Outcome of bleomycin electrosclerotherapy of slow-flow malformations in adults and children.

OBJECTIVES: To evaluate the safety and clinical outcome of bleomycin electrosclerotherapy (BEST) for treating extracranial slow-flow malformations. METHODS: In this retrospective investigation of a multicenter cohort presenting symptomatic slow-flow malformations, patient records were analyzed with respect to procedural details and complications. A treatment-specific, patient-reported questionnaire was additionally evaluated, obtained 3-12 months after the last treatment, to assess the subjective outcomes, including mobility, aesthetic aspects, and pain, as well as the occurrence of postprocedural skin hyperpigmentation. All outcome parameters were compared according to patients' age. RESULTS: Overall, 325 BEST treatments were performed in 233 patients after intralesional and/or intravenous bleomycin injection. The total complication rate was 10.2% (33/325), including 29/352 (8.9%) major complications. Patient-reported mobility decreased in 10/133 (8.8%), was stable in 30/113 (26.5%), improved in 48/113 (42.5%), and was rated symptom-free in 25/113 (22.1%) patients. Aesthetic aspects were rated impaired compared to baseline in 19/113 (16.8%), stable in 21/133 (18.6%), improved in 62/113 (54.9%), and perfect in 11/133 (9.7%) patients. Postprocedural skin hyperpigmentation occurred in 78/113 (69%) patients, remaining unchanged in 24/78 (30.8%), reduced in 51/78 (65.5%), and completely resolved in 3/78 (3.8%) patients. The median VAS pain scale was 4.0 (0-10) preprocedural and 2.0 (0-9) postprocedural. Children/adolescents performed significantly better in all parameters compared to adults (≥ 16 years) (mobility, p = 0.011; aesthetic aspects, p < 0.001; pain, p < 0.001). CONCLUSIONS: BEST is effective for treating slow-flow vascular malformations, with few but potentially significant major complications. Regarding patient-reported outcomes, children seem to benefit better compared to older patients, suggesting that BEST should not be restricted to adults. CLINICAL RELEVANCE STATEMENT: Bleomycin electrosclerotherapy is a safe and effective approach and therapy should not be restricted to adults due to good clinical outcomes in children.

Clinical Outcome and Quality of Life of Multimodal Treatment of Extracranial Arteriovenous Malformations: The APOLLON Study Protocol.

PURPOSE: Arteriovenous malformations (AVMs) as rare diseases are diagnostically and therapeutically challenging. Due to the limited evidence regarding treatment outcome, prospective data are needed on how different treatment regimens affect outcome. The aims of this prospective trial are to determine effectiveness, safety, and clinical outcome of multimodal treatment in patients with extracranial AVMs. MATERIALS AND METHODS: After clinical and magnetic resonance imaging (MRI)-based diagnosis and informed consent, 146 patients (> 4 years and < 70 years) undergoing multimodal therapy in tertiary care vascular anomalies centers will be included in this prospective observational trial. Treatment options include conservative management, medical therapy, minimally invasive image-guided procedures (embolization, sclerotherapy) and surgery as well as combinations of the latter. The primary outcome is the patient-reported QoL 6 months after completion of treatment using the short form-36 health survey version 2 (SF-36v2) and the corresponding short form-10 health survey (SF-10) for children. In addition, clinical presentation (physician-reported signs), MRI imaging (radiological assessment of devascularization), recurrence rate, and therapeutic safety will be analyzed. Further follow-up will be performed after 12, 24, and 36 months. Moreover, liquid biopsies are being obtained from peripheral blood at multiple time points to investigate potential biomarkers for therapy response and disease progression. DISCUSSION: The APOLLON trial is a prospective, multicenter, observational open-label trial with unequal study groups to generate prospective evidence for multimodal treatment of AVMs. A multicenter design with the potential to assess larger populations will provide an increased understanding of multimodal therapy outcome in this orphan disease. TRIAL REGISTRATION: German Clinical Trials Register (identification number: DRKS00021019) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021019 .

Reconstruction after ablative treatment of arteriovenous malformations of the head and neck.

