Dermoscopy use in UK primary care: a survey of GPs with a special interest in dermatology.

BACKGROUND: Melanoma accounts for 90% of skin cancer mortality and typically presents in primary care, where it can be challenging to distinguish from benign lesions. Dermoscopy is a tool for skin visualization that is routinely used for melanoma diagnosis in secondary care. However, the role of dermoscopy in primary care remains unclear. OBJECTIVES: To determine views on, and use of, dermoscopy by dermatology-interested general practitioners (GPs). METHODS: An online questionnaire was emailed to the UK Primary Care Dermatology Society members in February 2018, and responses collected over the following 4 weeks. RESULTS: A total of 205 responses were analysed. Most respondents were GPs (94%), aged over 50 (53%), had a postgraduate dermatological qualification (67%) and used dermoscopy regularly when reviewing pigmented skin lesions (97%). Dermoscopy use was commoner amongst GPs who had worked longer in primary care and had experience of secondary care dermatology. Most had undertaken training in dermoscopy (91%), although one-fifth (20%) had not updated their training in over 5 years. Most of those who had received only 1 day of face-to-face training reported feeling confident using a dermatoscope. Few respondents (11%) reported access to teledermatology or teledermoscopy for urgent or routine referrals. CONCLUSIONS: UK GPs with a special interest in dermatology are routinely using dermoscopy in the primary care setting. More research is needed to establish optimal approaches to training and updating GP dermoscopy skills. When dermoscopy has been shown to be safe, effective, acceptable and cost-effective in this setting, more GPs may also be able to gain and maintain the skills to implement dermoscopy into routine primary care. Technological advances, including incorporation of artificial intelligence (AI) and algorithms to guide GPs, could also contribute to widening use of dermoscopy among GPs.

Determination of threshold values for determining the size of the fraction of steroid hormone receptor-positive tumor cells in paraffin-embedded breast carcinomas.

BACKGROUND: For 4 years we used a multiparameter DNA flow cytometric (MP-FCM) technique to assess steroid hormone receptor expression in the diagnostic workup of routinely processed formalin-fixed, paraffin-embedded breast carcinomas as an alternative to immunohistochemistry (IHC) for the quantification of hormone receptor-positive cells. In all cases a positive fraction of hormone receptor-expressing epithelial cells was detected. This observation raised the question of what the cutoff value might be to distinguish receptor-negative from receptor-positive tumors. METHODS: In our search for a possible threshold value of positivity for estrogen receptor (ER) and progesterone receptor (PR) in MP-FCM, we developed four steps. First, we compared IHC results in our own laboratory with the results obtained by MP-FCM on a small series of breast tumors (n = 42). Second, after collecting our first 843 tumors, we made a comparison with the literature of the distribution of receptor positivity according to age classes. Third, using the most likely threshold that resulted from this comparison, we compared a subset of 340 node-negative tumors for their combined ER/PR profiles with the data from a similar group of node-negative tumor cases from the National Cancer Institute's Surveillance, Epidemiology and End-Result (SEER) study. Fourth, with the results of these comparisons, we prospectively collected IHC data and MP-FCM results of the same tumor samples for a period of 1 year. In this way, we collected data for an additional 180 tumors. RESULTS: The first step in this process resulted in an previous publication where 20% of steroid hormone receptor-positive cells seemed to be an acceptable cutoff point for positivity. However, the second step provided the best correlation at approximately 35% of ER reactive cells in the cytokeratin-positive cell population. With this cutoff, the distribution of combined ER/PR profiles in our patient population of node-negative breast cancers also showed a distribution similar to the data from the SEER study. The fourth step, using the 35% threshold value, resulted in a good correlation (r = 0.85, P < 0.0001) for ER and PR between IHC and MP-FCM in the 180 tumors investigated. CONCLUSION: By comparing in-house data with those from large external data collections in the literature, a threshold percentage can be defined that distinguishes steroid hormone receptor-negative from hormone receptor-positive tumors. As a result, information about DNA content and cell cycle distribution can be obtained. This observational study provides additional support to our opinion that MP-FCM is an alternative for IHC determination of ER and PR positivity. It is more objective and quantification can be done more appropriately. The additional value of this approach is that we generate continuous variables of ER/PR content instead of categorical classes, which can be used at different threshold levels for evaluation of clinical relevance.

A single session of intraluminal brachytherapy in palliation of oesophageal cancer.

Between September 1987 and September 1993, 88 patients with oesophageal cancer were treated by a single session of intraluminal brachytherapy of 15 Gy prescribed at 1 cm distance from the central axis, using MDR137Cs (n = 51) during the first part of the study and HDR192Ir (n = 37) during the second part of the study. All patients were regarded as inoperable. Improvement of dysphagia, assessed 4-6 weeks after treatment, was noted in 50 of 75 (67%) evaluable patients, whereas swallowing ability was completely restored in 47% of them. Relapse of dysphagia occurred in 28 (37%) patients during follow-up. Additional palliative treatment consisted of endoprosthesis in 14 (19%), a second course of brachytherapy in 13 (17%), one or more dilatations only in 11 (15%) and laser treatment in four (5%) patients. One non-fatal haemorrhage and five fistulae occurred, all in the presence of tumour. Two severe ulcerations without evidence of tumour were noted, both managed by combined curative treatment. The median survival of the group investigated was 5.5 months. An exophytic, non-circular growth pattern was associated with a better response. In a multivariate analysis the presence of distant metastases (p = 0.0028), weight loss (p = 0.0051) and an exophytic growth pattern (p = 0.0199) were associated with a worse survival. The present data indicate that a single session of ILB is appropriate in the palliation of dysphagia in patients with inoperable oesophagal cancer showing bad prognostic signs. Up to now there has been no clear evidence for benefit of addition of ERT.

