Clinical and functional outcome following robotic Heller-myotomy with partial fundoplication in patients with achalasia.

Robotic-assisted myotomy with partial fundoplication for patients with achalasia has been established as a safe and effective procedure with similar short-term results and lower rates of intraoperative esophageal perforations. Our aim was to investigate a defined patient cohort undergoing robotic-assisted and laparoscopic surgery providing pre- and postoperative symptom score and high-resolution manometry to evaluate the clinical and functional outcome.All patients underwent clinical, endoscopic, radiological and manometric investigation to verify the diagnosis of achalasia. High-resolution manometry was performed preoperatively and 6 months postoperatively and categorized according to the Chicago Classification (v4.0). We used the Eckardt Score to evaluate symptomatic outcome. All patients underwent either robotic-assisted or laparoscopic myotomy with partial anterior fundoplication (180° Dor) using the DaVinci Xi surgical system (Intuitive, Sunnyvale, California, USA). From a total amount of 101 patients, we analyzed the data of 78 (47 robotic and 31 laparoscopic) procedures between 2015 and 2020. All patients showed a significant decrease of the Eckardt Score in the robotic group (median 6 vs. 2) as well as in the laparoscopic group (median 7.5 vs. 3). The postoperative LESP and 4 s-IRP was significantly reduced in all patients in the robotic group [median LESP (mmHg) 34.16 vs. 16.9; median 4 s-IRP (mmHg) 28.85 vs. 14.55], as well as in the laparoscopic group [median LESP (mmHg) 35.34 vs. 17.3; median 4 s-IRP (mmHg) 25.6 vs. 15.9]. There was no significant difference for these parameters between the groups. There was no event of intraoperative esophageal perforation in the robotic cohort, whereas there were 2 in the laparoscopic group. Our data support the safe and effective robotic approach for the surgical treatment of achalasia. Not only the clinical outcome but also the functional results measured by high-resolution manometry are similar to the laparoscopic procedure. Further investigations in larger prospective multicenter studies are needed.

Hyperspectral Imaging (HSI) in Acute Mesenteric Ischemia to Detect Intestinal Perfusion Deficits.

BACKGROUND: Acute mesenteric ischemia is a life-threatening acute condition, which requires an interdisciplinary approach, including vascular recanalization and surgical treatment. Visual evaluation of intestinal perfusion might be misleading, and therefore, additional tools are necessary to reliably be able to resect the ischemic intestine. Hyperspectral imaging (HSI) has been shown to be feasible and safe for real-time assessment of tissue perfusion in visceral surgery but has never been used in cases of acute mesenteric ischemia. Therefore, we applied HSI in acute mesenteric ischemia to evaluate it for potential aid in the objectively discriminating ischemic and well-perfused intestine during explorative laparotomy. METHODS: We recorded HSI measurements in 11 cases of acute mesenteric ischemia during explorative laparotomy. We evaluated the recorded images for macroscopic visual perfusion quality and divided it into three groups. Of those three groups, we calculated and compared the HSI indexes of tissue saturation, near-infrared perfusion index, organ hemoglobin index, and tissue water index, as well as the reflectance spectra. RESULTS: We found significant differences in tissue saturation (0.7% versus 0.45%; P = 0.002) and near-infrared perfusion index (0.58 versus 0.23; P < 0.001) in poorly perfused intestinal segments compared with the viable intestine. Furthermore, we could detect an increasing peak at 630 nm of the reflectance spectra in less viable tissues, indicating a maximum in necrotic tissues. We attributed this peak to an increase in met-hemoglobin content in necrotic tissues, which is supported by the increase in the HSI organ hemoglobin index. CONCLUSIONS: HSI is able to discriminate tissue perfusion in acute mesenteric ischemia reliably and therefore might be helpful for resection. In addition, HSI gives information on tissue viability via reflectance spectra.

Tissue classification of oncologic esophageal resectates based on hyperspectral data.

PURPOSE: Esophageal carcinoma is the eighth most common cancer worldwide. Esophageal resection with gastric pull-up is a potentially curative therapeutic option. After this procedure, the specimen is examined by the pathologist to confirm complete removal of the cancer. An intraoperative analysis of the resectate would be less time-consuming and therefore improve patient safety. METHODS: Hyperspectral imaging (HSI) is a relatively new modality, which has shown promising results for the detection of tumors. Automatic approaches could support the surgeon in the visualization of tumor margins. Therefore, we evaluated four supervised classification algorithms: random forest, support vector machines (SVM), multilayer perceptron, and k-nearest neighbors to differentiate malignant from healthy tissue based on HSI recordings of esophago-gastric resectates in 11 patients. RESULTS: The best performances were obtained with a cancerous tissue detection of 63% sensitivity and 69% specificity with the SVM. In a leave-one patient-out cross-validation, the classification showed larger performance differences according to the patient data used. In less than 1 s, data classification and visualization was shown. CONCLUSION: In this work, we successfully tested several classification algorithms for the automatic detection of esophageal carcinoma in resected tissue. A larger data set and a combination of several methods would probably increase the performance. Moreover, the implementation of software tools for intraoperative tumor boundary visualization will further support the surgeon during oncologic operations.

