Rapid Lump Examination (RLE) - a bedside 3-dimensional microscopy of tumor specimens.

BACKGROUND: Due to rising skin cancer incidence rates there is an urgent need for a quick, reliable and cost-effective therapy. Previous studies showed that fresh tumor tissue and margins could be directly examined microscopically with high sensitivity and specificity. OBJECTIVE: Comparing the accuracy of rapid lump examination (RLE) for the detection of basal cell carcinoma (BCC) during micrographic surgery with formalin-fixed paraffin-embedded hematoxylin and eosin (HE)-stained sections. METHODS AND MATERIALS: 382 specimens of 118 excised samples with suspected BCC were examined with RLE and compared with formalin-fixed paraffin-embedded HE-stained sections. For RLE, following a standardized 60 sec staining protocol, the fresh tissue samples were observed directly with a stereomicroscope. RESULTS: For BCC, RLE had a high but insufficient diagnostic accuracy compared to the gold standard of formalin-fixed paraffin-embedded HE-stained sections. The sensitivity was 76 % (95 % CI = [66.18 %; 84.5 %]) and specificity was 91 % (95 % CI = [86.73 %; 93.75 %]). CONCLUSIONS: RLE is a fast and simple technique for microscopically controlled surgery (MCS) of basal cell carcinomas that requires training. The experience of the examiner has a major influence on the results. RLE has great potential to speed up the workflow in Mohs surgery but should be improved in the future.

Rapid Lump Examination as a New Aid to Speedup Mohs Micrographic Surgery: A Pilot Study.

BACKGROUND: Although most cases of basal cell carcinoma (BCC) are curable, facial and recurrent BCCs require time consuming and labor-intensive Mohs micrographic surgery (MMS) to ensure complete removal with optimal cosmetic results. To handle the skin cancer epidemic, there is an urgent need to speedup MMS. Recently, rapid lump examination (RLE) has been shown to enable quick histologic examination, but its usefulness within MMS is unknown. OBJECTIVE: To evaluate the accuracy of RLE for the detection of residual BCC during MMS. MATERIALS AND METHODS: Twenty-two BCCs of various subtypes were evaluated by means of RLE and standard fresh frozen section (FFS) examination. For RLE, the freshly excised tissue was stained with toluidine blue and imaged with a stereomicroscope before being subdivided into sections suitable for processing into FFS. Fresh frozen sections were stained with hemotoxylin and eosin and evaluated with light microscopy. RESULTS: Using FFS examination as the gold standard for the detection of residual BCC, RLE had a sensitivity, specificity, positive predictive value, and negative predictive value of 83.8%, 94.0%, 83.8%, and 94.0%, respectively. CONCLUSION: As RLE enables quick 3-dimensional visualization of surgical margins for the detection of residual BCC, it holds the potential to speedup histologic examination during MMS.

Banana leaves as an alternative wound dressing.

BACKGROUND: There is a need for cheap and efficacious wound dressings in developing countries. Banana leaves have been described as an excellent, inexpensive, easily available dressing material in tropical countries. As a natural product, banana leaves are heavily contaminated with various pathogens that must be removed before they can be used as wound dressings, but effective sterilization methods that do not affect the beneficial wound-dressing properties of banana leaves have not been described. OBJECTIVES: To study different sterilization methods and determine which can be used on banana leaves without affecting their beneficial wound-dressing properties. MATERIALS AND METHODS: We first compared the use of different decontamination techniques to reduce the natural microflora of the leaves and then tested the wound-dressing properties of the leaves in a mouse model of skin transplantation and in postsurgical patients in Uganda, Africa. RESULTS: Steam sterilization proved to be the optimal sterilization technique. Banana leaves displayed wound-dressing properties that equaled those of petroleum jelly gauze dressings and were tested successfully in a clinical setting in postsurgical patients in Uganda, Africa. CONCLUSION: We found banana leaves to be an excellent alternative wound dressing, combining the desirable properties of modern wound-dressing material with low cost.

Topical timolol for small hemangiomas of infancy.

Propranolol has become the treatment of choice of large and complicated infantile hemangiomas. There is a controversy concerning the safety of systemic propranolol. Here we show that topical use of the beta-blocker timolol can also inhibit the growth and promote regression of infantile hemangiomas. In this case series we treated 11 infantile hemangiomas in nine children including six preterm babies with the nonselective betablocker timolol. A timolol containing gel was manufactured from an ophthalmic formulation of timolol 0.5% eyedrops. This gel was applied using a standardized occlusive dressing (Finn-Chambers) containing approximately 0.25 mg of timolol. In all infants topical timolol was associated with growth arrest, a reduction in redness and thickness within the first 2 weeks. Seven hemangiomas showed almost complete resolution, and four became much paler and thinner. No data are available on the transdermal absorption of timolol. Even supposing complete absorption of timolol from the occlusive dressing, a maximum dose of 0.25 mg of timolol would result per day and hemangioma. Regression of infantile hemangiomas treated using 0.5% timolol gel in this case series occurred earlier than spontaneous regression which is generally not observed before the age of 9-12 months. The promising results need to be verified in prospective randomized trials on topical beta blocker administration for infantile hemangiomas which should address dose, duration, and mode of application.

