bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesothelial Cell Recruitment Towards Sites of Post-Surgical Adhesion Formation in the Peritoneal Cavity
Authors: Bayer J , Büchi I , Candinas D , Keogh-Stroka D , Zindel J 
Published: June 2023

Abstract

Background
Abdominal surgeries are often inevitable and live-saving procedures, however, they can be associated with post-surgical complications, such as the formation of irreversible scar bands called peritoneal adhesions. Adhesions in the peritoneal cavity can lead to serious health burden by causing small bowel obstruction, infertility, and chronic pelvic pain. Unfortunately, no effective treatment for adhesion patients exists today. Mesothelial cells and mesothelial cell-derived mesenchymal myofibroblasts have been identified as key players in the pathogenesis of adhesions, and thus represent a novel target for pharmacological interventions.

Aims
Our aim is to study the molecular mechanisms of mesothelial cell recruitment towards peritoneal adhesion sites, which could serve as potential drug targets to effectively prevent the formation of adhesions.

Methods
By exploiting genetic lineage tracing and experimental animal surgery, we have established a surgical-transgenic mouse model system that allows us to study mesothelial cell recruitment during processes of scar-free wound healing and wound healing associated with adhesion formation. To identify candidate molecules predominantly required for the recruitment of mesothelial cells towards adhesion sites, we apply an untargeted transcriptomics-based research strategy (spatial transcriptomics, single cell RNA sequencing).

Results
Histological characterization of our mouse model showed that over seven days post-surgery increasing numbers of mesothelial or mesothelial cell-derived cells accumulate at adhesion sites whereas their numbers stay constant in wounds healing without scar formation. Along with these findings, we have determined candidate molecules potentially triggering mesothelial cell migration towards sites of adhesion formation and will next test their proposed function in vivo and in vitro.

Conclusions
Mesothelial cells and mesothelial cell-derived mesenchymal myofibroblasts particularly accumulate at sites of adhesion formation. Therapeutic targeting of the recruitment mechanism of these cells might represent a novel strategy to prevent post-surgical adhesion formation in the peritoneal cavity.
Insights into DNA Damage in Regenerating Young and Aged Mouse Livers
Authors: Asensio Aldave A , Dommann N , Rossetti G , Karamichali A , Dionellis V , Keogh A , Candinas D , Halazonetis T , Stroka D 
Published: June 2023

Abstract

Background
The maintenance of genome stability is a key process to slow aging. One of the mechanisms ensuring this stability is the correct coordination of origins of replication (ORI), resulting in the successful transmission of DNA. Previously, we mapped and compared ORI firing between young and aged mice in vivo, using a regenerating liver mouse model. We confirmed a decreased hepatocyte ORI efficiency in aged mice, known to have impaired liver regeneration. ORI firing proved to be fully rescued when blocking the aged mice's ATR serine/threonine-protein kinase, suggesting that the DNA replication checkpoint actively mediates ORI firing impairment upon DNA damage detection.

Aims
To explore DNA damage differences between young and aged mice regenerating livers.

Methods
To induce proliferation, mice were subjected to partial hepatectomy (PH) and liver sections were harvested at different timepoints. Immunohistochemistry staining (IHC) were used to address proliferation and DNA damage, using Ki67 and serine 139 phosphorylated histone H2AX (g-H2AX) as markers, respectively.

Results
We confirmed a lack of Ki67 signal in young and aged mice prior to PH. The signal takes off at 24-28h post-PH and reaches its peak at 36-48h, which is significantly lower in aged mice. After 48h post-PH, young hepatocytes’ Ki67 reaches its basal level 120h post-PH. However, aged hepatocytes’ Ki67 is maintained at low levels overtime. Next, we compared DNA damage kinetics between young and aged mice livers. Both mouse groups present an increase of g-H2AX upon PH, higher in young mice. The g-H2AX signal decreases in young hepatocytes after 48h post-PH until disappearing 120h post PH. Aged mice hepatocytes maintain the g-H2AX rates overtime after 48h post-PH.