An unwanted side effect of hydroxyurea in a patient with idiopathic myelofibrosis.

A patient with idiopathic myelofibrosis is reported who developed a drug fever after treatment with hydroxyurea, a generally effective and well-tolerated drug in chronic myeloproliferative syndromes. Typically, this form of fever develops after a few weeks of exposure to the drug and disappears with discontinuation of the drug. Possible interactions with prostaglandin or leukotriene metabolism may play a role.

Meningeal melanoma associated with nevus of Ota: case report and review.

A case report is presented of a 30-year old woman with a primary meningeal melanoma associated with an ipsilateral nevus of Ota (oculodermal melanosis). Nine similar cases described in the literature are reviewed including additional personal communications after follow-up of three of these patients. The mean age of the patients is 42 years. In half of these tumors a dural attachment has been documented, the present case included. All patients with a dural melanoma were alive at least 2 years and 4 months after the primary craniotomy with a maximal survival of 8 years.

Palliation in esophageal cancer with a single session of intraluminal irradiation.

From September 1987 to December 1989, 36 patients with advanced esophageal cancer entered a study in order to determine the efficacy of palliation by a single session of intraluminal irradiation. A dose of 15 Gy was administered at 1 cm distance from the central axis of the applicator. In 22 of 32 patients alive at least 6 weeks after treatment dysphagia improved, in 14 this relief was complete. Re-obstruction occurred in 8 of the 22 responders, but a second treatment with intraluminal irradiation gave improvement in six. Intraesophageal prostheses were needed in only 6 of the 36 patients. Intraluminal irradiation is easy to administer and safe, it forms a useful addition to the therapeutic possibilities for the palliation of esophageal cancer.

Non-Hodgkin lymphoma of the puerperal uterus.

Non-Hodgkin lymphoma was diagnosed initially in a curettage specimen of a puerperal uterus 3 weeks after normal delivery of a healthy infant. The disease, which probably existed during the last trimester of pregnancy, was classified as clinical stage IVb. Combination chemotherapy resulted in immediate improvement and complete remission after several months. Histopathologic examination of the uterus 10 months after starting therapy demonstrated complete disappearance of the malignant lymphoma.

A randomized comparative trial of combined versus alternating therapy with cytostatic drugs and high-dose medroxyprogesteron acetate in advanced breast cancer.

A prospective multicenter trial was conducted in 155 consecutive patients with Stage IV breast cancer randomly allocated to receive either (1) vincristin (V) 1.2 mg/m2 (maximum dose, 2 mg), Adriamycin (A) (doxorubicin) 40 mg/m2, and cyclophosphamide (C) 500 mg/m2, all intravenously on day 1, every 4 weeks, in combination with medroxyprogesteron acetate (MPA) 600 mg orally on days 1 through 14, 500 mg intramuscularly on days 1 through 28, and twice weekly afterwards (combined chemoendocrine approach) or (2) the same combination chemotherapy (VAC) for three cycles alternating with MPA in the above-mentioned dosage during 8 weeks (alternating chemoendocrine approach). Results show an overall response rate of 73% with 26% complete responses in the combined treatment arm, whereas in the alternating arm, an overall response rate of 76% with 20% complete responses was observed. In patients with more than one metastatic site, response rate was higher in the combination treatment, and only in this arm were complete responses observed in these patients. Although the median duration of response was long in both treatment arms (combination, 19 months versus alternating, 21 months), the median overall survival in both groups was not definitely prolonged (22 versus 24 months, respectively). However, results in subsets of patients suggest that the alternating chemoendocrine approach may be better for estrogen receptor (ER)-negative patients, for patients younger than 51 years of age, and for patients with a disease-free interval of 1 year or less. Patients with these parameters probably belong to the same population. It is concluded that combination of chemotherapy and high-dose MPA may be indicated in ER-positive patients when a clinical response is urgently needed. In ER-negative patients, the alternating use of both treatment modalities deserves further investigation.

The effect of diabetes regulation on platelet release, fibrinolysis and coagulation tests, before and after stimulation with DDAVP.

In this longitudinal study we measured beta-TG, PF4, fibrinolytic activity (extrinsic and euglobulin fraction), fibrinogen, FVIII RAg and FVIII Rcof before and after i.v. DDAVP (FPA was only measured before DDAVP) in 20 patients with diabetes mellitus. These parameters were measured on three occasions: phase I: during disregulation, phase II: after three weeks of strict control, phase III: after nine weeks of good control. Twenty-two healthy volunteers served as normal controls. No significant differences related to metabolic control were found for beta-TG, PF4, FPA and fibrinogen. There was no change after i.v. DDAVP administration. Fibrinolytic activity showed a significant increase after i.v. DDAVP. Baseline values and post-DDAVP increase were not significantly different from our normal controls. FVIII RAg and FVIII Rcof were both significantly elevated in diabetes mellitus. Both increased significantly after DDAVP. The FVIII RAg release (delta FVIII RAg) was significantly less in the diabetics. Fibrinolytic activity, FVIII RAg and FVIII Rcof are independent of the degree of metabolic control in patients with diabetes.

Insulin requirements in diabetic patients treated with sulphinpyrazone.

Forty-one adult diabetic patients of either sex who had been controlled by insulin alone for at least one year were randomly allocated in a double-blind, between-patient study, to either sulphinpyrazone (600--800 mg daily) or an identnd at the end of it, no clinically or statistically significant change of the insulin needs of the patients was observed. It is concluded that no clinical interaction occurs between sulphinpyrazone (800 mg/day or 600 mg/day) and insulin when they are administered simultaneously for long periods. In the doses used the tolerability of sulphinpyrazone was very good.