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Lung cancer continues to be the leading cause for cancer-related deaths in men and women worldwide. Sufficient screening tools enabling early diagnosis are essential to improve patient outcomes. The aim of this study was to evaluate serum midkine (S-MK) both as a diagnostic and prognostic biomarker in non-small cell lung cancer (NSCLC). This single-center analysis included 59 NSCLC patients counting 30 squamous cell cancers and 29 adenocarcinomas. Preoperative S-MK concentration was determined using ELISA. Patients were followed up to five years. S-MK was found to be significantly overexpressed in patients with NSCLC compared to healthy controls (p < 0.001). The discriminative power of S-MK to differentiate NSCLC subjects from controls was fairly high with an area under the receiver operating characteristic curve of 0.83 (p < 0.001). Optimal sensitivity of 92 % and reasonable specificity of 68% was reached at a threshold of 416 pg/ml S-MK. Patients with high S-MK concentration showed a significantly shorter overall survival compared to patients with low S-MK expression (p < 0.05). In conclusion, S-MK is overexpressed in patients with NSCLC and serves as an independent prognostic factor for overall survival. S-MK may thus be considered as an additional non-invasive biomarker not only for NSCLC screening but also for outcome prediction.

Colorectal carcinoma (CRC) is one of the most common carcinomas worldwide. Early detection is crucial for reducing morbidity and mortality. Several promising studies described the use of midkine (MK) as a tumor marker. This study aimed to investigate a larger collective to ascertain if the preoperative serum midkine level (S‐MK) is suitable as a marker for screening and if S‐MK correlates with tumor progression and localization. It was also investigated for the first time whether patients with high S‐MK show poor survival. This prospective single‐center study included 299 patients with CRC. The preoperative serum midkine level (S‐MK) was determined using ELISA. Established tumor markers Carcinoembryonic antigen (CEA) and Carbohydrate antigen 19‐9 (CA 19‐9) were collected for comparison. The median follow‐up period was 65 months. S‐MK was significantly elevated in patients with CRC (P, This study shows that preoperative serum midkine level (S‐MK) is suitable as marker for screening of patients with colorectal carcinoma. Moreover S‐MK correlates with poor survival.

Aim:To compare the efficacy and safety of the misoprostol vaginal insert (MVI) with an off-label use of oral misoprostol (OM).Methods:Pair-matched case-control study comparing the induction of labor with a retrievable MVI to OM. The primary outcomes were the time from induction to delivery and the cesarean section rate. Secondary outcomes included uterine tachysystole, tocolysis, fetal scalp blood testing, meconium-stained amniotic fluid, umbilical arterial pH, and Apgar score.Results:One hundred and thirty eight women ≥37/0 weeks pregnant undergoing labor induction with misoprostol were included. The mean time from application to delivery was significantly shorter and the caesarean section rate significantly higher in the MVI group (PConclusion:The MVI compared with OM significantly shortened the time from application to delivery at the expense of a higher cesarean section rate and negative effects on neonatal outcomes.

