[Results of a single center vascular screening program in Germany]. / Ergebnisse eines monozentrischen Gefäßscreeningprogramms in Deutschland.

BACKGROUND: Cardiovascular diseases are the main cause of death in Europe with a relevant socioeconomic burden. A screening program for vascular diseases in asymptomatic persons with a defined risk constellation can lead to an early diagnosis. OBJECTIVE: The study examined a screening program for carotid stenosis, peripheral arterial occlusive disease (PAOD) and abdominal aortic aneurysms (AAA) in persons without any known vascular disease with respect to demographic data, risk factors, pre-existing conditions, medication intake, detection of pathological findings and/or findings requiring treatment. MATERIAL AND METHODS: Test subjects were invited using various information material and filled in a questionnaire on cardiovascular risk factors. The screening took place with measurement of the ABI and duplex sonography as a monocentric prospective single arm study within 1 year. Endpoints were the prevalence of risk factors and pathological and/or results requiring treatment. RESULTS: A total of 391 persons participated, 36% presented with at least 1 cardiovascular risk factor, 35.5% with 2 and 14.4% with 3 or more. The sonography showed results requiring control with a carotid stenosis of < 50-> 75% or occlusion in 9%. An AAA with a diameter of 3.0-4.5 cm was diagnosed in 0.9% and a pathological ABI < 0.9 or > 1.3 in 12.3%. The indications for a pharmacotherapy were found in 17% and no operation was recommended. CONCLUSION: The practicability of a screening program for carotid stenosis, PAOD and AAA of a defined risk population was shown. Vascular pathologies that required treatment were hardly found in the catchment area of the hospital. Consequently, the implementation of this screening program in Germany based on the collected data cannot currently be recommended in this form.

Perioperative functional imaging after extracranial carotid endarterectomy for the detection of cerebral hyperperfusion syndrome.

INTRODUCTION: SyngoDynaPBVNeuro® is a tool to perform cerebral blood volume (CBV) measurements intraoperatively by functional imaging producing CT-like images. Aim of this prospective study was to analyze the clinical relevance and benefit of CBV measurement with regard to neurological complications like cerebral hyperfusion syndrome (CHS). METHODS: Forty-five patients undergoing endarterectomy (CEA) of the internal carotid artery were included; functional imaging with CBV measurement was performed before and after CEA. To evaluate and analyze CBV, six regions of interest (ROI) were identified for all patients with an additional ROI in patients with symptomatic ICA stenosis and previous stroke. The primary endpoint of the study was a perioperative change in CBV measurements. Secondary outcomes were incidence of stroke, TIA, CHS, and perioperative morbidity and mortality. RESULTS: Thirty-day stroke incidence and thirty-day mortality were 0%. Thirty-day morbidity was 6.7%. Two patients from the asymptomatic group suffered from transient neurological symptoms without signs of intracerebral infarction in CT or MR scan, meeting diagnostic criteria for CHS. In 83.3% of ROIs in these patients, an increase of blood volume was detected. Overall, 26.7% patients suffered from unilateral headache as expression of potential CHS. A total of 69.4% of ROIs in patients with postoperative unilateral headache showed an increase when comparing pre- and postoperative CBV measurements. CONCLUSION: The results show that increased CBV measured by functional imaging is a possible surrogate marker of neurological complications like CHS after CEA. By using intraoperative CBV measurement, the risk of CHS can be estimated early and appropriate therapeutic measures can be applied.

[Treatment of retroperitoneal sarcoma in Germany : Results of a survey of the German Society of General and Visceral Surgery, the German Interdisciplinary Sarcoma Study Group and the advocacy group Das Lebenshaus]. / Behandlung retroperitonealer Sarkome in Deutschland : Eine Umfrage der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie, der Deutschen Interdisziplinären Studiengruppe Sarkome und der Patientenorganisation Das Lebenshaus.

OBJECTIVE: Retroperitoneal sarcomas (RPSs) are rare cancers with some variability in clinical and histopathological presentation. In Germany, general treatment strategies of retroperitoneal sarcoma are unknown since centralized registries do not exist. The objective of this survey was to access the medical care of RPS patients in Germany. METHODS: In cooperation with the German Society of General and Visceral surgery, the German Interdisciplinary Sarcoma Study Group and the patient advocacy group Das Lebenshaus we designed an online survey assessing diagnostic and treatment strategies (e. g. performance of tumor biopsies, administration of multimodal therapies and surgical strategy). All departments for general and visceral surgery in Germany were addressed (n = 976). RESULTS: Responses were received from 191 of 976 departments. Only 11 surgical departments treat more than 10 RPS patients per year. A multidisciplinary sarcoma board exists in 19 hospitals. Staging is generally performed by cross-sectional imaging. In 54% of the departments pretreatment tumor biopsy is a standard procedure. Surgery is performed as compartment resection in 85% of the departments. A systematic lymph node dissection is done in 40%. Adjuvant radio- or chemotherapy is performed as a standard treatment in 27% and 22% departments, respectively. CONCLUSION: The survey demonstrates a large heterogeneity in RPS diagnostic and treatment strategies. Dedicated education programs and centralized treatment strategies are warranted to improve the standard of care.

