Heinz Herbert Homann

Major and Lethal Complications of Liposuction: A Review of 72 Cases in Germany between 1998 and 2002

Background: Liposuction is the most frequently performed cosmetic operation in Germany, with approximately 200,000 procedures performed in 2003. The public perception of liposuction as minor surgery fails to consider the potential of major complications or a possibly fatal outcome. Methods: A retrospective analysis of severe or lethal complications related to cosmetic liposuction is presented. To collect pertinent information, the authors sent 3500 questionnaires to departments of pathology and forensic medicine, intensive care units, and others. After the identification of cases with major complications, the second phase of the investigation consisted of interviews with the physicians performing the liposuction. Results: Two thousand two hundred seventy-five questionnaires (65 percent) were returned. The analyzed data showed 72 cases of severe complications, including 23 deaths following cosmetic liposuction in a 5-year period from 1998 to 2002. The most frequent complications were bacterial infections such as necrotizing fasciitis, gas gangrene, and different forms of sepsis. Further causes of lethal outcome were hemorrhages, perforation of abdominal viscera, and pulmonary embolism. Fifty-seven of 72 complications were clinically evident within the first 24 postoperative hours; 41 of these 72 liposuction procedures were performed using tumescent anesthesia and 17 of 72 were performed using true tumescent anesthesia, with four deaths. Conclusions: Major risk factors for the development of severe complications are insufficient standards of hygiene, the infiltration of multiple liters of wetting solution, permissive postoperative discharge, and selection of unfit patients. The lack of surgical experience was a notorious contributing factor, particularly regarding the timely identification of developing complications. This is in fact the first study reporting deaths related to liposuction performed entirely under true tumescent anesthesia.

Beta-catenin in soft tissue sarcomas: expression is related to proliferative activity in high-grade sarcomas.

Besides its role in cell adhesion, β-catenin exerts a function as an oncoprotein. The aim of this study was the characterization of its expression, possible mutation, and the assessment of β-catenin as a prognostic indicator for soft tissue sarcomas. A total of 115 soft tissue sarcomas were analyzed using immunohistochemistry, immunogold-electron microscopy, and DNA analysis. Information from 56 patients was available for follow-up. A statistically significant correlation was found between intracellular distribution of β-catenin and the proliferative activity (MIB-1 expression) in high-grade sarcomas (P = .0008). β-catenin was identified with intracytoplasmic and nuclear accumulation, showing additional membranous staining in sarcomas with epithelioid pattern. Ultrastructurally, a colocalization between β-catenin and nuclear heterochromatin was demonstrated. In 22 analyzed tumors, only one (yet undescribed) mutation of the β-catenin gene (C-A transversion) could be detected. Prognostic validity of the cellular expression of β-catenin, however, was not proven. Apart from its membranous function as an effective molecule for cell-adhesion in sarcomas with epithelioid pattern, β-catenin may act as an oncoprotein in sarcomas with intracytoplasmic and nuclear localization with binding to nuclear DNA. A previously discussed stimulation of cell proliferation caused by an increased β-catenin level can also be postulated for high-grade soft tissue sarcomas in correlation with the rate of proliferation. Mutations of the β-catenin gene are probably of lesser importance for the accumulation of β-catenin in soft tissue sarcomas.

MFH revisited: outcome after surgical treatment of undifferentiated pleomorphic or not otherwise specified (NOS) sarcomas of the extremities—an analysis of 140 patients

BackgroundUndifferentiated pleomorphic sarcoma/NOS (not otherwise specified; former pleomorphic and storiform MFH) of the extremities is a common malignant soft tissue tumor in adults. The objective of this study is to determine prognostic factors for the outcome after surgical treatment with respect to the recent developments in classification.MethodsFrom 1996 to 2004, 140 undifferentiated pleomorphic sarcomas/NOS were identified out of 1,200 soft tissue sarcomas of the extremities that were treated at our institution and recorded in a prospective database. Overall survival (OS) and isolated local recurrence (ILR) were determined by Kaplan–Meier analysis. All tumors were retrospectively analyzed regarding prognostic factors of the disease, including patient’s background (primary or recurrent), histological grade (G2/G3), adjuvant chemotherapy and radiotherapy, size (T1–2) and depth of the tumor, and surgical margins (R0, R1, R2).ResultsIn 123 patients, a wide resection was performed (limb-sparing surgery). In nine patients, an amputation was necessary. The overall 5-year survival rate was 72% (median follow up: 52xa0months). There was a significant difference between the group presenting with primary tumors (5-year survival: 84%, pu2009<u20090.05) and recurrent tumors (5-year survival: 62%, pu2009<u20090.05). Isolated local recurrence occurred in 36 patients.ConclusionsIn terms of OS and ILR, primary or recurrence, negative surgical margins, size and grading had a highly significant influence, whereas the site of surgery and adjuvant chemotherapy, adjuvant radiation and tumor depth did not. Prognosis for patients with undifferentiated pleomorphic sarcoma of the extremities depends predominantly on adequate wide resection of the primary tumor.