Conclusions
Our data suggests that hepatocytes develop DNA damage upon proliferation, which is able to be resolved in young mice hepatocytes but remains present in aged livers, ultimately leading to impaired liver regeneration.
Feasibility and Safety of Intraoperative Bile Duct Clearance by Sphincter Oddi Balloon Dilatation: A Prospective Observational Pilot Study
Authors: Prevost G A , Huber C , Schnell B , Candinas D , Wiest R , Schnüriger B 
Published: June 2023

Abstract

Background
Concomitant cholecysto- and choledocholithiasis is common. Standard treatments are ERCP followed by cholecystectomy or laparoendoscopic rendez-vous. ERCP has drawbacks such as post-ERCP-pancreatitis (5%) or -bleeding (5%) and potentially more than one intervention to address common bile duct (CBD) stones. Safety and feasibility of an intraoperative antegrade transcystic single-stage approach during cholecystectomy with papillary balloon dilation and pushing of concrements to the duodenum has not been evaluated prospectively.

Aims
The aim of the study was to evaluate this procedure regarding safety and stone clearance rate.

Methods
Prospective single centre intervention study. 80 consecutive patients admitted to our institution between 1/2021 and 4/2022 with suspected or confirmed choledocholithiasis (stones ≤ 6 mm) and known cholecystolithiasis were included. Success of the procedure was defined as lack of filling defects in the intraoperative control cholangiography and absence of symptoms at 6 weeks follow up. Simon's two stage design was used to determine sample size. Aiming for 95% positive outcomes (no pancreatitis) and tolerating at most 15% negative outcomes, power analysis revealed 57 participants (80% power, alpha 0.05).

Results
57/80 patients (71%) fulfilled the inclusion criteria. While there was no postoperative pancreatitis, 2 patients (3.5%) had asymptomatic amylasemia 4h postoperatively. Stone clearance was achieved in 54 patients (94%). The main reason for failed stone clearance was the inability to push the guide wire along the concrement into the duodenum. Median number of CBD-stones was 1 (1-6). Median stone diameter was 4 mm (0.1-6 mm). Median intervention time was 28 min (14-129 min).

Conclusions
Intraoperative bile duct clearance by balloon dilation of the sphincter Oddi appears to be safe and highly feasible. Its overall superiority to the current standards requires evaluation in a randomized controlled trial.
Anti-Recem18 Antibody Levels are Associated with Lesion Size and Determine Follow-Up after Resection of Hepatic Alveolar Echinococcosis
Authors: Gloor S , Jiang W , Maurer M , Gottstein B , Oberli A , Hagemann J , Hotz J F , Candinas D , Lachenmayer A , Grüner B , Beldi G 
Published: June 2023

Abstract

Background
Best monitoring practices for patients after resection of hepatic alveolar echinococcosis remain unclear.

Aims
The current study tested if assessment of anti-recEm18 allows for postsurgical patient surveillance.

Methods
A retrospective study with patients undergoing liver resection for alveolar echinococcosis at the University Hospital Berne from December 2002 to December 2020 and at the University Hospital and Medical Center Ulm from January 2011 to December 2017 was performed. Analysis was directed to determine a potential association of pre- and postoperative values of anti-recEm18 with clinical outcomes.

Results
Among 147 patients who underwent liver resection for alveolar echinococcosis in curative intent, perioperative results of recEm18-serology were available in 88 patients. In patients without residual disease, the postoperative anti-recEm18 value after 12 months dropped to a mean of 2 AU/ml (standard deviation: 4 AU/ml). Three trajectories of anti-recEm18 were identified based on a threshold of 10 AU/ml: “Em18-low” (n = 31, 35%) with anti-recEm18 values below 10 AU/ml pre- and postoperatively, “responders” (n = 53, 60%) with preoperative values above 10 AU/ml and a postoperative decrease of more than 80% of the initial anti-recEm18 and “residual disease” (n = 4, 5%) with the postoperative presence of residual disease. The decline of anti-recEm18 in “responders” reached a plateau after 11.4 months at which levels decreased by 80%. The only recurrence in the entire population was identified by a secondary increase of anti-recEm18. Anti-recEm18 levels had a linear correlation to the maximum lesion diameter (R2 = 0.558).