Arteriovenous malformations are high-flow congenital vascular malformations that are characterized by abnormal connections between arteries and veins across an abnormal capillary bed. The head and neck region is the most common location for extracranial arteriovenous malformations. Due to their highly invasive, aggressive, and locally destructive nature, arteriovenous malformations are difficult to treat, and management through a multimodal, multidisciplinary approach is recommended. The mainstay of treatment is embolization and surgical excision. With the advent of genetic research, adjuvant targeted medical therapy is starting to play a larger role. Successful surgical treatment with or without embolization requires removal of the nidus. Large, focal, or diffuse lesions involving multiple anatomic areas usually necessitates surgical reconstruction. Free tissue transfer has many advantages over more conservative methods with restoration of function and contour. Herein, the authors describe the surgical treatment and reconstruction in head and neck arteriovenous malformations.

Towards a better treatment of patients with vascular malformations: certified interdisciplinary centers are mandatory.

BACKGROUND: Vascular anomalies are orphan diseases that occur in all age groups and range from purely aesthetic to potentially life-threatening conditions. This thesis paper outlines the typical conferring problems in patient management and possible structural solutions for a better patient treatment in the future. METHODS: A multi-perspective author panel consisting of key stakeholders from the German Interdisciplinary Society of Vascular Anomalies and the German Society for Surgery defined problem areas and possible solutions including quality indicators as criteria for certified interdisciplinary Vascular Anomalies Centers (VAC). RESULTS: According to the literature available, clearly defined nomenclature and nosological entities often remain unused in this field, and consented diagnostic and therapeutic evidence is rare. Expert opinions dominate and in some cases lead to disparate recommendations. Typical patient problems arise from this situation, exemplified in patient vignettes. Centralized and standardized patient treatment in interdisciplinary VAC may be a solution to this problem. These centers should agree on a set of general principles and quality indicators with an additional minimum set of structural and procedural criteria. DISCUSSION: The present position paper outlines perspectives for implementing certified interdisciplinary VAC. There is a need for a comprehensive nomenclature, access to interdisciplinary treatment centers, more scientific evidence, and further education in this rare group of diseases. CONCLUSION: Use of scientifically sound and patient-relevant criteria for certifying the interdisciplinary quality of VAC is expected to improve health care in Germany.

Additive value of transarterial embolization to systemic sirolimus treatment in kaposiform hemangioendothelioma.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor in children, which can be accompanied by life-threatening thrombocytopenia, referred to as Kasabach-Merritt phenomenon (KMP). The mTOR inhibitor sirolimus is emerging as targeted therapy in KHE. As the sirolimus effect on KHE occurs only after several weeks, we aimed to evaluate whether additional transarterial embolization is of benefit for children with KHE and KMP. Seventeen patients with KHE and KMP acquired from 11 hospitals in Germany were retrospectively divided into two cohorts. Children being treated with adjunct transarterial embolization and systemic sirolimus, and those being treated with sirolimus without additional embolization. Bleeding grade as defined by WHO was determined for all patients. Response of the primary tumor at 6 and 12 months assessed by magnetic resonance imaging (MRI), time to response of KMP defined as thrombocyte increase >150 × 103 /µL, as well as rebound rates of both after cessation of sirolimus were compared. N = 8 patients had undergone additive embolization to systemic sirolimus therapy, sirolimus in this group was started after a mean of 6.5 ± 3 days following embolization. N = 9 patients were identified who had received sirolimus without additional embolization. Adjunct embolization induced a more rapid resolution of KMP within a median of 7 days vs 3 months; however, tumor response as well as rebound rates were similar between both groups. Additive embolization may be of value for a more rapid rescue of consumptive coagulopathy in children with KHE and KMP compared to systemic sirolimus only.

Bleomycin electrosclerotherapy in therapy-resistant venous malformations of the body.