Predictors of overall and recurrence-free survival after neoadjuvant chemotherapy for gastroesophageal adenocarcinoma: Pooled analysis of individual patient data (IPD) from randomized controlled trials (RCTs).

BACKGROUND: Neoadjuvant chemotherapy improves prognosis of patients with locally advanced gastroesophageal adenocarcinoma. The aim of this study was to identify predictors for postoperative survival following neoadjuvant therapy. These could be useful in deciding about postoperative continuation of chemotherapy. METHODS: This meta-analysis used IPD from RCTs comparing neoadjuvant chemotherapy with surgery alone for gastroesophageal adenocarcinoma. Trials providing IPD on age, sex, performance status, pT/N stage, resection status, overall and recurrence-free survival were included. Survival was calculated in the entire study population and subgroups stratified by supposed predictors and compared using the log-rank test. Multivariable Cox models were used to identify independent survival predictors. RESULTS: Four RCTs providing IPD from 553 patients fulfilled the inclusion criteria. (y)pT and (y)pN stage and resection status strongly predicted postoperative survival both after neoadjuvant therapy and surgery alone. Patients with R1 resection after neoadjuvant therapy survived longer than those with R1 resection after surgery alone. Patients with stage pN0 after surgery alone had better prognosis than those with ypN0 after neoadjuvant therapy. Patients with stage ypT3/4 after neoadjuvant therapy survived longer than those with stage pT3/4 after surgery alone. Multivariable regression identified resection status and (y)pN stage as predictors of survival in both groups. (y)pT stage predicted survival only after surgery alone. CONCLUSION: After neoadjuvant therapy for gastroesophageal adenocarcinoma, survival is determined by the same factors as after surgery alone. However, ypT stage is not an independent predictor. These results can facilitate the decision about postoperative continuation of chemotherapy in pretreated patients.

Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials.

Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis. Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression. Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55-0.75) and OS (HR 0.83; 95%-CI, 0.76-0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41-3.58). Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.

[Advanced gastrointestinal stromal tumors : What role does surgery currently play in multimodal concepts?]. / Fortgeschrittene gastrointestinale Stromatumoren : Welche Rolle spielt die Chirurgie im multimodalen Konzept heute?

BACKGROUND: Gastrointestinal stromal tumors (GIST) have an incidence of 1-2/100,000 and thus constitute the most common mesenchymal neoplasm of the digestive tract. Their specific tumor biology with mutations in the protooncogenes c-KIT and PDGFR α acting as drivers of tumor growth facilitate targeted therapy with tyrosine kinase inhibitors. In this context, there are several specific indications for surgery in patients with advanced GIST. OBJECTIVE: This article discusses the importance of surgery within multimodal therapeutic concepts for advanced GIST. MATERIAL AND METHODS: The results of a selective literature search including own studies and case reports are presented. RESULTS: For large GIST at unfavorable anatomical locations, which are not amenable to organ-sparing resection, neoadjuvant imatinib therapy is the standard upfront treatment prior to surgery in the case of imatinib-sensitive mutations in the c-KIT protooncogene. This usually reduces the extent of resection without increasing perioperative morbidity. In the metastatic setting, surgery can constitute a significant part of multimodal therapy in patients with a generalized response to drug therapy by resection of residual tumor masses, although there are no prospective studies to prove a beneficial effect on overall survival. In patients with focal progression on anti-proliferative therapy, local therapeutic measures can make an important contribution to multimodal tumor control. In patients with generalized progression, an operation should only be performed in highly selected cases with the goal of symptom control. Local ablative therapies, such as radiofrequency ablation (RFA), irreversible electroporation (IRE) and selective internal radiotherapy (SIRT) are a therapeutic option particularly for liver metastases. CONCLUSION: Surgery plays an important role in the multimodal therapy of advanced GIST particularly in the neoadjuvant setting. Its role is more limited in metastatic stages where systemic treatment represents the frontline therapeutic approach.

[Reading behavior and preferences regarding subscriptions to scientific journals : Results of a survey of members of the German Society for General and Visceral Surgery]. / Leseverhalten und Präferenzen hinsichtlich Abonnements wissenschaftlicher Fachzeitschriften : Ergebnisse einer Umfrage unter den Mitgliedern der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie.

