Optimization of the preoperative requirements of blood units for the surgical treatment of extra-abdominal soft tissue sarcoma: the TRANSAR score.

BACKGROUND AND OBJECTIVES: Excessive preoperative blood orders frequently occur during the preoperative planning of resections of sarcomas. We aimed to develop a prediction score model that would be able to identify a patient cohort in which the cross-matching could be safely evaded. PATIENTS AND METHODS: We retrospectively analyzed data of 309 consecutive patients with extra-abdominal soft tissue sarcomas treated between September 2012 and December 2014. Scorecard scores for variables were calculated and summarized to a total score that can be used for risk stratification. The score was used in a logistic regression model. Results of the optimized model were described as a receiver operating characteristic curve. RESULTS: Preoperative units of red blood cells were requested for 206 (66.7%) patients, of which only 31 (10%) received them. Five parameters were identified with high predictive power. In the visualized barplot, there was an increased risk of blood transfusion with a higher score of TRANSAR. CONCLUSION: A TRANSAR score is a new tool that can predict the probability of transfusion for patients with sarcoma. This may reduce the number of preoperative cross-matching and blood product ordering and associated costs without compromising patient care.

Efficacy of hyperthermic isolated limb perfusion in the treatment of locally recurrent high-grade soft tissue sarcoma of the extremities.

BACKGROUND: This novel study compared the use of tumor necrosis factor (TNF)-alpha and melphalan-based isolated limb perfusion (TM-ILP) to the standard treatment of locally recurrent soft tissue extremity sarcoma. The aim was to assess whether TM-ILP positively influences the recurrence-free survival of locally recurrent high-grade soft tissue sarcoma (STS) of the extremities. METHODS: We retrospectively analyzed our clinical database for patients with STS. Variables were analyzed using chi-square test or Mann-Whitney rank-sum test. Furthermore, Kaplan-Meier survival plots were calculated and a proportional hazard regression model was developed. RESULTS: Out of 448 patients with extraabdominal STS treated between August 2012 and December 2015, 52 cases involving 47 patients had locally recurrent STS. Twenty-eight of these patients were treated with TM-ILP prior to surgical resection (TM-ILP-group), and 24 were treated with standard therapy (without TM-ILP). The 3-year recurrence-free survival for the TM-ILP-group was estimated at 75% (95% confidence interval (CI), 71.5-78.5). Local recurrence-free survival in the standard group was significantly lower (LRFS: 43.4%, 95% CI 38.7-48.1, p = 0.026). Multivariable analysis revealed resection with negative margins, lower number of previous recurrences, and TM-ILP as positive predictors for recurrence-free survival. CONCLUSIONS: TM-ILP and consecutive resection of residual tumor with negative resection margins significantly improves local recurrence-free survival for patients with a first local recurrence of high-grade STS in the extremities.

Somatic Leiomyosarcoma of the Soft Tissues: A Single-Institutional Analysis of Factors Predictive of Survival in 164 Patients.

BACKGROUND: Somatic leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma entity with a high metastatic potential. The purpose of this study was to identify prognostic indicators of survival in patients with somatic LMS of the soft tissues. METHODS: We retrospectively assessed the relationship between local recurrence-free survival (LRFS), disease-specific survival (DSS), overall survival (OS) and potential prognostic factors in 164 patients who were suitable for surgical treatment in curative intent. Patients with soft tissue LMS of the extremities, the truncal wall and the head and neck area were included. The median follow-up time was 4.9 years. RESULTS: In the entire cohort, the 5-year estimate of the DSS, OS and LRFS rate were 74.5% (95% confidence interval [CI] 65.0-81.8), 70.6% (95% CI: 60.9-78.3) and 63.4% (95% CI 53.4-71.9), respectively. Thirty-eight patients (23.2%) developed distant metastases with a median survival time of 1.5 years after diagnosis of metastasis. Surgical margins attained at the initial oncologic resection and eventual re-excisions did not influence DSS, OS and LRFS significantly. Within the R0 subgroup, close and wide negative margins led to similar outcomes. High histologic grade (P < 0.001), size >5 cm (P = 0.002) and subfascial localisation (P = 0.002) were associated with significantly diminished DSS in univariate analysis. In multivariate analysis, only histologic grade was found to be an independent prognostic factor of DSS. CONCLUSIONS: The data from this study could not determine a prognostic significance of surgical margins suggesting that tumour characteristics other than margin status are important. Tumour biology reflected by the histologic grade dictates the final outcome.