OBJECTIVE: Bleomycin is one of the most commonly used agents in sclerotherapy for slow-flow vascular malformations worldwide. However, its efficiency remains unknown. The objective of the present study was to assess whether reversible electroporation combined with bleomycin would increase the sclerotherapy effect in patients with previously unsuccessfully treated venous malformations (VMs). METHODS: We performed, to the best of our knowledge, the first retrospective observational case series from January 2019 to January 2020 of 17 patients (20 lesions) with symptomatic VMs, who had previously undergone at least two unsuccessful invasive treatments. Reversible electroporation was performed with various electrodes and directly injected bleomycin. All patient records, magnetic resonance imaging data, documentation of previous treatments, and data regarding the intervention, complications, and clinical symptoms were analyzed. RESULTS: The 17 VM patients (mean age, 20.8 ± 8.2 years; 9 females) had previously undergone an average of 4.2 invasive treatments. These patients had subsequently undergone 22 electrosclerotherapy sessions of 20 lesions. The median dose of bleomycin was 3 mg. The median magnetic resonance imaging-derived lesion volume before treatment was 24.9 cm3, which had decreased by 86% to 3.5 cm3 after treatment. After 3.7 months, eight patients were asymptomatic without residual symptoms and nine patients showed improvement. CONCLUSIONS: Bleomycin electrosclerotherapy appears to be an effective therapy for patients with VMs resistive to previous invasive therapy. Because of the small sample size and short follow-up period, our results should be examined further using a larger patient population.

Cutaneous Cephalic Neurocristic Hamartoma on the Head With Melanocytic, Cartilage, Blood Vessel, Neural, and Bony Tissue.

ABSTRACT: We report on a congenital tumor of the face and scalp in a male newborn, histologically proven to contain melanocytes, cartilage, and bone, vascular, and neural tissue as part of a pigmented congenital tumor. Thus, this tumor was classified as a cutaneous cephalic neurocristic hamartoma.

[Morbidity and Mortality of Single Incision Cholecystectomy: Results of a 3-Year Register Analysis]. / Morbidität und Letalität der Single-Incision-Cholezystektomie: eine 3-Jahres-Registeranalyse.

INTRODUCTION: Two decades ago, single-incision surgery was established as a new concept in minimally invasive surgery. Single incision cholecystectomy is the most frequently performed procedure in clinical routine. Most of the results have been based on randomised trials. Large prospective multicentre observational datasets from clinical routine do not exist. This analysis of clinical health service research is based on the SILAP study (single-incision multiport/single port laparoscopic abdominal surgery study). PATIENTS AND METHODS: The data of the register were collected in 47 hospitals in the period of 2012 to 2014. Overall morbidity and mortality were the primary outcome. Multiple linear and logistic regression analyses were performed. Statistical significance was set at p < 0.05. RESULTS: Data from 975 patients in clinical routine with single incision cholecystectomy were collected. Intraoperative complications were recorded in 3.2% of cases. Bile duct injuries were registered in 0.1% of cases. Postoperative complications were detected in 3.7% of cases. The mortality rate was 0.2%.The median operating time dropped from 60.0 to 51.5 min (p < 0.001) during the study. The use of an extra trocar was necessary in 10.3% of cases. Conversion to open surgery was performed in 0.7% of cases. Body mass index (p = 0.024), male gender (p = 0.012) and operating time (p < 0.001) had a significant effect on intraoperative complications in multivariate analysis. Classification of ASA III (p = 0.001) and modification or conversion of single incision technique (p = 0.001) were significantly associated with postoperative complications. CONCLUSION: The register analysis of the prospective multicentre data shows that single incision cholecystectomy is feasible in clinical routine even outside the selective criteria of randomised studies. The only limitation is a BMI > 30 kg/m2 which has a significant influence on the intraoperative rate of complications in mild adverse events.

Multidisciplinary long-term care and modern surgical treatment of congenital melanocytic nevi - recommendations by the CMN surgery network.