Conclusions
Anti-recEm18 antibody levels correlate with the lesion size preoperatively and response to surgery postoperatively. Anti-recEm18 allows to be applied as serological surveillance marker during postoperative follow-up in patients with elevated preoperative anti-recEm18 levels.
Impact of Cirrhosis on the Choice of Liver Resection in Patients with Hepatocellular Carcinoma
Authors: Zeindler J , Hess G F , von Heesen M , Aegerter N , Reber C , Schmitt A , Muenst S , Bolli M , Soysal S D , Kollmar O 
Published: June 2023

Abstract

Background
Hepatocellular carcinoma (HCC) usually occurs within an underlying chronic liver disease such as cirrhosis with limited liver function. Liver resection is an effective treatment option. Most studies investigating the benefits of anatomic (ALR) versus non-anatomic (NALR) liver resections in cirrhotic HCC patients involve Asian populations with different underlying chronic liver diseases.

Aims
NALR limits the resection of liver parenchyma, and therefore could reduce postoperative liver failure, while the effects on survival rates remain unclear. European data are desperately needed.

Methods
This is a retrospective and prospective multicentre cohort study, including all patients undergoing liver resection for HCC between 2009 and 2020 from 3 specialised centres in Switzerland and Germany. Patients were stratified for cirrhosis and no cirrhosis. Complications and survival rates were analysed using univariate and multivariate Cox regression models.

Results
298 patients were included. Median follow-up time was 52.76 months. 158/298 (53%) patients presented with cirrhosis. Cirrhotic patients after ALR (n=64/158) showed a significantly longer ICU stay (p=0.017) and postoperative in-hospital stay (p=0.007) compared to after NALR (n=94/158), while the NALR group showed significantly more postoperative complications (p&lt;0.001), but the rate of liver insufficiency was not significantly different after NALR versus ALR (p=0.846). Overall survival (OS) and recurrence free survival (RFS) in cirrhotic versus non-cirrhotic patients were not significantly different (adjusted HR 0.78 (95% CI 0.53-1.15, p=0.21) and adjusted HR 0.82 (95% CI 0.64-1.24, p=0.27), respectively). A trend towards better OS and RFS could be observed favouring NALR in cirrhotic patients (for OS adjusted HR 0.55 (95% CI 0.28-1.07, p=0.08) and for RFS adjusted HR 0.55 (95% CI 0.30-1.01, p=0.06)).

Conclusions
European patients with cirrhosis could benefit from NALR regarding longer OS and RFS. NALR is associated with a significantly higher complication rate compared to ALR, but not with a higher rate of postoperative liver insufficiency.
Watchful Waiting after Definitive Radiochemotherapy in Patients with Esophageal Cancer: Independent Predictors for Recurrence
Authors: Gerber S , Berger M D , Hemmatazad H , Candinas D , Haltmeier T , Borbély Y 
Published: June 2023

Abstract

Background
Treatment of Esophageal Cancer (EC) consists of neoadjuvant radiochemotherapy (RCT) followed by resection. However, esophagectomy is associated with considerable morbidity in patients already burdened with comorbidities, malnutrition, and unhealthy lifestyle.
In this context, a watch and wait (WW) strategy has gained importance in patients with complete response to RCT and has been adopted by our center a decade ago.

Aims
To investigate independent predictors for recurrence in patients with EC undergoing WW.

Methods
We retrospectively analyzed data of all patients with potentially curable EC and complete response to RCT from 01/2014–12/2020 at a tertiary university hospital. Patients underwent staging (computed tomography (CT), upper endoscopy with ultrasound and biopsies (EUS), and positron-emission tomography (PET)), followed by RCT with restaging six weeks after completion. Routine follow-up consisted of EUS every three and CT every six months. Clinical data were extracted from electronic medical records. Factors associated with recurrence were adjusted for patient- and tumor-characteristics in multivariate regression analysis.

Results
A total of 40 patients were included. Of these, 22 (55%) had cancer recurrence. Tumor type was squamous cell carcinoma in 24 (60%) and adenocarcinoma in 16 (40%), respectively. T3-stage was most frequent (n=26, 65%), 35 (88%) patients were nodal-positive. Mean age was 67 years (SD 8.8), 30 (75%) patients were male. Recurrence occurred after a mean of 413 days (SD 171). Multivariate analysis revealed a circumferential tumor extent &gt;50% in staging (OR 15.229, p=0.017) and dysphagia at restaging (OR 6.336, p=0.023) as independent risk factors for recurrence.