Extramammary Paget's disease: extended subclinical growth detected using three-dimensional histology in routine paraffin procedure and course of the disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare tumor of the skin characterized by extended irregular subclinical growth and high recurrence rates after surgery. OBJECTIVE: To show that, using three-dimensional (3D) histology in surgical excision, the size of the safety margin can be individually determined and locally adjusted to subclinical growth and to evaluate the course of the disease in 33 patients. METHODS: The clinical records of 33 patients with primary lesions of EMPD were prospectively documented, retrospectively confirmed, and analyzed. RESULTS: EMPD was found more frequently in women (54.5%). Dermal invasion was found in 21.2%, and regional lymph node metastases were present in one patient; 30.3% of the patients had secondary internal malignancies. In 25 cases examined using 3D histology, a mean surgical margin of 22 mm in asymmetric shape (range 5-65 mm) was achieved, with a recurrence rate of 28%. Surgery with conventional histologic examination had a higher recurrence rate of 62.5% using a mean surgical margin of 19 mm (range 7-40 mm). CONCLUSIONS: Subclinical spread of EMPD demonstrated using 3D histology with paraffin sectioning can be large. Three-dimensional histology allows individually defined safety margins to be locally adjusted to subclinical growth and gives low recurrence rates. The authors have indicated no significant interest with commercial supporters.

Rapid lump examination (RLE) - a new tool for Mohs surgery?

BACKGROUND: "Micrographic surgery" spares tissue and results in fewer recurrences. Various techniques have been described using paraffin-embedded and cryostat sections or even optical sections from ex vivo confocal laser scanning microscopy. The presented technique is the rapid direct microscopy of the surface of a specimen (lump) for a pathological examination (RLE). METHODS: Fresh surgical tissue was stained first without sectioning and then was examined directly under microscope. A 95 sec staining protocol for basal cell carcinoma (BCC) was established. 129 specimens were examined using a digital microscope and 78 specimens using a stereo microscope. RESULTS: RLE had a high diagnostic accuracy compared to paraffin-embedded H&E-stained sections. Sensitivity and specificity of RLE was 91 % and 90 % for the digital and 90 % and 94 % for the stereo microscope. In addition we developed a 7 min RLE-immunohistology protocol using the BerEp4-antibody. DISCUSSION: RLE is a simple and accurate technique for fresh tissue examination. Here, the technique has been established for BCC but the principle may also be transferred to histological bedside diagnosis of other tumors. The technique does not alter or destroy tissue, so that after RLE was done subsequent conventional histology is still possible. RLE might yield a time- and cost-saving diagnosis in micrographic surgery.

Wavelet analysis of skin blood flow in dermatosurgery using primary closure with tension.

Primary closure in dermatologic surgery is state of the art in small lesions at the head, but also in larger lesions at the trunk or the extremities. Microcirculatory effects on the skin blood flow near to the wound edges affected by primary closure. Forty three patients were investigated. Before and after surgery, skin blood flow was measured using Laser Doppler Fluxmetry (LDF). During primary closure, tension in the suture was measured and the tension on the wound edges was calculated. Times series were analyzed using continuous wavelet analyses, before, after 2 h and 24 h after surgery. After three months, the cosmetic results were requested. Median horizontal diameter was 22 mm (quartiles 20/48 mm), median vertical diameter was 44 mm (quartiles 26/60 mm). Mean string force was 12.0 SD 10.2 N. During the whole course of investigation, we found no change of microcirculatory parameters such as mean LDF or any scaling level following wavelet analysis caused by primary closure. Average of the cosmetic result was 1.8. It is a relative small number of patients and the defects are located in different areas. Skin blood flow and the microcirculatory pattern is not affected in the area by the tension on wound edges and provides therefore a fast healing process without any vegetatively induced complications even if the string force is high. In dermatosurgery, wounds can be closed directly without changing the microcirculatory pattern in the direct area of the wound margins.

Confocal laser scanning microscopy vs 3-dimensional histologic imaging in basal cell carcinoma.