In recent years, our knowledge of congenital melanocytic nevi (CMN) has greatly expanded. This has led to a paradigm shift. The present article represents a commentary by an interdisciplinary group of physicians from German-speaking countries with extensive experience in long-term care and surgical treatment of children and adults with CMN (CMN surgery network, "Netzwerk Nävuschirurgie", NNC). The authors address aspects such as the indication for treatment as well as treatment planning and implementation under these new premises. Adequate counseling of parents on conservative and/or surgical management requires an interdisciplinary exchange among physicians and individualized planning of the intervention, which frequently involves a multi-stage procedure. Today, the long-term aesthetic outcome is at the center of any therapeutic endeavor, whereas melanoma prevention plays only a minor role. The premise of "removal at any cost" no longer holds. Potential treatment-related adverse effects (hospitalization, wound healing disorders, and others) must be carefully weighed against the prospects of a beneficial outcome. In this context, the use of dermabrasion in particular must be critically evaluated. At a meeting of the NNC in September 2018, its members agreed on a consensus-based position on dermabrasion, stating that the procedure frequently leads to impaired wound healing and cosmetically unfavorable or hypertrophic scarring. Moreover, dermabrasion is considered to be commonly associated with considerable repigmentation that usually occurs a number of years after the procedure. In addition, the NNC members saw no benefit in terms of melanoma prevention. In the future, physicians should therefore thoroughly caution about the potential risks and often limited cosmetic benefits of dermabrasion.

Vascular anomalies of the head and neck: a review of genetics.

PURPOSE: Vascular anomalies comprise malformations, hemangiomas, and rare tumors. The commonality among these lesions is their origin in vascular endothelia. Most occur sporadically, but occasional inheritance is observed and thus allows genetic research and insight into etiology. This review highlights those vascular anomalies in which genetic inheritance has been demonstrated. METHODS: A comprehensive literature search was performed on PubMed. Fifty-five full-length articles were reviewed. RESULTS: Five categories of vascular anomalies with patterned inheritance were identified: arteriovenous malformation (AVM), capillary malformation (CM), lymphatic malformation (LM), venous malformation (VM), and infantile hemangioma (IH). Capillary and arteriovenous malformation subtypes are associated with a RASA-1 gene mutation and show autosomal dominant inheritance. VEGFR3 mutations have been associated with generalized forms of LM and lymphedema. Mutations in TIE2/TEK genes cause inherited forms of venous malformations also with autosomal dominant inheritance. Familial clustering and atopic disease are associated with infantile hemangioma, and gene expression varies with the developmental stage of these lesions. CONCLUSION: Most vascular anomalies occur sporadically, but several genes and genetic disorders have been associated with them. Specific forms of capillary malformation appear to be most convincingly associated with genomic errors. Further research promises new insights into the development of this diverse group of disorders.

Endoscopic ultrasonography (EUS) in preoperative staging of gastric cancer--demand and reality.

UNLABELLED: Exact pretherapeutic staging is considered to be essential for decision-making in the therapeutic algorithm of gastric cancer. THE AIM OF THE STUDY was to characterize the role and value of EUS in the diagnostic and therapeutic management of gastric cancer in daily surgical practice. MATERIAL AND METHODS: Thousand one hundred thirty nine patients with primary gastric cancer from 80 hospitals of each profile of care were enrolled in this systematic clinical prospective multicenter observational study over a time period of 12 months. The characteristics of the diagnostic management, in particular, of EUS were documented. The preoperative EUS findings were compared with the T stage (T1 to T4) and the N category (N+ or N-) revealed by the histopathologic investigation of the surgical specimen. By the mean of χ² test, the impact of EUS on the therapeutic decision-making was determined. RESULTS: Pretherapeutic EUS was only performed in 27.4% (n=312) of all patients. Overall, the diagnostic accuracy for the T stage was 42.6% in average. The subgroup analysis showed the following results: T1, 31.5%; T2, 42.6%; T3, 65.2%; T4, 17.6%. The correct predictive value of the N category was 71.3% reaching a sensitivity of 69.7% and a specificity of 73.3%. Overstaging was observed in 45.8%, understaging in only 10.8%. Additional diagnostic information by EUS was only provided in 4.7% of subjects. CONCLUSIONS: The present study indicates the variability, limited reliability and only moderate acceptance of EUS in diagnosing gastric cancer in daily practice. In particular, the prediction of the T stage does not reach the data reported in the literature, which were mostly achieved in specific EUS studies.

Current treatment of parotid hemangiomas.

