Sweat-gland tumours: a clinical review of cases in one centre over 20 years.

AIMS: Sweat-gland tumours (SGTs) are uncommon, but malignant varieties are very rare. We have added our data on 30 new cases seen at the Royal Marsden NHS Foundation Trust to the published literature, particularly concentrating on clinical issues. We include a literature review. MATERIALS AND METHODS: The Royal Marsden NHS Foundation Trust database was searched for cases of SGT from 1972. Data were collected on all cases, including patient demographics and tumour characteristics, treatment and outcome. RESULTS: Thirty cases were confirmed histologically to be SGTs. Fourteen were malignant, 15 benign and the degree of malignancy in one was histologically indistinguishable. Mean age was 55 years (64 for malignant, 47 for benign tumours). The 15 patients with benign tumours were almost all treated with complete excision. Those with local relapse underwent successful re-excision. Their 5-year disease-free survival was 78% and cause-specific survival was 100%. Twelve of the 14 malignant tumours had localised disease at diagnosis, one had nodal disease and one had metastatic tumour nodules. All except one were treated with wide local excision. The patient with nodal involvement also had a lymph-node dissection. Two received adjuvant radiotherapy to the tumour bed. One received a melphalan limb perfusion. Eight of the 14 had no relapse. Six had locoregional relapse, and four of these also developed distant metastases. Visceral disease was always fatal. Radiotherapy and chemotherapy at relapse were unsuccessful. Five-year disease-free survival was 45%, and cause-specific survival was 57%. CONCLUSION: These rare tumours should be treated initially with complete wide local excision. In malignant tumours, lymph-node involvement is a poor prognostic sign. Wide local excision remains the primary treatment. Adjuvant radiotherapy may be useful in high-risk cases.

The hyfrecator: a treatment for radiation induced telangiectasia in breast cancer patients.

Radiation induced telangiectasia is a common problem in breast cancer survivors. By interfering with choice of clothing and acting as an unpleasant visible reminder of their disease, it negatively affects quality of life. The hyfrecator, based on the principles of electrosurgery, is a standard treatment modality for facial telangiectasia. This study aims to demonstrate the efficacy and tolerability of the hyfrecator as a treatment for radiation induced telangiectasia. Patients with radiation induced telangiectasia of breast or chest wall were prospectively identified from the breast cancer follow up clinic and offered treatment with the hyfrecator (sessions at 8 weekly intervals). Pre- and post-treatment photographs were obtained in a standardized manner and two blinded physician observers evaluated response. A linear analogue scale (LAS) was used by the patients to evaluate treatment response and any discomfort. At the end of treatment, patients completed a quality of life questionnaire. Of 16 patients enrolled, 15 completed the study. Treatment benefited all patients with severe or marked telangiectasia. Complete disappearance of telangiectasia was achieved in the majority (88%) of patients by the end of treatment. A median of six sessions (range 3-9) was required. All but one (93%) considered the treatment worthwhile. The majority (69%) judged the treatment to be painless or only mildly painful. 73% reported an improvement in self-confidence. The treatment was well tolerated by all the patients. All patients showed a remarkable clearance of vessels with a high degree of satisfaction with the results. Treatment with the hyfrecator is very effective for radiation induced telangiectasia. Three to four sessions achieve a substantial objective and subjective reduction in telangiectasia with a concomitant improvement in quality of life. It is a cost effective, ambulant out patient procedure requiring no local anaesthesia.

Long-term morbidity following short-course, pre-operative radiotherapy and total mesorectal excision for rectal cancer.

