[Therapy of esophageal motility disorders]. / Therapieoptionen von primären Motilitätsstörungen des Ösophagus.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2020 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

[Diagnosis of esophageal motility disorders - Significance of the new Chicago classification v4.0]. / Diagnostik von Motilitätsstörungen des Ösophagus ­ Bedeutung der neuen Chicago-Klassifikation v4.0.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2021 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

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.

[Therapy of esophageal motility disorders]. / Therapieoptionen von primären Motilitätsstörungen des Ösophagus.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2020 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

[Diagnosis of esophageal motility disorders - Significance of the new Chicago classification v4.0]. / Diagnostik von Motilitätsstörungen des Ösophagus ­ Bedeutung der neuen Chicago-Klassifikation v4.0.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2021 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

Video: Clinical evaluation of a laparoscopic hyperspectral imaging system.

BACKGROUND: Hyperspectral imaging (HSI) during surgical procedures is a new method for perfusion quantification and tissue discrimination. Its use has been limited to open surgery due to large camera sizes, missing color video, or long acquisition times. A hand-held, laparoscopic hyperspectral camera has been developed now to overcome those disadvantages and evaluated clinically for the first time. METHODS: In a clinical evaluation study, gastrointestinal resectates of ten cancer patients were investigated using the laparoscopic hyperspectral camera. Reference data from corresponding anatomical regions were acquired with a clinically approved HSI system. An image registration process was executed that allowed for pixel-wise comparisons of spectral data and parameter images (StO2: oxygen saturation of tissue, NIR PI: near-infrared perfusion index, OHI: organ hemoglobin index, TWI: tissue water index) provided by both camera systems. The mean absolute error (MAE) and root mean square error (RMSE) served for the quantitative evaluations. Spearman's rank correlation between factors related to the study design like the time of spectral white balancing and MAE, respectively RMSE, was calculated. RESULTS: The obtained mean MAEs between the TIVITA® Tissue and the laparoscopic hyperspectral system resulted in StO2: 11% ± 7%, NIR PI: 14±3, OHI: 14± 5, and TWI: 10 ± 2. The mean RMSE between both systems was 0.1±0.03 from 500 to 750 nm and 0.15 ±0.06 from 750 to 1000 nm. Spearman's rank correlation coefficients showed no significant correlation between MAE or RMSE and influencing factors related to the study design. CONCLUSION: Qualitatively, parameter images of the laparoscopic system corresponded to those of the system for open surgery. Quantitative deviations were attributed to technical differences rather than the study design. Limitations of the presented study are addressed in current large-scale in vivo trials.

New Intraoperative Imaging Tools and Image-Guided Surgery in Gastric Cancer Surgery.

Innovations and new advancements in intraoperative real-time imaging have gained significant importance in the field of gastric cancer surgery in the recent past. Currently, the most promising procedures include indocyanine green fluorescence imaging (ICG-FI) and hyperspectral imaging or multispectral imaging (HSI, MSI). ICG-FI is utilized in a broad range of clinical applications, e.g., assessment of perfusion or lymphatic drainage, and additional implementations are currently investigated. HSI is still in the experimental phase and its value and clinical relevance require further evaluation, but initial studies have shown a successful application in perfusion assessment, and prospects concerning non-invasive tissue and tumor classification are promising. The application of machine learning and artificial intelligence technologies might enable an automatic evaluation of the acquired image data in the future. Both methods facilitate the accurate visualization of tissue characteristics that are initially indistinguishable for the human eye. By aiding surgeons in optimizing the surgical procedure, image-guided surgery can contribute to the oncologic safety and reduction of complications in gastric cancer surgery and recent advances hold promise for the application of HSI in intraoperative tissue diagnostics.

Nrf2/Keap1-Pathway Activation and Reduced Susceptibility to Chemotherapy Treatment by Acidification in Esophageal Adenocarcinoma Cells.

Chronic acid reflux causes cellular damage and inflammation in the lower esophagus. Due to these irritating insults, the squamous epithelium is replaced by metaplastic epithelium, which is a risk factor for the development of esophageal adenocarcinoma (EAC). In this study, we investigated the acid susceptibility in a Barrett's cell culture in vitro model, using six cell lines, derived from squamous epithelium (EPC1 and EPC2), metaplasia (CP-A), dysplasia (CP-B), and EAC (OE33 and OE19) cells. Cells exposed to acidic pH showed a decreased viability dependent on time, pH, and progression status in the Barrett's sequence, with the highest acid susceptibility in the squamous epithelium (EPC1 and EPC2), and the lowest in EAC cells. Acid pulsing was accompanied with an activation of the Nrf2/Keap1- and the NFκB-pathway, resulting in an increased expression of HO1-independent of the cellular context. OE33 showed a decreased responsiveness towards 5-FU, when the cells were grown in acidic conditions (pH 6 and pH 5.5). Our findings suggest a strong damage of squamous epithelium by gastroesophageal reflux, while Barrett's dysplasia and EAC cells apparently exert acid-protective features, which lead to a cellular resistance against acid reflux.

