Meta-analysis of randomized controlled trials and individual patient data comparing minimally invasive with open oesophagectomy for cancer.

BACKGROUND: Minimally invasive oesophagectomy (MIO) for oesophageal cancer may reduce surgical complications compared with open oesophagectomy. MIO is, however, technically challenging and may impair optimal oncological resection. The aim of the present study was to assess if MIO for cancer is beneficial. METHODS: A systematic literature search in MEDLINE, Web of Science and CENTRAL was performed and randomized controlled trials (RCTs) comparing MIO with open oesophagectomy were included in a meta-analysis. Survival was analysed using individual patient data. Random-effects model was used for pooled estimates of perioperative effects. RESULTS: Among 3219 articles, six RCTs were identified including 822 patients. Three-year overall survival (56 (95 per cent c.i. 49 to 62) per cent for MIO versus 52 (95 per cent c.i. 44 to 60) per cent for open; P = 0.54) and disease-free survival (54 (95 per cent c.i. 47 to 61) per cent versus 50 (95 per cent c.i. 42 to 58) per cent; P = 0.38) were comparable. Overall complication rate was lower for MIO (odds ratio 0.33 (95 per cent c.i. 0.20 to 0.53); P < 0.010) mainly due to fewer pulmonary complications (OR 0.44 (95 per cent c.i. 0.27 to 0.72); P < 0.010), including pneumonia (OR 0.41 (95 per cent c.i. 0.22 to 0.77); P < 0.010). CONCLUSION: MIO for cancer is associated with a lower risk of postoperative complications compared with open resection. Overall and disease-free survival are comparable for the two techniques. LAY SUMMARY: Oesophagectomy for cancer is associated with a high risk of complications. A minimally invasive approach might be less traumatic, leading to fewer complications and may also improve oncological outcome. A meta-analysis of randomized controlled trials comparing minimally invasive to open oesophagectomy was performed. The analysis showed that the minimally invasive approach led to fewer postoperative complications, in particular, fewer pulmonary complications. Survival after surgery was comparable for the two techniques.

Oesophagectomy for cancer is associated with a high risk of complications. A minimally invasive approach might be less traumatic, leading to fewer complications and may also improve oncological outcome. A meta-analysis of randomized controlled trials comparing minimally invasive to open oesophagectomy was performed. The analysis showed that the minimally invasive approach led to fewer postoperative complications, in particular, fewer pulmonary complications. Survival after surgery was comparable for the two techniques.

Fit-for-Discharge Criteria after Esophagectomy: An International Expert Delphi Consensus.

There are no internationally recognized criteria available to determine preparedness for hospital discharge after esophagectomy. This study aims to achieve international consensus using Delphi methodology. The expert panel consisted of 40 esophageal surgeons spanning 16 countries and 4 continents. During a 3-round, web-based Delphi process, experts voted for discharge criteria using 5-point Likert scales. Data were analyzed using descriptive statistics. Consensus was reached if agreement was ≥75% in round 3. Consensus was achieved for the following basic criteria: nutritional requirements are met by oral intake of at least liquids with optional supplementary nutrition via jejunal feeding tube. The patient should have passed flatus and does not require oxygen during mobilization or at rest. Central venous catheters should be removed. Adequate analgesia at rest and during mobilization is achieved using both oral opioid and non-opioid analgesics. All vital signs should be normal unless abnormal preoperatively. Inflammatory parameters should be trending down and close to normal (leucocyte count ≤12G/l and C-reactive protein ≤80 mg/dl). This multinational Delphi survey represents the first expert-led process for consensus criteria to determine 'fit-for-discharge' status after esophagectomy. Results of this Delphi survey may be applied to clinical outcomes research as an objective measure of short-term recovery. Furthermore, standardized endpoints identified through this process may be used in clinical practice to guide decisions regarding patient discharge and may help to reduce the risk of premature discharge or prolonged admission.