Evaluation of hyperspectral imaging (HSI) for the measurement of ischemic conditioning effects of the gastric conduit during esophagectomy.

BACKGROUND: Hyperspectral imaging (HSI) is a relatively new method used in image-guided and precision surgery, which has shown promising results for characterization of tissues and assessment of physiologic tissue parameters. Previous methods used for analysis of preconditioning concepts in patients and animal models have shown several limitations of application. The aim of this study was to evaluate HSI for the measurement of ischemic conditioning effects during esophagectomy. METHODS: Intraoperative hyperspectral images of the gastric tube through the mini-thoracotomy were recorded from n = 22 patients, 14 of whom underwent laparoscopic gastrolysis and ischemic conditioning of the stomach with two-step transthoracic esophagectomy and gastric pull-up with intrathoracic anastomosis after 3-7 days. The tip of the gastric tube (later esophagogastric anastomosis) was measured with HSI. Analysis software provides a RGB image and 4 false color images representing physiologic parameters of the recorded tissue area intraoperatively. These parameters contain tissue oxygenation (StO2), perfusion-(NIR Perfusion Index), organ hemoglobin (OHI), and tissue water index (TWI). RESULTS: Intraoperative HSI of the gastric conduit was possible in all patients and did not prolong the regular operative procedure due to its quick applicability. In particular, the tissue oxygenation of the gastric conduit was significantly higher in patients who underwent ischemic conditioning ([Formula: see text] = 78%; [Formula: see text] = 66%; p = 0.03). CONCLUSIONS: HSI is suitable for contact-free, non-invasive, and intraoperative evaluation of physiological tissue parameters within gastric conduits. Therefore, HSI is a valuable method for evaluating ischemic conditioning effects and may contribute to reduce anastomotic complications. Additional studies are needed to establish normal values and thresholds of the presented parameters for the gastric conduit anastomotic site.

Natural Keratin and Coconut Fibres from Industrial Wastes in Flame Retarded Thermoplastic Starch Biocomposites.

Natural keratin fibres derived from Mexican tannery waste and coconut fibres from coconut processing waste were used as fillers in commercially available, biodegradable thermoplastic starch-polyester blend to obtain sustainable biocomposites. The morphology, rheological and mechanical properties as well as pyrolysis, flammability and forced flaming combustion behaviour of those biocomposites were investigated. In order to open up new application areas for these kinds of biocomposites, ammonium polyphosphate (APP) was added as a flame retardant. Extensive flammability and cone calorimeter studies revealed a good flame retardance effect with natural fibres alone and improved effectiveness with the addition of APP. In fact, it was shown that replacing 20 of 30 wt. % of APP with keratin fibres achieved the same effectiveness. In the case of coconut fibres, a synergistic effect led to an even lower heat release rate and total heat evolved due to reinforced char residue. This was confirmed via scanning electron microscopy of the char structure. All in all, these results constitute a good approach towards sustainable and biodegradable fibre reinforced biocomposites with improved flame retardant properties.

Before and after Esophageal Surgery: Which Information Is Needed from the Functional Laboratory?

BACKGROUND: Indications for benign esophageal surgery and postoperative follow-up need to be highly elaborated with differentiated and structured algorithms, based on objective functional workup in the esophageal laboratory. Functional outcome is of utmost interest and has to be driven by the need for comprehensive but purposeful diagnostic methods. METHODS: Preoperative diagnostic workup procedures by the functional laboratory include 24-h pH-monitoring, impedance testing, and high-resolution manometry (HRM) - in addition to upper gastrointestinal endoscopy and barium swallow/timed barium esophagogram. RESULTS: The most frequent indications for benign esophageal surgery are gastroesophageal reflux disease and achalasia; quite rare indications are esophageal diverticula and benign tumors. Esophageal motility testing in addition to 24-h pH-monitoring is crucial before antireflux surgery (ARS) in order to rule out ineffective esophageal motility and to tailor the wrap. With respect to achalasia surgery, the exact type of achalasia (I-III) has to be labeled according to the Chicago classification, and other motility disorders have to be excluded. The postoperative functional evaluation in the early phase (6 months) after either ARS or Heller's myotomy serves as the new baseline motility testing in case of later occurring disturbances in the follow-up. CONCLUSION: A complete and proper preoperative esophageal function assessment is crucial in order to rule out a primary motility disorder and to avoid postoperative functional complications.