AIM: Short-course pre-operative radiotherapy (SCPRT) and total mesorectal excision (TME) have been shown to reduce the rate of relapse and improve survival in patients with rectal cancer. Concerns about morbidity have limited its application in some centres. The aim of this study was to assess long-term toxicity of pre-operative RT in patients with rectal cancer. METHODS: Permanent toxicity was assessed in 20 patients who were alive >12 months after pre-operative RT (25Gy/ 5#), using a validated LENT SOMA scoring system. Ten patients with rectal cancer who had been operated on >12 months ago, but had not received pre-operative RT were assessed similarly. RESULTS: Patients who had received SCPRT appeared to have a significantly higher rectal toxicity, urinary and male sexual dysfunction, compared with the controls. No significant difference was noted in female sexual dysfunction. CONCLUSION: The combination of pre-operative RT and TME appears to be associated with significant long-term toxicity. Better methods of staging the tumours may improve selection of patients for SCPRT.

Bile duct stents: is there an increased rate of complications in patients receiving chemotherapy?

The aim of this study was to determine whether palliative chemotherapy accelerates the rate of biliary stent occlusion, in patients with a malignant biliary obstruction. Such treatment can induce neutropenia and increase the risk of bacterial sepsis. Overgrowth of bacteria within the bile of patients receiving chemotherapy could accelerate the rate of stent occlusion. Retrospective analysis of treatment records for 80 consecutive patients with a diagnosis of adenocarcinoma arising from the pancreas, bile ducts or gall bladder was conducted. Two groups were identified, those with a biliary stent in situ (primary stent group: 47/80; 59%) at the time of referral and those without (no stent group: 33/80; 41%). The majority of patients went on to receive chemotherapy, 64% and 70% in the primary stent group and no stent group, respectively. The rate of febrile neutropenia was similar in the two groups (5% versus 7% of all chemotherapy cycles in the primary stent group and no stent group, respectively). The rate of stent occlusion was not significantly different between those exposed to chemotherapy (37%; 95% CI 20-54%) and those unexposed (39%; 95% CI 19-59%). Similarly, the mean duration of patency was not shortened by chemotherapy (105 days in the chemotherapy group versus 119 days in the non-chemotherapy group; P = 0.97, Mann-Whitney U-test). We conclude that there is no evidence of increased rate of bile duct-related complications in patients receiving chemotherapy. In particular, we find no indication for the use of prophylactic antibiotics.

Heterotopic bone formation: irradiation of high risk patients.

The Royal Marsden Hospital has adopted a policy for patient selection for the use of adjuvant radiotherapy to prevent heterotopic new bone formation (HTBF) limited to those at greater than 50% risk. The treatment protocol is 7 Gy post-operative megavoltage radiotherapy at mid-plane, in one fraction, given within 72 h of surgery. Since the introduction of this protocol in 1993, 26 joints have been treated in 25 patients. The majority of cases were young people with acetabular fractures resulting from road traffic accidents, often alcohol related. Follow-up studies in this group of patients has proved difficult, as many fail to attend for follow up, and others have moved out of the catchment area. Of the 14 cases for which follow-up data is available, 13 remain fully mobile. One has not mobilized since the time of treatment and continues to use crutches. There is one case of recurrent HTBF seen on X-ray after 8 months, but the joint was mobile. By 5 years, all cases have failed to attend for follow-up. The true long-term risks of this treatment policy may not be known for 30 years. The failure of patients to attend even short-term follow-up is a potential problem for clinical oncologists.

Response of metastatic anal carcinoma to single agent carboplatin.

The management of locoregional squamous cell carcinoma of the anus with a combined modality approach comprising chemotherapy and radiotherapy is well established. However, the optimum regimen for the management of metastatic disease has yet to be determined. Cisplatin has been shown to have some efficacy in this disease. We report a case of partial response of metastatic disease to single agent carboplatin, and discuss its role in this situation.

Factors affecting acute skin toxicity in patients having breast irradiation after conservative surgery: a prospective study of treatment practice at the Royal Marsden Hospital.

