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  • PMC (PubMed Central)  (24)
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  • 1
    In: PLoS ONE, 2018, Vol.13(3)
    Description: [This corrects the article DOI: 10.1371/journal.pone.0189514.].
    Keywords: Correction
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: Innovative surgical sciences, September 2016, Vol.1(1), pp.3-11
    Description: Over the last decades, neoadjuvant treatment has been established as a standard of care for a variety of tumor types in visceral oncology. Neoadjuvant treatment is recommended in locally advanced esophageal and gastric cancer as well as in rectal cancer. In borderline resectable pancreatic cancer, neoadjuvant therapy is an emerging treatment concept, whereas in resectable colorectal liver metastases, neoadjuvant treatment is often used, although the evidence for improvement of survival outcomes is rather weak. What makes neoadjuvant treatment attractive from a surgical oncology viewpoint is its ability to shrink tumors to a smaller size and to increase the chances for complete resection with clear surgical margins, which is a prerequisite for cure. Studies suggest that local tumor control is increased in some visceral tumor types, especially with neoadjuvant chemoradiotherapy. In some other studies, a better control of systemic disease has contributed to significantly improved survival rates. Additionally, delaying surgery offers the chance to bring the patient into a better general condition for major surgery, but it also confers the risk of progression. Although it is a relatively rare event, cancers may progress locally during neoadjuvant treatment or distant metastases may occur, jeopardizing a curative surgical treatment approach. Although this is seen as risk of neoadjuvant treatment, it can also be seen as a chance to select only those patients for surgery who have a better control of systemic disease. Some studies showed increased perioperative morbidity in patients who underwent neoadjuvant treatment, which is another potential disadvantage. Optimal multidisciplinary teamwork is key to controlling that risk. Meanwhile, the neoadjuvant treatment period is also used as a "window of opportunity" for studying the activity of novel drugs and for investigating predictive and prognostic biomarkers of chemoradiotherapy and radiochemotherapy. Although the benefits of neoadjuvant treatment have been clearly established, the risk of overtreatment of cancers with an unfavorable prognosis remains an issue. All indications for neoadjuvant treatment are based on clinical staging. Even if staging is done meticulously, making use of all recommended diagnostic modalities, the risk of overstaging and understaging remains considerable and may lead to false indications for neoadjuvant treatment. Finally, despite all developments and emerging concepts in medical oncology, many cancers remain resistant to the currently available drugs and radiation. This may in part be due to specific molecular resistance mechanisms that are marginally understood thus far. Neoadjuvant treatment has been one of the major advances in multidisciplinary oncology in the last decades, requiring a dedicated treatment team and an optimal infrastructure for complex oncology care. This article discusses the goals and novel directions as well as limitations in neoadjuvant treatment of visceral cancers.
    Keywords: Chemoradiotherapy ; Chemotherapy ; Morbidity ; Mortality ; Neoadjuvant ; Respectability
    E-ISSN: 2364-7485
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  • 3
    In: PLoS ONE, 2017, Vol.12(12)
    Description: Cancer resistance is a major cause for longevity of the naked mole-rat. Recent liver transcriptome analysis in this animal compared to wild-derived mice revealed higher expression of alpha2-macroglobulin (A2M) and cell adhesion molecules, which contribute to the naked mole-rat’s cancer resistance. Notably, A2M is known to dramatically decrease with age in humans. We hypothesize that this might facilitate tumour development. Here we found that A2M modulates tumour cell adhesion, migration and growth by inhibition of tumour promoting signalling pathways, e.g. PI3K / AKT, SMAD and up-regulated PTEN via down-regulation of miR-21, in vitro and in tumour xenografts. A2M increases the expression of CD29 and CD44 but did not evoke EMT. Transcriptome analysis of A2M-treated tumour cells, xenografts and mouse liver demonstrated a multifaceted regulation of tumour promoting signalling pathways indicating a less tumorigenic environment mediated by A2M. By virtue of these multiple actions the naturally occurring A2M has strong potential as a novel therapeutic agent.