[Pretherapeutic misclassification of esophageal cancer and adenocarcinoma of the esophagogastric junction : Possibilities and clinical consequences]. / Prätherapeutische Fehlklassifikationen bei Ösophaguskarzinomen und Adenokarzinomen des ösophagogastralen Übergangs : Möglichkeiten und klinische Konsequenzen.

During the course of a malignant disease, the tumor needs to be classified repeatedly in order to facilitate decision-making in treatment and to estimate patients prognosis; however, a wrong classification of tumors can occur in different stages of the disease course with tremendous consequences for the affected patients. This review discusses the possible misclassifications which can occur in patients with esophageal cancer or adenocarcinoma of the esophagogastric junction (EGJ), along with the consequences.

Diagnostic criteria and symptom grading for delayed gastric conduit emptying after esophagectomy for cancer: international expert consensus based on a modified Delphi process.

Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air-fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process.

[Updated German S3 guidelines on esophageal cancer and supplements from a surgical perspective]. / Aktualisierte S3-Leitlinie zum Ösophaguskarzinom und Ergänzungen aus chirurgischer Sicht.

The updated German S3 guidelines recommend transthoracic subtotal esophagectomy with 2­field lymphadenectomy for surgical treatment of esophageal cancer in patients with squamous cell carcinoma and adenocarcinoma of the esophagogastric (AEG type I) junction of the middle and lower third. For AEG type III transhiatal extended total gastrectomy with distal esophageal resection is favored. Patients with AEG type II can be treated by both procedures under the prerequisite that an R0 resection can be achieved. A limited resection of the distal esophagus and the proximal stomach can only be considered in cT1 N0 M0 possibly cT2 AEG junction without an oncological risk constellation, i.e. grade G1/G2, intestinal type and no poorly cohesive carcinoma, because the rate of lymph node metastasis at the distal stomach is less than 2%. Minimally invasive procedures provide advantages compared to open esophagectomy due to the lower rate of postoperative total and especially pulmonary complications. This is true for hybrid esophagectomy (laparoscopy and thoracotomy) versus open access in cases of intrathoracic anastomoses and for total minimally invasive esophagectomy including robotic techniques versus open access in cervical esophagogastrostomy.

Surgical management of esophageal sarcoma: a multicenter European experience.

Esophageal sarcomas are rare and evidence in literature is scarce making their management difficult. The objective is to report surgical and oncological outcomes of esophageal sarcoma in a large multicenter European cohort. This is a retrospective multicenter study including all patients who underwent en-bloc esophagectomy for esophageal sarcoma in seven European tertiary referral centers between 1987 and 2016. The main outcomes and measures are pathological results, early and long-term outcomes. Among 10,936 esophageal resections for cancer, 21 (0.2%) patients with esophageal sarcoma were identified. The majority of tumors was located in the middle (n = 7) and distal (n = 9) third of the esophagus. Neoadjuvant chemoradiotherapy was performed in five patients. All the patients underwent en-bloc transthoracic esophagectomy (19 open, 2 minimally invasive). Postoperative mortality occurred in 1 patient (5%). One patient received adjuvant chemotherapy. Definitive pathological results were carcinosarcoma (n = 7), leiomyosarcoma (n = 5), and other types of sarcoma (n = 9). Microscopic R1 resection was present in one patient (5%) and seven patients (33%) had positive lymph nodes. Median follow-up was 16 (3-79) months in 20 of 21 patients (95%). One-, 3-, and 5-year overall survival rates were 74%, 43%, and 35%, respectively. One-, 3- and 5-years disease-free survival rates were 58%, 40%, and 33%, respectively. Median overall survival was 6 months in N+ patients vs. 37 months for N0 patients (p = 0.06). At the end of the follow-up period, nine patients had died from cancer recurrences (43%), three patients died from other reasons (14%), one patient was still alive with recurrence (5%) and the seven remaining patients were free of disease (33%). Recurrence was local (n = 3), metastatic (n = 3), or both (n = 4). In conclusion, carcinosarcoma and leiomyosarcoma were the most common esophageal sarcoma histological subtypes. Lymph node involvement was seen in one third of cases. A transthoracic en-bloc esophagectomy with radical lymphadenectomy should be the best surgical option to achieve complete resection. Long-term survival remained poor with a high local and distant recurrence rate.