The results are presented of a prospective study of acute skin toxicity in 197 patients with early stage breast cancer, who were treated by conservative surgery and postoperative radiotherapy. We have examined the factors determining the severity of the acute skin reaction with particular reference to the degree of dry or moist desquamation at the completion of treatment. One hundred and ten patients had treatment with radiotherapy alone. The remaining 87 received synchronous chemotherapy with breast irradiation, using either the 3M or the 2M regimen, consisting of mitoxantrone and methotrexate, with (3M) or without Mitomycin-C (2M). Patients were analysed according to both the severity and the site of the skin reaction, age, dose, dose variation across the central outline, treatment technique, beam energy, field separation and breast size. A univariate analysis of these results, which has been presented as an odds ratio of the likelihood of developing a moderate or severe reaction in comparison with those scored as mild, has shown that several factors are associated with an increase in the acute skin reaction. These include the use of the semi-supine technique (odds ratio (OR) = 7.3 (95% CI 3.7-14.6)), beam energy (60Co: 6-10 MV photons OR = 5.9 (95% CI 2.6-13.4)), field separation (> or = 20 cm: < 20 cm OR = 4.1 (95% CI 2.2-7.8)), dose variation across the central outline (> or = 10%: < 10% OR = 9.7 (95% CI 2.6-36.4)), inclusion of the axilla (OR = 4.6 (95% CI 2.4-8.9)), and bust size (bra cup size C and D: A and B OR = 4.6 (95% CI 2.7-11.9)). Using multivariate logistic regression, the technique of radiation delivery and bust size were shown to be independently significant variables affecting acute skin reaction. In view of the high correlation between variables (e.g. radiotherapy technique and beam energy) it is still not possible to specify with definite certainty which is the primary variable causing the skin reaction. However 20/57 (35%) of patients treated by the semisupine technique sustained a severe skin reaction, with > 10% dry or moist desquamation in the treatment field. This compares with only 6/140 (4%) patients treated by the supine method. A possible mechanism by which treatment using the semisupine technique may enhance acute toxicity is discussed. We conclude that there are both treatment and patient related factors that will increase the acute skin reaction after breast irradiation.

Diagnostic laparotomy in suspected malignant lymphoma.

The place of laparotomy in the initial diagnosis of malignant lymphoma is investigated by reviewing a group of 25 patients with suspected lymphoma referred for diagnostic laparotomy. Intra-abdominal malignancy was found in 11 patients, although only 7 of these had a malignant lymphoma. A positive alternative diagnosis was made in a further 8 of the remaining 14 patients, but 6 patients remained undiagnosed following laparotomy. A scheme for the investigation of patients with suspected malignant lymphoma is therefore proposed. Patients with an abdominal mass other than a palpable liver or spleen should undergo early laparotomy, while those with no abdominal mass should undergo an extensive screening programme, appropriate to the mode of presentation and similar to that used in the investigation of a pyrexia of unknown origin, in which diagnostic laparotomy is used only as the final step.

A painful shoulder.

A case is outlined of a patient presenting with a painful shoulder. Metastatic malignant melanoma was diagnosed. The sites of origin of melanotic lesions as well as metastatic sites are described. Both gross and radiological appearances of such lesion are not uniform, varying from osteolytic to osteoblastic forms. Treatment is for the most part ineffective. The outcome is rapid and invariably fatal.

Radiotherapy: a novel treatment for pneumothorax.

Pneumothorax is a relatively common condition that is usually managed either conservatively, by chest tube drainage or, if a refractory air leak persists, then with cardiothoracic intervention. However, there is a small group of patients with a persistent air leak in whom surgical intervention is felt to be inappropriate. This study looks at a novel management strategy in a patient presenting with this scenario. A male with underlying bullous lung disease presented with a right pneumothorax. Complete re-expansion was not achieved, despite chest tube drainage and suction. Cardiothoracic intervention was felt to be inappropriate and the air leak persisted despite prolonged conservative management. Ventilation scintigraphy was therefore used to localise the air leak prior to targeted radiotherapy in an attempt to seal the leak via radiation-induced fibrosis. Three weeks after the first fraction of radiotherapy, the air leak ceased. In complex cases of pneumothorax with persistent air leak where cardiothoracic intervention is deemed inappropriate, identification of the air leak site and localised radiotherapy could be considered.