Response rate of fibrosarcoma cells to cytotoxic drugs on the expression level correlates to the therapeutic response rate of fibrosarcomas and is mediated by regulation of apoptotic pathways

BackgroundBecause of the high resistance rate of fibrosarcomas against cytotoxic agents clinical chemotherapy of these tumors is not established. A better understanding of the diverse modes of tumor cell death following cytotoxic therapies will provide a molecular basis for new chemotherapeutic strategies. In this study we elucidated the response of a fibrosarcoma cell line to clinically used cytostatic agents on the level of gene expression.MethodsHT1080 fibrosarcoma cells were exposed to the chemotherapeutic agents doxorubicin, actinomycin D or vincristine. Total RNA was isolated and the gene expression patterns were analyzed by microarray analysis. Expression levels for 46 selected candidate genes were validated by quantitative real-time PCR.ResultsThe analysis of the microarray data resulted in 3.309 (actinomycin D), 1.019 (doxorubicin) and 134 (vincristine) probesets that showed significant expression changes. For the RNA synthesis blocker actinomycin D, 99.4% of all differentially expressed probesets were under-represented. In comparison, probesets down-regulated by doxorubicin comprised only 37.4% of all genes effected by this agent. Closer analysis of the differentially regulated genes revealed that doxorubicin induced cell death of HT1080 fibrosarcoma cells mainly by regulating the abundance of factors mediating the mitochondrial (intrinsic) apoptosis pathway. Furthermore doxorubicin influences other pathways and crosstalk to other pathways (including to the death receptor pathway) at multiple levels. We found increased levels of cytochrome c, APAF-1 and members of the STAT-family (STAT1, STAT3), while Bcl-2 expression was decreased. Caspase-1, -3, -6, -8, and -9 were increased indicating that these proteases are key factors in the execution of doxorubicin mediated apoptosis.ConclusionThis study demonstrates that chemotherapy regulates the expression of apoptosis-related factors in fibrosarcoma cells. The number and the specific pattern of the genes depend on the used cytotoxic drug. The response rates on the gene expression level, i.e. the number of genes regulated by the drugs actinomycin D, doxorubicin and vincristine, correlate to the clinical effectiveness of the drugs. Doxorubicin seems to exert its cytotoxic mechanism by regulating genes, which are involved in several different apoptosis regulating pathways. The exact knowledge of the genes affected by the drugs will help to understand the diverse modes of soft tissue sarcoma cell death in response to cytotoxic therapies.

The Effectiveness of Pedicled Groin Flaps in the Treatment of Hand Defects: Results of 49 Patients

PURPOSEnDespite the growing number of free and local flaps used for repairing defects of the hand, groin flaps are also still widely used. The aims of this study were to evaluate the outcome of a large series of patients whose defects were covered by pedicled groin flaps, and to find out whether it is still indicated in replacing damaged soft tissue of the hand in the era of microsurgery.nnnMETHODSnFrom 1982 to 2009, we treated 85 patients with soft tissue defects on the hand and distal forearm with pedicled groin flaps in our department and recorded them in a prospective database. We interviewed and examined 49 patients in this cohort.nnnRESULTSnThe mean age of the 85 patients was 33 years, the male/female ratio was 4:1, the mean hospital stay was 29 ± 13 days, and the mean follow-up was 9 years. The duration to flap division was 24 ± 5 days. Altogether, we performed a mean of 4.6 operations per patient, including thinning of the flap, deepening of the interdigital fold, and stump and flap revisions. One flap loss occurred. Of the 49 patients, results were mostly classified as good, and 82% of patients would undergo the procedure again. The mean Disabilities of the Arm, Shoulder, and Hand score value was 23 ± 17. The Vancouver Scar Scale showed nearly normal height and vascularity of the groin flap (0.2 ± 0.4 and 0.3 ± 0.6, respectively), pigmentation was slightly abnormal (0.8 ± 0.6), and pliability was evaluated between supple and yielding (1.5 ± 1.2).nnnCONCLUSIONSnResults achieved with the groin flaps were positive. Most patients were satisfied with the results, and the operation was easily performed when McGregors recommendations were followed. Nevertheless, considering the high number of secondary operations, the long hospital stay, and immobilization of the arm, groin flaps should be used only when free flaps or regional pedicle flaps are either not feasible or not indicated.nnnTYPE OF STUDY/LEVEL OF EVIDENCEnTherapeutic III.

