Diverse prognostic value of the GTn promoter polymorphism in squamous cell and adeno carcinoma of the oesophagus.

The basal transcription of heme oxygenase-1 (HO-1) regulation is dependent upon a GT repeat germ line polymorphism (GTn) in the promoter of the HO-1 gene. We determined the prognostic value of HO-1 promoter polymorphism on the natural postoperative course of complete resected oesophageal cancer. Genomic DNA from 297 patients was amplified by polymerase chain reaction and sequenced. The results were correlated with clinicopathological parameters, disseminated tumour cells in bone marrow (DTC) and clinical outcome. Depending on short allele with <25 and long allele with ≥25, GTn repeats three genotypes (SS, SL and LL) were defined. A diverse role of GTn was evident in squamous cell carcinoma (SCC) and adenocarcinoma (AC). In SCC, the SS genotype presented less advanced tumours with lower rate DTC in bone marrow and relapse compared with L-allele carriers. In contrast, AC patients with the SS genotype displayed a complete opposing tumour characteristic. The disease-free (DFS) and overall survival (OS) in SCC patients was markedly reduced in LL genotypes (p < 0.001). In AC contrarily the SS genotype patients displayed the worst DFS and OS (p < 0.001). GTn is a strong prognostic factor with diverse prognostic value for recurrence and survival in AC and SCC.

Non-trauma Emergency Pancreatoduodenectomies: A Single-Center Retrospective Analysis.

OBJECTIVE: To retrospectively assess the frequency and indications for emergency pancreatoduodenctomies in a tertiary referral center. METHODS: Pancreatoduodenectomies between January 2005 and January 2014 were retrospectively assessed for emergency indications defined as surgery following unplanned hospital admission in less than 24 h. Data on indications and on the intraoperative as well as the post-operative course were collected. RESULTS: Out of 583 pancreatoduodenectomies during the interval, a total of 10 (1.7 %) were performed as an emergency surgery. Indications included uncontrollable bleeding, duodenal and proximal jejunal perforations, and endoscopic retrograde cholangiopancreatography-related complications. Three of the 10 (30.0 %) patients died during the hospital course. In one patient, an intraoperative mass transfusion was necessary. No intraoperative death occurred. All but one patient were American Society of Anesthesiologists class three or higher. In two cases, the pancreatic remnant was left without anastomosis for second-stage pancreatojejunostomy. Median operation time was 326.5 min (SD 100.3 min). Hospital stay of the surviving patients was prolonged (median 43.0 days; SD 24.0 days). CONCLUSION: Emergency pancreatoduodenectomies are non-frequent, have a diverse range of indications and serve as an ultima ratio to cope with severe injuries and complications around the pancreatic head area.

Presence of the coxsackievirus and adenovirus receptor (CAR) in human neoplasms: a multitumour array analysis.

BACKGROUND: The Coxsackie- and Adenovirus Receptor (CAR) has been assigned two crucial attributes in carcinomas: (a) involvement in the regulation of growth and dissemination and (b) binding for potentially therapeutic adenoviruses. However, data on CAR expression in cancer types are conflicting and several entities have not been analysed to date. METHODS: The expression of CAR was assessed by immunohistochemical staining of tissue microarrays (TMA) containing 3714 specimens derived from 100 malignancies and from 273 normal control tissues. RESULTS: The expression of CAR was detected in all normal organs, except in the brain. Expression levels, however, displayed a broad range from being barely detectable (for example, in the thymus) to high abundance expression (for example, in the liver and gastric mucosa). In malignancies, a high degree of variability was notable also, ranging from significantly elevated CAR expression (for example, in early stages of malignant transformation and several tumours of the female reproductive system) to decreased CAR expression (for example, in colon and prostate cancer types). CONCLUSION: Our results provide a comprehensive insight into CAR expression in neoplasms and indicate that CAR may offer a valuable target for adenovirus-based therapy in a subset of carcinomas. Furthermore, these data suggest that CAR may contribute to carcinogenesis in an entity-dependent manner.