AVMs are rare tumorous vascular lesions derived from placental tissue that may present with massive post-partum hemorrhage (PPH) causing potentially life-threatening anemic shock. Current treatment options include the embolization of uterine arteries and emergency postpartum hysterectomy. We present a new form of minimally invasive, highly specific sonographically guided treatment in the form of the application of a human fibrin sealant leading to the instant cease of blood loss.A management protocol was established and a case series of 14 patients is presented. Diagnosis by endovaginal color Doppler sonography is followed by the sonographically guided application of biological glue (TISSEELThe procedure was technically successful in all 14 patients, 3 of whom (21 %) had a repeated procedure after 4 - 7 days. The mean age (yrs.) of the patients was 31 (25 - 40), the gravity was median 2 (1 - 5) and the parity was median 1 (0 - 4), the lowest Hb value was on average 9.35 ± 2.25 (5.2 - 14.2) g/dl, the lowest Ht was on average 30.82 ± 6.02 (18 - 41 %). Spectral Doppler analysis revealed an average of 80.71 ± 11.2 (66 - 115) cm/sec for the maximal detectable PSV. In the period of 4 - 55 months after treatment, 7 patients (50 %) had 8 successful pregnancies and 2 miscarriages.In PPH there is vital interest in timely diagnosis of the underlying cause, thus allowing fertility-sparing, minimally invasive and super-selective emergency treatment. In AVMs causing PPH, a positive impact on perinatal morbidity and mortality may be achieved by sonographically guided application of this biological glue.Arterio-venöse Malformationen (AVM) sind seltene Gefäßfehlbildungen ausgehend von Resten plazentaren Gewebes, die zu lebensbedrohlichen Blutungen in Form von massiven postpartalen Hämorrhagien (PPH), führen können. Embolisation der uterinen Gefäße oder aber einer notfallmäßigen Hysterektomie sind derzeit therapeutische Optionen. Wir präsentieren eine innovative, minimal-invasive Therapie mittels ultraschallgesteuerter, superselektiver Injektion eines Fibrinklebers, die zu einer unmittelbaren Blutstillung führt.Ein Standart zum Management von intrauterinen AVM wurde erstellt und eine Fallserie von 14 Patienten wird präsentiert. Nach Diagnostik durch vaginale Farb-Doppler Sonografie erfolgt die Applikation eines biologischen zwei-Komponenten Gewebekleber unter Ultraschallkontrolle. Der Gewebekleber, gewonnen aus tiefgefrorenem, gepooltem, humanem Frischplasma, beinhaltet eine Mischung aus konzentriertem Fibrinogen, Fibronectin und Albumin. Die verwendete Thrombin-Lösung enthält Calciumchlorid. Durch diese beiden Komponenten wird eine superselektive Okklusion der zuführenden Gefäße zur AVM erreicht und das Restgewebe kann durch Abrasio und/oder Hysteroskopie entfernt werden.Die Behandlung konnte in allen 14 Patienten erfolgreich durchgeführt werden, in 3 (21 %) Patienten musste der Eingriff innerhalb von 4 – 7 Tagen wiederholt werden. Das mittlere Alter der Patienten war 31 (25 – 40) Jahre, die Gravidität war median 2 (1 – 5) und die Parität median 1 (0 – 4). Der niedrigste Hb-Wert war im Mittel 9,35 ± 2,25, (5,2 – 14,2) g/dl, der niedrigste Hk-Wert war im Mittel 30,82 ± 6,02 (18 – 41)%. Spektral Doppler Analyse eine maximal nachweisbare PSV von 80,71 ± 11,2 (66 – 115) cm/sec. Im Abstand von 4 – 55 Monaten nach der Behandlung hatten 7 Patienten (50 %) eine erfolgreiche Schwangerschaft, wovon eine eine monochoriale Zwillingsschwangerschaft war. Zwei Patienten hatte eine frühe Fehlgeburt im ersten Trimenon.Beim Auftreten einer PPH besteht die lebenswichtige Notwendigkeit einer zeitnahen Diagnostik, so dass noch rechtzeitig minimal invasive und superselektive Therapiemaßnahmen ergriffen werden können, um somit die perinatale Morbidität und Mortalität zu senken. Die Applikation eines biologischen zwei-Komponenten Gewebekleber unter Ultraschallkontrolle könnte die Rate an anämisierenden Metrorrhagien senken.

Background: Current preliminary data is advocating cfDNA testing in twin pregnancies since both increasing use of ART and higher maternal ages have raised the incidence of (discordant) aneuploidies. Procedures and findings:This report is raising ethical implications deriving from a twin pregnancy discordant for trisomy 21 conceived from egg donation and diagnosed by cfDNA testing after low risk conventional first-trimester screening. For More Information : https://symbiosisonlinepublishing.com/