[Profit center analysis of esophagectomy : Economical analysis of transthoracic esophagectomy depending on postoperative complications]. / Profit-Center-Analyse der Ösophagektomie : Ökonomische Analyse der transthorakalen Ösophagektomie in Abhängigkeit von postoperativen Komplikationen.

Due to increasing medical costs and yet limited financial resources, medical treatment and economic analyses can no longer be separated; therefore, direct costing and cost unit accounting become more and more relevant as controlling tools in hospital management. Transthoracic esophagectomy is an integral part of the current treatment concept in patients with esophageal carcinoma. The question of the present study was whether the present diagnosis-related groups (DRG) system is a cost-effective tool to represent transthoracic esophagectomy. In this retrospective study at a high-volume center, 161 consecutive patients with esophageal carcinoma were included. All patients were surgically treated according to the current S3 guidelines by a transthoracic esophagectomy. Detailed and standardized documentation of the postoperative complications was made according to the classification of Clavien-Dindo and the guidelines of the Esophagectomy Complications Consensus Group (ECCG). For each individual patient, the respective actual costs were analyzed according to the Institute for the Remuneration System in Hospitals (InEK) cost accounting approach comparing DRG payments (DRG G03A) on a case level including all extra fees per DRG catalogue. The mean costs per case of all included 161 patients were 24,338 € (median: 19,210 €, range: 12,149-127,376 €), while mean payments per case of 22,591 € were recorded. For the entire study population, the profit margin was -281,330 € (mean: -1747 €). Only patients with an uncomplicated course (Clavien-Dindo 0) yielded a slightly positive profit margin of 2514 €. With increasing complication score the profit margin became increasingly negative (Clavien-Dindo I: -2878 €, Clavien-Dindo IVb: -58,543 €). Within the analysis of the InEK target cost matrix, main cost drivers can be identified as medical services (22.3%) and non-medical infrastructure (18.7%). Surgical treatment according to the existing guidelines of patients with esophageal carcinoma is not cost-covering in high-volume centers and cannot be solely financed by existing DRG revenues.

Impact of the Weekday of Surgery on Outcome in Gastric Cancer Patients who Underwent D2-Gastrectomy.

BACKGROUND: The impact of the weekday of surgery in major elective cases of the upper-GI has been discussed controversially. The objective of this study was to assess whether weekday of surgery influences outcome in patients undergoing D2-gastrectomy. MATERIALS AND METHODS: Patients who underwent D2-gastrectomy for gastric adenocarcinoma between 1996 and 2016 were included. Weekday of surgery was recognized, and subgroups were analyzed regarding clinical and histopathological differences. Survival analysis was performed based on weekday of surgery, and early weekdays (Monday-Tuesday) were compared with late weekdays (Wednesday-Friday). RESULTS: In total, 460 patients, 71% male and 29% female, were included into analysis. The median age was 65 years. Distribution to each weekday was equal and ranged from 86 cases (Wednesday) to 96 cases (Tuesday). The pT, pN and M category and the rate of patients who underwent neoadjuvant treatment did not show significant differences (p = 0.641; p = 0.337; p = 0.752; p = 0.342, respectively). The subgroups did not differ regarding the number of dissected lymph nodes and rate of R-1/2 resections (p = 0.590; p = 0.241, respectively). Survival analysis showed a median survival of 43 months (95% CI 31-55 months), and there was no single weekday or a combination of weekdays (Mon/Tue vs Wed/Thu/Fri) with a significant favorable or worse outcome (p = 0.863; p = 0.30, respectively). The outcome did not differ regarding mortality within the first 90 days after surgery (p = 0.948). CONCLUSIONS: The present study does not show any evidence for a significant impact of weekday of surgery on short- and long-term outcome of patients undergoing gastrectomy for gastric adenocarcinoma.

A structured training program for minimally invasive esophagectomy for esophageal cancer- a Delphi consensus study in Europe.

