The Fate of Implanted BioBridgetm Collagen Matrix - Findings in Histology, Scanning, and Transmission Electron Microscopy.

The technique of lymphangioplasty or capillary thread drainage was historically performed with subcutaneously implanted surgical threads. It has recently been revived by introducing a thread-like aligned nanofibrillar collagen matrix (BioBridgetm). These collagen threads consitute subcutaneous neocollectors along which guided lymphangiogenesis is said to occur secondarily. We present for the first time a tissue examination of a 10-month implanted BioBridgetm sample with surrounding tissue from a human subject by histology, scanning and transmission electron microscopy.

Proposal of a new classification system for complete mesocolic excison in right-sided colon cancer.

BACKGROUND: Although complete mesocolic excision has been performed for 10 years there remains no published prospective data. The lack of a classification which includes completeness of mesocolic tissue removal as well as plane of surgery contributes to the problem of comparing studies. The aim of the present study was to develop such a classification for right hemicolectomy. METHODS: In a prospective, non-randomized trial we collected specimens of right hemicolectomies from 38 German hospitals between February 2012 and October 2016. The degree of radicality of resection was reported. Photographs were taken of the specimens. After screening the images it became apparent that the specimens could be divided into four main groups according to the degree of missing mesocolic tissue, and three subgroups reflecting the plane of surgery. RESULTS: Of 1373 patients 1097 images were available. Grading was possible in 1077 (98.2%). Distribution was Type 0 (best) 38.6%, Type I 43.3%, Type II 8.5%, Type III (poorest) 7.8%. Surgery was considered to be in a suboptimal plane of surgery in 15.2% overall, highest in Type III (37%) and lowest in Type 0 (7.8%, p < 0.001). CONCLUSIONS: The proposed classification may be a relevant tool for the further investigation of CME for right colon cancer because it allows us to differentiate the aspects of lymphadenectomy and the preservation of the integrity of the mesocolon.

[Vascular anomaly in the midcheek region of an infant--review of the diagnostic procedure]. / Gefäßanomalie in der Wangenregion eines Säuglings - Diagnostischer Prozess anhand einer Kasuistik.

Clinical history, physical examination, evolution and imaging findings (Colour Doppler sonography, MRI if available) are of pivotal importance in the diagnostic pathway of an infantile vascular anomaly. Histopathology with specific stains and markers is contributive in difficult cases. Differentiation between vascular tumors (hemangioma) and vascular malformations is now well known and integrated into the ISSVA classification. We report here a 6-months-old boy, who presented with a localized cutaneous and expansive vascular birthmark in the left cheek and developed bleedings at the age of 18 months. Diagnostic features of a hemangioma were not evident, and the final diagnosis of a venous malformation was confirmed by histopathology.

[Sarcoma of the hand and wrist]. / Sarkome an Hand und Handgelenk.

Sarcomas of the hand and wrist are rare malignancies, which should be referred to high-volume comprehensive cancer centres providing multidisciplinary treatment options. The tumour board should propose patient-oriented oncological pathways as well as sophisticated hand and plastic reconstructive procedures. In Addition, isolated limb perfusion with TNF-alpha and melphalan is likely to lead to preoperative tumour shrinkage allowing for R0 resection in sano. Our clinical results in long-term survivors demonstrate reduced amputation rates and salvage of basic hand function when a risk-adapted treatment rationale is applied.

EPHB4 tyrosine-kinase receptor expression and biological significance in soft tissue sarcoma.

Soft tissue sarcomas (STS) are heterogeneous malignant tumors of mesenchymal origin. Due to low incidence and high number of different histological subtypes, their pathogenesis and thus potential targets for their therapy remain barely investigated. Several studies revealed significant higher EPHB4 expression in malignancies such as prostate and colorectal cancer showing survival advantages for these tumor cells. Therefore we studied the expression of EPHB4 in a total of 46 clinical human specimens of different STS and human fibroblasts. EPHB4 mRNA and protein expression were significantly increased in synovial sarcoma. After targeting EPHB4 in fibrosarcoma, synovial sarcoma, liposarcoma and MFH sarcoma cell lines by siRNA or by inhibition of autophosphorylation using the specific EPHB4 kinase inhibitor NVP-BHG712 a decreased proliferation rate/vitality of synovial- and fibrosarcoma cells was observed. Silencing of EPHB4 significantly reduced the transmigration of synovial sarcoma cells towards fibroblasts and endothelial cells. In addition, we assessed the anti-metastatic effect of EPHB4 inhibition in vivo by intraperitoneal administration of the EPHB4 inhibitor in an appropriate sarcoma lung metastasis xenograft model. As result 43% of NVP-BHG712 treated mice (n = 3/7) developed pulmonary metastases whereas all control mice (n = 5) revealed lung metastases. The residual 57% of mice (n = 4/7) showed only small local tumor cell spots. Size measurements of the Vimentin positive area explained significant decrease in lung metastasis formation (p < 0.05) after EPHB4 kinase inhibition. In summary, these data provide first evidence of the importance of EPHB4 in the tumorigenesis of synovial sarcoma and present EPHB4 as a potential target in the therapy of this malignancy.