Imagine a world without cancer.

BACKGROUND: Since the "War on Cancer" was declared in 1971, the United States alone has expended some $300 billion on research, with a heavy focus on the role of genomics in anticancer therapy. Voluminous data have been collected and analyzed. However, in hindsight, any achievements made have not been realized in clinical practice in terms of overall survival or quality of life extended. This might be justified because cancer is not one disease but a conglomeration of multiple diseases, with widespread heterogeneity even within a single tumor type. DISCUSSION: Only a few types of cancer have been described that are associated with one major signaling pathway. This enabled the initial successful deployment of targeted therapy for such cancers. However, soon after this targeted approach was initiated, it was subverted as cancer cells learned and reacted to the initial treatments, oftentimes rendering the treatment less effective or even completely ineffective. During the past 30 plus years, the cancer classification used had, as its primary aim, the facilitation of communication and the exchange of information amongst those caring for cancer patients with the end goal of establishing a standardized approach for the diagnosis and treatment of cancers. This approach should be modified based on the recent research to affect a change from a service-based to an outcome-based approach. The vision of achieving long-term control and/or eradicating or curing cancer is far from being realized, but not impossible. In order to meet the challenges in getting there, any newly proposed anticancer strategy must integrate a personalized treatment outcome approach. This concept is predicated on tumor- and patient-associated variables, combined with an individualized response assessment strategy for therapy modification as suggested by the patient's own results. As combined strategies may be outcome-orientated and integrate tumor-, patient- as well as cancer-preventive variables, this approach is likely to result in an optimized anticancer strategy. SUMMARY: Herein, we introduce such an anticancer strategy for all cancer patients, experts, and organizations: Imagine a World without Cancer.

Classic Type of Epithelioid Sarcoma of the Distal Upper Extremity: Clinical and Oncological Characteristics.

BACKGROUND: The classic type of epithelioid sarcoma (ES) is a rare, aggressive soft tissue neoplasm that most commonly affects the distal upper extremities of young patients. This study aimed to assess clinical features and provide a long-term report of the oncological outcome. METHODS: We retrospectively analyzed our clinical database for patients with ES of the distal upper extremities. RESULTS: Twenty-three patients with ES of the distal upper extremity were treated surgically between January 1990 and August 2018. ES affected most commonly the palmar side of young patients. The most common site affected by a sarcoma was the wrist in 47.8% of cases, followed by metacarpals and fingers with 34.8% and 17.4%, respectively. Most of the patients were treated according to the protocols of interdisciplinary tumor boards with multimodal therapy. A local recurrence was observed in 7 patients (30.4%). The 5 - and 10-year recurrence-free survival was 80.4% (95% confidence interval [CI]: 68.6-76.8) and 60.9% (95% CI: 53.5-68.3), respectively. The 5- and 10-years disease-specific survival was 89.9% (95% CI: 87-92.8) and 61.9% (95% CI: 56.5-67.3), respectively. Five patients (21.7%) had metastasis in regional lymph nodes. CONCLUSION: The classic type of ES represents a group of high-grade sarcomas, which affect the dominantly distal upper extremity. Specific clinical, diagnostic, and oncological characteristics make it difficult to diagnose and therapy. Wide tumor resection as a part of multimodal therapy remains a more viable and common treatment option for patients with ES on distal extremities. High rates of lymph node metastasis are typical for ES.

Outcome of Surgery as Part of Palliative Care of Patients with Symptomatic Advanced or Metastatic Extra-Abdominal High-Grade Soft Tissue Sarcoma.