VEGFR-2, CXCR-2 and PAR-1 germline polymorphisms as predictors of survival in pancreatic carcinoma.

BACKGROUND: Hypoxic environment of pancreatic cancer (PC) implicates high vascular in-growth, which may be influenced by angiogenesis-related germline polymorphisms. Our purpose was to evaluate polymorphisms of vascular endothelial growth factor receptor 2 (VEGFR-2), CXC chemokine receptor 2 (CXCR-2), proteinase-activated receptor 1 (PAR-1) and endostatin (ES) as prognostic markers for disease-free (DFS) and overall survival (OS) in PC. PATIENTS AND METHODS: Genotyping of 173 patients, surgically treated for PC between 2004 and 2011, was carried out by TaqMan(®) genotyping assays or polymerase chain reaction. Chi-square test, Kaplan-Meier estimator and Cox regression hazard model were used to assess the prognostic value of selected polymorphisms. RESULTS: VEGFR-2 -906 T/T and PAR-1 -506 Del/Del genotypes predicted longer DFS (P = 0.003, P = 0.014) and OS (VEGFR-2 -906, P = 0.011). CXCR-2 +1208 T/T genotype was a negative predictor for DFS (P < 0.0001). Combined analysis for DFS and OS indicated that patients with the fewest number of favorable genotypes simultaneously present (VEGFR-2 -906 T/T, CXCR-2 +1208 C/T or C/C and PAR-1 -506 Del/Del) were at the highest risk for recurrence or death (P < 0.0001). CONCLUSION: VEGFR-2 -906 C>T, CXCR-2 +1208 C>T and PAR-1 -506 Ins/Del polymorphisms are potential predictors for survival in PC.

Surgery of esophageal cancer.

BACKGROUND: Surgery is the only option for curative treatment in patients with esophageal carcinoma. Despite the debates related to the peri-operative therapy regime, a generally accepted consensus on surgical approach is not reached yet. The debate focuses mainly on pros and cons between radical transthoracic resection and the (limited) transhiatal resection in the last decade. METHODS: The PubMed database was searched for randomized trials, meta-analyses, and retrospective single-center studies. The search terms were "esophageal carcinoma," "esophageal junction carcinomas," "transhiatal," "transthoracic," "morbidity," "mortality," and "surgery." RESULTS: The radical transthoracic approach should be the standard of care for esophageal carcinoma since it does not go along with an increased risk of postoperative morbidity or mortality but reveals an improved survival. Patient-related co-morbidities are the most influencing factors for the postoperative outcome. For type II esophageal junction carcinoma, treatment options from transhiatal extended gastrectomy to esophagectomy with hemigastrectomy or esophagogastrectomy with colonic interposition are existing. In type III esophagogastric junction carcinomas, the transhiatal extended gastrectomy is the standard of care, and the minimally invasive approach should be performed in specialized centers. CONCLUSION: Based on current available study results, this expert review provides a decision support for the best surgical strategy depending on tumor localization and patients' characteristics.

Staging and outcome depending on surgical treatment in adenocarcinomas of the oesophagogastric junction.

BACKGROUND: Owing to controversial staging and classification of adenocarcinoma of the oesophago-gastric junction (AOG) before surgery, the choice of appropriate surgical approach remains problematic. In a retrospective study, preoperative staging of AOG and the impact of preoperative misclassification on outcome were analysed. METHODS: Data from patients with AOG were analysed from a prospectively collected database with regard to surgical treatment, preoperative and postoperative staging, and outcome. RESULTS: One-hundred and thirty patients with Siewert types I and II AOG who did not have neoadjuvant treatment were included in the study: 41 patients with an AOG type I who underwent oesophagectomy, 51 patients with an AOG staged before surgery as type I who underwent oesophagectomy but in whom the final histology showed a type II tumour, and 38 patients whose tumours were staged as AOG type II before and after operation who underwent gastrectomy. Among patients who had an oesophagectomy, lymph node metastases (P = 0.022), tumour relapse (P = 0.009) and recurrent distant metastases (P = 0.028) were significantly more frequent in patients with AOG type II; those with AOG type II had shorter overall survival than those with type I tumours (P = 0.024). Among those with AOG type II, recurrence-free survival was significantly shorter after oesophagectomy compared with extended gastrectomy (P = 0.019). Thoracoabdominal oesophagectomy had a favourable influence on outcome compared with the transhiatal approach. CONCLUSION: Accurate preoperative staging of AOG and appropriate surgical therapy are crucial for outcome. AOG type II is a more aggressive tumour with higher recurrence rates than AOG type I. These patients therefore benefit from more radical surgical treatment.

