Consensus Document of the International Union of Angiology (IUA)-2013. Current concept on the management of arterio-venous management.

Arterio-venous malformations (AVMs) are congenital vascular malformations (CVMs) that result from birth defects involving the vessels of both arterial and venous origins, resulting in direct communications between the different size vessels or a meshwork of primitive reticular networks of dysplastic minute vessels which have failed to mature to become 'capillary' vessels termed "nidus". These lesions are defined by shunting of high velocity, low resistance flow from the arterial vasculature into the venous system in a variety of fistulous conditions. A systematic classification system developed by various groups of experts (Hamburg classification, ISSVA classification, Schobinger classification, angiographic classification of AVMs,) has resulted in a better understanding of the biology and natural history of these lesions and improved management of CVMs and AVMs. The Hamburg classification, based on the embryological differentiation between extratruncular and truncular type of lesions, allows the determination of the potential of progression and recurrence of these lesions. The majority of all AVMs are extra-truncular lesions with persistent proliferative potential, whereas truncular AVM lesions are exceedingly rare. Regardless of the type, AV shunting may ultimately result in significant anatomical, pathophysiological and hemodynamic consequences. Therefore, despite their relative rarity (10-20% of all CVMs), AVMs remain the most challenging and potentially limb or life-threatening form of vascular anomalies. The initial diagnosis and assessment may be facilitated by non- to minimally invasive investigations such as duplex ultrasound, magnetic resonance imaging (MRI), MR angiography (MRA), computerized tomography (CT) and CT angiography (CTA). Arteriography remains the diagnostic gold standard, and is required for planning subsequent treatment. A multidisciplinary team approach should be utilized to integrate surgical and non-surgical interventions for optimum care. Currently available treatments are associated with significant risk of complications and morbidity. However, an early aggressive approach to elimiate the nidus (if present) may be undertaken if the benefits exceed the risks. Trans-arterial coil embolization or ligation of feeding arteries where the nidus is left intact, are incorrect approaches and may result in proliferation of the lesion. Furthermore, such procedures would prevent future endovascular access to the lesions via the arterial route. Surgically inaccessible, infiltrating, extra-truncular AVMs can be treated with endovascular therapy as an independent modality. Among various embolo-sclerotherapy agents, ethanol sclerotherapy produces the best long term outcomes with minimum recurrence. However, this procedure requires extensive training and sufficient experience to minimize complications and associated morbidity. For the surgically accessible lesions, surgical resection may be the treatment of choice with a chance of optimal control. Preoperative sclerotherapy or embolization may supplement the subsequent surgical excision by reducing the morbidity (e.g. operative bleeding) and defining the lesion borders. Such a combined approach may provide an excellent potential for a curative result. Conclusion. AVMs are high flow congenital vascular malformations that may occur in any part of the body. The clinical presentation depends on the extent and size of the lesion and can range from an asymptomatic birthmark to congestive heart failure. Detailed investigations including duplex ultrasound, MRI/MRA and CT/CTA are required to develop an appropriate treatment plan. Appropriate management is best achieved via a multi-disciplinary approach and interventions should be undertaken by appropriately trained physicians.

Laser-induced weal and flare reactions: clinical aspects and pharmacological modulation.