Conclusions
The current study revealed tumor extent and dysphagia as independent risk factors for recurrence. These predictors may help in the early identification of patients with EC recurrence, thus contributing to a personalized follow-up.
Laparoscopic Hiatal Hernia Repair with RefluxStop: Outcomes in 30 Patients with a Minimal Follow-Up of 12 Months
Authors: Fringeli Y , Kessler U , Linas I , Zehetner J 
Published: June 2023

Abstract

Background
Laparoscopic hiatal hernia repair with RefluxStop is an innovative technique to treat patients with gastroesophageal reflux disease (GERD). While feasibility and safety of this technique have already been demonstrated, consistent 12-months follow-up data is lacking.

Aims
To report 12-months outcomes and complications of a novel surgical anti-reflux technique with RefluxStop.

Methods
Among the 60 patients who underwent hiatal hernia surgery with RefluxStop since 2020 at our institution, we performed a retrospective chart review of the first 30 patients who achieved a minimal follow-up of 12 months. Follow-up data were reviewed until December 2022. Primary outcome was the clinical improvement of GERD related symptoms (heartburn and regurgitation) at 3 and 12 months after surgery. Secondary outcomes were need for dilatations and occurrence of implant related complications.

Results
The median follow-up was 19.5 months (range, 13-31). Preoperatively, 23 patients (76.7%) presented with esophageal dysmotility, and the median length of the concomitant hiatal hernia was 4cm (range, 2-8). Mean GERD-HRQL score (0-75 points) was 37.6 ± 15.8 before surgery, 4.2 ± 7.1 at 3 months, and 4.4 ± 6.9 at 12 months (p&lt;0.001). Three patients (10%) required postoperatively balloon dilatation due to persistent dysphagia. One patient experienced an asymptomatic partial migration of the implant, one patient presented with a recurrence of hiatal hernia after 2 years who required surgical repair, and in one case the implant was removed after 16 months to due persisting left thoracic pain.

Conclusions
This study confirmed excellent clinical outcomes beyond 1 year with significant improvement of reflux symptoms in all patients.
Gut Microbiota Conditioning Promotes Anti-Tumor Immunity and Responsiveness to Immunological Checkpoint Blockade in Colorectal Cancer
Authors: Basso C , Cianfarani A , Djordjevic J , Sorrenti E , Galafassi J , Roesel R , Christoforidis D , Majno-Hurst P E , Iezzi G 
Published: June 2023

Abstract

Background
Colorectal cancer (CRC) infiltration by T lymphocytes is associated with prolonged survival. However, immune infiltration spontaneously occurs in &lt;20% of tumors and no therapies able to promote it are currently available. CRC tissue is populated by gut bacteria translocated across the neoplastic epithelium. We previously showed that direct contact between tumor cells and bacteria induces overexpression of genes encoding immune cell-recruiting chemokines in tumor cells, and we identified a panel of bacterial species associated with enhanced chemokine expression, high T cell infiltration and favorable prognosis.

Aims
In this project we tested the ability of identified bacterial species to boost T-cell infiltration and promote tumor regression in orthotopic CRC experimental models.

Methods
Luciferase-expressing mismatch repair (MMR)-proficient or -deficient murine CRC cells from established cell lines were injected intra-cecum in syngeneic mice. Tumor growth was monitored by bioluminescence. Bacterial species of interest, defined as Operational Taxonomic Units (OTUs), were cultured under anaerobic conditions, and, following tumor development, were administered to tumor-bearing mice by oral gavage. In specific experiments, bacteria administration was combined with immunological checkpoint blockade (ICB), based on injection of anti-PD-1 antibodies. Immune cell infiltration was evaluated by flow cytometry, following tumor harvesting and enzymatic tissue digestion.

Results
In MMR-deficient tumors, known to be immunogenic and responsive to immunotherapy, administration of the bacterial species OTU8, was sufficient to reduce tumor growth. In MMR-proficient tumors, scarcely infiltrated by immune cells and poorly responsive to ICB, OTU8, did not per se affect tumor growth, but enhanced infiltration by cytotoxic CD8+ T cells, ultimately leading, in combination with anti-PD-1 antibodies, to tumor growth inhibition.