[Sequential information processing in children with and without auditory processing disorder]. / Sequenzielle Informationsverarbeitung bei Kindern mit und ohne auditive Verarbeitungs- und Wahrnehmungsstörung.

BACKGROUND: It is a controversial issue whether sequential processing in children with auditory processing disorders (APD) is a unimodal auditory impairment. PATIENTS AND METHODS: Normal achieving controls (n=12; mean age: 101.1 months; SD 20.3) and children referred to clinical facilities for assessment including children with monosymptomatic APD (n=25; mean age: 90.8 months; SD 9.8), children with developmental language disorder (DLD]) + APD (n=11; mean age: 89.5 months; SD 14.9), children with dyslexia + APD (n=10; mean age: 113.8 months; SD 17.1) were compared using the subtest digit recall of the German version of the K-ABC (Melchers & Preuss 2001) and the K-ABC subtest hand movements in the visual modality. RESULTS: On average all groups tended to perform alike in visual sequential processing and memory (T-score>50). Normal controls (non-APD) showed on average the best test performance (T-score 57.4; SD 10.5), but the mean performance did not differ significantly from children with APD. All groups also presented on average normal test performance in the auditory modality however, children of the clinical groups were below the age mean (DLD + APD: T-W 43.1; SD 6.8; monosymptomatic APD: T-W 45.8; SD 9.8; dyslexia + APD: 46.7; SD5.8). Children with DLD + APD and those with monosymptomatic APD exhibited a significantly lower but not poor performance in auditory processing of sequences compared to their performance in visual sequential processing. The results of auditory and visual processing of sequences were significantly correlated in the clinical groups DLD + APD (0.58) and monosymptomatic APD (0.34), but not in the smallest group dyslexia + APD (0.48) and in normal achieving controls (0.32). CONCLUSION: On the basis of the results of the present study it may be concluded that a normal test performance on visual measure does not exclude a bimodal or pansensory seriation disorder in children with APD. It does, however, indicate the existence of a primary auditory sequential processing deficit, because at least the processing of phonological and visual stimuli was not separately carried out in children with DLD + APD.

What predicts the outcome in patients with intestinal ischemia? A single center experience.

BACKGROUND: Acute mesenteric ischemia (AMI) is associated with a mortality of 60-80%. Early diagnosis and rapid treatment have a decisive influence on therapy. The aim of this study was to evaluate the prognostic value of AMI markers on mortality, in order to better anticipate the clinical course and to initiate therapeutic steps at an early stage. STUDY DESIGN: An analysis from our prospective database of 302 consecutive patients with AMI who were treated surgically in the Department of General Surgery between February 2003 and October 2014 was performed. Uni- and multivariate analysis of risk factors for mortality have been performed in the total cohort and in two subgroups according to their stay in intensive care unit (ICU) at the time of AMI diagnosis. RESULTS: Of the 302 patients with AMI, 115 were in ICU at the time of diagnosis. Totally, 203 patients underwent computed tomography scan (CT-scan) of the abdomen for diagnosis and 68% of them showed specific signs of AMI. A total of 63 (21%) embolectomies were performed during the surgical procedure. The post-operative mortality rate was 68% (204 patients). Among survivors, 85 (87%) patients developed a short bowel syndrome in the post-operative course. Multivariate analysis showed a significant association between mortality and preoperative lactate>3mmol/L, C-reactive protein>100mg/L and ICU stay at the time of AMI diagnosis. CONCLUSION: Mortality of patients with AMI remains high. Elevated lactate, elevated C-reactive protein and ICU stay are factors associated with increased mortality. Their presence in a patient with suspicion of AMI should trigger a multidisciplinary management in emergency.