BACKGROUND: Among the adverse effects of cutaneous laser therapy, weal and flare reactions immediately after treatment have received little attention, and the pathomechanisms are unclear. OBJECTIVES: To study clinical features and possible mechanisms of laser-induced weal and flare reactions in order to identify means of possible therapeutic intervention. METHODS: Normal skin from the inner arm of 20 volunteers was treated with an argon laser, and the size of weal and flare reactions was measured over a 60-min period. Skin biopsies were taken from four volunteers before and up to 24 h after laser treatment and examined histologically and immunohistologically. Possible underlying mechanisms were also explored using various topical or systemic pharmacological agents. RESULTS: Wealing was noted in 19 of 20, and flare reactions in all volunteers, with peak values at 15 min. Skin biopsies showed central coagulation of the tissue, cleft formation between epidermis and dermis, normal numbers of morphologically intact mast cells on toluidine blue staining close to the lesion, and only minor upregulation of endothelial and leucocyte adhesion molecules. In agreement with these findings, pretreatment with acetylsalicylic acid, the H1-blocker loratadine and triamcinolone cream was ineffective or resulted in a non-significant reduction of weal and flare reactions. In contrast, local anaesthetics as well as neuropeptide depletion of skin with capsaicin abolished the reactions almost completely. CONCLUSIONS: Transient weal and flare reactions in response to laser treatment occur in almost all persons and are based primarily on a neurogenic rather than a histamine- or mast cell-dependent mechanism.

Diffuse neonatal hemangiomatosis associated with Simpson-Golabi-Behmel syndrome: a case report.

Diffuse neonatal hemangiomatosis (DNH) is a rare disorder characterized by multiple cutaneous and visceral hemangiomas that usually presents in newborns and has a high mortality rate. While previously reported cases of DNH describe multiple cutaneous hemangiomas, we present a patient with a single hemangioma of the ear, who also had DNH of the central nervous system and visceral organs. Furthermore, in this report we present a new constellation of findings, namely, a Simpson-Golabi-Behmel syndrome (SGBS). The practical implication on the basis of the experience with our patient is the need to ensure adequate diagnostics for patients with large hemangiomas as well as for patients with multiple cutaneous hemangiomas, because DNH also can occur in single hemangiomas in rare cases.

PHACE syndrome: new views on diagnostic criteria.

The association of large facial hemangiomas with posterior fossa malformations and vascular anomalies has been termed the PHACE syndrome. It is characterized by the association of posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and other cardiac defects, and eye abnormalities. Since most articles focus on isolated case reports, an extended retrospective literature review of all reports of large hemangiomas with associated abnormalities of the central nervous system and other malformations was performed to examine the clinical features, and other not as yet reported associated anomalies. Reports were found on 59 patients with PHACE syndrome, to which we added ten cases of our own. The Dandy-Walker syndrome is the most common CNS abnormality reported in association with PHACE syndrome and was seen in 48 (81 %) patients. Arterial malformations were found in 13 (22 %) cases; only 11 patients (19 %) had structural arterial abnormalities without associated Dandy-Walker complex. As published, about one third of patients (31 %) had further ophthalmologic abnormalities, and cardiac anomalies, including coarctation of the aorta. Subglottic hemangiomas were seen in 4 (7 %) patients and ventral developmental defects also in 3 cases. In seven of 59 patients (12 %) with PHACE syndrome, intracranial hemangiomas were present. This study demonstrates that among other CNS abnormalities, special attention should be given to intracranial hemangiomas which seems to be a peculiar phenotype of PHACE syndrome. We therefore suggest that a sixth criterion should be added to the five minimal inclusion criteria for PHACE syndrome. The inclusion criteria would then be: arterial abnormalities or/and intracranial hemangiomas. On the basis of our experience with our patients and with those previously reported, we stress the importance of using contrast-enhanced imaging to detect intracranial lesions.

[Treatment of hemangiomas in infancy and childhood with the flash lamp-pumped dye laser: cutaneous versus mixed cutaneous-subcutaneous hemangiomas]. / Die Behandlung von Hämangiomen im Säuglings- und Kindesalter mit dem blitzlampengepumpten Farbstofflaser. Kutane versus gemischte kutan-subkutane Hämangiome.