Evidence suggests that structured training programs for laparoscopic procedures can ensure a safe standard of skill acquisition prior to independent practice. Although minimally invasive esophagectomy (MIO) is technically demanding, no consensus on requirements for training for the MIO procedure exists. The aim of this study is to determine essential steps required for a structured training program in MIO using the Delphi consensus methodology. Eighteen MIO experts from 13 European hospitals were asked to participate in this study. The consensus process consisted of two structured meetings with the expert panel, and two Delphi questionnaire rounds. A list of items required for training MIO were constructed for three key domains of MIO, including (1) requisite criteria for units wishing to be trained and (2) to proctor MIO, and (3) a framework of a MIO training program. Items were rated by the experts on a scale 1-5, where 1 signified 'not important' and 5 represented 'very important.' Consensus for each domain was defined as achieving Cronbach alpha ≥0.70. Items were considered as fundamental when ≥75% of experts rated it important (4) or very important (5). Both Delphi rounds were completed by 16 (89%) of the 18 invited experts, with a median experience of 18 years with minimally invasive surgery. Consensus was achieved for all three key domains. Following two rounds of a 107-item questionnaire, 50 items were rated as essential for training MIO. A consensus among European MIO experts on essential items required for training MIO is presented. The identified items can serve as directive principles and core standards for creating a comprehensive training program for MIO.

Endoscopic and histopathologic reflux-associated mucosal damage in the remnant esophagus following transthoracic esophagectomy for cancer-5-year long-term follow-up.

Gastroesophageal reflux is a common problem following esophagectomy and reconstruction with gastric interposition. Despite a routine prescription of proton pump inhibitors, reflux-associated mucosal damage in the remnant esophagus is frequently observed. Purpose of this study is to evaluate mucosal damage in the esophageal remnant during long-term follow-up and to compare the prevalence of this damage between the subgroups of esophageal squamous cell and adenocarcinoma. All patients undergoing transthoracic Ivor-Lewis esophagectomy were prospectively entered in our IRB approved database. All patients underwent a routine check-up program with yearly surveillance endoscopies following esophagectomy. Only patients with a complete follow-up were included into this study. Endoscopic and histopathologic mucosal changes of the remnant esophagus were analyzed in close intervals. A total of 50 patients met the inclusion criteria, consisting of 31 adenocarcinomas (AC) and 19 squamous cell carcinomas (SCC). Mucosal damage was already seen 1 year after surgery in 20 patients macroscopically (43%) and in 21 patients microscopically (45%). At 5-year follow-up the prevalence for macroscopic and microscopic damage was 55% and 60%, respectively. The prevalence of mucosal damage was higher in AC patients than in SCC patients (1y-FU: 51% [AC] vs. 28% [SCC]; 5y-FU: 68% [AC] vs. 35% [SCC], P < 0.05). Newly acquired Barrett's esophagus was seen in 10 patients (20%) with two of those patients (20%) showing histopathologic proof of neoplasia. This study shows a high prevalence of reflux-associated mucosal damage in the remnant esophagus one year out of surgery and only a moderate increase in prevalence in the following years. Mucosal damage was more frequently seen in AC patients and the occurrence of de-novo Barrett's esophagus and de-novo neoplasia was high. Endoscopic surveillance with targeted biopsies seems to be an indispensable tool to follow patients after esophagectomy appropriately.

Neoadjuvant chemotherapy or chemoradiation for patients with advanced adenocarcinoma of the oesophagus? A propensity score-matched study.

