Five-year results from the prospective European multicentre cohort study on radiofrequency segmental thermal ablation for incompetent great saphenous veins.

BACKGROUND: This was a prospective study of radiofrequency segmental thermal ablation (RFA) for the treatment of incompetent varicose great saphenous veins (GSVs). The present report describes long-term follow-up at 5 years. METHODS: The 5-year follow-up of this multicentre European study included assessment of the Venous Clinical Severity Score (VCSS), and GSV occlusion and reflux on duplex imaging. RESULTS: A total of 225 patients had 295 GSVs treated by RFA, achieving an initial vein occlusion rate of 100 per cent. With 80·0 per cent compliance, Kaplan-Meier analyses showed a GSV occlusion rate of 91·9 per cent and a reflux-free rate of 94·9 per cent at 5 years. Among the 15 GSVs noted with reflux during follow-up, only three showed full recanalization of the GSV at 1 week, 6 months and 3 years. Of the 12 legs with partial recanalization, reflux originated at the saphenofemoral junction in ten, with a mean length of the patent segment of 5·8 (range 3·2-10) cm; only six patients were symptomatic. Mean(s.d.) VCSS scores improved from 3·9(2·1) at baseline to 0·6(1·2), 0·9(1·3) and 1·3(1·7) at 1, 3 and 5 years. CONCLUSION: At 5 years RFA proved to be an efficient endovenous treatment for incompetent GSVs in terms of sustained clinical and anatomical success for the vast majority of treated patients.

Radiofrequency-powered segmental thermal obliteration carried out with the ClosureFast procedure: results at 1 year.

This prospective and multicenter study shows the results at 1 year of radiofrequency-powered segmental thermal obliteration (RSTO) carried out with the ClosureFast procedure. The RSTO clinical and duplex ultrasound imaging results were evaluated at 3 days, 3 months, 6 months, and 1 year. All procedures were carried out on outpatients under tumescent local anesthesia. Among the 295 members who were treated, 289 were reexamined at 3 days, 290 at 3 months, 289 at 6 months, and 220 at 1 year. Occlusion scores were 99.7%, 99.3%, 98.6%, and 96.9% at, respectively, 3 days, 3 months, 6 months, and 1 year. At 3 cm below the saphenofemoral junction, before the procedure, the greater saphenous vein (GSV) diameter was 5.4+/-2 mm (range 2-18). It decreased to 4.5+/-1.7 mm at 3 days, 2.4+/-1.5 mm at 6 months, and 1.3+/-0.9 mm at 1 year. In members reexamined at 1 year, the decrease in diameter of the treated vein compared with the preprocedural measurement was 79% (p<0.001, t-test). At 1 year, in 58% of the cases, duplex ultrasound imaging at mid-thigh level could not show the GSV trunk. Preprocedural pain that was present in 57.5% of the cases decreased to 10.8% of the cases at 3 days and 2% of the cases at 1 year (p<0.001, chi2 test). Among the treated limbs, 70.1% did not present with any postprocedural pain at any time of the follow-up. On the third day, the patients evaluated the mean pain intensity at 0.7+/-1.6 on a visual analog scale of 0-10. During the follow-up, no painful indurations were noticed in 67.7% of the legs. No thromboembolic complications were reported. Paresthesias were observed in 3.4% of the cases. Invalidity clinical score, evaluated at 3.9+/-2 before the procedure, decreased to 3.5+/-1.2 on the third day, 0.9+/-1.5 at 3 months, 0.7+/-1.2 at 6 months, and 0.5+/-1.1 at 1 year. This study confirms the efficacy of RSTO when using ClosureFast, which allows obliteration of the GSV trunk in 97% of cases at 1 year with few side effects and almost no postprocedural pain.

[Cellulite]. / Zellulitis.

Cellulite is a condition affecting the dermal and subdermal compartment and developing on thighs and buttocks of almost every woman. Macroscopically, cellulite is characterized by dimpling, visible either spontaneously or after provoking maneuvers. While published concepts on the pathophysiology of cellulite are in parts inconclusive or contradictory, there are at least some recent studies describing or confirming structural and anatomic changes on dermal and subdermal tissues: (1) A gender specific dimorphism with subdermal septae oriented orthogonally towards the skin surface as well as protrusion of fat tissue into the dermis. (2) These intradermal fat protrusions additionally correlate with the presence of cellulite. (3) There is also a correlation between the thickness of the subdermal fat layer and the presence of cellulite. (4) Cellulite also correlates with focal hypertrophic subcutaneous septae and a reduced density of septae in general. Treatment of cellulite aims at (1) the reduction of the subcutaneous fat layer, (2) increase in dermal thickness and elasticity and (3) dissection of hypertrophic connective tissue septae, responsible for the most pronounced dermal indentions. A variety of treatment options have evolved ranging from topical retinol to interstitial laser.

Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: a randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group.

PURPOSE: The combination of interferon alfa-2a (IFN alpha) and high-dose interleukin-2 (IL-2) is active in metastatic melanoma. The addition of cisplatin (CDDP) has resulted in response rates greater than 50%. This study was performed to determine whether the addition of CDDP to a cytokine treatment regimen with IFN alpha and high-dose IL-2 influences survival of patients with metastatic melanoma. PATIENTS AND METHODS: Patients with advanced metastatic melanoma were randomly assigned to receive treatment with IFN alpha 10 x 10(6) U/m2 subcutaneously on days 1 through 5 and a high-dose intravenous decrescendo regimen of IL-2 on days 3 through 8 (18 mIU/ m2/6 hours, 18 mIU/m2/12 hours, 18 mIU/m2/24 hours, and 4.5 mIU/m2/24 hours x 3) without (arm A) or with (arm B) CDDP 100 mg/m2 on day 1. Treatment cycles were repeated every 28 days to a maximum of four cycles. RESULTS: One hundred thirty-eight patients with advanced metastatic melanoma, of whom 87% had visceral metastases, were accrued for the trial. Both regimens were feasible in a multicenter setting. The objective response rate was 18% without and 33% with CDDP (P = .04). The progression-free survival was 53 days without and 92 days with CDDP (P = .02, Wilcoxon; P = .09, log-rank). There was no statistically significant difference in survival between treatment arms, with a median overall survival duration for all patients of 9 months. CONCLUSION: The addition of CDDP to cytokine treatment with IFN alpha and IL-2 does not influence survival of patients with advanced metastatic melanoma, despite a significant increase in response rate and progression-free survival.

Detection of early micrometastases in subcutaneous fat of primary malignant melanoma patients by identification of tyrosinase-mRNA.

To improve survival following melanoma excision, wide margin resection including subcutaneous fat, is indicated. Subcutaneous fat, resected with primary melanomas, was investigated using the tyrosinase PCR method originally described for detection of melanoma cells in peripheral blood. Identification of tyrosinase transcripts was possible in 4 melanoma patients (3 Clark level IV, 1 level III), while negative results were obtained from 6 other patients (2 level IV, 3 level III and 1 level I). In control experiments, after infiltration of the reference cell line SkMel into normal fat tissue, the PCR was positive in 33% (3/9) with 10(2) infiltrated cells, 69% (9/13) with 10(4) cells and in 100% (7/7) with 10(6) cells. We conclude that detection of melanoma cells in subcutaneous fat tissue is possible by tyrosinase PCR. Follow-up studies should show whether such positive tyrosinase PCR can define patients at very high risk of tumour relapse.

Identification of lymph node metastases by use of polymerase chain reaction (PCR) in melanoma patients.

Diagnosis of clinically suspected lymph node metastases in melanoma patients can be confirmed with high sensitivity and specificity by fine needle aspiration (FNA) cytology. However, small lymph nodes or haemorrhagic metastases may yield negative or unevaluable cytology. We tested whether the sensitivity and specificity of presurgical diagnosis could be improved by a polymerase chain reaction (PCR) method, identifying tyrosine-mRNA in samples obtained by fine needle aspiration (FNA-PCR). PCR was positive in 17 of 18 histopathologically proven melanoma metastases, while conventional cytopathology detected 16 of 18. 4 of 9 disease-free melanoma patients with negative FNA cytology had positive PCR results, but controls gave negative results. FNA-PCR analysis cannot be recommended as superior to conventional FNA cytological examination. Whether the positive FNA-PCR in four of the nine clinically unsuspicious regional lymph nodes correlates with earlier disease progression or indicates lower specificity of the method will need further investigation.

A phase II study of dacarbazine, cisplatin, interferon-alpha and high-dose interleukin-2 in 'poor-risk' metastatic melanoma.