[Complete Mesocolic Excision for Right-Sided Colon Cancer - The Role of Central Lymph Nodes]. / Die komplette mesokolische Exzision beim rechtsseitigen Kolonkarzinom - welche Rolle spielen die zentralen Lymphknoten?

BACKGROUND: Complete mesocolic excision (CME) and central vascular ligation (CVL) for right-sided colon cancer may be superior to standard hemicolectomy in terms of oncological results. This hypothesis is currently being investigated in a large multicentre trial conducted by the authors of this paper (Resektatstudie). Because CVL in right-sided hemicolectomy is technically rather demanding the incidence of central node involvement is of special interest. Therefore, during the single centre pilot phase of our multicentre trial we have analysed the incidence of central lymph node metastasis in CME specimens. PATIENTS: In 51 patients with right-sided colon adenocarcinoma (cT1-3, cM0) an open CME with CVL was performed. In the fresh specimen the central four centimetres of the ileocolic vessels that would have been presumably left in place during a standard hemicolectomy were marked with a suture. The lymph nodes in this segment were separately analysed. RESULTS: In the CME specimen the mean lymph node count was 52.6 (range: 27-171). 35.0 % (range: 13.1-65.6 %) of the nodes were located in the central 4 cm segment. The proportion of patients with positive nodes was 25.5 % (13/51). Of all nodes 1.97 % (53/2686) were metastatic. In 3/51 (5.8 %) patients the central nodes were involved. In one patient the central nodes were the only metastatic site. UICC stage was influenced in two of the three patients who had central involvement (stage migration: UICC IIB to IIIB, UICC IIIB to IIIC). CONCLUSION: CME with CVL in right-sided colon adenocarcinoma increases the probability of complete removal of the local lymph node drainage and thus local metastatic lymph nodes. Considering this result an improvement of long-term survival by the CME procedure seems conceivable but needs to be confirmed by the current multicentre trial.

[Relapse of a parosteal osteochondromateous proliferation (Nora's lesion) of the distal thumb]. / Rezidiv einer bizarren paraossären osteochondromatösen Proliferation (Nora-Läsion) des Daumenendgliedes.

We report the case of a 29-year-old female patient with a relapse of a Nora lesion in an atypic location. The literature for this rare benign lesion is reviewed and etiology, diagnostics and therapy are discussed.

[Soft tissue sarcoma : resection and plastic reconstruction]. / Bösartige Weichgewebsgeschwülste : Resektion und plastische Wiederherstellung.

Adequate surgical removal of soft tissue sarcomas of the trunk and extremities employing safety margins of 1-2 cm is the accepted basis of multidisciplinary treatment. In cases of high risk tumors (grades G2/G3) the tumor board decision should include radiochemotherapy under study conditions. Difficult peripheral locations or perioperative complications require additional techniques, such as hyperthermic perfusion with tumor necrosis factor alpha or the complete spectrum of reconstructive plastic procedures. Patients with soft tissue sarcoma of the trunk or of the extremities should always be referred to high volume centers.

[Soft tissue sarcoma. Resection and plastic reconstruction]. / Bösartige Weichgewebsgeschwülste. Resektion und plastische Wiederherstellung.

Adequate surgical removal of soft tissue sarcomas of the trunk and extremities employing safety margins of 1-2 cm is the accepted basis of multidisciplinary treatment. In cases of high risk tumors (grades G2/G3) the tumor board decision should include radiochemotherapy under study conditions. Difficult peripheral locations or perioperative complications require additional techniques, such as hyperthermic perfusion with tumor necrosis factor alpha or the complete spectrum of reconstructive plastic procedures. Patients with soft tissue sarcoma of the trunk or of the extremities should always be referred to high volume centers.

[Surgical margins in soft tissue sarcoma of the extremities]. / Resektionsgrenzen bei Weichgewebssarkomen der Extremitäten.