Background: The modern multimodal treatment of malignant tumors has increased disease-specific survival and decreased the burden of tumor-associated complications. The main focus of palliative surgery is not based primarily on quantitative success parameters of tumor response but is instead mainly on the question of quality of life. Aim: The current study was conducted to analyze the clinical and oncological outcomes of palliative patients with soft tissue sarcoma. Design: Of 309 patients with extra-abdominal high-grade soft tissue sarcoma treated between August 2012 and December 2014, our retrospective analysis revealed 33 palliative patients for this study. All patients were evaluated and managed by a multidisciplinary team with expertise and experience in sarcoma treatment. The survival analysis was made using the Kaplan-Meier method. Results: The main sarcoma symptoms were pain (27.3%) and ulcerated tumors or shortly before ulceration (24.2%). Thirteen patients (39.4%) were operated on with negative margins, 15 (45.5%) with positive margins, 2 with tumor debulking (6.1%), and 3 patients (9.1%) were treated only with palliative hyperthermic isolated limb perfusion. Ten pedicle flaps were performed after sarcoma resection. The median operation time was 85 minutes (range, 37-216 minutes). The median hospitalization stay was 9.5 days (range, 3-27 days). No patients died during hospitalization. Twelve-month disease-free survival was 48.5% (95% confidence interval: 45.4-51.6). Conclusions: Palliative surgery of metastatic or advanced soft tissue sarcoma can improve the wound care and quality of life. Closed noninfected wounds enable further treatment options, such as chemotherapy, immunotherapy, and radiotherapy. This surgery should be considered during the discussion on interdisciplinary tumor boards.

"The Baltic Sea Germ": A Case Report of Necrotizing Fasciitis following Vibrio vulnificus Infection.

Reported is an 80-year-old patient with septic shock from necrotizing fasciitis secondary to a Vibrio vulnificus (Vv) infection. The patient reports having been swimming in the Baltic Sea after a minor trauma to the left leg. Emergency superficial necrosectomy followed by intensive medical therapy was performed. Antibiotic therapy was initiated with a third-generation cephalosporin and a tetracycline. Vv was detected in the intraoperative microbiological smears. Instead of a leg amputation and a flap, due to the patient's age, a split skin covering to consolidate the wound was performed. Vv is a gram-negative rod bacterium of the genus Vibrio. Vv occurs in warm, low-salinity seawater (brackish water). In Germany, Vv occurs primarily in river mouths of the low-salinity Baltic Sea. Infections by Vv can occur through open wounds or by eating raw infected seafood, especially oysters. Infection via wounds often take a fulminant lethal course. Patients with chronic diseases, weakened immune system, and open wounds are particularly at risk. Infections with Vv are rare, but occur worldwide. Global warming is expected to spread Vv as water temperature increases and the dilution effect of sea level rise further decreases ocean salinity, and natural disasters promote the spread of Vv.

Oncolytic designer host defense peptide suppresses growth of human liposarcoma.

Sarcomas display a rare and heterogeneous group of tumors. Treatment options are limited. Host defense peptides (HDPs), effector molecules of the innate immune system, might provide a more effective treatment option. The aim of our study was to analyze the oncolytic activity and mode of action of a designer HDP. In vitro, the human liposarcoma cell line SW-872 and primary human fibroblasts as a control were exposed to [D]-K(3)H(3)L(9), a 15-mer D,L-amino acid designer peptide. Cell growth (MTT assay), proliferation (BrdU assay) and genotoxicity (TUNEL assay) were analyzed. The mode of action was examined via fluorescence-activated cell sorter (FACS) analysis and confocal laser scanning microscopy. In vivo, [D]-K(3)H(3)L(9) (n = 7) was administered intratumorally in a SW-872 xenograft mouse model (Foxn1nu/nu). Phosphate buffered saline served as a control (n = 5). After 4 weeks, tumor sections were histologically analyzed with respect to proliferation, cytotoxicity, vessel density and signs of apoptosis and necrosis, respectively. In vitro, [D]-K(3)H(3)L(9) highly significantly (p < 0.01) inhibited cell metabolism and proliferation. TUNEL assay revealed corresponding genotoxicity. FACS analysis suggested induction of necrosis as a cause of cell death. The mean tumor volume of the control group exponentially increased sevenfold, whereas the mean tumor growth was negligible in the treatment group. Macroscopically, [D]-K(3)H(3)L(9) induced full tumor remission in 43% of treated animals and partial remission in 43%. Vessel density was significantly reduced by 52%. Morphological analyses supported the hypothesis of cancer cell killing by necrosis. In summary, [D]-K(3)H(3)L(9) exerts very promising oncolytic activity on liposarcoma cells. Our study demonstrates the potential of HDPs as a novel therapeutic option in future soft tissue sarcoma therapy.