BACKGROUND: Multimodal therapies are the standard of care for advanced adenocarcinomas of the oesophagus and gastro-oesophageal junction (AEG Types I and II). Only three randomised trials have compared preoperative chemotherapy with and without radiation. The results showed a small benefit for combined chemoradiation. In the meantime, newer therapy protocols are available. AIM: In a propensity-score matched study, we analysed patients with locally advanced AEG type I or II, treated with chemotherapy (FLOT-protocol) or chemoradiation (CROSS-protocol), followed by oesophagectomy, in a single high-volume centre. PATIENTS AND METHODS: Between 2011 and 2015, 137 patients with advanced (cT3NxcM0) adenocarcinoma received pre-operative therapy; 70% had chemoradiation (CROSS-protocol) and 30% had chemotherapy (FLOT-protocol). After propensity-score matching, 40 patients from the CROSS-group were selected for analysis. Postoperative histopathological response and prognosis were analysed. RESULTS: The two groups were comparable according to the matching criteria age, gender, tumour location, and year of surgery. R0-resection was achieved in 97% of patients in the CROSS-group and 85% of the FLOT-group (p = 0.049). Major response of the primary tumour was evident more often in the CROSS-group (17/40 pts. 43%) versus FLOT-group (11/40 pts. 27%) as well no lymph node metastasis (ypN0 = 68% versus ypN0 = 40%) (p = 0.014). Prognosis were not significantly different between the two groups. In multivariate analysis, only ypN-category was an independent prognostic factor. CONCLUSION: Compared to FLOT-chemotherapy, neoadjuvant chemoradiotherapy with the CROSS-protocol in locally advanced adenocarcinoma AEG types I and II resulted in better response by the primary tumour and less lymph node metastasis but without superior survival.

[Impact of perioperative nutritional therapy on risk and complication management in patients undergoing esophagectomy for cancer]. / Bedeutung der perioperativen Ernährungstherapie beim Risiko- und Komplikationsmanagement von Patienten mit Ösophaguskarzinom.

Esophagectomy is considered to be a high risk procedure regarding postoperative morbidity and mortality. Therefore, in Germany, these operations are limited to hospitals fulfilling a minimum quantity. This systematic review focuses on risk and complication management regarding the impact of perioperative nutritional therapy, including the recent S3-guideline recommendations and comments of the German Working Group of Medical Societies (AWMF) which were established with contributions from the authors.

[New S3 guideline for esophageal cancer : Important surgical aspects]. / Die neue S3-Leitlinie zum Ösophaguskarzinom : Wichtige chirurgische Aspekte.

The current German S3 guideline represents the recommendations for the diagnosis and therapy of squamous cell carcinomas and adenocarcinomas of the esophagus based on evidence from the literature and interdisciplinary expert consensus. Esophagogastroscopy with biopsy, endosonography, and spiral CT scan of the neck, thorax, and abdomen are decisive in staging and the choice of therapy. For a curative approach, surgery, especially transthoracic esophagectomy and gastric pull-up, is the most important therapeutic option, except in the case of mucosal carcinomas or cervical squamous cell carcinomas. The significance of total minimally invasive esophageal resection or a hybrid technique is still uncertain. In category cT3 or resectable cT4 tumors, neoadjuvant radiochemotherapy should be performed in squamous cell carcinomas or adenocarcinomas. Alternatively, perioperative chemotherapy can be carried out in adenocarcinoma. Palliative resections should be avoided and replaced by interventional procedures for palliation.

Management of Tracheo- or Bronchoesophageal Fistula After Ivor-Lewis Esophagectomy.

BACKGROUND: The development of tracheo- or bronchoesophageal fistula (TBF) after Ivor-Lewis esophagectomy remains to be a rare complication associated with a high mortality rate. METHODS: In this retrospective study, the charts of patients with TBF after esophagectomy were analyzed in terms of individual patient characteristics, esophagotracheal complications, respiratory function, management, and outcome. RESULTS: Between January 2000 and December 2014, 1204 patients underwent Ivor-Lewis esophagectomy for esophageal cancer; 13 patients (1.1 %) developed a TBF. In all 13 patients, a concomitant leakage of the intrathoracic esophagogastrostomy was evident, either prior to diagnosis of TBF (metachronous TBF) or simultaneously (synchronous TBF). TBF was predominantly located in the left main bronchus (n = 6, 46.1 %) or trachea (n = 5, 38.5 %). Management of TBF included re-thoracotomy (n = 7), interventional endoscopic (n = 10) or bronchoscopic therapy (n = 4). In the majority of patients (n = 8), management consisted of two subsequent treatment modalities. In 3 out of four patients, TBF was successfully treated by endoscopic stenting only. Five patients (38.5 %) died following a septic course with multiple organ failure. CONCLUSIONS: The development of TBF after Ivor-Lewis esophagectomy is always combined with anastomotic leakage of the esophagogastrostomy. Treatment options primarily depend on the vascularization of the gastric conduit, the severity of the concomitant aspiration pneumonia, and the volume of the air leakage.