    Keywords: Research Article ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Research And Analysis Methods ; Research And Analysis Methods ; Biology And Life Sciences
    E-ISSN: 1932-6203
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  • 4
    Language: English
    In: BMC Surgery, 01 July 2017, Vol.17(1), pp.1-8
    Description: Abstract Background Cost reduction measures in medicine are gaining greater importance nowadays, especially in high-volume procedures such as laparoscopic appendectomy (LAE). Currently there are two common methods of dissecting the appendix from the caecal pole: linear stapler and endoloops. The endoloop is the cheaper device but can only be used in uncomplicated cases of appendicitis. Therefore both methods are used in LAE depending on intraoperative findings. The goal of this study was to retrospectively evaluate possible cost reduction due to increased use of endoloop in LAE in our general surgery department of a tertiary referral university hospital. Methods We previously used the stapler for appendix dissection in LAE as our local protocol but introduced the endoloop as standard method in 2015 to reduce intraoperative costs. We conducted a retrospective analysis of patients who underwent LAE between June 2014 and October 2015 in our department. Our purpose is to show the effects on cost reduction during the introductory period adjusting for a potential bias due to the individual learning curve of every surgeon. We estimated costs for LAE by taking into account average device costs and duration of operation (DO) as well as patient outcome. Results A total of 177 patients underwent LAE, 73 in 2014 (phase I) and 104 in 2015 (phase II). The median DO was 61 (± 24 SD) min during the entire period, and increased by 14 min from phase I to II (from 51 (±23 SD) min to 65 (±24 SD) min respectively, p 〈 0.001). The use of endoloops increased from 10% to 55% (p 〈 0.001). Patients’ characteristics and outcomes did not differ significantly. A median saving of 5.9€ per operation was calculated in phase II compared to phase I (p = 0.80). Conclusion Introducing the endoloop as standard device for LAE leads to a marginal reduction in intraoperative costs without increasing negative outcomes. In our model the cost-reduction achieved by cheaper devices was overcome by increased costs for DO during the initial phase of use of endoloops. A longer follow up might show a more pronounced cost reduction.
    Keywords: Laparoscopic Appendectomy ; Endoloop ; Stapling Device ; Cost-Reduction
    E-ISSN: 1471-2482
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  • 5
    Language: English
    In: BMC Surgery, 01 May 2017, Vol.17(1), pp.1-10
    Description: Abstract Background Transabdominal Preperitoneal (TAPP) and Lichtenstein operation are established methods for inguinal hernia repair in clinical practice. Meta-analyses of randomized controlled studies, comparing those two methods for repair of primary inguinal hernia, are still missing. In this study, a systematic review and meta-analysis of published randomized controlled trials was performed to compare early and long term outcomes of the two methods. Methods A literature search was carried out to identify randomized controlled trials, which compared TAPP and Lichtenstein repair for primary inguinal hernia. Outcome measures included duration of operation, length of hospital stay, acute postoperative and chronic pain, time to return to work, hematoma, wound infection, neuralgia, numbness, scrotal swelling, seroma and hernia recurrence. A quantitative meta-analysis was performed, using Odds Ratios (OR) or Standardized Mean Difference (SMD), and Confidence Interval (CI). Results Eight controlled randomized studies were identified suitable for the analysis. The mean duration of the operation was shorter in Lichtenstein repair (SMD = 6.79 min, 95% CI, −0.68 – 14.25), without significant difference. Comparing both techniques, patients of the laparoscopic group showed postoperatively significantly less chronic inguinal pain (OR = 0.42; 95% CI, 0.23–0.78). Analyses of the remaining outcome measures did not show any significant differences between the two techniques. Conclusion The results of this analysis indicate that complication rate and outcome of both procedures are comparable. TAPP operation demonstrated only one advantage over Lichtenstein operation with significantly less chronic inguinal pain postoperatively.
    Keywords: Tapp ; Lichtenstein Repair ; Inguinal Hernia ; Outcome ; Meta-Analysis
    E-ISSN: 1471-2482
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  • 6
    In: BioMed Research International, 2018, Vol.2018, 7 pages
    Description: . Incisional negative pressure wound therapy (iNPWT) has been of recent interest in different surgical fields as beneficial outcomes on high-risk wounds have been reported. Nevertheless, its mechanisms of function are not widely studied to date.. We established two ex vivo setups of iNPWT in porcine and human abdominal wall for measuring pressures within the wound which result from iNPWT application. For pressure measurements, a high-resolution manometry catheter and a balloon catheter probe were used in a wound sealed with either a commercially available PREVENA VAC kit or a self-made iNPWT kit. Furthermore, we evaluated seroma evacuation by iNPWT.. Both setups showed similar characteristics of pressure curves within the wound when applying increasing negative pressures. Application of high pressures did not result in a similar increase in wound pressure. Only subtotal evacuation of seroma by iNPWT application (about 75% of volume) could be detected. Our ex vivo model of iNPWT in porcine and human abdominal wall could show reproducible measurements of pressures within the wounds in both types of tissue. As intrawound pressures did not increase in the same way as the applied negative pressure, we suggest that our results do not advocate the idea of using iNPWT for wound care especially as seroma evacuation remains insufficient.