Evaluation of signal transduction pathways after transient cutaneous adenoviral gene delivery.

BACKGROUND: Adenoviral vectors have provided effective methods for in vivo gene delivery in therapeutic applications. However, these vectors can induce immune responses that may severely affect the ability of vector re-application. There is limited information about the mechanisms and signal transduction pathways involved in adenoviral recognition. For optimization of cutaneous gene therapy it is necessary to investigate molecular mechanisms of virus recognition in epidermal cells. The aim of this study was to investigate the signal transduction of the innate immunity after adenoviral DNA internalization in keratinocytes. METHODS: In vitro, keratinocytes were transfected with DNA, in the presence and absence of inhibitors for signalling molecules. In vivo, immunocompetent and athymic mice (n = 3 per group) were twice transduced with an Ad-vector. RESULTS: The results show an acute induction of type-I-interferon after in vitro transfection. Inhibition of PI3K, p38 MAPK, JNK and NFkappaB resulted in a decreased expression of type-I-interferon. In contrast to immunocompetent mice, athymic mice demonstrated a constant transgene expression and reduced inflammatory response in vivo. CONCLUSION: The results suggest an induction of the innate immunity triggered by cytoplasm localised DNA which is mediated by PI3K-, p38 MAPK-, JNK-, NFkappaB-, JAK/STAT- and ERK1/2-dependent pathways. A stable transgene expression and a reduced inflammatory response in immunodeficient mice have been observed. These results provide potential for an effective adenoviral gene delivery into immunosupressed skin.

The versatility of the pedicled vertical rectus abdominis myocutaneous flap in oncologic patients.

PURPOSE: The vertical rectus abdominis muscle (VRAM) flap is considered a safe and simple option to cover defects of the trunk and proximal thigh. Detailed long-time follow-up studies in oncologic patients including complications and donor site morbidity are rare. In this study, complications and donor site morbidity were analysed. METHODS: Data of 78 consecutive patients with oncologic disease, having received VRAM flaps, were analysed retrospectively. Patients with soft tissue sarcomas (n = 38), radiation ulcers (n = 18), carcinoma (n = 10), wound-healing difficulties after tumour resection (n = 8), breast reconstruction after ablation (n = 3) and malignant melanoma (n = 1) were included. Statistics concerning patients' satisfaction, the occurrence of wound-healing difficulties, incisional herniation, loss of abdominal wall strength in correlation to operative and (neo)adjuvant treatment and patients' history were performed. The mean follow-up time was 5.5 years. RESULTS: No complete flap loss was observed. A body mass index over 30 was positively correlated with wound-healing difficulties; radiation had no negative effect. A contralateral cutaneous pedicle could reduce the risk of lymphoedema in groin defect patients. Incisional hernia was present in 13%. Strength endurance of the abdominal wall was reduced compared to an age-matched control. Most patients were satisfied with the postoperative result. CONCLUSIONS: VRAM flaps are reliable tools for defect coverage in the oncologic patient to prevent chronic ulceration, lymphangitis or more severe complications like septic rupture of femoral vessels and hip disarticulation. Donor site morbidity is tolerable, and patients' satisfaction is high.

Tendon transfers for drop foot correction: long-term results including quality of life assessment, and dynamometric and pedobarographic measurements.