Melanoma patients with very advanced disease have usually not been included in chemo-immunotherapy trials. We report on 22 melanoma patients, including 5 with reduced performance status (Karnofsky PS < 70), 8 with metastatic ocular melanoma, 6 with brain metastases, and 4 who had pretreatment with interleukin-2. These were treated with a combination regimen of dacarbazine (250 mg/m2, days 1-3), cisplatin (30 mg/m2, days 1-3), interferon-alpha 2a (IFN-alpha, 10 Mio IU/m2 s.c., days 1-5) and IL-2 (i.v., 18 Mio IU/m2 for 6, 12, 24 h, followed by 13.5 Mio IU/m2 in 72 h). In the case of brain metastases radiotherapy was added. No grade IV toxicity occurred and no dose reductions were necessary. 21 patients were evaluable for response. 6 (29%) had disease progression, 5 (24%) had partial response and 10 (48%), had stable disease. Sites of response included skin, lymph nodes, muscle, lung, pleura, liver, pancreas, adrenal gland and brain. The described treatment schedule is safe and active even in patients with metastatic melanoma and poor prognosis.

Long-term outcome of treatment with dacarbazine, cisplatin, interferon-alpha and intravenous high dose interleukin-2 in poor risk melanoma patients.

Melanoma patients with very advanced disease are usually excluded from chemoimmunotherapy trials; however, the efficacy of intensive treatment regimens needs to be established for this patient population. This study aimed to evaluate the response rate and survival achieved with chemoimmunotherapy in very advanced melanoma patients. Forty-two patients received dacarbazine (250 mg/m2, days 1-3), cisplatin (30mg/m2, days 1-3), interferon-alpha (10 Mio IU/m2 subcutaneously, days 1-5) and intravenous interleukin-2 (18 Mio IU/m2 over 6 h, 12 h then 24 h, followed by 13.5 MioIU/m2 in 72 h). In cases of brain metastases (n = 12) radiation therapy was added. Ten patients (24%) achieved a partial response, 11 (26%) had stable disease and 21 (50%) had disease progression in an intention-to-treat analysis. The median overall survival of patients with a partial response or stable disease was 9 months in contrast to 3.5 months in patients with disease progression. Normal serum lactate dehydrogenase before the start of treatment was a strong favourable prognostic marker for survival (P< 0.002). We conclude that the described treatment schedule offers safe palliation in patients with very advanced metastatic melanoma.

[Surgical therapy of venous leg ulcers]. / Operative Ulkustherapie.

Surgical treatment of venous leg ulcers is a domain of dermatology. Special knowledge of differential diagnosis considerations and various treatment options are necessary to develop complex, sometimes interdisciplinary treatment plans together with angiologists,vascular surgeons and interventional radiologists. Besides surgical treatment options aiming towards normalization of venous hemodynamics, local options such as shave or total ulcer excision are well established. Additionally, new surgical techniques such as subfascial endoscopic perforator surgery (SEPS) or implantation of iliac stents now have their place in the surgical treatment of venous ulcer disease.

[Behçet disease with primary involvement of the cerebral vessels]. / Morbus Behçet mit primärem Befall zerebraler Gefässe.

HISTORY AND CLINICAL FINDINGS: Two months after the onset of mainly frontal headaches a 25-year-old man of Turkish descent additionally developed double vision. Fundoscopy revealed bilateral choked discs and right trochlear paralysis. Computed tomography and digital subtraction angiography demonstrated thrombosis of the superior sagittal sinus. On admission to hospital the patient was fully conscious but had marked meningism, bilaterally positive Lasègue's sign (painful straight leg raising) at a 50 degree angle, and multiple oral aphthous ulcers. The sinus thrombosis suggested a chronic inflammatory process, while the oral ulcers pointed to Behçet's syndrome. INVESTIGATIONS: Inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein and white blood cell count) were increased and the HLA-B27 test was positive. Other laboratory tests, cerebrospinal fluid, chest radiogram and ECG were unremarkable. TREATMENT AND COURSE: Despite intravenous administration of heparin nad cefuroxim for one week the sagittal sinus thrombosis spread to the straight sinus. In the third week scrotal ulcerations were noted and taken to confirm Behçet's syndrome. Immunosuppressive treatment with methylprednisolone (initially 80 mg daily) and 2 weeks later together with chlorambucil (0.1 mg/kg daily) was started. Four weeks later the patient was free of symptoms and discharged. CONCLUSION: Neurological signs are not adequately stressed by the International Study Group for Behçet's Disease among its listed diagnostic criteria.

Gravimetrically controlled efficacy of subcorial curettage: a prospective study for treatment of axillary hyperhidrosis.

