Combined indocyanine green and quantitative perfusion assessment with hyperspectral imaging during colorectal resections

Anastomotic insufficiencies still represent one of the most severe complications in colorectal surgery. Since tissue perfusion highly affects anastomotic healing, its objective assessment is an unmet clinical need. Indocyanine green-based fluorescence angiography (ICG-FA) and hyperspectral imaging (HSI) have received great interest in recent years but surgeons have to decide between both techniques. For the first time, two data processing pipelines capable of reconstructing an ICG-FA correlating signal from hyperspectral data were developed. Results were technically evaluated and compared to ground truth data obtained during colorectal resections. In 87% of 46 data sets, the reconstructed images resembled the ground truth data. The combined applicability of ICG-FA and HSI within one imaging system might provide supportive and complementary information about tissue vascularization, shorten surgery time, and reduce perioperative mortality

Survival after chemotherapy and/or radiotherapy versus self-expanding metal stent insertion in the setting of inoperable esophageal cancer: a case-control study

<p>Abstract</p> <p>Background</p> <p>Our aim was to compare survival of the various treatment modality groups of chemotherapy and/or radiotherapy in relation to SEMS (self-expanding metal stents) in a retrospective case-control study. We have made the hypothesis that the administration of combined chemoradiotherapy improves survival in inoperable esophageal cancer patients.</p> <p>Methods</p> <p>All patients were confirmed histologically as having surgically non- resectable esophageal carcinoma. Included were patients with squamous cell carcinoma, undifferentiated carcinoma as well as Siewert type I--but not type II - esophagogastric junctional adenocarcinoma. The decision to proceed with palliative treatments was taken within the context of a multidisciplinary team meeting and full expert review based on patient's wish, co-morbid disease, clinical metastases, distant metastases, M1 nodal metastases, T4-tumor airway, aorta, main stem bronchi, cardiac invasion, and peritoneal disease. Patients not fit enough to tolerate a radical course of definitive chemo- and/or radiation therapy were referred for self-expanding metal stent insertion. Our approach to deal with potential confounders was to match subjects according to their clinical characteristics (contraindications for surgery) and tumor stage according to diagnostic work-up in four groups: SEMS group (A), Chemotherapy group (B), Radiotherapy group (C), and Chemoradiotherapy group (D).</p> <p>Results</p> <p>Esophagectomy was contraindicated in 155 (35.5%) out of 437 patients presenting with esophageal cancer to the Department of General and Abdominal Surgery of the University Hospital of Mainz, Germany, between November 1997 and November 2007. There were 133 males and 22 females with a median age of 64.3 (43-88) years. Out of 155 patients, 123 were assigned to four groups: SEMS group (A) n = 26, Chemotherapy group (B) n = 12, Radiotherapy group (C) n = 23 and Chemoradiotherapy group (D) n = 62. Mean patient survival for the 4 groups was as follows: Group A: 6.92 ± 8.4 months; Group B: 7.75 ± 6.6 months; Group C: 8.56 ± 9.5 months, and Group D: 13.53 ± 14.7 months. Significant differences in overall survival were associated with tumor histology (<it>P </it>= 0.027), tumor localization (<it>P </it>= 0.019), and type of therapy (<it>P </it>= 0.005), respectively, in univariate analysis. Treatment modality (<it>P </it>= 0.043) was the only independent predictor of survival in multivariate analysis. The difference in overall survival between Group A and Group D was highly significant (<it>P </it>< 0.01) and in favor of Group D. As concerns Group D versus Group B and Group D versus Group C there was a trend towards a difference in overall survival in favor of Group D (<it>P </it>= 0.069 and <it>P </it>= 0.059, respectively).</p> <p>Conclusions</p> <p>The prognosis of inoperable esophageal cancer seems to be highly dependent on the suitability of the induction of patient-specific therapeutic measures and is significantly better, when chemoradiotherapy is applied.</p

Expression of chemokine receptor CXCR4 in esophageal squamous cell and adenocarcinoma