Comparison of environmental risk factors for esophageal atresia, anorectal malformations, and the combined phenotype in 263 German families.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and anorectal malformations (ARM) represent the severe ends of the fore- and hindgut malformation spectra. Previous research suggests that environmental factors are implicated in their etiology. These risk factors might indicate the influence of specific etiological mechanisms on distinct developmental processes (e.g. fore- vs. hindgut malformation). The present study compared environmental factors in patients with isolated EA/TEF, isolated ARM, and the combined phenotype during the periconceptional period and the first trimester of pregnancy in order to investigate the hypothesis that fore- and hindgut malformations involve differing environmental factors. Patients with isolated EA/TEF (n = 98), isolated ARM (n = 123), and the combined phenotype (n = 42) were included. Families were recruited within the context of two German multicenter studies of the genetic and environmental causes of EA/TEF (great consortium) and ARM (CURE-Net). Exposures of interest were ascertained using an epidemiological questionnaire. Chi-square, Fisher's exact, and Mann-Whitney U-tests were used to assess differences between the three phenotypes. Newborns with isolated EA/TEF and the combined phenotype had significantly lower birth weights than newborns with isolated ARM (P = 0.001 and P < 0.0001, respectively). Mothers of isolated EA/TEF consumed more alcohol periconceptional (80%) than mothers of isolated ARM or the combined phenotype (each 67%). Parental smoking (P = 0.003) and artificial reproductive techniques (P = 0.03) were associated with isolated ARM. Unexpectedly, maternal periconceptional multivitamin supplementation was most frequent among patients with the most severe form of disorder, i.e. the combined phenotype (19%). Significant differences in birth weight were apparent between the three phenotype groups. This might be attributable to the limited ability of EA/TEF fetuses to swallow amniotic fluid, thus depriving them of its nutritive properties. Furthermore, the present data suggest that fore- and hindgut malformations involve differing environmental factors. Maternal periconceptional multivitamin supplementation was highest among patients with the combined phenotype. This latter finding is contrary to expectation, and warrants further analysis in large prospective epidemiological studies.

Mass spectrometry-based ligand binding assays on adenosine A1 and A2A receptors.

Conventional methods to measure ligand-receptor binding parameters typically require radiolabeled ligands as probes. Despite the robustness of radioligand binding assays, they carry inherent disadvantages in terms of safety precautions, expensive synthesis, special lab requirements, and waste disposal. Mass spectrometry (MS) is a method that can selectively detect ligands without the need of a label. The sensitivity of MS equipment increases progressively, and currently, it is possible to detect low ligand quantities that are usually found in ligand binding assays. We developed a label-free MS ligand binding (MS binding) assay on the adenosine A(1) and A(2A) receptors (A(1)AR and A(2A)AR), which are well-characterized members of the class A G protein-coupled receptor (GPCR) family. Radioligand binding assays for both receptors are well established, and ample data is available to compare and evaluate the performance of an MS binding assay. 1,3-Dipropyl-8-cyclopentyl-xanthine (DPCPX) and 4-(2-((7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a]-[1,3,5]triazin-5-yl)amino)ethyl)phenol (ZM-241,385) are high-affinity ligands selective for the A(1)AR and A(2A)AR, respectively. To proof the feasibility of MS binding on the A(1)AR and A(2A)AR, we first developed an MS detection method for unlabeled DPCPX and ZM-241,385. To serve as internal standards, both compounds were also deuterium-labeled. Subsequently, we investigated whether the two unlabeled compounds could substitute for their radiolabeled counterparts as marker ligands in binding experiments, including saturation, displacement, dissociation, and competition association assays. Furthermore, we investigated the accuracy of these assays if the use of internal standards was excluded. The results demonstrate the feasibility of the MS binding assay, even in the absence of a deuterium-labeled internal standard, and provide great promise for the further development of label-free assays based on MS for other GPCRs.