    Keywords: Research Article
    ISSN: 2314-6133
    E-ISSN: 2314-6141
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  • 7
    Language: English
    In: Scandinavian journal of trauma, resuscitation and emergency medicine, 11 April 2016, Vol.24, pp.45
    Description: Caustic ingestions are rare but potentially life-threatening events requiring multidisciplinary emergency approaches. Although particularly respiratory functions may be impaired after caustic ingestions, studies involving acute emergency care are scarce. The goal of this study was to explore acute emergency care with respect to airway management and emergency department (ED) infrastructures. We retrospectively evaluated adult patients after caustic ingestions admitted to our university hospital over a 10-year period (2005-2014). Prognostic analysis included age, morbidity, ingested agent, airway management, interventions (endoscopy findings, computed tomography (CT), surgical procedures), intensive care unit (ICU) admission, length of stay in hospital and hospital mortality. Twenty-eight patients with caustic ingestions were included in the analysis of which 18 (64%) had suicidal intentions. Ingested agents were caustic alkalis (n = 22; 79%) and acids (n = 6; 21%). ICU admission was required in 20 patients (71%). Fourteen patients (50%) underwent tracheal intubation and mechanical ventilation, of which 3 (21%) presented with difficult airways. Seven patients (25%) underwent tracheotomy including one requiring awake tracheotomy due to progressive upper airway obstruction. Esophagogastroduodenoscopy (EGD) was performed in 21 patients (75%) and 11 (39%) underwent CT examination. Five patients (18%) required emergency surgery with a mortality of 60%. Overall hospital mortality was 18% whereas the need for tracheal intubation (P = 0.012), CT-diagnostic (P = 0.001), higher EGD score (P = 0.006), tracheotomy (P = 0.048), and surgical interventions (P = 0.005) were significantly associated with mortality. Caustic ingestions in adult patients require an ED infrastructure providing 24/7-availability of expertise in establishing emergent airway safety, endoscopic examination (EGD and bronchoscopy), and CT diagnostic, intensive care and emergency esophageal surgery. We recommend that - even in patients with apparently stable clinical conditions - careful monitoring of respiratory functions should be considered as long as diagnostic work-up is completed.
    Keywords: Airway Management ; Caustic Ingestion ; Emergency Management ; Endoscopic Management ; Intoxication ; Critical Care ; Drinking ; Airway Management -- Methods ; Caustics -- Administration & Dosage
    E-ISSN: 1757-7241
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  • 8
    Language: English
    In: BMC cancer, 15 February 2012, Vol.12, pp.70
    Description: Our aim was to compare survival of the various treatment modality groups of chemotherapy and/or radiotherapy in relation to SEMS (self-expanding metal stents) in a retrospective case-control study. We have made the hypothesis that the administration of combined chemoradiotherapy improves survival in inoperable esophageal cancer patients. All patients were confirmed histologically as having surgically non- resectable esophageal carcinoma. Included were patients with squamous cell carcinoma, undifferentiated carcinoma as well as Siewert type I--but not type II - esophagogastric junctional adenocarcinoma. The decision to proceed with palliative treatments was taken within the context of a multidisciplinary team meeting and full expert review based on patient's wish, co-morbid disease, clinical metastases, distant metastases, M1 nodal metastases, T4-tumor airway, aorta, main stem bronchi, cardiac invasion, and peritoneal disease. Patients not fit enough to tolerate a radical course of definitive chemo- and/or radiation therapy were referred for self-expanding metal stent insertion. Our approach to deal with potential confounders was to match subjects according to their clinical characteristics (contraindications for surgery) and tumor stage according to diagnostic work-up in four groups: SEMS group (A), Chemotherapy group (B), Radiotherapy group (C), and Chemoradiotherapy group (D). Esophagectomy was contraindicated in 155 (35.5%) out of 437 patients presenting with esophageal cancer to the Department of General and Abdominal Surgery of the University Hospital of Mainz, Germany, between November 1997 and November 2007. There were 133 males and 22 females with a median age of 64.3 (43-88) years. Out of 155 patients, 123 were assigned to four groups: SEMS group (A) n = 26, Chemotherapy group (B) n = 12, Radiotherapy group (C) n = 23 and Chemoradiotherapy group (D) n = 62. Mean patient survival for the 4 groups was as follows: Group A: 6.92 ± 8.4 months; Group B: 7.75 ± 6.6 months; Group C: 8.56 ± 9.5 months, and Group D: 13.53 ± 14.7 months. Significant differences in overall survival were associated with tumor histology (P = 0.027), tumor localization (P = 0.019), and type of therapy (P = 0.005), respectively, in univariate analysis. Treatment modality (P = 0.043) was the only independent predictor of survival in multivariate analysis. The difference in overall survival between Group A and Group D was highly significant (P 〈 0.01) and in favor of Group D. As concerns Group D versus Group B and Group D versus Group C there was a trend towards a difference in overall survival in favor of Group D (P = 0.069 and P = 0.059, respectively). The prognosis of inoperable esophageal cancer seems to be highly dependent on the suitability of the induction of patient-specific therapeutic measures and is significantly better, when chemoradiotherapy is applied.