BACKGROUND: Drop foot deformity is a common problem with severe restrictions in quality of life and impairment of daily activities. A technique of posterior tibial tendon transfer through the interosseus membrane and fixation to the anterior tibial and the long peroneal tendon "Bridle procedure" (stirrup-plasty) offers a physiological alternative to surgical correction. METHODS: Data of 53 consecutive patients treated by stirrup-plasty were acquired from patient's charts; 31 were interviewed with standardized questionnaires; 20 were examined physically; 19 received pedobarography, and 8 underwent dynamometric muscle function tests. Follow-up time averaged 6.5 years. RESULTS: The mean range of motion (ROM) in the ankle joint was 8° dorsiflexion and 15° plantar flexion. Most patients achieved plantigrade foot position and the majority developed gait without orthotic devices. As expected, maximum dorsiflexion torque averaged a third of the non-operated leg, according to reduced muscle diameter and strength of the transferred muscle. Pressure distribution of the sole during gait was not relevantly altered by the tendon transfer compared to the non-operated leg. Most patients were satisfied with the operative results and reported a significant increase in quality of life. CONCLUSIONS: Fusion of the transposed posterior tibial, anterior tibial and the peroneus longus tendon prevents drop foot deformity sufficiently. The stirrup mechanism, in combination with tenodesis of the toe extensors, provides a balanced foot and avoids equinovarus and cavus deformity without immobilizing the ankle joint. Improvements in quality of life parameters justify the risk of the operative procedure for the patient.

Sterilization of heat-sensitive silicone implant material by low-pressure gas plasma.

BACKGROUND: In recent years, plasma treatment of medical devices and implant materials has gained more and more acceptance. Inactivation of microorganisms by exposure to ultraviolet (UV) radiation produced by plasma discharges and sterilization of medical implants and instruments is one possible application of this technique. The aim of this study was to evaluate the effectiveness of this sterilization technique on silicone implant material. METHODS: Bacillus atrophaeus spores (10(6) colony-forming units [CFUs]) were sprayed on the surfaces of 12 silicone implant material samples. Four plasma sets with different gas mixtures (argon [Ar], argon-oxygen [Ar:O(2)], argon-hydrogen [Ar:H(2)] and argon-nitrogen [Ar:N(2)]) were tested for their antimicrobial properties. Post-sterilization mechanical testing of the implant material was performed in order to evaluate possible plasma-induced structural damage. RESULTS: The inductively coupled low-pressure plasma technique can achieve fast and efficient sterilization of silicone implant material without adverse materials effects. All four gas mixtures led to a significant spore reduction, and no structural damage to the implant material could be observed.

Localized Angiosarcoma, Not One Disease: A Retrospective Single-Center Study on Prognosis Depending on the Primary Site and Etiology.

BACKGROUND: Angiosarcomas are rare and heterogeneous tumors with poor prognosis. The clinical subtypes are classified depending on the primary site and etiology. METHODS: We conducted a retrospective, monocentric study of 136 patients with localized AS between May 1985 and November 2018. Overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) were estimated using the Kaplan-Meier method. To identify prognostic factors, univariate and multivariate analyses were performed based on Cox regressions. RESULTS: The median age was 67 years (19-72.8 years). Primary sites were cutaneous (27.2%), breast (38.2%), and deep soft tissue (34.6%). The majority was primary angiosarcomas (55.9%) followed by postradiation (40.4%) and chronic lymphedema angiosarcomas (2.9%). Prognosis significantly differed depending on the primary site and etiology. Shortest median OS and MFS were observed in deep soft tissue angiosarcomas, whereas cutaneous angiosarcomas, angiosarcomas of the breast, and radiation-associated angiosarcomas displayed worse median LRFS. Univariate analyses showed better OS for tumor size <10 cm (p = 0.009), negative surgical margins (p = 0.021), and negative lymph node status (p = 0.007). LRFS and MFS were longer for tumor size <10 cm (p = 0.012 and p = 0.013). In multivariate analyses, age <70 years was the only independent positive prognostic factor for OS in all subgroups. For LRFS, secondary AS of the breast was a negative prognostic factor (HR: 2.35; p = 0.035). CONCLUSIONS: Different behaviors and prognoses depending on the primary site and etiology should be considered for the treatment of this heterogeneous disease. In cutaneous angiosarcomas of the head/neck and postradiation angiosarcomas of the breast, local recurrence seems to have a crucial impact on OS. Therefore, improved local therapies and local tumor staging may have to be implemented. However, in deep soft tissue angiosarcomas, distant recurrence seems to have a major influence on prognosis, which indicates a benefit of additional perioperative chemotherapy.