Type 1 neurofibromatosis (NF-1), also known as von Recklinghausen disease, is caused by a disorder of a single gene on chromosome 17 that usually restrains cell division. A sequence that is frequently associated with NF-1 is tumor progression from neurofibromas to malignant peripheral nerve sheath tumors (MPNSTs). The aim of this study was to determine the expression of the neural L1 cell adhesion molecule in dermal-diffuse neurofibromas, plexiform neurofibromas, and MPNSTs of NF-1. We retrospectively analyzed surgically resected primary tumors, including 20 dermal neurofibromas, 23 plexiform neurofibromas, and 17 MPNSTs, by immunohistochemistry in paraffin sections of NF-1 tumors with the use of the L1-specific monoclonal antibody UJ127, which does not cross-react with other members of the L1 family. Immunostainings for CD34 and S100 were included to distinguish and allocate L1-expressing Schwann cells and perineural (specialized) fibroblasts. Our data showed that L1 is highly expressed in all benign NF-1 tumors and in some but not all MPNSTs. Furthermore, we demonstrated a correlation between L1 expression and differentiation grade of MPNSTs. There was a significant trend toward lower or nondetectable expression in the poorly differentiated MPNSTs, in contrast to all other tumor entities so far investigated, in which L1 expression correlated positive with malignancy, except for juvenile but not adult-derived neuroblastomas. Future studies are warranted to elucidate the molecular basis of the varying effects of the degree of L1 expression, receptor, and signal transduction mechanisms in different tumors.

A previous study identified midkine (MK) expression in primary gastrointestinal stromal tumor (GIST) as a prognostic marker. The aim of the current study was to compare serum midkine (S-MK) concentrations of GIST patients with those of healthy controls and to determine if MK can serve as a prognostic serum marker for these patients. S-MK concentrations were measured by enzyme-linked immunosorbent assay in GIST patients (n = 96) and healthy controls (n = 148). S-MK levels were then correlated with clinicopathological data and the administration of imatinib therapy. In addition, MK expression was evaluated in 39 surgically resected GIST and in 17 leiomyoma specimens on a tissue microarray. S-MK concentrations in GIST patients were significantly higher than in healthy controls: median (25th and 75th percentiles) S-MK concentration was 235 (139 and 376) pg/ml in the GIST patients and 99 (33 and 198) pg/ml in the controls (P

Esophageal cancer is one of the most frequent cancers worldwide and is associated with poor outcome. Besides clinicopathological data, few prognostic molecular markers exist. Esophageal-cancer-related gene1 (ECRG1) short tandem repeats are associated with higher risk for developing esophageal squamous cell carcinoma. The aim of the present study was to evaluate the impact of DNA polymorphisms in the coding region of ECRG1 in esophageal carcinoma. Genomic DNA of 107 patients with esophageal cancer that underwent complete surgical resection between 1997 and 2005 was extracted. DNA was analyzed for ECRG1 polymorphisms Arg290Arg, Arg290Gln, and Gln290Gln by PCR and gel electrophoresis. Polymorphisms were correlated with survival data by the Kaplan–Meier method, multivariate Cox regression analysis, and odds ratio were determined. For all variables, cross tables were generated, followed by calculation of the p value by using the chi-square test/Fisher-exact test. Follow-up data of 102 patients with esophageal cancer were available after complete surgical resection for a median follow-up time of 24.3 months. Polymorphism Arg290Arg was found in 47 patients (46.1%), Arg290Gln in 48 patients (47.0%), and Gln290Gln in seven cases (6.9%). Arg290Arg polymorphism was significantly associated with reduced overall survival (p = 0.01) and tumor-free survival (p = 0.01) by the log-rank test. Multivariate regression analysis by Cox revealed polymorphism Arg290Arg to be a significant prognostic factor for survival (p = 0.012). Polymorphism Arg290Arg in ECRG1 is associated with poor clinical outcome after complete surgical resection in patients with esophageal cancer.

Background Short tandem repeat (STR) polymorphisms in exon 4 of the esophageal cancer-related gene 2 ( ECRG2 ) are a risk marker for esophageal carcinoma. The aim of the present study was to correlate these STRs with clinical outcome. Methods Genomic DNA of 86 patients who underwent complete surgical resection was analyzed for STRs TCA 3 /TCA 3 , TCA 3 /TCA 4 , and TCA 4 /TCA 4 in exon 4 of ECRG2 by polymerase chain reaction and DNA sequencing. Results ECRG2 STR TCA 3 /TCA 3 and TCA 3 /TCA 4 were found in 40 (47%) patients, respectively, and TCA 4 /TCA 4 in 6 (7%) cases. TCA 3 /TCA 3 genotype was significantly associated with reduced survival ( P 3 /TCA 3 STR was the strongest prognostic factor determined by multivariate Cox regression analysis. Conclusions Genetically fixed STR polymorphism TCA 3 /TCA 3 in exon 4 of ECRG2 is associated with poor clinical outcome in surgically treated esophageal cancer patients and might be a potential prognostic marker. The usefulness of these genetic markers to predict responsiveness toward neoadjuvant treatment of esophageal cancer patients would be of high clinical interest and should be examined in future studies.