[Status of minimally invasive gastrectomy : Current advancements: robotic surgery and intraoperative imaging for gastric cancer]. / Stellenwert der minimal-invasiven Gastrektomie : Aktuelle Weiterentwicklungen: Robotik und intraoperatives Imaging beim Magenkarzinom.

The surgical treatment of gastric cancer has arrived at a turning point towards the routine application of minimally invasive techniques. After the first results of prospective randomized trials from Asia confirmed the surgical and oncological safety, the latest results of international trials provided evidence for minimally invasive gastrectomy of advanced gastric cancer in a multimodal setting. A new addition in the field of minimally invasive procedures is robotic-assisted surgical techniques, which have already been implemented for these indications in many centers in Germany. The technical advantages that are applicable in the robotics setting in comparison to laparoscopy lead to a rapid dissemination of the procedure but still need to be evaluated in controlled trials. Further developments for the surgical treatment of gastric cancer are found in the field of intraoperative imaging procedures. In this field various technologies are available, such as fluorescence imaging using a near-infrared camera, which requires the use of a fluorescent agent or the hyperspectral camera system, which does not require the application of a fluorophore and merges pictures from visible and non-visible wavelengths to a functional image. It is to be expected that in the future various technological advancements can make a valuable contribution to the surgical treatment of gastric cancer in the clinical routine, especially if they support and facilitate the use of minimally invasive surgical techniques.

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.

[Hybrid esophagectomy with intraoperative hyperspectral imaging : Video article]. / Hybridösophagektomie mit intraoperativem Hyperspektral-Imaging : Videobeitrag.

The technique of hybrid esophagectomy with systematic 2­field lymphadenectomy for esophageal cancer showed a significant reduction in postoperative morbidity in a recently published prospective randomized study. This video publication presents the abdominothoracic hybrid procedure with (i) laparoscopic gastrolysis and ischemic conditioning of the stomach and (ii) 2-stage transthoracic esophagectomy with gastric pull-up, intrathoracic gastric tube formation and anastomosis. Intraoperative hyperspectral imaging (HSI) during the thoracic part of the operation is used for identification of the ideally perfused anastomotic region.

Incisional negative pressure wound therapy does not reduce surgical site infections in abdominal midline incisions: a case control study.

Purpose: There is evidence from various surgical specialties that incisional negative pressure wound therapy (iNPWT) might reduce postoperative surgical site infections (SSIs). In visceral and general surgery, there is varying evidence of its efficacy in reducing surgical site infections.Methods: A prospectively registered patient cohort of 43 patients with abdominal wall and visceral surgery received treatment with iNPWT and was compared to a matched retrospective cohort to analyze its effects on SSI occurrence and respective risk factors. Groups were matched by procedure, sex, body mass index and age. We used two different systems of iNPWT: (i) PREVENATM or (ii) self-made epicutaneous iNPWT from common VAC material.Results: We could not find a total reduction in postoperative SSIs by application of iNPWT. But within the iNPWT cohort, patients with self-made iNPWT suffered more often from SSIs compared to the commercial iNPWT subgroup. No patient specific risk factors could be identified to advocate the use of iNPWT.Conclusion: Our data do not support the use of an incisional negative pressure wound therapy on closed wounds in midline laparotomy incisions. Although, differences exist between the commmercial and self-made systems.

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in patients with peritoneal metastasized colorectal, appendiceal and small bowel cancer.

BACKGROUND: Patients with intestinal cancer (colorectal, appendiceal, and small bowel) with peritoneal metastases (PM) have a poor prognosis. We assessed whether pressurized intraperitoneal aerosol chemotherapy (PIPAC) together with systemic chemotherapy is an effective treatment option for these entities in palliative intent. METHODS: Between November 2015 and February 2018, prospective data registry was performed (NCT03100708). Thirteen patients with intestinal cancer (median age 61 years [range 49-77]) underwent 26 PIPAC procedures with a median number of 2 interventions per patient (range 1-6). A chemoaerosol consisting of cisplatin/doxorubicin was administered during standard laparoscopy. RESULTS: The median peritoneal carcinomatosis index according to Sugarbaker before the first PIPAC was 14 (range 2-27), and the median ascites volume was 10 mL (range 0-6300 mL). Six patients who received 2 or more PIPAC procedures had decreased and stable ascites volumes, while only 1 patient displayed increased ascites. The median overall survival was 303 days (range 30-490) after the first PIPAC procedure. CONCLUSIONS: PIPAC offers a novel treatment option for patients with PM. Our data show that PIPAC is safe and well-tolerated. Ascites production can be controlled by PIPAC in patients with intestinal cancer. Further studies are required to document the significance of PIPAC within palliative therapy concepts. TRIAL REGISTRATION: NCT03100708.