Diagnosis and management of primary breast sarcoma.

Primary sarcoma of the breast is an extremely rare and heterogeneous disease. The rarity of this tumour limits most studies to small retrospective case reviews and case reports and has made clinicopathological study difficult. This article reviews the current literature on the diagnosis and management of breast sarcoma. The optimal treatment of breast sarcoma involves a multidisciplinary team prior to the initiation of treatment. Patients with tumours less than 5 cm that are easily resectable should undergo complete resection to the extent required to provide negative surgical margins. Negative surgical margins are more important for local recurrence and overall survival than the extent of surgical resection. Thus, neoadjuvant chemotherapy should be considered in order to shrink the tumour and help obtain negative surgical margins. Whether chemotherapy is indicated is primarily determined by tumour size. There is evidence that tumours larger than 5 cm are associated with an elevated risk of systemic failure and a poor prognosis. After surgical resection, patients with chemosensitive tumours should undergo additional adjuvant chemotherapy to treat micrometastatic disease. Radiation therapy should be used to improve local control in cases in which the tumour is larger than 5 cm and in cases with positive surgical margins. We propose to treat the patients according to the clinical practice guidelines in use for soft tissue sarcomas and address them to a reference centre for sarcoma. The appropriate treatment of breast sarcoma requires a multidisciplinary team approach necessitating experienced sarcoma surgeons, pathologists, radiotherapists and medical oncologists. Treating rare tumours in the same place should permit us to standardise pathological data and to include patients into multicentric radiotherapy or chemotherapy protocols to improve overall survival.

Exogenous nitric oxide donation causes desensitization of arteriolar relaxing activity in vivo: an intravital analysis in mice.

BACKGROUND: The NO/cGMP pathway plays a crucial role in regulation of tissue perfusion. However, a NO-induced desensitization of cGMP-mediated relaxation has been reported in isolated tissue. To examine whether a similar phenomenon can be detected in vivo, we analyzed relaxations of microvessels in response to repeated applications of NO. MATERIALS AND METHODS: The investigations were performed by means of dynamic intravital fluorescence microscopy in the dorsal skinfold chamber of female balb/mice. First, the microvasculature was maximally preconstricted by the application of the vasoconstrictor 5-hydroxytryptamine. Subsequently, relaxation was induced by applying an NO-donator, the S-nitrosoglutathione, to the contracted vessels. Following buffer exchange, constriction and relaxation were repeated. Drugs were given topically into the chamber, directly onto the skin muscle. The response of arterioles to topical administration of vasoactive drugs was determined as the change of the diameter, and quantified using standard software. RESULTS: The relaxation of arterioles was reduced after repetitive application. The short pretreatment with NO-donor entailed a reduced relaxation of arterioles in response to following application. The absolute change in vessel diameter induced by S-nitrosoglutathione was significantly reduced from 21 µm to 16 µm after the first and the second application, respectively. However, the data also revealed a noticeable reduction of the constricting activity of 5-hydroxytryptamine during the second application, indicating a possible desensitization of the 5-hydroxytryptamine response or a humoral and/or neuronal compensatory mechanisms. CONCLUSIONS: The NO-induced cGMP-mediated relaxation of microvessels was quantified, and the phenomenon of desensitization visualized in vivo by means of dynamic fluorescence microscopy.

Evaluation of toxic side effects of clinically used skin antiseptics in vitro.