Preoperative airway colonization prior to transthoracic esophagectomy predicts postoperative pulmonary complications.

PURPOSE: Respiratory complications are responsible to a high degree for postoperative morbidity and mortality after Ivor-Lewis esophagectomy. The etiology of respiratory failure is known to be multifactorial with preoperative impaired lung function being the most important one. The aim of this study was to investigate the correlation between preoperative airway colonization (PAC) and postoperative respiratory complications. METHODS: In this observational study, 64 patients with esophageal cancer were included. All patients underwent Ivor-Lewis esophagectomy with laparoscopic or open gastric mobilization. After induction of anesthesia and intubation with a double-lumen tube, bronchial exudate was collected by random endoluminal suction for further microbiological work-up. Length of postoperative mechanical ventilation (<24 h, 24-72 h, >72 h), re-intubation, and tracheostomy were recorded as primary and secondary study endpoints. RESULTS: In 13 of 64 study patients (20.3 %), pathological colonization of the bronchial airways could be proved prior to esophagectomy. Haemophilus species was the most frequently identified pathogen. PAC was associated with a longer history of smoking (p = 0.025), a lower preoperative forced expiratory volume (FEV1, p = 0.009) or vital capacity (VC, p = 0.038), a prolonged postoperative mechanical ventilation (p < 0.001), and a higher frequency of re-intubation (p < 0.001) and tracheostomy (p = 0.017). In the multivariate analysis, PAC was identified as an independent predictor of respiratory failure (hazard ratio 11.4, 95 % confidence interval 2.6-54, p = 0.002). Mortality in the PAC group was 30.8 % compared to 0 % in patients without PAC (p < 0.0001). CONCLUSION: PAC is a significant risk factor for postoperative respiratory failure. A routine bronchoscopy and bronchoalveolar lavage as part of preoperative management prior to esophagectomy need to be discussed.

Economic burden of Clostridium difficile associated diarrhoea: a cost-of-illness study from a German tertiary care hospital.

PURPOSE: Clostridium difficile associated diarrhoea (CDAD) is the most common cause of health-care-associated infectious diarrhoea. In the context of the German health-care system, direct and indirect costs of an initial episode of CDAD and of CDAD recurrence are currently unknown. METHODS: We defined CDAD as presence of diarrhoea (≥3 unformed stools/day) in association with detection of Clostridium difficile toxin in an unformed faecal sample. Patients treated with metronidazole (PO or IV) and/or vancomycin (PO) were included. Comprehensive data of patients were retrospectively documented into a database using the technology of the Cologne Cohort of Neutropenic Patients (CoCoNut). Patients with CDAD were matched to control patients in a 1:1 ratio. Analysis was split in three groups: incidence group (CDAD patients without recurrence), recurrence group (CDAD patients with ≥1 recurrence) and control group (matched non-CDAD patients). RESULTS: Between 02/2010 and 12/2011, 150 patients with CDAD (114 patients in the incidence and 36 (24 %) in the recurrence group) and 150 controls were analysed. Mean length of stay was: 32 (95 %CI: 30-37), 94 (95 %CI: 76-112) and 24 days (95 %CI: 22-27; P = <0.001), resulting in mean overall direct treatment costs per patient of €18,460 (95 %CI: €14,660-€22,270), €73,900 (95 %CI: €50,340-€97,460) and €14,530 (95 %CI: €11,730-€17,330; P = <0.001). In the incidence and recurrence group, the mean cumulative number of antibiotic CDAD treatment days was 11 (95 %CI: 10-12) and 36 (95 %CI: 27-45; P = <0.001). CONCLUSIONS: Especially CDAD recurrence was associated with excessive costs, which were mostly attributable to a significantly longer overall length of stay. Innovative treatment strategies are warranted to reduce treatment costs and prevent recurrence of CDAD.