Exploring the Modes of Action of Phosphorus-Based Flame Retardants in Polymeric Systems.

Phosphorus-based flame retardants were incorporated into different, easily preparable matrices, such as polymeric thermoset resins and paraffin as a proposed model for polyolefins and investigated for their flame retardancy performance. The favored mode of action of each flame retardant was identified in each respective system and at each respective concentration. Thermogravimetric analysis was used in combination with infrared spectroscopy of the evolved gas to determine the pyrolysis behavior, residue formation and the release of phosphorus species. Forced flaming tests in the cone calorimeter provided insight into burning behavior and macroscopic residue effects. The results were put into relation to the phosphorus content to reveal correlations between phosphorus concentration in the gas phase and flame inhibition performance, as well as phosphorus concentration in the residue and condensed phase activity. Total heat evolved (fire load) and peak heat release rate were calculated based on changes in the effective heat of combustion and residue, and then compared with the measured values to address the modes of action of the flame retardants quantitatively. The quantification of flame inhibition, charring, and the protective layer effect measure the non-linear flame retardancy effects as functions of the phosphorus concentration. Overall, this screening approach using easily preparable polymer systems provides great insight into the effect of phosphorus in different flame retarded polymers, with regard to polymer structure, phosphorus concentration, and phosphorus species.

Novel Nor-Homo- and Spiro-Oxetan- Steroids Target the Human Androgen Receptor and Act as Antiandrogens.

The prostate adenocarcinoma is the cancer with the highest incidence for men in Western countries. Targeting the androgen receptor (AR) by antagonists is used as hormone therapy for prostate cancer (PCa), however, eventually therapy resistance occurs in most patients. In most of these cancer the AR signaling is active and thus AR remains an important drug target. Since many years we are characterizing novel chemical structural platforms to provide a broader possibility for compounds that bind to and act as AR antagonists. Here, we describe the chemical synthesis of a battery of novel steroidal derivatives as nor-homo-, spiro-oxolan- and spiro-oxetan- steroids. They modulate the transcriptional activity of the human AR. As AR antagonists, the spiro-oxetan- steroid derivatives seem to be the most potent steroid derivatives. They inhibit the transcriptional activity of both wild-type AR as well as the AR mutant T877A. In line with this, these compounds bind to the human AR and inhibit the proliferation of the human androgen-dependent growing PCa cell line LNCaP. Interestingly, the castration-resistant AR expressing human PC3-AR cells are also growth inhibited. On mechanistic level, fluorescence resonance energy transfer (FRET) assays with living cells indicate that the androgen-induced N/C terminal interaction of the AR is inhibited by the investigated compounds. Using fluorescence recovery after photobleaching (FRAP) assays in living cells suggest a higher mobility of the AR in the cell nuclei in the presence of spiro-oxetan- steroidal antagonists. Together, these findings suggest that spiro-oxetan- steroids are very useful as a chemical platform for novel AR antagonists.

C-H-Functionalization logic guides the synthesis of a carbacyclopamine analog.

The chemical synthesis of carbacyclopamine analog 2, a cyclopamine analog with an all-carbon E-ring, is reported. The use of C-H-functionalization logic and further metal-catalyzed transformations allows for a concise entry to this new class of acid-stable cyclopamine analogs.

A biomimetic approach to C-nor-D-homo-steroids.

A biomimetic three-step transformation of classical "6-6-6-5"-steroids into their C-nor-D-homo-counterparts gives an easy and fast access to this highly important substructure of natural products, as it is found in cyclopamine, and nakiterpiosin. A novel reagent combination allows for the rearrangement even of 17-keto steroids with high endoselectivity. In several examples the broadness of this strategy is outlined.

Synthesis of all diastereomers of the piperidine--alkaloid substructure of cyclopamine.

All four diastereomers of the trisubstituted piperidine-alkaloids of the veratramine and jervine type were synthesized with complete stereocontrol starting from enantiopure citronellic acids. The flexible, high-yielding, and scalable route described here will facilitate convergent syntheses and give access to analogues of cyclopamine and other biologically active and diverse steroid alkaloids.