Effectiveness of topical steroids in the control of radiation dermatitis: a randomised trial using 1% hydrocortisone cream and 0.05% clobetasone butyrate (Eumovate).

Radiation dermatitis often presents as a problem for patients and radiotherapists during treatment. Topical corticosteroids have been shown to have an anti-inflammatory effect in the treatment of many skin diseases and are commonly prescribed during a course of radiation treatment. A comparison of two different steroid creams, 1% hydrocortisone cream and 0.05% clobetasone butyrate (Eumovate), in a double blind trial was carried out in 54 patients undergoing radiation therapy for breast cancer. 'The cream' was administered when patients reached a given dose of 2000 rad (or earlier if required) whether a skin reaction was present or not. The aim of the trial was to evaluate the general effectiveness of steroids in controlling radiation dermatitis and whether one type of cream was superior to the other. The majority of patients using either cream derived benefit in its soothing effect. There was, however, a significant difference in the intensity of reactions seen, patients using clobetasone butyrate developed more severe radiation reactions despite both groups having similar radiation doses. The possibility of two differing populations having different responses to radiation is discussed as is the 'breakthrough phenomenon' described in the literature. It is concluded that neither cream should be used as first choice in the control of radiation dermatitis.

Oophoropexy and ovarian function in the treatment of Hodgkin's disease.

Fifty-four female patients under 45 years of age were followed-up for assessment of ovarian function after treatment for Hodgkin's disease. Forty-six patients had oophoropexy performed, but it was found that in only 28 (60.8%) were the ovaries sufficiently displaced from their normal positions that, had an inverted 'Y' field of irradiation been applied, the ovaries would have been spared. In the 12 patients who were treated by irradiation alone (including an inverted 'Y' field), only one patient maintained normal ovarian function. Therefore, it is suggested that oophoropexy and the shielding performed at inverted 'Y' irradiation has proved of limited value in preserving ovarian function further measures should be taken.

Ear-lobe keloids: treatment by a protocol of surgical excision and immediate postoperative adjuvant radiotherapy.

There is no universally agreed policy for treating keloid scars of the ear lobe following piercing. We treated 35 patients (34 women) for high-risk ear-lobe keloids; the average age was 24 years (range: 16-44 years). All had failed to respond to prior treatment with massage and silicone, and corticosteroid injection. The keloids were excised extralesionally and the defects were closed with interrupted prolene sutures. The operative scar was covered with topical 2% lignocaine-0.25% chlorhexidine sterile lubricant gel under a transparent adhesive dressing. Adjuvant postoperative radiotherapy of 10 Gy, applied as 100 kV photons (4 mm high-voltage therapy (HVT) Al), was given within 24 h of surgery. All keloid scars were controlled at 4 weeks' follow-up. At 1 year, three out of 34 cases followed up had relapsed (probability of control: 91.2%). At 5 years, a further four out of the remaining 31 patients had relapsed (cumulative probability of control at 5 years: 79.4%). There were no cases of serious toxicity.

A phase II study of continuous-infusion 5-fluorouracil with cisplatin and epirubicin in inoperable pancreatic cancer.