Metastatic disease is the main cause of morbidity and mortality in esophageal carcinoma and the leading cause of death. While in the early stages surgical resection is the best therapeutic option, in late stages the conventional therapies surgery, chemotherapy, and radiation are limited. The expression of the chemokine receptor CXCR4 is known to be involved in metastatic homing and is associated with a poor prognosis in esophageal cancer patients. Trastuzumab treatment leads to significant tumor growth reduction in a model of HER-2 positive esophageal carcinoma. In the present report, we show the effects of the humanized monoclonal antibody trastuzumab, the CXCR4 inhibitor AMD3100 and their combined use in a metastastic orthotopic nude mouse model of esophageal cancer. Although both single therapies lead to tumor growth reduction the effect is further enhanced by their combination and leads to significant reduction of metastases. Tumor progression was monitored by non invasive MR imaging. High correlation between HER-2 and CXCR4 expression in primary tumor and metastatic organs was observed and might suggest a link between the chemokine receptor CXCR4 and receptor tyrosine kinase HER-2 in tumor progression and metastases. The results of this study suggest an effective treatment of metastatic prostate cancer by the combined use of drugs that target HER-2 and CXCR4. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1674. doi:10.1158/1538-7445.AM2011-1674

AIM: To investigate the outcomes of early and delayed elective resection after initial antibiotic treatment in patients with complicated diverticulitis. METHODS: The study, a non-randomized comparison of the two approaches, included 421 consecutive patients who underwent surgical resection for complicated sigmoid diverticulitis (Hinchey classification I-II) at the Department of Surgery, University Medical Center Hamburg-Eppendorf between 2004 and 2009. The operating procedure, duration of hospital and intensive care unit stay, outcome, complications and socioeconomic costs were analyzed, with comparison made between the early and delayed elective resection strategies. RESULTS: The severity of the diverticulitis and American Society of Anesthesiologists score were comparable for the two groups. Patients who underwent delayed elective resection had a shorter hospital stay and operating time, and the rate of successfully completed laparoscopic resections was higher (80% vs 75%). Eight patients who were scheduled for delayed elective resection required urgent surgery because of complications of the diverticulitis, which resulted in a high rate of morbidity. Analysis of the socioeconomic effects showed that hospitalization costs were significantly higher for delayed elective resection compared with early elective resection (9296 € ± 694 € vs 8423 € ± 968 €; P = 0.001). Delayed elective resection showed a trend toward lower complications, and the operation appeared simpler to perform than early elective resection. Nevertheless, delayed elective resection carries a risk of complications occurring during the period of 6-8 wk that could necessitate an urgent resection with its consequent high morbidity, which counterbalanced many of the advantages. CONCLUSION: Overall, early elective resection for complicated, non-perforated diverticulitis is shown to be a suitable alternative to delayed elective resection after 6-8 wk, with additional beneficial socioeconomic effects.

Background L1 cell adhesion molecule (CD171) is expressed in many malignant tumors and its expression correlates with unfavourable outcome. It thus represents a target for tumor diagnosis and therapy. An earlier study conducted by our group identified L1 expression levels in primary gastrointestinal stromal tumors (GIST) as a prognostic marker. The aim of the current study was to compare L1 serum levels of GIST patients with those of healthy controls and to determine whether levels of soluble L1 in sera could serve as a prognostic marker. Methods Using a sensitive enzyme-linked immunosorbent assay (ELISA), soluble L1 was measured in sera of 93 GIST patients und 151 healthy controls. Soluble L1 levels were then correlated with clinicopathological data. Results Median levels of soluble L1 were significantly higher (p < 0.001; Mann-Whitney U test) in sera of GIST patients compared to healthy individuals. Median soluble L1 levels were particularly elevated in patients with recurrence and relapse (p < 0.05; Mann Whitney U test). Conclusion These results suggest that high soluble L1 levels predict poor prognosis and may thus be a promising tumor marker that can contribute to individualise therapy.