BACKGROUND: The purpose of surgical literature is to publish the latest study results and to provide continuing medical education to readers. For optimal allocation of resources, institutional subscribers, professional societies and scientific publishers require structured data on reading and subscription preferences of potential readers of surgical literature. OBJECTIVES: To obtain representative data on the preferences of German general and visceral surgeons regarding reading of and subscription to scientific journals. MATERIAL AND METHODS: All members of the German Society for General and Visceral Surgery (DGAV) were invited to participate in a web-based survey. Questions were asked on the affiliation and position of the member, individual journal subscriptions, institutional access to scientific journals, preferences regarding electronic or print articles and special subscriptions for society members. Answers were descriptively analyzed. RESULTS: A total of 630 out of 4091 (15 %) members participated in the survey and 73 % of the respondents had at least 1 individual subscription to a scientific journal. The most frequently subscribed journal was Der Chirurg (47 % of respondents). The institutional access to journals was deemed insufficient by 48 % of respondents, predominantly in primary care hospitals and outpatient clinics. Almost half of the respondents gave sufficient importance to reading printed versions of articles for which they would pay extra fees. A group subscription for society members was perceived as advantageous as long as no relevant extra costs were incurred. CONCLUSION: This structured survey among members of the DGAV provides data on preferences regarding reading of and subscription to scientific journals. Individual subscriptions to journals are still common, possibly due to suboptimal institutional access particularly at smaller non-academic institutions. In an age of online publications it seems surprising that many respondents place a high value on printed versions. The results are relevant for potential institutional subscribers, professional societies and scientific publishers.

[Importance of PET for surgery of gastrointestinal stromal tumors]. / Bedeutung der PET für die Chirurgie des gastrointestinalen Stromatumors.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the digestive tract. The GIST differ substantially from gastrointestinal carcinomas regarding tumor biology, treatment strategies and indications for surgery. Every surgeon involved in the treatment of GIST should be acquainted with these aspects. OBJECTIVES: The aims of this article are to discuss the value of positron emission tomography (PET) in the surgical treatment of patients with GIST and to provide an outlook on the development of molecular tracers specifically tailored for GIST. RESULTS: PET is an invaluable decision aid in the multimodal therapy of GIST and particularly for deciding on surgical indications. Specific scenarios in which PET is used are primary staging monitoring during neoadjuvant therapy and staging and response assessment in the metastatic setting. The routinely used tracer is 18F-fluorodeoxyglucose (18F-FDG) and uptake reliably correlates with the metabolism of GIST lesions. Compared to computed tomography and magnetic resonance imaging (CT/MRI), 18F-FDG-PET often allows a more timely and accurate response assessment. GIST-specific molecular tracers, which could provide a direct prognosis regarding response and development of resistance to treatment, are currently in preclinical development. However, pharmacokinetic and immunological issues still need to be resolved. A distant aim is the development of "theranostics", i.e. substances which serve both diagnostic and therapeutic purposes. DISCUSSION: PET has an established value in the multimodal treatment of GIST and is particularly useful for deciding on surgical indications.

Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer.

PURPOSE: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. PATIENTS AND METHODS: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed. CONCLUSION: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity.

The effect of a clinical pathway for enhanced recovery of rectal resections on perioperative quality of care.

PURPOSE: There is ample evidence of the benefits of clinical pathways (CPs), but this study is the first to investigate the potential additional benefits of a CP for rectal resections in a setting with an already established policy of enhanced postoperative recovery. METHODS: We compared 36 patients who underwent rectal resections with ileostomy placement and were treated according to a CP (CP group) with 67 patients treated before CP implementation (prepathway group). Indicators of process quality were placement of central venous line and epidural catheter, day of removal of Foley catheter in relation to removal of the epidural catheter, day of first mobilization, day of resumption of regular diet, day of first passage of stool through the stoma, and length of stay. Outcome quality was assessed by morbidity, mortality, reoperation, and readmission rates. RESULTS: We found that patients in the CP group resumed regular diet significantly sooner (p = 0.001). There were no significant differences regarding the day of first mobilization (p = 0.69), epidural catheter (p = 0.74), central venous line placement (p = 0.92), and removal of Foley catheter (p = 0.23). The first stool was passed through the stoma earlier (p = 0.04) in the prepathway group. Median length of hospital stay was significantly shorter in the CP group (12.5 vs. 15.0 days; p = 0.008). There were no significant changes in outcome quality, except for a significantly higher need for revisional surgery in the CP group (13.9 vs. 3%, p = 0.05). CONCLUSIONS: After implementation of a CP for rectal resections, one parameter of process quality improved and length of stay decreased.

Clinical, pathological and surgical characteristics of duodenal gastrointestinal stromal tumor and their influence on survival: a multi-center study.