OBJECTIVE: To compare ex vivo confocal laser scanning microscopy (CLSM), which offers rapid images without the need for tissue processing, vs 3-dimensional histologic imaging, the criterion standard treatment for basal cell carcinomas in high-risk areas of the face. DESIGN: Single-center prospective trial. SETTING: Dermatosurgical unit of a university hospital. Patients Seventy-two consecutive surgically removed basal cell carcinomas were examined using CLSM vs standard paraffin-embedded 3-dimensional histologic imaging. Interventions A total of 312 images, including 73 midsections, 196 lateral margins, 23 "muffins," and 20 "bread loaf sections," were obtained using CLSM. Immediately after surgery, the CLSM images were evaluated by the surgeon. The following day, the 3-dimensional histologic slides were evaluated and compared with the CLSM images. MAIN OUTCOME MEASURES: Diagnostic accuracy of ex vivo CLSM to detect tumor strands of basal cell carcinomas and the practicality of using CLSM vs 3-dimensional histologic slides in micrographic surgery. RESULTS: The sensitivity of CLSM reached 94.0% in midsections, 73.7% in lateral margins, 80.0% in muffins, and 80.0% in bread loaf sections. The CLSM images were evaluated by the surgeon within 7.5 minutes. CONCLUSIONS: Confocal laser scanning microscopy lacks high sensitivity to detect small tumor strands of basal cell carcinomas. In the future, CLSM may represent a time-saving and less expensive alternative to cryostat histopathologic examination.

Sentinel lymph node dissection in primary melanoma reduces subsequent regional lymph node metastasis as well as distant metastasis after nodal involvement.

BACKGROUND: In many countries sentinel lymph node dissection (SLND) followed by complete lymphadenectomy if positive is routinely performed treatment for primary cutaneous melanoma. However, the potential survival benefit of SLND is still controversial. METHODS: Patients with primary cutaneous melanoma (tumor thickness 1.00 mm or greater) diagnosed in the Department of Dermatology, University of Tuebingen, Germany between 1991 and 2000 were included in the study. A total of 439 patients who received SLND were compared retrospectively with 440 patients without SLND with regards to occurring patterns of metastases and disease-free and overall survival. SLND-positive cases and SLND-negative patients with subsequent development of regional lymph node metastasis (SLND-LN+) were compared with non-SLND patients who had developed regional lymph node metastasis (non-SLND-LN+). RESULTS: Regional lymph node metastases as the first recurrence occurred more frequently in the non-SLND collective (16.5%) compared with the SLND group (7.3%; P = 0.001), whereas satellite/in-transit metastases and distant metastases did not differ. Driven by the reduction of regional lymph node metastases, disease-free survival was improved in the SLND collective (P = 0.003). No significant difference in overall survival was observed (P = 0.090).The risk of dying from melanoma was 2.2 times higher in the non-SLND-LN+ group than in the SLND-LN+ group (P = 0.009), while the risk of developing distant metastasis was 2.3 times higher (P = 0.002). CONCLUSIONS: SLND reduced subsequent regional lymph node metastases and improved disease-free survival, while overall survival remained unaffected. SLND reduced distant metastases and improved overall survival in the subgroups of patients with regional lymph node involvement.

Nodular malignant melanoma and multiple cutaneous neoplasms under immunosuppression with azathioprine.

Immunosuppressed patients are at increased risk of skin cancer. A 67-year-old renal transplant recipient developed a nodular malignant melanoma after 30 years of immunosuppression with azathioprine and prednisolone. The patient died of metastatic disease 3 months after the diagnosis was made. The function of the renal graft was not affected at all. Renal transplant recipients are at high risk of developing nonmelanocytic skin tumors when on immunosuppressive therapy with cyclosporine A. Less common is the development of skin cancer during immunosuppression with azathioprine. Latest reports show the increased incidence of malignant melanoma in immunosuppressed patients. Our case illustrates the necessity of close dermatological surveillance of allograft recipients, to assure an early recognition of any malignant skin tumor and to reduce the risk of systemic metastatic disease.

Sun protection by red wine?

BACKGROUND: There is increasing evidence that polyphenols, antioxidants from plants such as green tea or grapes, may impair the UV-induced erythema reaction as well as carcinogenesis and metastasis of melanoma and epithelial skin cancer. The UVB-protective potential of wine polyphenols has not been studied so far in humans. PATIENTS AND METHODS: We tested the influence of local and systemic application of three red wines on the minimal erythema dose (MED) after UVB exposure in 15 healthy male physicians. Baseline MED were determined in all subjects. Irradiation was carried out prior to and immediately following 20 minutes of occlusive application of red wine as well as 12 % alcohol to the back. The systemic effect was tested by ultraviolet irradiation immediately prior to oral intake, RESULTS: There were no topical effects. Wine A also provided no protection systemically. Drinking wine B has led to an almost significant rise of MED, while wine C, which had the highest polyphenol content, produced a statistically significant higher MED (p = 0.031). CONCLUSIONS: "Wine baths" will not have sun protective properties. A significant rise of the MED following oral intake of the wine with the highest polyphenol content might be due to these substances. Further research is needed to clarify the role of polyphenol content, dose and duration of wine consumption.