The efficacy of flashlamp-pumped pulsed dye laser therapy at 585 nm for cutaneous and mixed hemangiomas was assessed in 165 children with 225 separate hemangiomas were treated in 332 sittings over 2.5 years. The patients were divided into three groups: 100 patients with 153 flat cutaneous hemangiomas, 47 patients with 54 mixed cutaneous-subcutaneous hemangiomas and 18 patients with 18 superficial hemangiomas in the involution phase. In the first group of 100 patients with 153 flat cutaneous hemangiomas, 52 (34%) of the lesions showed total lightening. 21 of the 153 lesions showed proliferation of the subcutaneous component, although these lesions were flat at first presentation. Of the 54 mixed hemangiomas, 33 (61%) had continued proliferation of the subcutaneous component. The cutaneous component responded to therapy in 21 (39%) hemangiomas while the subcutaneous component of the mixed hemangiomas remained unchanged. No lesions in this group involuted completely and therapy was discontinued because of a relatively poor response to therapy. 12 (67%) of the 18 patients with superficial hemangiomas in the involution phase had excellent results, and 6 (33%) had good results. We conclude that treatment with the flashlamp-pumped pulsed dye laser is very effective and may be the treatment of choice for selected hemangiomas, especially cutaneous hemangiomas at sites of potential functional impairment (hands or feet, anogenital-region), and on the face. Furthermore, laser therapy should be initiated as early as possible, even in the first days or weeks of life, when the hemangioma is flat, to prevent enlargement, promote involution, or eliminate these vascular lesions.

Association of large facial hemangiomas with Dandy-Walker syndrome. Case study concerning three infants.

Hemangiomas are the most common benign tumors of infancy and are observed in 2-3% of newborns. The Dandy-Walker syndrome is characterized by a cystic expansion of the fourth ventricle, a dysgenesis of the vermis of the cerebellum and atresia of the foramina of Luschka and Magendie. We report on three infants with large bilateral facial hemangiomas in association with a Dandy-Walker syndrome. We conclude that although the three diseases are not based on one common genetic disorder, as far as we know, one should bear this association in mind in cases with large facial hemangiomas.

Flashlamp-pumped pulsed dye laser for hemangiomas in infancy: treatment of superficial vs mixed hemangiomas.

OBJECTIVE: To study in a compared manner the efficacy of flashlamp-pumped pulsed dye laser (FPDL) therapy for superficial and mixed hemangiomas. DESIGN: Nonrandomized control trial. SETTING: Department of Lasermedicine, General Hospital Neukölln, Berlin, Germany. PATIENTS: To investigate variation in response to treatment, a prospective study of 165 children with 225 separate hemangiomas treated with the FPDL was undertaken. Patients were aged 2 days to 7 years; mean follow-up was 5 months. INTERVENTIONS: During a 2 1/2-year period, we administered 332 treatments, for a mean+/-SD of 2.0+/-1.1 treatments per patient. MAIN OUTCOME MEASURE: Patients received therapy until the lesion was almost clear or until the lesion did not respond to treatment. Evaluation was performed by comparing pretreatment and posttreatment photographs. In addition, pathologic flow of vessels and thickness were determined before, during, and after completion of therapy with color-coded duplex sonography. RESULTS: In the first group of 100 patients with 153 flat cutaneous hemangiomas, 52 hemangiomas (34%) had excellent results; 80 (52%) had good results; and 21 (14%) showed proliferation of the subcutaneous component, although these lesions were flat at first presentation. Of the 54 mixed hemangiomas, 33 (61%) had continued proliferation of the subcutaneous component. The cutaneous component responded to therapy in 21 hemangiomas (39%), whereas the subcutaneous component of the mixed hemangiomas remained unchanged. No lesions in this group involuted completely, and therapy was discontinued because of relatively poor response. Twelve (67%) of 18 patients with superficial hemangiomas in the involution phase had excellent results and 6 (33%) had good results. CONCLUSIONS: Treatment with the FPDL is effective and may be the treatment of choice for superficial cutaneous hemangiomas at sites of potential functional impairment and on the face. Hemangiomas with a deep component do not benefit from FPDL treatment because the efficacy of the FPDL is limited by its depth of vascular injury. Furthermore, early therapeutic intervention with the FPDL may not prevent proliferative growth of the deeper or subcutaneous component of the hemangioma despite early intervention.