Carcinomas of the exocrine pancreas respond poorly to most chemotherapy regimens. Recently continuous infusional 5-fluorouracil (200 mg m-(2)day-1) with 3 weekly cisplatin (60 mg m-2) and epirubicin (50 mg m-2) (the ECF regimen) has proven to be an active regimen in gastric and breast cancer and consequently worthy of further study in pancreatic cancer. Thirty-five patients were treated with the ECF regimen as above, of whom 29 were evaluable for response and 32 were evaluable for toxicity. The mean age was 59 years (range 37-75). Sixteen patients had locally advanced disease at presentation and 19 had metastases. Objective tumour responses were documented in five (17.3%) patients who achieved a partial response; in 18 (62%) patients there were no change and six (20.7%) patients progressed on therapy. Patients with either stable disease or partial response had a significantly improved overall survival (median = 253 days) compared with patients who progressed (median = 170 days; P = 0.01). Grade 3/4 (WHO) toxicity (all cycles) included alopecia in 18 (56%) patients, nausea/vomiting in eight (25%) stomatitis in three (9%) and diarrhoea in seven (22%) patients, with rhinorrhoea and excessive lacrimation in one patient each. Neutropenic sepsis occurred in 13 cycles in ten patients, and there was one toxic death due to sepsis. There were eight other episodes of non-neutropenic sepsis requiring hospital admission. Fourteen patients (40%) experienced complications with their Hickman lines, including thrombotic episodes (six patients) or their line falling out (five patients). ECF can prolong survival in patients with locally advanced or metastatic pancreatic cancer who demonstrate a response or stabilisation of their disease. However, this is associated with considerable toxicity.

Accuracy of grey-scale ultrasonography of liver and spleen in Hodgkin's disease and the other lymphomas compared with isotope scans.

Complementary techniques to laparotomy are required to monitor patients with lymphomas both before and after treatment. Our preliminary experience with grey-scale ultrasonography is presented. Fifty-two patients, themajority with Hodgkin's disease or other lymphomas, were examined with ultrasound equipment which was custom built. The essential difference between grey-scale equipment and conventional machines is the ability to display the internal consistency of soft organs. Of 20 spleens examined prior to splenectomy, the ultrasonic scan was considered suggestive of involvement in seven of nine that showed histological evidence of Hodgkin's disease. Threeof 11 histologically negative spleens were considered to be positive preoperatively and two of nine read as negative on the scan contained histological disease. Fifty livers were examined with ultrasound. Of seven patients with histological involvement four were read as positive and three as negative and six of 43 patients with no macroscopic or microscopic evidence of liver infiltration were also considered to have a positive ultrasonic scan. Ultrasonic scanning has proved useful for demonstrating enlarged lymph nodes in the porta hepatis, upper para-aortic lymph nodes and bulky mesenteric nodes. On the basis of these preliminary observations the potential value and application of the technique is discussed.

Postchemotherapy staging laparotomy in Hodgkin's disease.

Seventeen patients with Hodgkin's disease who had a staging laparotomy (SL) within 2 months of the completion of initial chemotherapy are presented. Only 1 patient had a positive laparotomy. Postchemotherapy SL allows any residual active disease to be assessed, but the incidence of positive finding may be small, and such findings are unlikely to alter subsequent management. SL following chemotherapy is therefore not recommended either for patients in clinical remission or for patients with evidence of relapsed disease.

Carboplatin: a very active new cisplatin analog in the treatment of small cell lung cancer.

Carboplatin, a cisplatin analog without significant clinical nephrotoxicity, has been evaluated in the treatment of 56 patients with small cell lung carcinoma at a dose of 300-400 mg/m2 iv monthly in a phase II study. Twenty-three patients (41%) achieved a response, including five (9%) complete remissions. Of 30 previously untreated patients, 18 (60%) achieved a response, including three (10%) complete remissions. Median response duration was 4.5 months (range, 2-9). No nephrotoxicity was seen and hydration was not required. Nausea or vomiting occurred in only 24 patients (43%) and was rarely severe. Myelosuppression was dose-limiting: 20 patients (36%) developed leukopenia and eight (14%) developed thrombocytopenia, but leukopenic infections occurred in only three patients. Carboplatin is a very active new agent in the treatment of small cell lung cancer, with less toxicity and better tolerance than cisplatin. It merits further investigation in combination chemotherapy and against non-small cell lung cancer.