Negative surgical margins (R0 resection) play a key role in the prevention of local recurrences of soft tissue sarcoma of the extremities in the multimodal therapy concept. The prognostic relevance for long-term survival is still under dispute. Despite the fact that numerous recommendations and guidelines have existed for over 100 years, strong evidence-based data from prospective randomized studies are still not available today. These studies should include parameters like tumor localization, subtype and biological aggressiveness. Recommendations as to surgical therapy diverge considerably. They range from amputation and compartment resection to centimetre and millimetre surgical margins. The present article analyses currently available data and definitions and discusses the impact on functional restriction, lymph drainage, local recurrence and the perioperative irradiation field. In the absence of surgical standards, it is doubtful whether existing studies and multicenter trials currently underway are valid. Close co-operation between surgeon and pathologist is imperative to further substantiate the significance of histological examinations and resection margins.

Efficacy of topically delivered moxifloxacin against wound infection by Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus.

Wound infection is a common risk for patients with chronic nonhealing wounds, causing high morbidity and mortality. Currently, systemic antibiotic treatment is the therapy of choice, despite often leading to several side effects and the risk of an insufficient tissue penetration due to impaired blood supply. If systemically delivered, moxifloxacin penetrates well into inflammatory blister fluid, muscle, and subcutaneous adipose tissues and might therefore be a possible option for the topical treatment of skin and infected skin wounds. In this study, topical application of moxifloxacin was investigated in comparison to mupirocin, linezolid, and gentamicin using a porcine wound infection and a rat burn infection model. Both animal models were performed either by an inoculation with methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. Wound fluid, tissue, and blood samples were taken, and bacterial counts as well as the moxifloxacin concentration were determined for a 14-day follow-up. A histological comparison of the rat burn wound tissues was performed. Both strains were susceptible to moxifloxacin and gentamicin, whereas mupirocin and linezolid were effective only against MRSA. All antibiotics showed efficient reduction of bacterial counts, and except with MRSA, infected burn wounds reached bacterial counts below 10(5) CFU/g tissue. Additionally, moxifloxacin was observed to promote wound healing as determined by histologic analysis, while no induction of bacterial resistance was observed during the treatment period. The use of topical antibiotics for the treatment of infected wounds confers many benefits. Moxifloxacin is therefore an ideal candidate, due to its broad antibacterial spectrum, its high efficiency, and its potential to promote wound healing.

Bisphosphonate-related osteonecrosis of the maxilla and sinusitis maxillaris.

Bisphosphonates (BPs) are widely used as bone-stabilizers, but side effects of BP therapy include bisphosphonate-related osteonecrosis of the jaw (BRONJ), which is resistant to therapy. The aim of this study was to evaluate the outcome of maxillary BRONJ involving sinusitis maxillaris. 21 patients presenting with maxillary BRONJ, from 2005 to 2008, were included in the study. In 18 cases BP had been administered for carcinoma and in 3 cases for osteoporosis, with an average exposure time of 47.4 months. 12 patients spontaneously developed BRONJ. The 10 patients diagnosed with stage III BRONJ presented with concomitant sinusitis maxillaris. Despite treatment, there were six recurrences of BRONJ, four of them with additional sinusitis maxillaris. Whether BRONJ occurred spontaneously or after extraction there was no difference in the outcome. Patients with advanced maxillary BRONJ often suffer from sinusitis maxillaris, both of which are frequently resistant to therapy.

[Aneurysm of the radial artery in a patient with marfan syndrome]. / Aneurysma der Arteria radialis bei Marfan-Syndrom.

We present a 52-year-old male patient suffering from Marfan syndrome who developed an aneurysm of the distal radial artery. The histology showed the typical marfanoid structure of a thrombosed aneurysm. As far as we know, this is the first description of a hand aneurysm in a patient with Marfan syndrome.

A novel human skin chamber model to study wound infection ex vivo.

Wound infections with multi-drug resistant bacteria increase morbidity and mortality and have considerable socioeconomic impact. They can lead to impaired wound healing, resulting in rising treatment costs. The aim of this study was to investigate an ex vivo human wound infection model. Human full-thickness skin from the operating room (OR) was placed into the Bo-Drum and cultivated for 7 days in an air-liquid interphase. On day 8, the skin was inoculated with either (1) Pseudomonas aeruginosa, (2) Staphylococcus aureus (10(5) CFU, n = 3) or (3) carrier control. 1, 3 and 7 days after inoculation colony forming units in the tissue/media were determined and cytokine expression was quantified. A reliable and reproducible wound infection could be established for 7 days. At this time point, 1.8 x 10(8) CFU/g tissue of P. aeruginosa and 2 x 10(7) CFU/g tissue of S. aureus were detected. Immunohistochemical analysis demonstrated bacterial infection and epidermolysis in infected skin. RT-PCR analysis exhibited a significant induction of proinflammatory cytokines after infection. The BO-drum is a robust, easy-to-use, sterilizable and reusable ex vivo full-skin culture system. For investigation of wound infection, treatment and healing, the BO-drum presents a convenient model and may help to standardize wound research.

