders (46%), using a standard field size (20%) or using ultrasound localization (15%).

Extraosseous osteosarcoma of the penis.

Osteosarcomas have been reported as arising in a number of extraosseous primary sites, most commonly in the retroperitoneum and the muscles of the thighs and limb girdles, but also in a variety of other organs. We present a case arising in the penis, which we believe to be only the fifth reported in the literature and the only documented long-term survivor. Careful histopathological analysis and surgical management remain of key importance in the management of all sarcomas arising in soft tissue.

Restoration of vision by radiotherapy for severe, acute, steroid-refractory, congestive thyroid orbitopathy.

We report the case history of a patient treated with radiotherapy for severe acute thyroid orbitopathy that failed to respond to high-dose corticosteroid therapy. The clinical response to irradiation was rapid, dramatic and sustained after extended follow-up. Although radiotherapy has been used in dysthyroid eye disease, there remains debate over the precise indications for and the timing of its utilization. A review of the literature on the use of radiotherapy for acute thyroid orbitopathy has been undertaken, emphasizing its steroid-sparing potential and its role in avoiding the necessity for surgical orbital decompression.

Recurrent inflammation in a site of previous necrotising fasciitis during intravenous CMF chemotherapy.

We present the case history of a patient with breast carcinoma who developed repeated inflammation at the site of previous necrotising fasciitis following each cycle of intravenous CMF chemotherapy. This complication has not previously been reported.

Margin assessment by cavity shaving after breast-conserving surgery: analysis and follow-up of 543 patients.

AIMS: To analyse cavity shaving as a method of assessing completeness of surgical excision after breast-conserving surgery. METHODS: Shavings were taken from the wall of the cavity remaining in the breast after breast-conserving surgery in 543 women. Each shaving was extensively sectioned and the presence and type of microscopic disease recorded. Disease in cavity shavings (tumour bed positivity) was correlated with clinicopathological factors as well as overall survival. RESULTS: Tumour bed positivity (TBP) was found in 37% of patients (16% with invasive disease). Patients were selected for further surgery according to the extent of positivity, which varied widely. A total of 15% of patients underwent re-excision or mastectomy. TBP was significantly associated with high tumour grade, presence of an extensive intraduct component, young age and large tumour diameter. It was also associated with a significantly shorter overall survival when compared to patients who were tumour bed negative. CONCLUSIONS: Cavity shaving is a practical and sensitive method of assessing completeness of excision after breast-conserving surgery. In addition it may provide useful prognostic information.

Ultrasound localization of the ovaries for radiation-induced ovarian ablation.

The case notes and simulator films were reviewed from 70 sequential patients who received pelvic irradiation to induce an early menopause as part of their treatment for breast cancer at the Staffordshire Oncology Centre. These patients underwent ultrasound localization of the ovaries immediately prior to simulation. Altogether, 128 ovaries were plotted on a diagrammatic representation of a gynaecoid pelvis to represent their position in both craniocaudal and lateral dimensions in relation to the true bony pelvis. The craniocaudal ovarian position varied from 2.5 cm above the lower aspect of the sacroiliac joint to 2.0 cm above the symphysis pubis. Three (4.6%) right sided ovaries were within 1 cm medial to the right lateral side wall, with none lying lateral to the wall. Seventeen (26%) left sided ovaries were lying within 1 cm of the left pelvic side wall, with four of these lying outside. The limits of the pelvic fields used were from the top of the sacroiliac joint to the bottom of the symphysis pubis. Sixty-one (88%) upper borders were on or above the lower sacroiliac joint. Twenty-six (38%) and 49 (71%) fields were outside the right and left pelvic side walls respectively. This would suggest that field sizes were larger than standard; however, 87% were smaller than 150 cm(2) (assuming a 10x15-cm field as standard). Only one patient failed to respond to treatment. This was thought to be due to underdosing rather than a geographical miss. This patient was successfully retreated. The authors advocate the use of ultrasound localization prior to planning an irradiation menopause, to ensure that the ovaries are encompassed in the pelvic field, thus preventing a geographical miss and reducing field sizes.

Metastatic breast cancer presenting as Tolosa-Hunt syndrome.