Conclusions
We demonstrated that administration of defined bacteria promotes endogenous immune responses against CRC. Gut microbiota conditioning might represent an innovative therapeutic strategy to enhance responsiveness to ICB and to broaden its indication beyond MMR-deficient tumors.
Robotic Versus Open Incisional Ventral Hernia Repair with Sublay Mesh in Overweight Patients: A Case-Control Analysis of Clinical Outcomes and Costs
Authors: Douissard J , Gramolini L , Dupuis A , Mareschal J , Chevallay M , Hagen M , Toso C 
Published: June 2023

Abstract

Background
Robotic incisional hernia repair (RIHR) with sublay mesh is gaining traction as a minimally-invasive alternative to open retro-rectus reconstruction (OIHR). Obesity is a known risk factor for complications following hernia repair.

Aims
The objective of this study is to compare the clinical outcomes and costs of RIHR versus OIHR with sublay mesh in overweight patients.

Methods
Patients with a body mass index (BMI) of 25-35 kg/m2 who underwent OIHR or RIHR with sublay mesh over a 2 years’ period were included. Recurrent hernias after mesh repair were excluded. The main outcome was length of hospital stay (LOS). Secondary outcomes included surgical site complications (SSC), visual analog pain score (VAS), analgesic methods, and general complications.

Results
Ninety patients were included, 45 in each group. The mean length of stay (LOS) was significantly shorter in RIHR (6.8 days ± 4.6 vs. 2.3 days ± 2, p &lt; 0.001), as were VAS at day 0 (3.0 ± 2.7 vs. 1.7 ± 1.8, p = 0.005) and day 1 (4.2 ± 2.2 vs. 2.4 ± 1.8, p &lt; 0.001), with a significant reduction in morphine consumption and epidural analgesia. The mean operative time was 163 min. ± 65 in OIHR and 191 min. ± 94 in RIHR (p = 0.06), despite a higher proportion of component separation in the robotic group (18% vs 33.3%, p = 0.005). The open group had higher rates of SSC (20% vs 2.2%, p = 0.015) and general complications (40% vs 13.3%, p = 0.004). General costs per diagnosis showed a mean reduction of 4797 CHF in the robotic group, mostly due to reduced hospitalization costs (9364 CHF vs. 3472 CHF).

Conclusions
The robotic approach improved post-operative outcomes of incisional hernia repair with sublay mesh compared to the open approach in overweight patients, without significantly increasing operative time and costs.
The Impact of the Gastric Pouch and Gastro-Jejunostomy Size after Laparoscopic Roux-En-Y Gastric Bypass - A Prospective, CT-Volumetry Based Study
Authors: Lazaridis I , Kraljevic M , Köstler T , Mattiello D , Andreou A , Zingg U , Delko T 
Published: June 2023

Abstract

Background
Some patients who undergo laparoscopic Roux-en-Y gastric bypass (LRYGB) may present with insufficient weight loss or weight regain. Anatomical factors that may lead to failure of LRYGB include the size of the gastric pouch and the diameter of the gastro-jejunostomy.

Aims
This study explores the gastric pouch size and the size of the gastro-jejunostomy after LRYGB and investigates their impact on weight loss, appetite and quality of life (QoL).

Methods
Patients undergoing LRYGB in a single centre underwent computed tomography (CT) with oral contrast one day and one year after LRYGB. Volumetry of the gastric pouch and calculation of the size of the gastro-jejunostomy was performed. Appetite was assessed pre-operatively and one year after LRYGB using the Edmonton Appetite Assessment questionnaire. QoL was assessed pre-operatively one year after surgery using the GIQLI and BAROS questionnaires.

Results
61 patients were included. Of those, 55 patients (90.2%) underwent CT one year after LRYGB. The mean preoperative Body Mass Index was 40.7±3.97kg/m2. The mean Excess weight loss (%EWL) one year after surgery was 82.1±21.5%. There was no significant change in mean gastric pouch size one day and one year after LYRGB (15.73±11.8cm3 and 14.4±11.5cm3, respectively, p=0.55). The mean size of the gastrojejunostomy increased significantly from 2.63cm2 to 3.60cm2 (p&lt;0.0001). Mean GIQLI and BAROS values improved significantly one year after LRYGB, but no significant changes in the mean Edmonton Appetite Assessment values were found. %EWL and improvement in GIQLI and BAROS values one year after surgery did not correlate with the initial size of the gastric pouch and the increase of the size of the gastro-jejunostomy.

Conclusions
One year after LRYGB, the size of the gastro-jejunostomy increased significantly, but no difference in the gastric pouch volume was found. Both gastric pouch volume and dilatation of the gastro-jejunostomy did not correlate with weight loss and QoL outcomes.