BACKGROUND: Prognosis of esophageal cancer is poor despite curative surgery. The chemokine receptor CXCR4 has been proposed to distinctly contribute to tumor growth, dissemination and local immune escape in a limited number of malignancies. The aim of our study was to evaluate the role of CXCR4 in tumor spread of esophageal cancer with a differentiated view of the two predominant histologic types – squamous cell and adenocarcinoma. METHODS: Esophageal cancer tissue samples were obtained from 102 consecutive patients undergoing esophageal resection for cancer with curative intent. The LSAB+ System was used to detect the protein CXCR4. Tumor samples were classified into two groups based on the homogeneous staining intensity. A cut-off between CXCR4w (= weak expression) and CXCR4s (= strong expression) was set at 1.5 (grouped 0 – 1.5 versus 2.0 – 3). Long-term survival rates were calculated using life tables and the Kaplan-Meier method. Using the Cox's proportional hazards analysis, a model of survival prediction was established. RESULTS: The overall expression rate for CXCR4 in esophageal squamous cell carcinoma was 94.1%. Subdividing these samples, CXCR4w was found in 54.9% and CXCR4s in 45.1%. In adenocarcinoma, an overall expression rate of 89.1% was detected with a weak intensitiy in 71.7% compared to strong staining in 29.3% (p = 0.066 squamous cell versus adenocarcinoma). The Cox's proportional hazards analysis identified the pM-category with a hazard ratio (HR) of 1.860 (95% CI: 1.014–3.414) (p = 0.045), the histologic tumor type (HR: 0.334; 95% CI: 0.180–0.618) (p = 0.0001) and the operative approach (transthoracic > transhiatal esophageal resection) (HR: 0.546; 95% CI: 0.324–0.920) (p = 0.023) as independent factors with a possible influence on the long-term prognosis in patients with esophageal carcinoma, whereas CXCR4 expression was statistically not significant (>0.05). CONCLUSION: Expression of the chemokine receptor CXCR4 in esophageal cancer is of major relevance in both histologic entities – squamous cell and adenocarcinoma. Though with lack of statistical significance, strong CXCR4 expression revealed a poorer long-term prognosis following curative esophagectomy in both histologic subtypes. Thus, the exact biological functions of CXCR4 in terms of tumor dissemination of esophageal cancer is yet undetermined. Inhibition of esophageal cancer progression by CXCR4 antagonists might be a promising therapeutic option in the future

The Frequency Following Response (FFR) May Reflect Pitch-Bearing Information But is Not a Direct Representation of Pitch

The frequency following response (FFR), a scalp-recorded measure of phase-locked brainstem activity, is often assumed to reflect the pitch of sounds as perceived by humans. In two experiments, we investigated the characteristics of the FFR evoked by complex tones. FFR waveforms to alternating-polarity stimuli were averaged for each polarity and added, to enhance envelope, or subtracted, to enhance temporal fine structure information. In experiment 1, frequency-shifted complex tones, with all harmonics shifted by the same amount in Hertz, were presented diotically. Only the autocorrelation functions (ACFs) of the subtraction-FFR waveforms showed a peak at a delay shifted in the direction of the expected pitch shifts. This expected pitch shift was also present in the ACFs of the output of an auditory nerve model. In experiment 2, the components of a harmonic complex with harmonic numbers 2, 3, and 4 were presented either to the same ear (“mono”) or the third harmonic was presented contralaterally to the ear receiving the even harmonics (“dichotic”). In the latter case, a pitch corresponding to the missing fundamental was still perceived. Monaural control conditions presenting only the even harmonics (“2 + 4”) or only the third harmonic (“3”) were also tested. Both the subtraction and the addition waveforms showed that (1) the FFR magnitude spectra for “dichotic” were similar to the sum of the spectra for the two monaural control conditions and lacked peaks at the fundamental frequency and other distortion products visible for “mono” and (2) ACFs for “dichotic” were similar to those for “2 + 4” and dissimilar to those for “mono.” The results indicate that the neural responses reflected in the FFR preserve monaural temporal information that may be important for pitch, but provide no evidence for any additional processing over and above that already present in the auditory periphery, and do not directly represent the pitch of dichotic stimuli