Choroidal involvement is a well-recognized manifestation of metastatic disease, particularly from breast and lung primaries. However, breast cancer can involve other ocular structures. The two patients presented illustrate diffuse orbital involvement of the extraocular muscles, simulating Tolosa-Hunt syndrome. This association has not been reported previously. Both patients responded well to local radiotherapy.

Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Scottish Cancer Trials Breast Group.

BACKGROUND: To determine whether, when primary breast cancer is treated by local excision supported by systemic therapy appropriate to the oestrogen receptor status (ER) of the tumour, local radiotherapy can be avoided. METHODS: We carried out a randomised controlled trial in 585 patients aged less than 70 years with primary breast cancers of 4 cm or less in size in four specialist units and seven other hospitals in Scotland. After local excision of the tumour (1 cm margin) and an axillary lymph-node clearance or sample, all patients received systemic therapy with oral tamoxifen 20 mg daily or six 3-weekly intravenous bolus injections of cyclophosphamide 600 mg, methotrexate 50 mg, and fluorouracil 600 mg per m2, depending upon the ER concentration in the primary tumour. Patients were then randomly allocated to postoperative radical radiotherapy (50 Gy to breast with boost to the tumour bed) or to no further local treatment. The median follow-up of living patients was 5.7 years. The primary analysis was by intention to treat but since some patients did not receive systemic therapy appropriate to their ER status, a subsidiary analysis was restricted to 464 patients in whom all details of the protocol had been observed. FINDINGS: In the primary analysis survival was equal in the radiotherapy and non-radiotherapy groups (hazard ratio [HR] 0.98, 95% CI 0.67-1.44). Event-free survival showed an advantage in the irradiated patients (HR 0.54, 95% CI 0.39-0.74), largely due to fewer loco-regional relapses (HR 0.20, 95% CI 0.12-0.33). The relapse rate in the ipsilateral breast was 24.5% in the non-irradiated group and 5.8% following breast irradiation. The subsidiary analysis confirmed these findings and indicated the advantage of radiotherapy irrespective of ER concentration. There was a non-significant trend towards fewer distant metastases in the irradiated group. INTERPRETATION: After local excision of a primary breast cancer, we conclude that radiotherapy to the residual breast tissue is advisable even when selective adjuvant systemic therapy is given.

Cystosarcoma phylloides: heterogeneity in a rare tumour type.

Mammary cystosarcoma phylloides is a rare tumour, and clear guidelines for its clinical management are lacking. We present three cases from the Western Infirmary which illustrate the range of behaviour that these tumours can manifest, and discuss some of the clinical problems that they present.

Phase I study of accelerated FEC with granulocyte colony-stimulating factor (Lenograstim) support.

With the aim of increasing the dose intensity of chemotherapy in breast cancer, 14 patients with stage II-IV breast cancer were treated with FEC chemotherapy at 2 week intervals together with granulocyte colony-stimulating factor (G-CSF) 5 micrograms kg-1 s.c. on days 2-14. Five of six patients completed six courses of 5-fluorouracil 600 mg m-2, epirubicin 60 mg m-2 and cylcophosphamide 600 mg m-2 within 11 weeks. Eight patients were treated with 5-fluorouracil 700 mg m-2, epirubicin 70 mg m-2 and cyclophosphamide 700 mg m-2 and four had dose-limiting toxicity with sepsis, thrombocytopenia or mucositis. All patients who received G-CSF had satisfactory neutrophil counts by day 15 of each course. Cumulative anaemia and thrombocytopenia were observed, but treatment at the first dose was tolerable. Seven of eight patients with measurable disease had partial responses. This regimen permits a 50% increase in dose intensity compared with conventional treatment at 3 week intervals and warrants further evaluation.

Ulcerative skin reaction from subcutaneous infusion of isotonic methotrimeprazine and diamorphine.

We report an ulcerative skin reaction resulting from a subcutaneous infusion of isotonic methotrimeprazine and diamorphine. Skin reactions are a recognized side effect of this treatment, although they are reduced by the use of the isotonic formulation of methotrimeprazine. Frank ulceration has not been previously reported. It occurred in our patient despite low doses of diamorphine and methotrimeprazine, an isotonic formulation, and a short infusion time.