[Lasers in medicine]. / Laser in der Medizin.

Laser systems are widely spread in the field of medicine. The applications are divided into therapeutical and diagnostic applications. The main field however are therapeutical procedures. Depending on the indication lasers were used for removing and cutting of smooth and hard tissue or for coagulation. A relative new procedure is the photodynamic therapy. Substances--mostly dyes--are applied to the body and stay for a certain time in tumorous tissue. After an interval it is possible to irradiate this tissue. Only the cells with the incorporated substances react with a cell death.

Photodynamic Therapy of Malignant Ovarian Tumours Cultivated on CAM.

The disappointing results with either surgery alone and/or chemotherapy in the treatment of malignant ovarian tumours have led to an increased interest in additional treatment schedules. Photodynamic therapy (PDT), a modality involving the use of a photosensitising drug and activating light, is being used increasingly as a local treatment for neoplastic lesions. The synthesis and evaluation of new photosensitisers for the treatment of gynaecological lesions and malignancies continues to be an active area of investigation for proper application of the photodynamic process in the gynaecological field. The effect of PDT using methylene blue (free and combined with liposomes) as a photosensitiser for treating human ovarian malignant tumours cultivated on the chorioallantoic membrane was evaluated. Two days after PDT, the treated implanted tumours were markedly decreased in size. Areas of necrosis with black coloration, dryness and eschar formation were observed. Five days after PDT, tumour remission was clearly observed in all the treated tumours. Photodynamic therapy using methylene blue (aqueous and coupled with liposomes) is effective for treating the ovarian malignancies and it will be capable of achieving complete eradication of visible tumours in patients with superficial lesions.

Laser-Induced Thermotherapy (LITT) for Retreatment of Locally Advanced Recurrences of Breast Cancer.

The effect of laser-induced thermotherapy (LITT) as a palliative method for treatment of patients with local recurrence of breast cancer is investigated. This report describes the use of interstitial laser photocoagulation to manage such lesions. The interstitial laser applications were performed in seven women with locally recurrent breast carcinoma on the chest wall after mastectomy. All patients had been heavily pretreated with conventional modes of therapy (radiotherapy, chemotherapy, hormonal therapy, surgical resection). A Nd:YAG laser with a wavelength of 1064 nm was used to heat the lesions. Heat expansion was controlled digitally and monitored by ultrasonography and colour-coded duplex sonography (CCDS). In five women this minimally invasive method enabled the precise coagulation of the subcutaneous tumour without destruction of the skin or ulceration, although these areas had been pretreated by irradiation up to 60 Gy. In two patients with extensive multiple metastases and with skin infiltration, secondary skin ulceration and delayed healing was observed. For palliative reasons, LITT under CCDS guide can aid in local control of chest wall recurrence following mastectomy in selected patients.

13(2)-hydroxy-bacteriopheophorbide a methyl ester pharmacokinetics measurements with fluorescence versus absorption spectroscopy. Is there a difference?

OBJECTIVE: Quantification of photosensitizer concentration in tissue improves the planning and, subsequently, the outcome of photodynamic therapy. This study was designed to determine if the method of photosensitizer evaluation influences the accuracy of pharmacokinetic results. MATERIALS AND METHODS: In vivo 13(2)-Hydroxy-bacteriopheophorbide a methyl ester (13(2)-OH-BPME) pharmacokinetics in mice bearing LEWIS lung carcinoma was studied using fluorescence in situ and absorption spectroscopy (following photosensitizer chemical extraction) as photosensitizer quantification methods. The correlation of 13(2)-OH-BPME fluorescence intensity and its concentration using the absorption spectroscopy were determined for each tissue. RESULTS: The parenchymatous organs showed maximum 13(2)-OH-BPME concentration and fluorescence intensity at 2 h post-injection (lung, liver, spleen), and at 2 h post-injection in the kidney with both quantification methods (identical correlation). There was a difference in the time of maximum photosensitizer fluorescence intensity and its concentration in tumor, muscle, and skin (low correlation). The time of maximum fluorescence intensity in muscle, skin, and tumor was at 4 h, 12 h, and 12 h post injection respectively while its maximum concentration was at 2 h, 4 h, and 8 h post-injection. CONCLUSION: The method of photosensitizer evaluation affects the accuracy of its pharmacokinetic results.