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.

Retroperitoneal space-occupying lesion with displacement of the inferior vena cava.

INTRODUCTION: The differential diagnosis and therapy of retroperitoneal masses suspicious for soft tissue tumors remains difficult and needs individual decisions as to the best management of patients. We report an unusual case of retroperitoneal schwannoma (RS). PRESENTATION OF CASE: We report on a 57-year-old female patient with a retroperitoneal space-occupying lesion with displacement, but no infiltration of surrounding vessels, especially the inferior vena cava. As presence of malignancy could not be completely excluded by imaging and biopsy, we performed an open resection of the tumor with plastic reconstruction of the right renal vein. Curative resection of the tumor could be achieved and benign RS verified. DISCUSSION: Preoperative work-up, including a broad spectrum of differential diagnoses, and consecutive appropriate surgical resection are challenging. Characteristic features of the pre-therapeutic diagnostics of retroperitoneal schwannomas are discussed and differential diagnostic considerations as well as surgical therapeutic options are outlined. CONCLUSION: Deeper understanding of retroperitoneal schwannomas gained from preoperative radiologic diagnostics may serve to underline the need for targeted biopsy. This and its histopathological examination necessitate expert interventional radiologists and pathologists. Thus, even the pre-therapeutic diagnostic management should be performed in a specialized center. If doubts remain regarding the entity of the retroperitoneal lesion and findings are still controversial after thorough assessment, surgical oncologic resection represents the therapy of choice, if the surgical risk is adequate.

In-depth characterization of the Wnt-signaling/ß-catenin pathway in an in vitro model of Barrett's sequence.

BACKGROUND: An altered Wnt-signaling activation has been reported during Barrett's esophagus progression, but with rarely detected mutations in APC and ß-catenin (CTNNB1) genes. METHODS: In this study, a robust in-depth expression pattern analysis of frizzled receptors, co-receptors, the Wnt-ligands Wnt3a and Wnt5a, the Wnt-signaling downstream targets Axin2, and CyclinD1, as well as the activation of the intracellular signaling kinases Akt and GSK3ß was performed in an in vitro cell culture model of Barrett's esophagus. Representing the Barrett's sequence, we used normal esophageal squamous epithelium (EPC-1, EPC-2), metaplasia (CP-A) and dysplasia (CP-B) to esophageal adenocarcinoma (EAC) cell lines (OE33, OE19) and primary specimens of squamous epithelium, metaplasia and EAC. RESULTS: A loss of Wnt3a expression was observed beginning from the metaplastic cell line CP-A towards dysplasia (CP-B) and EAC (OE33 and OE19), confirmed by a lower staining index of WNT3A in Barrett's metaplasia and EAC, than in squamous epithelium specimens. Frizzled 1-10 expression analysis revealed a distinct expression pattern, showing the highest expression for Fzd2, Fzd3, Fzd4, Fzd5, Fzd7, and the co-receptor LRP5/6 in EAC cells, while Fzd3 and Fzd7 were rarely expressed in primary specimens from squamous epithelium. CONCLUSION: Despite the absence of an in-depth characterization of Wnt-signaling-associated receptors in Barrett's esophagus, by showing variations of the Fzd- and co-receptor profiles, we provide evidence to have a significant role during Barrett's progression and the underlying pathological mechanisms.

First genotype-phenotype study reveals HLA-DQß1 insertion heterogeneity in high-resolution manometry achalasia subtypes.

Background: Achalasia is a primary oesophageal motility disorder. Although aetiology remains mainly unknown, a genetic risk variant, rs28688207 in HLA-DQB1, showed strong achalasia association suggesting involvement of immune-mediated processes in the pathogenesis. High-resolution manometry recognises three types of achalasia. The aim of our study was to perform the first genotype-phenotype analysis investigating the frequency of rs28688207 across the high-resolution manometry subtypes. Methods: This was a cross-sectional retrospective study. Achalasia patients from tertiary centres in the Czech Republic (n = 163), Germany (n = 114), Greece (n = 70) and controls were enrolled. All subjects were genotyped for the rs28688207 insertion. The Kruskal-Wallis test was used for the genotype-phenotype analysis. Results: A total of 347 achalasia patients (type I - 89, II - 210, III - 48) were included. The overall frequency of the rs28688207 was 10.3%. The distribution of the insertion was significantly different across the high-resolution manometry subtypes (p = 0.038), being most prevalent in type I (14.6%), followed by type II (9.5%) and III (6.3%). Conclusion: The frequency of the HLA-DQB1 insertion differs among high-resolution manometry achalasia subtypes. The insertion is most prevalent in type I, suggesting that immune-mediated mechanisms triggered by the insertion may play a more prominent role in the pathogenesis of this subtype.

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.