BACKGROUND: Botulinum toxin A (BTX-A) proved to be effective for the treatment of axillary hyperhidrosis by means of gravimetry. Quantitatively controlled studies for surgical treatment are lacking so far. OBJECTIVE: To prospectively test the efficacy of subcorial axillary curettage by gravimetric evaluation of pre- and postsurgical sweat rates. METHODS: Conservatively pretreated patients received subcorial curettage under tumescent local anesthesia using a sharp spoon. Sweat rates of each axilla were determined gravimetrically before and 4-8 weeks after surgery. Evaluation was performed with respect to baseline sweat rates greater than 50 mg/min (group A), greater than 25 and less than 50 mg/min (group B), and less than 25 mg/min (group C). Side effects and patients' ratings were also recorded. RESULTS: Of 42 treated patients, 38 could be evaluated completely. In 29 axillae of group A (high sweat rates), an average reduction from the baseline of 85.6 mg/min to 21.6 mg/min could be achieved (P <.0001). Corresponding values for 22 axillae of group B (medium sweat rates) were 36.8 mg/min and 16.5 mg/min (P <.0001). In 25 axillae with low sweat rates (group C), a significant reduction in sweat rates could not be achieved. The results remained almost stable during a median follow-up of 11 months (range 4-24 months). Only minor side effects were observed and patient satisfaction was high in groups A and B. CONCLUSION: Subcorial curettage is an effective treatment of axillary hyperhidrosis for patients with baseline sweat rates greater than 25 mg/min.

Subfascial endoscopic perforator surgery with tumescent local anesthesia.

BACKGROUND: Subfascial endoscopic perforator surgery (SEPS) has become an established procedure. OBJECTIVE: To evaluate SEPS with tumescent local anesthesia (TLA) using an single-port device originally designed for that purpose. METHODS: Patients selected for SEPS received subcutaneous infiltration of TLA into the medial aspect of the calf 20 minutes before surgery. Bipolar coagulation and dissection were used to treat incompetent perforators. RESULTS: Fifty-one patients with 67 legs of CEAP stages C3-C6 underwent SEPS with TLA. In 40 patients or 53 legs (79.1%) TLA alone allowed successful completion of the SEPS procedure. Five patients with 7 legs (10.4%) required additional intravenous analgesics during surgery. In 4 patients or 4 legs (6.0%) with marked dermatoliposclerosis, pain control with TLA was so inadequate that SEPS had to be stopped. CONCLUSION: SEPS with TLA is feasible in patients with CEAP stage C3-C6. However, patients with pronounced dermatoliposclerosis are likely to need more invasive analgesic measures.

[Calciphylaxis]. / Calciphylaxie.

HISTORY AND CLINICAL FINDINGS: Acute, zigzag-shaped livid skin markings developed on both thighs of a 55-year-old woman who had been on dialysis for 6 years. Within 7 days these areas increased in size to about 10 cm in diameter and contained central dry and painful necroses. On legs, lower arms and hands hard subcutaneous nodules were palpable with a diameter up to 3 mm. For many years the phosphate and parathormone levels, as well as alkaline phosphatase activity had been raised. The patient had often failed to follow treatment recommendations. TESTS: There were increased serum concentrations of calcium (2.8 mmol/l) and phosphate (1.78 mmol/l). The calcium phosphate ion product was 4.98 (mmol/l)2. Furthermore, there were raised levels of alkaline phosphatase (315 U/l) and parathormone (1076 ng/l, normal: 10-65). X-ray film of the hands showed soft tissue and arterial calcifications, while histological examination of a deep skin biopsy revealed calcium phosphate emboli of the main vessels. TREATMENT AND COURSE: Excision of the cutaneous necroses was followed by parathyroidectomy at which only three parathyroid glands were identified and removed. The parathormone level fell postoperatively, but rose again after 4 weeks. The fourth parathyroid gland was then found and removed, after which the parathormone level fell below measurable levels. The skin ulcers healed completely 4 weeks after the second operation.

[Endoscopic fasciotomy and subfascial perforator division for chronic stasis ulcers]. / Die endoskopische Fasziotomie mit und ohne Perforansdiszision bei chronischem Ulcus cruris venosum.

Chronic venous ulcer disease is often refractory to conservative treatment modalities. After surgery of the superficial vein system, endoscopic methods can be used for division of incompetent perforators or to perform paratibial fasciotomy in cases of chronic functional compartment syndromes. We report on 13 endoscopically performed paratibial fasciotomies with or without concomitant endoscopic subfascial division of perforators (ESDP) in patients with stasis ulcers present for a median duration of 15 years. In all patients we observed immediate reduction of pain and edema. In 8 of 13 cases the ulcers healed within 3 months, another ulcer healed within 6 months and the remaining 4 ulcers showed a reduction in size of more than 75%. We conclude that endoscopically performed fasciotomy with or without ESDP is highly effective and has its place in the treatment of chronic venous ulcer disease.