Is endometrial ablation a safe contraceptive method? Pregnancy following endometrial ablation.

A case of pregnancy following thermal endometrial ablation is presented in this report.

Elevated serum prolactin level with high-dose estrogen contraceptive pills.

BACKGROUND AND OBJECTIVES: There are currently groups of women using high-dose estrogen contraceptive pills, especially in the developing countries. The aim of this study was to determine the correlation between the duration of contraceptive pill intake, the dose of steroid contained in the contraceptive pills and the incidence and degree of serum prolactin level elevation in those women. STUDY DESIGN: This study was conducted in 100 contraceptive pill users. Women were randomly selected for this study with an age range from 19 to 35 years and duration of contraceptive pill intake from 6 to 120 months. Cases were classified into two groups. The first group (50 cases) were taking high-dose estrogen pills (50 micrograms) and the second group (50 cases) were taking low-dose estrogen pills (30 micrograms). RESULTS: The results of the present study showed that there was a significant elevation in serum prolactin level in both groups, with a more significant elevation in the high-dose pill users. CONCLUSIONS: There is a positive relationship between serum prolactin level and the duration of pill intake and their steroid content, and this relationship is not related to the age and parity of the women. The groups of women studied are scheduled for follow-up to determine if there is any future drawback which results as a consequence of the developed hyperprolactinemia. Prolactin determination should be considered for all women prior to pill intake. This determination of serum prolactin level prior to pill use will be useful in the evaluation of the future relationship between the estrogen content of the pills and the later development of hyperprolactinemia.

Novel human papillomavirus (HPV) DNA sequences from recurrent cutaneous and mucosal lesions of a stoma-carrier.

Recent studies have demonstrated a high prevalence of human papillomavirus (HPV) types originally believed to be restricted to patients with epidermodysplasia verruciformis (EV) in benign and malignant skin tumors of the general population. Other groups detected typical mucosal HPV in skin tumors. We have investigated recurrent leukoplakial cutaneous and mucosal lesions located around the ileostoma of a woman with ulcerative colitis for the presence of HPV. Cutaneous, mucocutaneous, and mucosal ileostoma-biopsies were analyzed by three different polymerase chain reaction protocols for genital, cutaneous, and cutaneous EV-associated HPV types. Polymerase chain reaction products were cloned, sequenced, and submitted to phylogenetic analyses. HPV-DNA sequences of the EV-HPV group could be detected in all biopsies, whereas genital/mucosal or cutaneous HPV types were not found. HPV types detected comprised HPV20, HPV23, HPV38, and four putatively novel HPV types that belong to different clusters of the EV-HPV group B1. Different HPV types prevailed in cutaneous, mucocutaneous, and mucosal lesions and the number of HPV sequences found per lesion varied between one and three. Our data show the association of recurrent lesions around a stoma and at the ileum with known and novel EV-HPV types. These results emphasize the plurality of HPV and yield data for the possible transmission of cutaneous HPV to mucosal areas of the intestine.

Creation of a caecostoma in mice as a model of an enterocutaneous fistula.