    Keywords: Stents ; Carcinoma -- Therapy ; Esophageal Neoplasms -- Therapy
    E-ISSN: 1471-2407
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  • 9
    Language: English
    In: Lenz, T. L., A. J. Deutsch, B. Han, X. Hu, Y. Okada, S. Eyre, M. Knapp, et al. 2015. “Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases.” Nature genetics 47 (9): 1085-1090. doi:10.1038/ng.3379. http://dx.doi.org/10.1038/ng.3379.
    Description: Human leukocyte antigen (HLA) genes confer strong risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen binding repertoires between a heterozygote’s two expressed HLA variants may result in additional non-additive risk effects. We tested non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (RA, Ncases=5,337), type 1 diabetes (T1D, Ncases=5,567), psoriasis vulgaris (Ncases=3,089), idiopathic achalasia (Ncases=727), and celiac disease (Ncases=11,115). In four out of five diseases, we observed highly significant non-additive dominance effects (RA: P=2.5×1012; T1D: P=2.4×10−10; psoriasis: P=5.9×10−6; celiac disease: P=1.2×10−87). In three of these diseases, the dominance effects were explained by interactions between specific classical HLA alleles (RA: P=1.8×10−3; T1D: P=8.6×1027; celiac disease: P=6.0×10−100). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (RA: 1.4%, T1D: 4.0%, and celiac disease: 4.1%, beyond a simple additive model).
    Keywords: Autoimmunity ; Complex Diseases ; Mhc ; Hla ; Genetic Architecture ; Non-Additive Effects ; Interactions
    ISSN: 1061-4036
    E-ISSN: 15461718
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  • 10
    Language: English
    In: World Journal of Surgical Oncology, 01 June 2005, Vol.3(1), p.37
    Description: Abstract Background The study was aimed to identify pre- and intraoperative risk factors that potentially influence morbidity and mortality after esophagectomy for esophageal carcinoma with particular emphasis on the predominant tumor types. Patients and methods Between September 1985 and March 2004, 424 patients underwent esophagectomy for esophageal carcinoma. Of these, 186 (43.9%) patients had a transhiatal, and 231 (54.5%) patients underwent a transthoracic procedure with two-field lymphadenectomy. Pre-, intraoperative risk factors and tumor characteristics were included in the risk analysis to assess their influence on postoperative morbidity and mortality. Results Multivariate analysis (logistic regression model) identified the surgical procedure as the most important risk factor for postoperative morbidity and mortality with the transthoracic technique associated with a significant higher risk. The comparison of the risk profile between the different histological tumor types, a significantly higher nutritional risk, poorer preoperative lung function and a higher prevalence of hepatopathy was observed in patients with squamous cell carcinoma (n = 229) compared to adenocarcinoma (n = 150) (p 〈 0.05). Although there was no significant difference in surgical complications between the two groups, the rate of general complications, length of postoperative intensive care unit-stay and mortality rate was significantly higher in patients with squamous cell carcinoma (p 〈 0.05). Conclusion The present risk analysis shows that the selection and the type of the surgical procedure are crucial factors for both the incidence of postoperative complications and the mortality rate. The higher risk of the transthoracic procedure is justified with a view to a better long term prognosis.
    Keywords: Medicine
    ISSN: 1477-7819
    E-ISSN: 1477-7819
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