Feasibility of chemosensitivity testing in soft tissue sarcomas

BackgroundSoft tissue sarcomas comprise less than 1% of all solid malignancies. The presentation and behavior of these tumors differs depending on location and histological characteristics. Standard therapy consists of complete surgical resection in combination with adjuvant radiotherapy. The role of chemotherapy is not clearly defined and is largely restricted to clinical trials. Only a limited number of agents have proved to be effective in soft tissue sarcomas. The use of doxorubicin, epirubicin and ifosfamide allowed response rates of more than 20%. In addition, recent chemotherapy trials did not demonstrate any significant differences in efficacy for various histological subtypes.MethodsThe objective of this study was to gain additional information about the chemosensitivity of soft tissue sarcomas to seven 7 different chemotherapy agents as single drugs and 4 combinations. Therefore we used an established ATP based in-vitro testing system and examined 50 soft tissue sarcomas. Chemosensitivity was assessed using a luciferin-luciferase-based luminescence assay providing individual chemosensitivity indices for each agent tested.ResultsThe sensitivity varied widely according to the histological subtypes. The tumors state of cellular dedifferentiation played a crucial role for the efficiency of the chemotherapeutic agents. The sensitivity also depended on the presentation of the sarcoma as a primary or recurrent tumor. The highest sensitivity was demonstrated for actinomycin D as a single agent, with 74% of the tumor samples exhibiting a high-grade sensitivity (20% low sensitivity, no resistance). The combination of actinomycin D and ifosfamide yielded a high sensitivity in 76% (2% resistance). Doxorubicin as a mono-therapy or in combination with ifosfamide achieved high sensitivity in 70% and 72%, respectively, and resistance in 6% of the samples.ConclusionChemosensitivity testing is feasible in soft tissue sarcomas. It can be used to create sensitivity and resistance profiles of established and new cytotoxic agents and their combinations in soft tissue sarcomas. Our data demonstrate measurable discrepancies of the drug efficiency in soft tissue sarcomas, sarcoma subtypes and tumor recurrencies. However, current therapeutic regime does not take this in consideration, yet.

Effects of desmopressin on thrombogenesis in aspirin‐induced platelet dysfunction

Summary. Aspirin causes a coagulation disorder. Desmopressin has haemostatic effects by increasing the plasma levels of coagulation factor VIII and von Willebrand factor. The precise effects of desmopressin on thrombogenesis are not known. In an in vivo model, we investigated the effect of the drug on thrombus formation and platelet function after aspirin use. Male Lewis rats weighing 250–300u2003g were used. Four groups with 10 animals each were formed: control, aspirin, desmopressin and aspirinu2003+u2003desmopressin. In each animal, the femoral artery was dissected. A thrombogenic vessel injury was created by inverting a full thickness portion of the proximal edge of the incised artery into the lumen. The following parameters were measured: maximum thrombus size, time period until maximum thrombus size was reached and overall platelet function. In addition, the thrombi generated were investigated histologically. Thrombus formation time was significantly shorter with desmopressin compared with the animals treated with aspirin (Pu2003<u20030·0001) and controls (Pu2003=u20030·008). Maximum thrombus size was larger in the desmopressin and desmopressinu2003+u2003aspirin groups when compared with the group treated with aspirin only. Overall platelet function was significantly enhanced with desmopressin compared with controls (Pu2003=u20030·025) and with aspirin (Pu2003<u20030·0001). The differences were confirmed histologically. In conclusion, desmopressin significantly accelerates thrombus formation in aspirin‐treated animals. It can also re‐establish thrombus size after the use of aspirin. Overall platelet function is significantly increased by desmopressin.