BACKGROUND: Skin antiseptics are widely used in health-care worldwide. However, there is a need to determine cytotoxicity of these medications on wounds. The aim of this study was to evaluate cytotoxic effects of five clinically used antiseptics on human skin cells. MATERIAL AND METHODS: Five clinically used skin antiseptics (Prontosan, Lavasept, Braunol, Octenisept, and Betaisodona) were tested. The minimal inhibitory concentration was determined against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli). The cytotoxic effects on primary keratinocytes, fibroblasts, and a HaCaT cell line were determined (MTT-assay and BrdU-ELISA) at a wide range of concentrations. RESULTS: The agents tested showed effective antibacterial properties (Octenisept, Lavasept, and Prontosan showed higher efficacy than Braunol and Betaisodona) and different degrees of cytotoxicity. Lavasept and Prontosan demonstrated less toxicity on primary human fibroblasts and keratinocytes, whereas Octenisept, Betaisodona, and Braunol showed a significant (P<0.05) decrease in cell viability to 0% on keratinocytes at concentrations of 4%, 7.5%, and 12.5%, and on fibroblasts at 7.5% and 10%, respectively. CONCLUSION: Due to the cytotoxic effect of some antiseptics on human skin cells, it is advised that health care professionals balance the cytotoxicity of the medication, their antiseptic properties, and the severity of colonization when selecting a wound care antiseptic. In this study, Lavasept and Prontosan showed best result regarding antibacterial efficacy and cell toxicity.

Malignant fibrous histiocytoma--pleomorphic sarcoma, NOS gene expression, histology, and clinical course. A pilot study.

PURPOSE: The new classification of malignant fibrous histiocytoma leaves only a small group of tumors without further line of differentiation, so-called pleomorphic sarcomas, not otherwise specified (NOS) as a pseudo-entity. This study focused on these tumors and analyzed the association of gene expression profiles to clinical outcome. MATERIALS AND METHODS: Ten fresh samples of pleomorphic NOS sarcomas were evaluated histopathologically and by means of microarray analysis. Analysis of expression profiles was performed by clustering methods as well as by statistical analysis of primary vs recurrent tumors, irradiated vs nonirradiated tumors, tumors of patients above and below 60 years of age, male and female, and of tumors that developed metastatic or recurrent disease during the clinical course and those that did not. RESULTS: Tumor clustering did not correlate to any histopathological or clinical finding. Detailed gene expression analysis showed a variety of genes whose upregulation (platelet-derived growth factor receptor alpha polypeptide, solute carrier family 39 member 14, solute carrier family 2 member 3, pleiotrophin, trophinin, pleckstrin and Sec7 domain containing 3, enolase 2, biglycan, SH3 and cysteine-rich domain, matrix metalloproteinases 16) and whose downregulation (tissue inhibitor of metalloproteinase 4, hairy/enhancer of split related with YRPW motif 2, protein tyrosine phosphatase receptor-type Z polypeptide 1, SH3 domain GRB2-like 2, microtubule-associated protein 7, potassium voltage-gated channel shaker-related subfamily member 1, RUN and FYVE domain containing 3, Sin3A-associated protein 18 kDa, proline-rich 4, calcium/calmodulin-dependent protein kinase ID, myeloid/lymphoid or mixed-lineage leukemia translocated to 3, insulin-like growth factor binding protein 5, nucleoside diphosphate-linked moiety X-type motif 9, NudC domain containing 3, imprinted in Prader-Willi syndrome, TAF6-like RNA polymerase II p300/CBP-associated factor 65 kDa, WD repeat and SOCS box-containing 2, adenosine diphosphate ribosylation factor 3, KRR1, proliferation-associated 2G4; CD36, complement component (3b/4b) receptor 1, solute carrier family 4 sodium bicarbonate cotransporter member 4, lipoprotein lipase (LPL), GATA binding protein 3, LPL, glutathione peroxidase 3, D: -aspartate oxidase, apolipoprotein E, sphingomyelin phosphodiesterase acid-like 3A) were associated with poor clinical outcome in terms of development of metastatic or recurrent disease. CONCLUSIONS: The classification of these tumors may undergo further changes in the future. Gene expression profiling can provide additional information to categorize pleomorphic sarcoma (NOS) and reveal potential prognostic factors in this "entity."