BACKGROUND: The duodenum is a rare site of primary gastrointestinal stromal tumor (GIST). Overall (OS) and disease-free survival (DFS) after limited resection (LR) versus pancreaticoduodenectomy (PD) were studied. METHODS: All patients who underwent surgery for primary, localized duodenal GIST between 2000 and 2011 were identified from four prospective institutional databases. OS and DFS were calculated by Kaplan-Meier method. Univariate analysis was performed. RESULTS: Eighty-four patients (median follow-up 42 months) underwent LR (n = 56, 67%) or PD (n = 28, 33%). Patients in the PD group had a larger median tumor size (7 cm vs. 5 cm, p = 0.024) and higher mitotic count (39% vs. 19% >5/50 high-power fields, p = 0.05). Complications were observed in five patients (9%) in the LR group and ten patients (36%) in the PD group. OS and DFS for the entire cohort were 89% and 64% at 5 years, respectively. No difference in outcome between LR and PD were observed. Eleven patients were treated with preoperative IM. A major RECIST response was obtained in nine (80%), whereas two had stable disease. Twenty-three patients received postoperative Imatinib (IM). A trend toward a better OS in IM-treated patients could be detected only in the high-risk group. CONCLUSIONS: Type of duodenal resection does not impact outcome. The choice should be determined by duodenal site of origin and tumor size. IM may be considered in cases at high risk of recurrence; in neoadjuvant setting, IM might facilitate resection and possibly increase the chance of preserving normal biliary and pancreatic anatomy.

Pattern of recurrence in patients with ruptured primary gastrointestinal stromal tumour.

BACKGROUND: This study assessed the outcomes of patients with a gastrointestinal stromal tumour (GIST) that ruptured before or during resection. METHODS: The records of 23 patients (8 women, 15 men; median age 54 years) with ruptured primary non-metastatic GIST were retrieved from a database of 554 patients. The written surgical and pathology reports were analysed. Review pathology was performed in all 23 cases, and mutational analysis of KIT and platelet-derived growth factor α (PDGFRA) genes was performed in 21 patients. Median follow-up was 52 months. RESULTS: Tumour rupture was spontaneous in 16 patients, following abdominal trauma in two and occurred during resection in five. Primary tumour location was the stomach in six patients, duodenum in one and small bowel in 16. Mean tumour size was 10·2 (range 4-28) cm. According to the Miettinen and Lasota risk classification, the distribution of very low-, low-, intermediate- and high-risk cases was one, two, five and 15 respectively. One patient remained disease-free at 83 months. Fifteen of 16 patients who did not receive adjuvant therapy developed tumour recurrence after a median of 19 months. Median recurrence-free survival in patients with KIT mutations involving codons 557-558 was 11 months. CONCLUSION: Patients with a rupture of GIST into the abdominal cavity have a risk of recurrence of nearly 100 per cent. In patients with deletion mutations involving codons 557-558, recurrence-free survival was less than 1 year. All patient groups are clear candidates for adjuvant drug therapy.

Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients?

BACKGROUND: Surgical indication for metastatic gastrointestinal stromal tumor (GIST) treated with imatinib is not yet established. MATERIALS AND METHODS: We analyzed 80 patients who underwent surgery for metastatic GIST after imatinib therapy from July 2002 to October 2007. Patients were divided into those with surgery at best clinical response (group A, n = 49) and those with surgery at focal progression (group B, n = 31). Primary end points were progression-free survival (PFS) and disease-specific survival (DSS). RESULTS: Two-year postoperative PFS was 64.4% in group A and 9.7% in group B (P < 0.01). In group A, median PFS was not reached; in group B, it was 8 months. Median DSS from the time of imatinib onset was not reached in either group. Five-year DSS was 82.9% in group A and 67.6% in group B (P < 0.01). Multivariate analysis confirmed a significantly shorter PFS and DSS in group B. Surgical morbidity occurred in 13 patients (16.3%). CONCLUSIONS: Surgery for focal progressive lesions could be considered as part of the second-line/third-line armamentarium in selected cases. Surgery of residual disease upon best clinical response seems associated with survival benefit compared with historical controls in similar patient collectives treated with imatinib alone. However, evidence from prospective randomized trials is needed to make definite recommendations.

[Parasites as a cause of urticaria. Helminths and protozoa as triggers of hives?]. / Parasiten als Ursache von Urtikaria. Helminthen und Protozooen als Auslöser der Nesselsucht?

Urticaria is one of the most prevalent disorders in dermatological practice. The disease can be incapacitating. There are clear pathophysiological and epidemiological hints that helminths and protozoa are rare but treatable causes of acute and chronic urticaria. Doctors and patients are often not aware that parasitic diseases are increasingly common even in industrialized countries due to a steep rise in migration and international travel. This review presents the most important parasitic causes of urticaria and provides relevant details regarding personal history, clinical presentation, diagnosis and therapy.