In vivo visualization of platelet/endothelium cell interaction in muscle flaps

Increasing evidence underlines the substantial pathophysiological impact of platelets on the development of ischemia/reperfusion injury (I/R) in flaps. Methods for studying dynamic platelet mechanisms in flaps in vivo are not available. The aim of this study was to develop a model enabling quantitative analysis of platelet kinetics and platelet-endothelium cell interaction within the microcirculation of muscle flaps in vivo. Balb/c mice (n = 16) were anesthetized, and an epigastric muscle flap was prepared. Autologous platelets were separated from blood donor animals (n = 16) and labeled ex vivo by means of rhodamine-6-G. After I/R (90 minutes’ clamping, 10 minutes’ reperfusion), the platelets were administered intra-arterially (i.a.). Microhemodynamics and kinetics of platelets were investigated by intravital fluorescence microscopy. I/R of muscle flaps induced disturbances in microcirculation. The number of rolling platelets, as well as platelets adhering to the inner vessel wall of venules, was increased in the ischemia group. Using intravital fluorescence microscopy, platelet kinetics were analyzed directly in flap microcirculation in vivo for the first time. Since platelet/endothelial cell interaction is a key event in the pathophysiology after microsurgical procedures, this model will help to understand basic molecular mechanisms of platelet behavior during I/R.

Influence of topically applied antimicrobial agents on muscular microcirculation.

Bacterial infections cause major complications in wound healing. Local antiseptics are used for daily wound care; however, their potential toxic effects on the vasculature have not yet been thoroughly investigated. The aim of this study was to assess the effects of antiseptics on microcirculation. Investigations were performed on a standardized cremaster muscle model on rats (n = 60). The arteriolar diameter and functional capillary density (FCD) were investigated using transillumination microscopy before and 60 and 120 minutes after application of each of the following antimicrobial agents: alcohol, hydrogen peroxide, imipenem, octenidine dihydrochloride, polyhexanide, and ethacridine lactate. Although polyhexanide caused a significant arteriolar dilatation (106.25 ± 3.23 vs. 88.54 ± 6.74 &mgr;m [baseline value]) and increase of FCD compared with baseline value (12.65 ± 0.82 vs. 9.10 ± 0.50 n/0.22 mm2), alcohol led to a significant decrease of both parameters (90.63 ± 10.80 vs. 52.09 ± 7.69 and 5.35 ± 0.54 vs. 1.68 ± 0.48) and was the only agent that caused arteriolar thrombosis. The FCD also increased significantly after treatment with hydrogen peroxide (10.55 ± 0.33 vs. 12.30 ± 0.48) and octenidine (6.82 ± 0.63 vs. 12.32 ± 0.63). However, no positive effect on arteriolar diameter could be found. Ethacridine lactate and imipenem did not impact either parameter. In addition to reducing bacteria, an antiseptic should be nontoxic, especially to the microcirculation. Polyhexanide seems to have a positive influence on vessel diameter and capillary density, whereas alcohol reduces both parameters. If the antimicrobial efficacy is comparable, the antiseptic with less toxic effects should be chosen, especially in critically perfused wounds.

Long-term comparison of a routine laboratory parameter-based severity score with APACHE II and SAPS II.

BACKGROUNDnRisk score models predicting mortality have tremendous value, but because of the additional effort involved, their clinical use remains low. The aim of this study is to compare three different scores that each requires different levels of effort during admission and throughout treatment: the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Simplified Acute Physiology Score II (SAPS II), and the Dense Laboratory Whole Blood Applied Risk Estimation (DELAWARE) score. Of the three, only the DELAWARE is based solely on routine laboratory parameters.nnnMETHODSnProspective data of the three scores were collected for 268 surgical patients admitted to the intensive care unit over 1 year. The predicted hospital mortality and survival were evaluated for the first 14 days.nnnRESULTSnWith a cutoff value of 0.65, the sensitivity of the DELAWARE was 71.6%, the specificity, 92.5%, and the correct classification rate, 87.3%. The APACHE II and SAPS II showed values of 41.2%/96.8%/86.2% and 62.7%/87.1%/82.5%, respectively. The r2 value was 0.884 for the DELAWARE, 0.876/0.814 for the APACHE II and SAPS II. Hospital mortality rate was overestimated by 20% to 65% in all scores. The discriminatory ability of the APACHE II and SAPS II increased throughout the course of treatment.nnnCONCLUSIONSnThe routine laboratory-based DELAWARE provides a reliable, valid risk assessment of the surgical intensive care patient at admission. It also provides additional information without added effort or poor interobserver reliability, which leads to better data comparability. We have to state that until now the data have been collected in a single-center and their general validity is therefore limited. By the end of treatment, the SAPS II and APACHE II had increased discriminatory ability and are therefore useful as process parameters.