Infrequent early recanalization of greater saphenous vein after endovenous laser treatment.

OBJECTIVE: The frequency of recanalization of the greater saphenous vein (GSV) after endovenous laser treatment (ELT) is unclear. This study was undertaken to establish the incidence of early recanalization after ELT and to study the histopathologic features of reperfused and excised GSV. METHODS: One hundred nine GSV in 85 consecutive patients with clinical stage C(2-6) E(P,S) A(S,P,D) P(R) disease were treated with ELT. Twelve months of follow-up with duplex scanning at regular intervals was possible in 104 treated veins (95.4%) in 82 patients (96.5%). Recanalized vessels were removed surgically and examined at histopathology. RESULTS: ELT-induced occlusion proved permanent at duplex scanning over 12 months of follow-up in 94 of 104 GSV (90.4%) in 73 patients. In 4 patients, 5 GSV (4.8%) were recanalized completely after 1 week, after 3 months (n = 3), or after 12 months. Another 5 GSV (4.8%) in 5 patients exhibited incomplete proximal recanalization over the 12 months of follow-up. Finally, 9 recanalized vessels (8.6%) required further treatment with high ligation and stripping. Histopathologic analysis of recanalized GSV revealed a multiluminal pattern, as commonly noted in reperfusion after spontaneous thromboplebotic occlusion of the GSV. During follow-up, secondary incompetency of untreated lateral accessory saphenous veins was observed in two legs (1.9%). CONCLUSION: Early recanalization requiring retreatment is observed in less than 10% of GSV after ELT. The histopathologic pattern mimics recanalization after thrombophlebotic occlusion.

[Anogenital condylomata acuminata, mucocutaneous candidiasis, vitiligo, keratopathy and primary hypoparathyroidism in an autoimmune polyglandular syndrome type 1]. / Genito-anale Condylomata acuminata, mukokutane Candidose, Vitiligo, Keratopathie und primärer Hypoparathyreoidismus bei autoimmunem polyglandulärem Syndrom Typ 1.

HISTORY: 6 months before admission a 21-year-old woman had developed anogenital condylomata acuminata (CA). Since early childhood she had been treated for primary hypoparathyroidism (PHPT) and recurrent mucocutaneous candidiasis. 5 years before admission corneal clouding had caused visual impairment. Recently, mainly truncal vitiligo with occipital poliosis had developed. INVESTIGATIONS: PHPT was confirmed (parathormone level 7.7 mg/l). In addition, liver transaminases were raised (GOT 105.8 U/l, GPT 145.6 U/l, gamma-GT 56.8 U/l), pointing to noninfectious hepatitis. An ACTH stress test could not exclude manifest adrenocortical insufficiency, and thyroid function was also normal. The Merieux Multitest indicated an anergy. DIAGNOSIS, TREATMENT AND COURSE: The constellation of test results suggested autoimmune polyglandular syndrome type I. The condylomata were treated by electrocautery and the intestinal candidiasis with amphotericin B suspension. Calcitriol capsules, 0.5 microgram, and calcium gluconate or lactate, 500 and 300 mg respectively, 3 times daily each, were given for the PHPT. CONCLUSION: This case demonstrates a complex syndrome which can be recognized early by simple clinical tests. Early diagnosis prevents possible life-threatening complications.

High ligation and stripping of the long saphenous vein using the tumescent technique for local anesthesia.

BACKGROUND: Advantages of tumescent local anesthesia (TLA) have been described for use in ambulatory phlebectomy removing large varicose side branches. OBJECTIVE: To evaluate the TLA method for high ligation and stripping of the long saphenous vein with or without administration of intravenous sedatives. METHODS: Forty-nine patients underwent 58 phlebosurgical procedures, including 41 ligations and strippings of the long saphenous vein. They were kept in the hospital for 24 hours after surgery to record potential complications and demand for medical assistance. RESULTS: The surgical procedures were easily performed under TLA without major complications. Minor complications were mild hematoma (n = 2) and temporary inguinal seroma (n = 1). Forty-one percent of the patients required additional i.v. sedation and analgesia perioperatively. Postsurgical guidance by a physician was necessary only in patients on full-dose heparin. CONCLUSION: The tumescent technique for local anesthesia allows high ligation and stripping of the long saphenous vein even in both legs in one session, however, frequently with additional i.v. medication.