Laser-mediated fixation of collagen-based scaffolds to dermal wounds.

BACKGROUND AND OBJECTIVE: Collagen scaffolds are popular for the reconstitution of dermal equivalents. Usually, these scaffolds are fixed with sutures or staples and in many cases these devices have to be removed in a second procedure. Laser-mediated tissue welding in a wet environment is a potential alternative for collagen scaffold fixation and may be advantageous to suture, staple, and tissue glue fixation. MATERIALS AND METHODS: Welding was performed with a continuous-wave diode laser system emitting radiation at a wavelength of 968 nm. Tensile strength after fixation to porcine skin and laser parameters were determined in vitro. In vivo, 24 excisional deep partial thickness wounds were created on flanks of two Goettingen mini pigs and covered with collagen scaffolds. These were randomized and fixated with either (1) staples, (2) fibrin glue, or (3) laser-mediated welding. Tissue biopsies for histological analysis were periodically performed and analyzed for wound healing progression, epidermal thickness, and extracellular matrix formation. RESULTS: Biomechanical stability after laser welding was time dependent. A dwell time of up to 10 seconds led to a strong bonding with a tensile strength of more than 30 g. In vivo, the wound healing process was macroscopically comparable in all groups and showed no significant differences. Microscopic analysis determined a more progressed and quicker wound closure in both the laser and staples group compared to the fibrin glue fixated scaffold. Laser-mediated fixation led to a significantly reduced epidermal thickness when compared with stapling or fibrin glue (P < 0.05). CONCLUSIONS: Laser tissue welding is a feasible approach for temporary fixation of collagen scaffolds to the wound bed. It improves wound healing properties and may lead to faster wound healing and cosmetically better scarring. Laser tissue welding is thus a very interesting and promising alternative to currently established fixation methods in a single step, no touch procedure.

Orthogonal polarization spectral imaging: a tool for assessing burn depths?

The estimation of burn depths is still a challenge, and even experienced surgeons often fail. In search of an objective method for differentiation between deep- and partial-thickness burns, we investigated the use of orthogonal polarization spectral (OPS) imaging to visualize the microcirculation in burn wounds. Twenty-seven burned patients were included in the study, 81 burn areas were investigated at day 1 and 4 post burn. The final therapy was compared with the therapy that would have been carried out as a consequence of the OPS imaging result. The patients were treated conservatively with dressings or surgically with necrectomy and split skin grafts. A comparison of the estimation of the burn depths of OPS imaging with the final therapy showed a correlation of 76.5%, about 5% less than the clinical assessment. It has proved a useful tool in particular for the prognosis as to whether the burn will heal spontaneously within 14 days or not. The presented OPS-Imaging device provides additional qualitative and quantitative information about the perfusion of the skin and therefore facilitates decisions about the follow on therapy. It is not an alternative to an experienced burn surgeon but provides important additional information.

Extended ray resection for sarcoma of the hand: long-term survival and functional results.

In this retrospective study, we analysed the long-term oncological and functional results after extended ray resection for sarcoma of the hand. Recurrence-free and overall survivals were calculated using the Kaplan-Meier method. The function of the operated hand was assessed with the Michigan Hand Questionnaire and compared with the contralateral side. Extended ray resection was performed in 25 out of 168 consecutive patients with soft-tissue and bony sarcomas of the hand. The overall 5- and 10-year, disease-specific survival rates were 86% and 81%, respectively. Local recurrences were observed in two patients. The Michigan Hand Questionnaire score for the affected hand at follow-up in nine patients was 82 points versus 95 for the healthy contralateral hands. We conclude that extended ray resection of osseous sarcomas breaking through the bone into the soft tissue or for soft tissue sarcomas invading bone is a preferable alternative to hand ablation when excision can be achieved with tumour-free margins. Level of evidence: III.