OBJECTIVES/HYPOTHESIS: Parotid hemangiomas are the most common salivary gland tumors in children. Their treatment has posed a challenge because of the lesions' expansive growth, resistance to treatment, and relationship with the facial nerve. Various treatment modalities have been attempted, and promising results have been achieved with surgical resection alone or in conjunction with endovascular sclerotherapy. Recently, bleomycin and oral propranolol have been introduced, and the results thus far are promising. Here we elucidate the treatment options and propose a treatment algorithm for parotid hemangiomas. STUDY DESIGN: Retrospective chart review. METHODS: We conducted a retrospective chart review of patients from 2004 to 2009 with hemangiomas involving the parotid gland. We included 56 patients and relevant parameters. RESULTS: Seventy percent of patients were female. The female-to-male ratio was 2.3 to 1. Thirty-nine percent had unilateral parotid hemangiomas, 12.5% had cutaneous segmental hemangiomas. All 22 patients who underwent systemic steroid therapy responded initially, but 68% of these rebounded after cessation of therapy. Sixteen patients (29%) underwent surgery with excellent results (facial symmetry, restoration of contour, preserved facial nerve function). Seven (44%) patients received sclerotherapy 24 to 48 hours before surgery, and five (8%) received endovascular sclerotherapy alone. Ten patients were treated medically with oral propranolol. Eight of 10 had significant shrinkage of the lesion within the first month of treatment. There were no reported side effects. CONCLUSIONS: Multiple treatment regimens have been used to successfully treat parotid hemangiomas. Although propranolol is a recent addition, it seems most promising. Further evaluation is warranted.

Incurable stenosing colorectal carcinoma: endoscopic stent implantation or palliative surgery?

BACKGROUND: Palliative surgery for the treatment of incurable obstructive colorectal carcinoma is associated with a considerable perioperative morbidity and mortality but no substantial improvement of the prognosis. The aim of the present study was to study the effectiveness of colorectal stenting compared with palliative surgery in incurable obstructive colorectal carcinoma. PATIENTS AND METHODS: From April 1999 to April 2005, data of consecutive patients with incurable stenosing colorectal carcinoma, either treated with stent implantation or palliative surgical intervention, were prospectively recorded with respect to age, sex, tumor location (including metastases), ASA-score, peri-interventional morbidity, mortality, rates of complications, and re-interventions as well as survival. RESULTS: Of 40 patients, 38 (95%) were successfully treated with a stent. Two patients (5%) underwent surgical intervention after stent dislocation. In contrast, 38 patients primarily underwent palliative surgical intervention. Stent patients were significantly older (P=0.020), had a higher ASA-score (P=0.012), and had more frequently distant metastases (P=0.011). After successful stent implantation, no early complications were observed, but late complications occurred in 11 subjects (29%). Following palliative surgical intervention, postoperative complications occurred in 12 individuals (32%) . Postoperative mortality was 5% in the surgery group, whereas no patient died following stent implantation. There was no significant differences in the survival of both groups (9.9 vs. 7.8 months, respectively; log rank: 0.506). CONCLUSIONS: Palliative treatment of incurable obstructive colorectal carcinoma using stents is an effective and suitable alternative to palliative surgery with no negative impact on the survival but less peri-interventional morbidity and mortality as well as comparable overall morbidity.

Comparison of the ovine and porcine animal models for biocompatibility testing of vascular prostheses.

OBJECTIVE: Evaluation of the pig and sheep models for biocompatibility investigations of vascular prostheses (VP). DESIGN: Comparative analysis of animal experimental investigations involving two different animal models. MATERIALS AND METHODS: Commercially available polyester vascular prostheses (PET-VP) were implanted into two different animal models (infrarenal porcine aorta and ovine carotid artery). The costs, surgical handling, patency rate, and healing on the basis of macroscopic, microscopic, and immunohistochemical criteria were analyzed over a period of 3 months. RESULTS: Handling and operating times (63 +/- 10 versus 76 +/- 16 min; P = 0.125) did not differ significantly. The cost of the two animal models was comparable. Integration of the VP was complete in the sheep model, but varied in the pig model (two complete, four incomplete). Complete endothelialization of all VPs was observed in the pig, which contrasted with the sheep with complete (circular) endothelialization only in the region of the anastomosis. The thickness of neointima in the region of the anastomosis differed insignificantly; immunohistochemically, only periprosthetic Ki67 was significantly reduced (28.7 +/- 9.9 versus 6 +/- 0.9%; P = 0.002) in the sheep. CONCLUSIONS: In the porcine model, extremely good endothelialization of the VP was observed, with formation of a rapid neointimal hyperplasia. The ovine model was characterized by the fact that postoperative follow-up investigations were easy to perform. Complete endothelialization was not observed.