Changes in acral blood flux under local application of ropivacaine and lidocaine with and without an adrenaline additive: a double-blind, randomized, placebo-controlled study.

Vascular effects of local anesthetics are especially important in dermatological surgery. In particular, adequate perfusion must be ensured in order to offset surgical manipulations during surgical interventions at the acra. However, the use of adrenaline additives appears fraught with problems when anesthesia affects the terminal vascular system, particularly during interventions at the fingers, toes, penis, outer ears, and tip of the nose. We studied skin blood flux at the fingerpads via laser Doppler flowmetry over the course of 24 hours in a prospective, double-blind, randomized, placebo-controlled study with 20 vascularly healthy test persons following Oberst's-method anesthetic blocks. In each case, 6 ml ropivacaine (7.5 mg/ml) (A), lidocaine 1% without an additive (B), and lidocaine 1% with an adrenaline additive (1:200,000) (C) was used respectively as a verum. Isotonic saline solution was injected as a placebo (D). Measurements were carried out with the aid of a computer simultaneously at D II and D IV on both hands. Administration of (A) led to increased blood flux (+155.2%); of (B) initially to a decrease of 27%; of (C) to a reduction of 55% which was reversible after 40 minutes and of (D) to no change.(A) resulted in sustained vasodilatation which was still demonstrable after 24 h. (B) had notably less vasodilative effect, although comparison with (D) clearly showed that (B) is indeed vasodilative. (C) resulted in only a passing decrease in perfusion; this was no longer measurable when checked after 6 and 24 h. This transient inadequacy of blood flux also appeared after administration of (D). These tests show that adrenaline additive in local anesthesia does not decrease blood flow more than 55% for a period of 16 min. Following these results an adrenaline additive can be safely used for anesthetic blocks at the acra in healthy persons.

Age and gender are significant independent predictors of survival in primary cutaneous melanoma.

BACKGROUND: The aim was to identify age- related and gender-related differences in the clinical presentation and outcome of patients with primary cutaneous melanoma (CM). METHODS: A total of 4785 CM patients without clinical evidence of metastasis diagnosed during the period 1976-2001 in southern Germany included in the analysis. Kaplan-Meier analyses were performed to estimate and to compare disease-specific survival (DSS) and survival after first recurrence (SAR). The Cox proportional hazards model was used to evaluate the effect of multiple variables on DSS and SAR. RESULTS: Increasing age and male gender were independently associated with thicker tumors (>2 mm) and histologic ulceration (P< .001). Patients older than 65 years had lower 10-year DSS than younger patients (81.8% vs 88.4%, P< .001) and this difference was more pronounced in women (P< .001) than in men (P= .06). Males had lower 10-year DSS than females (83.5% vs 88.5%, P< .001) but this difference did not reach statistical significance in patients older than 65 years (P= .162). In multivariate analysis adjusted for tumor thickness, ulceration, anatomic site, histologic subtype, DSS, site of first recurrence, time trend, sentinel lymph node status, age, and gender were independent predictors of DSS and SAR (P< .05). CONCLUSIONS: Older age and male gender are associated with prognostically unfavorable primary CM. Expansion of current preventive strategies to target these subgroups is warranted. Moreover, age and gender are independent predictors of the outcome of CM patients. Females have a better prognosis than males but this difference disappears after the age of 65. Younger patients have a more favorable prognosis than older patients, a difference more pronounced in women.

Outdoor sports and skin cancer.

Ultraviolet radiation is estimated to be one of the most important risk factors for nonmelanoma and melanoma skin cancers. Athletes practicing outdoor sports receive considerable UV doses because of training and competition schedules with high sun exposure, and in alpine sports, by altitude-related increase of UV radiation and reflection from snow- and ice-covered surfaces. Extreme UV exposure in outdoor sports such as skiing, mountaineering, cycling, or triathlon has been documented in a series of dosimetric studies. Sweating because of physical exercise may contribute to UV-related skin damage as it increases the individual photosensitivity of the skin, facilitating the risk of sunburns. Large epidemiological studies showed that recreational activities such as sun exposure on the beach or during water sports were associated with an increased risk of basal cell carcinoma, whereas skiing has been shown to be at increased risk for squamous cell carcinoma. Risk factors of cutaneous melanoma such as the number of melanocytic nevi and solar lentigines have been found to be more frequent in subjects practicing endurance outdoor sports. An increased risk for cutaneous melanoma may be assumed for these athletes. In addition to the important sun exposure, exercise-induced immunosuppression may increase the risk for nonmelanoma skin cancer and cutaneous melanoma in athletes. Frequently, athletes seem to know little about the risk of sun exposure. Protective means such as avoiding training and competition with considerable sun exposure, choosing adequate clothing, and applying water-resistant sunscreen still need to be propagated in the community of outdoor sportsmen.