Ecological genetics in the North Atlantic: environmental gradients and adaptation at specific loci

The North Atlantic intertidal community provides a rich set of organismal and environmental material for the study of ecological genetics. Clearly defined environmental gradients exist at multiple spatial scales: there are broad latitudinal trends in temperature, meso-scale changes in salinity along estuaries, and smaller scale gradients in desiccation and temperature spanning the intertidal range. The geology and geography of the American and European coasts provide natural replication of these gradients, allowing for population genetic analyses of parallel adaptation to environmental stress and heterogeneity. Statistical methods have been developed that provide genomic neutrality tests of population differentiation and aid in the process of candidate gene identification. In this paper, we review studies of marine organisms that illustrate associations between an environmental gradient and specific genetic markers. Such highly differentiated markers become candidate genes for adaptation to the environmental factors in question, but the functional significance of genetic variants must be comprehensively evaluated. We present a set of predictions about locus-specific selection across latitudinal, estuarine, and intertidal gradients that are likely to exist in the North Atlantic. We further present new data and analyses that support and contradict these simple selection models. Some taxa show pronounced clinal variation at certain loci against a background of mild clinal variation at many loci. These cases illustrate the procedures necessary for distinguishing selection driven by internal genomic vs. external environmental factors. We suggest that the North Atlantic intertidal community provides a model system for identifying genes that matter in ecology due to the clarity of the environmental stresses and an extensive experimental literature on ecological function. While these organisms are typically poor genetic and genomic models, advances in comparative genomics have provided access to molecular tools that can now be applied to taxa with well-defined ecologies. As many of the organisms we discuss have tight physiological limits driven by climatic factors, this synthesis of molecular population genetics with marine ecology could provide a sensitive means of assessing evolutionary responses to climate change

The Plastid Genome of Eutreptiella Provides a Window into the Process of Secondary Endosymbiosis of Plastid in Euglenids

Euglenids are a group of protists that comprises species with diverse feeding modes. One distinct and diversified clade of euglenids is photoautotrophic, and its members bear green secondary plastids. In this paper we present the plastid genome of the euglenid Eutreptiella, which we assembled from 454 sequencing of Eutreptiella gDNA. Comparison of this genome and the only other available plastid genomes of photosynthetic euglenid, Euglena gracilis, revealed that they contain a virtually identical set of 57 protein coding genes, 24 genes fewer than the genome of Pyramimonas parkeae, the closest extant algal relative of the euglenid plastid. Searching within the transcriptomes of Euglena and Eutreptiella showed that 6 of the missing genes were transferred to the nucleus of the euglenid host while 18 have been probably lost completely. Euglena and Eutreptiella represent the deepest bifurcation in the photosynthetic clade, and therefore all these gene transfers and losses must have happened before the last common ancestor of all known photosynthetic euglenids. After the split of Euglena and Eutreptiella only one additional gene loss took place. The conservation of gene content in the two lineages of euglenids is in contrast to the variability of gene order and intron counts, which diversified dramatically. Our results show that the early secondary plastid of euglenids was much more susceptible to gene losses and endosymbiotic gene transfers than the established plastid, which is surprisingly resistant to changes in gene content

Physiological responses to low-force work and psychosocial stress in women with chronic trapezius myalgia