In the past, physiological, oncological and pharmaceutical investigations led to the development of different models of enterocutaneous fistulas. For a few years, fistula models were also created to investigate the efficacy of minimal invasive therapies in closing these fistulas. As most experimental surgical procedures are difficult to perform and are often combined with a high mortality or spontaneous closure rate, a new model in mice was developed with the aim of avoiding these disadvantages. Twenty mice, divided into two groups of 10 animals each, had a caecostoma created surgically. The two groups differed regarding the technique of creating the stoma. All animals survived and gained weight during a postoperative period of 4 months. The operation was easy to perform and lasted no longer than about 30 min. Neither a spontaneous closure of the fistula nor any prior death of animals occurred. In conclusion, because of its simplicity and low complication rate, the presented model of an enterocutaneous fistula may offer an interesting alternative to other models for a variety of indications.

Pharmacokinetic analysis of octa-alpha-butyloxy-zinc phthalocyanine in mice bearing Lewis lung carcinoma.

OBJECTIVE: In this study, the pharmacokinetics of octa-alpha-butyloxy-zinc phthalocyanine (8-alpha-bo-ZnPc) was studied with regard to Lewis lung carcinoma in mice after intravenous administration of 7.8 mumole/kg body weight at different incubation intervals. SUMMARY BACKGROUND DATA: The newly synthesized potential photosensitizer 8-alpha-bo-ZnPc is characterized by a high absorption coefficient at the far red wavelength (735 nm) with a good singlet oxygen quantum yield. METHODS: After intravenous administration of 7.8 mumole/kg body weight in mice bearing Lewis lung carcinoma, the accumulated photosensitizer was chemically extracted (at incubation intervals of 2, 6, 12, 24, 48, and 168 hours) from selected tissues, and the concentrations were measured by absorption spectroscopy. RESULTS: The parenchymatous organs, liver, and spleen showed maximum 8-alpha-bo-ZnPc concentrations after 6 hours of incubation. An extensive uptake was detected in lung extracts taken at 6, 12, 24, and 48 hours. The malignant tissue did not accumulate high 8-alpha-bo-ZnPc during the entire investigation period. The photosensitizer extracted from muscle, representing normal tumor-surrounding tissue and skin, was even lower. CONCLUSIONS: Because of the extremely low accumulation rate of the tumor, 8-alpha-bo-ZnPc is suggested to be administered topically or in combination with a suitable carrier system in order to increase the photosensitizer concentration in the target tissue, as well as to decrease the loss of dye to other tissues.

Modulation of 5-ALA-induced PpIX xenofluorescence intensities of a murine tumour and non-tumour tissue cultivated on the chorio-allantoic membrane.

Exogenous administration of 5-aminolaevulinic acid (5-ALA), an early precursor in haem synthesis, induces accumulation of endogenous photo-active porphyrins, particularly protoporphyrin IX (PpIX). Modulation of 5-ALA-induced PpIX-xenofluorescence intensities of a murine tumour and normal (non-tumour) tissue was studied in vivo on the chorio-allantoic membrane (CAM) of fertilized chicken embryos. Tumours were grown from the murine fibrosarcoma cell line SSK II. Murine 3T3 fibroblasts (clone A31) were used for cultivating normal tissue. The autofluorescence and xenofluorescence intensities of 5-ALA-induced PpIX xenofluorescence were compared. After administration of 5-ALA to the CAM inoculated tissues, the SSK II tumours exhibited higher xenofluorescence intensities than the 3T3 tissues. Autofluorescence intensities of both types of tissue were not distinguishable. The effects of several biochemical reagents on the xenofluorescence intensities of the fibrosarcoma and fibroblast tissues were investigated. In both tissue types, the intensities increased after incubation with glucose and antimycin A, while nicotine-adenine-dinucleotide increased the 3T3 fibroblast xenofluorescence more than the SSK II fibrosarcoma xenofluorescence. Incubation with dimethyl sulphoxide (DMSO) attenuated 5-ALA-induced PpIX xenofluorescence, while oxamic acid attenuated the 3T3 fibroblast xenofluorescence more effectively than the xenofluorescence of SSK II fibrosarcoma. Ethanol and 2-iodoacetamide drastically decreased xenofluorescence intensities in both tumour and normal tissue.