Evaluation of the MDACC clinical classification system for pancreatic cancer patients in an European multicenter cohort.

BACKGROUND: The MDACC group recommends to extend the current borderline classification for pancreatic cancer into three groups: type A patients with resectable/borderline tumor anatomy, type B with resectable/borderline resectable tumor anatomy and clinical findings suspicious for extrapancreatic disease and type C with borderline resectable and marginal performance status/severe pre-existing comorbidity profile or age>80. This study intents to evaluate the proposed borderline classification system in a multicenter patient cohort without neoadjuvant treatment. METHODS: Evaluation was based on a multicenter database of pancreatic cancer patients undergoing surgery from 2005 to 2016 (n = 1020). Complications were classified based on the Clavien-Dindo classification. χ2-test, Kaplan-Meier estimator and Cox regression hazard model were used for statistical analysis. RESULTS: Most patients (55.1%) were assigned as type A patients, followed by type C (35.8%) and type B patients (9.1%). Neither the complication rate, nor the mortality rate revealed a correlation to any subgroup. Type B patients had a significant worse progression free (p < 0.001) and overall survival (p = 0.005). Type B classification was identified as an independent prognostic marker for progression free survival (p = 0.005, HR 1.47). CONCLUSION: The evaluation of the proposed classification in a cohort without neoadjuvant treatment did not justify an additional medical borderline subgroup. A new subgroup based on prognostic borderline patients might be the main target group for neoadjuvant protocols in future.

[Long-term follow-up of oral language development in children with permanent bilateral hearing loss]. / Orale Sprachentwicklung bilateral schallempfindungsgestörter Kinder--ein empirischer Längsschnitt.

OBJECTIVE: The aim of this study was to assess the oral language development of children with permanent bilateral hearing loss without additional disabilities longitudinally (5 time points t1-t5). METHOD: The present follow-up study evaluated both receptive and expressive language developmental quotients (DQ; desired value 1.0) with standardised developmental scales and receptive and expressive vocabulary size with standardised tests (results in T-scores; m=50, SD=10). Mean follow-up duration was 38.1 (SD 4.8) months. SAMPLE: A cohort of n=18 sensorineural hearing-impaired children was recruited from the German Göttinger Hör-Sprachregister. Mean diagnosis age was 21.4 (SD 16.6) months and mean age of amplification with hearing aids was 21.7 (SD 16.5) months. RESULTS: The mean DQs slowly increased from t1 to t4 (DQ receptive 0.37/0.48/0.55/0.56; DQ expressive: 0.51/0.51/0.55/0.55) and remained norm deviant. The diagnosis age of hearing loss and both the developmental quotients for receptive (-0.41/-0.42/-0.53; p<0.05/-0.80; p<0.01) and expressive language (-0.77; p<0.01/-0.55; p<0.05/-0.66; p<0.01/-0.79; p<0.01) were significantly correlated. The mean receptive vocabulary size apparently increased and came up to the lower norm range (29.6-34.2-43.8), however the mean expressive vocabulary remained far below the norm (26.8-29.8). Children with a hearing loss from 71-90 dB scored on average mostly higher than children with a loss > 90 dB who all had received a cochlear-implant up to t3. Children who were identified as hearing-impaired before the age of 18 months exhibited on average generally greater DQs. CONCLUSION: The individual best available amplification of hearing loss did not compulsively cause an age-adequate spoken language development, at least not in case of a hearing loss > 40 dB. So a newborn hearing screening must be the first step in identification, intervention and habilitation of an infant with hearing loss. Use of a cochlear implant seemed to have a great impact on the oral language development of children with a bilateral loss > 90 dB.