[Functional reconstruction of the superficial posterior compartment of the leg after tumour ablation in an infant]. / Funktionelle Rekonstruktion des M. triceps surae nach onkologiegerechter Tumorresektion beim Kleinkind.

A 33-month-old female child was diagnosed with a papillary intralymphatic angioendothelioma, a rare type of low-grade angiosarcoma, on the dorsal lower leg. The soleus and gastrocnemius muscle including the Achilles tendon and the subcutis and cutis were resected. The defect was functionally reconstructed by a neurovascular musculocutaneous latissimus dorsi free-flap transfer.

In vivo analysis of tissue response to plasma-treated collagen-I-coated titanium alloys.

PURPOSE: The aim of this study was to evaluate the in vivo tissue response to low-pressure plasma-pretreated collagen-I-coated titanium implant in a middle-term mouse model. METHODS: Plasma-treated collagen-coated titanium implants were transplanted into the dorsal skinfold chambers of BALB/c mice. Untreated, regular titanium implant material served as control. The neovascularization (functional vessel density) of the implant border zone and of the surrounding muscle tissue was analysed by intravital fluorescence microscopy. Additional histological analysis was performed to observe the inflammatory reaction. RESULTS: Statistical analysis revealed that the vessel density in the border zone of the implants was significantly enhanced in the plasma-treated collagen-I-coated group compared to controls. The histological examination of the two groups confirmed that the inflammatory response to the collagen-coated titanium implants was reduced compared to controls. CONCLUSION: Plasma pretreatment and collagen I coating of titanium implant material leads to an enhanced tissue vascularization and a reduced inflammatory response.

Antitumor activity of the HER2 dimerization inhibitor pertuzumab on human colon cancer cells in vitro and in vivo.

PURPOSE: The monoclonal antibody pertuzumab represents the first HER2 dimerization inhibitor with unknown activity in colon cancer treatment. We examined the antitumor activity of pertuzumab as a single agent or in combination with erlotinib or irinotecan in human colon cancer cells in vitro and in vivo. METHODS: Colon cancer cell lines were tested for HER1/HER2 expression by western blot analysis. The effect of pertuzumab on cell cycle distribution was analyzed by FACS. Nude mice bearing xenograft tumors were treated with pertuzumab alone, or in combination either with irinotecan or with erlotinib. Tumor volume was measured repeatedly. Tumor histology was analyzed for necrosis. RESULTS: Six of nine cell lines showed high expression of HER1/HER2. Pertuzumab inhibited cell cycle progression in various cell lines. Pertuzumab showed minor antitumor activity in xenograft tumors, but significantly inhibited tumor growth when combined with erlotinib (P < 0.001). Combination of pertuzumab with irinotecan had no additional effect on growth of additional tumors. Pertuzumab treated DLD-1 xenograft tumors did not show enhanced necrosis, which, however, was found in HCT116 derived xenografts. CONCLUSIONS: Pertuzumab has some antitumor activity on human colon cancer cells in vitro and in vivo, in particular when combined with erlotinib. In vivo, pertuzumab combination treatment was not superior to irinotecan monotherapy. These data warrant further investigation of simultaneous HER1/EGFR TKI inhibition and HER1/HER2 dimerization inhibition for colorectal cancer therapy.

Lymph node metastases in soft tissue sarcomas: a single center analysis of 1,597 patients.

PURPOSE: The aim of this study was to examine the clinical course of patients with the rare finding of regional lymph node metastasis (RLNM) from soft tissue sarcoma. MATERIALS AND METHODS: Data from 28 out of 1,597 consecutive soft tissue sarcoma patients with RLNM were from the patients' charts and interviewing patients and general practitioners. Survival, including possible influencing factors, was statistically calculated. RESULTS: RLNM was seen in 21.4% for epithelioid sarcoma and 17.6% for clear cell sarcoma. All other entities presented RLNM rates below 10%. At follow-up after an average of 9.6 years, only three patients were alive with no evidence of disease. Survival was independent from surgical resection status of the primary tumor and the RLNM as well as from adjuvant radiation and chemotherapy. Tumor entity as well as the length of the time period from primary to RLNM affect survival. CONCLUSIONS: Surgical treatment as well as radiation and chemotherapy may improve survival in selected cases but probably have their value much more in terms of local disease control and improvement life quality of patients who probably already suffer from an aggressive systemic disease at time of nodal involvement.