The significance of Meckel's diverticulum in appendicitis--a retrospective analysis of 233 cases.

Conflicting reports are found in the literature concerning whether to remove an incidentally discovered Meckel's diverticulum (MD). Between 1.1.1974 and 31.12.2000, at a single center, the perioperative data associated with appendectomy (AE) were recorded consecutively and analyzed retrospectively. All patients in whom an MD was discovered during an AE were included in the study. The clinical presentation, postoperative course, and follow-up in all MDs left in place were analyzed. During the course of 7927 AE, 233 MD (2.9%) were detected. Of these 80.7% (n = 188) were removed and 19.3% (n = 45) were left untouched. In 9% (n = 21) of all detected diverticula pathological changes were found. Ectopic tissue was seen in 12.2% (n = 23) of the MDs removed. The postoperative complication rates did not differ significantly between patients in whom the MD was removed (9.5%; n = 18) and those in whom it was not (17.7%; n = 8); in the latter group the appendicitis was of the more acute type (gangrenous or perforated) (24.4% vs. 4.3%). In 18 patients (40.0%) with non-removed MDs, a follow-up period of 14.1 5.8 years was achieved. Complications associated with a non-removed MD were not observed. If during the course of an AE a MD is detected, the present data, as well as those in the literature, suggest that an individualized approach should be taken. Meckel's diverticulum with obvious pathology should always be removed. In cases of gangrenous or perforated appendicitis, an incidentally discovered MD should be left in place, whereas in an only mildly inflamed appendix it should be removed.

Characteristics of titanium-coated polyester prostheses in the animal model.

Commercially available polyester vascular prostheses (n = 6) in the control group (CG) and titanium-coated vascular prostheses (TP; n = 7) were interposed within the infrarenal aorta of pigs. The respective healing characteristics and patency rates were compared after 3 months. For evaluation purposes, macroscopic, histological, and immunohistochemical criteria were applied. The macroscopic evaluation revealed complete healing of the TP in comparison with the CG. Extraluminal inspection revealed prominent firm cicatricial tissue in the prosthesis bed of the TP group. All TP were occluded. In the CG, occlusion of the prostheses occurred in n = 1 (16 %). On average, neointimal hyperplasia (NIH) in the proximal part of the anastomosis was not significantly different to the CG. The extraluminal proliferation index (Ki67) was reduced in the TP group (p = 0.002). The immunohistochemical analysis of intraluminal changes revealed no significant differences between CG and TP. All of the titanium-coated polyester vascular prostheses were found to be occluded. The additional coating of polyester prostheses with titanium would not appear to be of any particular benefit.

Ninety-four appendectomies for suspected acute appendicitis during pregnancy.

Acute appendicitis during pregnancy is a rare event, and large numbers of cases reported in the literature stem entirely from data stored in national registers. Between 1974 and 2000 relevant perioperative data on the treatment of appendicitis were collected consecutively and analyzed retrospectively. Surgical and obstetric data relating to the medical history, the clinical, intraoperative, and histologic findings, and the course of the pregnancy were recorded. Altogether, 9793 appendectomies were performed, 94 of which were in pregnant women (24.5% during the first trimester, 51% during the second trimester, and 24.5% during the third trimester). This represents 0.2% of the 46,960 deliveries during the period under observation. Fifty percent of the case histories during the second trimester were atypical. The overall perforation rate was 14.9%; it was 8.7%, 12.5%, and 26.1% during the three trimesters, respectively. Maternal mortality was 0%; the combined miscarriage/abortion rate was 8.5% (n = 8); and infant mortality was 3.2% (n = 3). The postoperative spontaneous abortion rate was 13.0% and the additional therapeutic/requested abortion rate 21.7% during the first trimester. In view of the elevated postoperative abortion rate and the facility of the clinical diagnosis during the first trimester, the indication for invasive diagnostic measures and surgery requires careful consideration. During the second and third trimesters the difficulty of establishing a clinical diagnosis makes it necessary to undertake exploratory surgery early.