Blood fibrinogen levels discriminate low- and high-risk intraductal papillary mucinous neoplasms (IPMNs).

BACKROUND: The risk assessment of intraductal papillary mucinous neoplasms (IPMN) to either guide patients to surgical resection or watchful waiting is still under debate. Additional markers to better separate low and high-risk lesions would improve patient selection. METHODS: Patients who underwent pancreatic resections for IPMNs between January 2008 and December 2012 with available blood samples were selected and retrospectively assessed. Data on cyst characteristics such as cyst size, duct relation and main-duct dilatation were collected and plasma fibrinogen levels were measured. RESULTS: A total of 73 patients fulfilled the inclusion criteria by pancreatic resection for pathologically confirmed IPMN and available blood sample. Histologically, IPMNs were classified as low-grade and borderline in 52 (71.2%, group 1) and as high-grade and invasive in 21 (28.8%, group 2) of all cases. Fibrinogen levels showed significant differences between the two groups (group 1: mean 3.62 g/L (SD ± 1.14); group 2: mean 4.49 g/L (SD ± 1.57); p = 0.027). A ROC-curve analysis calculated cut-off value of 4.71 g/L separated groups 1 and 2 (p = 0.008). Fibrinogen levels remained as the only significant factor in multivariable analysis, cyst size and duct relation were not significant. CONCLUSION: Blood fibrinogen differed between low and high risk IPMNs and therefore, the use of fibrinogen as an additional discriminator in the pre-operative risk assessment of IPMNs should be further evaluated.

Evaluation of the robotic approach concerning pitfalls in rectal surgery.

INTRODUCTION: The feasibility and advantages of robotic rectal surgery (RRS) in comparison to conventional open or laparoscopic rectal resections have been postulated in several reports. But well-known challenges and pitfalls of minimal invasive rectal surgery have not been evaluated by a prospective, multicenter setting so far. Aim of this study was to analyze the perioperative outcome of patients following RRS especially in regard to the pitfalls such as obesity, male patients and low tumors by a European multicenter setting. METHODS: This prospective study included 348 patients undergoing robotic surgery due to rectal cancer in six major European centers. Clinicopathological parameters, morbidity, perioperative recovery and short-term outcome were analyzed. RESULTS: A total of 283 restorative surgeries and 65 abdominoperineal resections were carried out. The conversion rate was 4.3%, mean blood loss was 191 ml, and mean operative time was 315 min. Postoperative complications with a Clavien-Dindo score >2 were observed in 13.5%. Obesity and low rectal tumors showed no significant higher rates of major complications or impaired oncological parameters. Male patients had significant higher rates of major complications and anastomotic leakage (p = 0.048 and p = 0.007, respectively). DISCUSSION: RRS is a promising tool for improvement of rectal resections. The well-known pitfalls of minimal-invasive rectal surgery like obesity and low tumors were sufficiently managed by RRS. However, RRS showed significantly higher rates of major complications and anastomotic leakage in male patients, which has to be evaluated by future randomized trials.

Effect of inflammation on the delivery of drugs to dental pulp.

Although numerous studies have evaluated the effects of drugs on inflammation, comparatively few studies have evaluated the effects of inflammation on drugs. In this study, we have evaluated whether pulpal inflammation alters the delivery of flurbiprofen or Evan's blue, two agents that bind with high affinity to plasma proteins. The results indicate that pulpal inflammation alters the delivery of these agents to inflamed molars, that activation of capsaicin-sensitive nerves increases pulpal content of protein-bound agents, and that reduced pH increases free drug concentrations of flurbiprofen. Thus, alterations in both plasma extravasation and tissue pH seem to be relevant factors regulating the delivery and bioavailability of this nonsteroidal anti-inflammatory drug to dental pulp. Because many drugs used in endodontics (e.g. nonsteroidal anti-inflammatory drugs, clindamycin, bupivacaine, etc.) are heavily bound to plasma proteins, it is likely that the status of pulpal inflammation is a contributing factor in modifying the pharmacological efficacy of these agents.