<p>Abstract</p> <p>Background</p> <p>Repetitive and stressful work tasks have been linked to the development of pain in the trapezius muscle, although the underlying mechanisms still remain unclear. In earlier studies, it has been hypothesized that chronic muscle pain conditions are associated with imbalance in the autonomic nervous system, predominantly expressed as an increased sympathetic activity. This study investigates whether women with chronic trapezius myalgia show higher muscle activity and increased sympathetic tone at baseline and during repetitive low-force work and psychosocial stress, compared with pain-free controls.</p> <p>Methods</p> <p>Eighteen women with chronic trapezius myalgia (MYA) and 30 healthy female controls (CON) were studied during baseline rest, 100 min of repetitive low-force work, 20 min of psychosocial stress (Trier Social Stress Test, TSST), and 80 min recovery. The subjects rated their pain intensity, stress and energy level every 20 min throughout the experiment. Muscle activity was measured by surface electromyography in the trapezius muscle (EMGtrap) and deltoid muscle (EMGdelt). Autonomic reactivity was measured through heart rate (HR), skin conductance (SCL), blood pressure (MAP) and respiration rate (Resp).</p> <p>Results</p> <p>At baseline, EMGtrap, stress ratings, and HR were higher in MYA than in CON. Energy ratings, EMGdelt, SCL, MAP and Resp were, however, similar in the two groups. Significant main group effects were found for pain intensity, stress ratings and EMGtrap. Deltoid muscle activity and autonomic responses were almost identical in MYA and CON during work, stress and recovery. In MYA only, pain intensity and stress ratings increased towards the end of the repetitive work.</p> <p>Conclusion</p> <p>We found increased muscle activity during uninstructed rest in the painful muscle of a group of women with trapezius myalgia. The present study could not confirm the hypothesis that chronic trapezius myalgia is associated with increased sympathetic activity. The suggestion of autonomic imbalance in patients with chronic local or regional musculoskeletal pain needs to be further investigated.</p

Surgical Data Science - from Concepts toward Clinical Translation

Recent developments in data science in general and machine learning in particular have transformed the way experts envision the future of surgery. Surgical Data Science (SDS) is a new research field that aims to improve the quality of interventional healthcare through the capture, organization, analysis and modeling of data. While an increasing number of data-driven approaches and clinical applications have been studied in the fields of radiological and clinical data science, translational success stories are still lacking in surgery. In this publication, we shed light on the underlying reasons and provide a roadmap for future advances in the field. Based on an international workshop involving leading researchers in the field of SDS, we review current practice, key achievements and initiatives as well as available standards and tools for a number of topics relevant to the field, namely (1) infrastructure for data acquisition, storage and access in the presence of regulatory constraints, (2) data annotation and sharing and (3) data analytics. We further complement this technical perspective with (4) a review of currently available SDS products and the translational progress from academia and (5) a roadmap for faster clinical translation and exploitation of the full potential of SDS, based on an international multi-round Delphi process

Definition, diagnosis and treatment of oligometastatic oesophagogastric cancer: A Delphi consensus study in Europe

BACKGROUND Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. METHODS In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%). RESULTS A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). CONCLUSION The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials

A Controversy That Has Been Tough to Swallow: Is the Treatment of Achalasia Now Digested?

Esophageal achalasia is a rare neurodegenerative disease of the esophagus and the lower esophageal sphincter that presents within a spectrum of disease severity related to progressive pathological changes, most commonly resulting in dysphagia. The pathophysiology of achalasia is still incompletely understood, but recent evidence suggests that degeneration of the postganglionic inhibitory nerves of the myenteric plexus could be due to an infectious or autoimmune mechanism, and nitric oxide is the neurotransmitter affected. Current treatment of achalasia is directed at palliation of symptoms. Therapies include pharmacological therapy, endoscopic injection of botulinum toxin, endoscopic dilation, and surgery. Until the late 1980s, endoscopic dilation was the first line of therapy. The advent of safe and effective minimally invasive surgical techniques in the early 1990s paved the way for the introduction of laparoscopic myotomy. This review will discuss the most up-to-date information regarding the pathophysiology, diagnosis, and treatment of achalasia, including a historical perspective. The laparoscopic Heller myotomy with partial fundoplication performed at an experienced center is currently the first line of therapy because it offers a low complication rate, the most durable symptom relief, and the lowest incidence of postoperative gastroesophageal reflux