Long-term quality of life after hybrid robot-assisted and open Ivor Lewis esophagectomy for esophageal cancer in a single center: a comparative analysis.

PURPOSE: Due to improved survival of esophageal cancer patients, long-term quality of life (QoL) is increasingly gaining importance. The aim of this study is to compare QoL outcomes between open Ivor Lewis esophagectomy (Open-E) and a hybrid approach including laparotomy and a robot-assisted thoracic phase (hRob-E). Additionally, a standard group of healthy individuals serves as reference. METHODS: With a median follow-up of 36 months after hRob-E (n = 28) and 40 months after Open-E (n = 43), patients' QoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire Core 30 (QLQ-C30) and the EORTC Esophagus specific QoL questionnaire 18 (QLQ-OES18). RESULTS: Patients showed similar clinical-pathological characteristics, but hRob-E patients had significantly higher ASA scores at surgery (p < 0.001). Patients and healthy controls reported similar global health status and emotional and cognitive functions. However, physical functioning of Open-E patients was significantly reduced compared to healthy controls (p = 0.019). Operated patients reported reduced role and social functioning, fatigue, nausea and vomiting, dyspnea, and diarrhea. A trend towards a better pain score after hRob-E compared to Open-E emerged (p = 0.063). Regarding QLQ-OES18, hRob-E- and Open-E-treated patients similarly reported eating problems, reflux, and troubles swallowing saliva. CONCLUSIONS: The global health status is not impaired after esophagectomy. Despite higher ASA scores, QoL of hRob-E patients is similar to that of patients operated with Open-E. Moreover, patients after hRob-E appear to have a better score regarding physical functioning and a better pain profile than patients after Open-E, indicating a benefit of minimally invasive surgery.

Anatomic versus non-anatomic liver resection for hepatocellular carcinoma-A European multicentre cohort study in cirrhotic and non-cirrhotic patients.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is increasing in the western world over the past decades. As liver resection (LR) represents one of the most efficient treatment options, advantages of anatomic (ALR) versus non-anatomic liver resection (NALR) show a lack of consistent evidence. Therefore, the aim of this study was to investigate complications and survival rates after both resection types. METHODS: This is a multicentre cohort study using retrospectively and prospectively collected data. We included all patients undergoing LR for HCC between 2009 and 2020 from three specialised centres in Switzerland and Germany. Complication and survival rates after ALR versus NALR were analysed using uni- and multivariate Cox regression models. RESULTS: Two hundred and ninety-eight patients were included. Median follow-up time was 52.76 months. 164/298 patients (55%) underwent ALR. Significantly more patients with cirrhosis received NALR (n = 94/134; p < 0.001). Complications according to the Clavien Dindo classification were significantly more frequent in the NALR group (p < 0.001). Liver failure occurred in 13% after ALR versus 8% after NALR (p < 0.215). Uni- and multivariate cox regression models showed no significant differences between the groups for recurrence free survival (RFS) and overall survival (OS). Furthermore, cirrhosis had no significant impact on OS and RFS. CONCLUSION: No significant differences on RFS and OS rates could be observed. Post-operative complications were significantly less frequent in the ALR group while liver specific complications were comparable between both groups. Subgroup analysis showed no significant influence of cirrhosis on the post-operative outcome of these patients.

Reversible oxidation/reduction steps in the metabolic degradation of the glycerol side chain of the S1P1 modulator ponesimod.

1. Ponesimod is a selective modulator of the sphingosine 1-phosphate receptor 1 (S1P1) approved for the treatment of active relapsing forms of multiple sclerosis. The chemical structure of ponesimod contains a glycerol side chain which is the major target of drug metabolism in humans.2. The two major metabolic pathways give the acids M12 (-OCH2CH(OH)COOH) and M13 (-OCH2COOH). While the former results from oxidation of the terminal alcohol, the mechanism yielding the chain-shortened acid M13 is less obvious. A detailed mechanistic study with human liver microsomes and hepatocytes using ponesimod, M12 and some of the suspected intermediates revealed an unexpectedly complex pattern of enzyme-mediated and chemical reactions.3. Metabolic pathways for both acids were not independent and several of the transformations were reversible, depending on reaction conditions. Formation of M13 occurred either via initial oxidation of the secondary alcohol, or as a downstream process starting from M12.4. The phenol metabolite M32 was produced as part of several pathways. Control experiments at various pH values and in the absence of metabolising enzymes support the conclusion that its formation resulted from chemical degradation rather than from metabolic processes.

Discovery of Nivasorexant (ACT-539313): The First Selective Orexin-1 Receptor Antagonist (SO1RA) Investigated in Clinical Trials.

The orexin system consists of two neuropeptides (orexins A and B) and two receptors (OX1 and OX2). Selective OX1 receptor antagonists (SO1RA) are gaining interest for their potential use in the treatment of CNS disorders, including substance abuse, eating, obsessive compulsive, or anxiety disorders. While blocking OX2 reduces wakefulness, the expected advantage of selectively antagonizing OX1 is the ability to achieve clinical efficacy without the promotion of sleep. Herein we report our discovery efforts starting from a dual orexin receptor antagonist and describe a serendipitous finding that triggered a medicinal chemistry program that culminated in the identification of the potent SO1RA ACT-539313. Efficacy in a rat model of schedule-induced polydipsia supported the decision to select the compound as a preclinical candidate. Nivasorexant (20) represents the first SO1RA to enter clinical development and completed a first proof of concept phase II clinical trial in binge eating disorder in 2022.

Discovery of a Novel Orally Active, Selective LPA Receptor Type 1 Antagonist, 4-(4-(2-Isopropylphenyl)-4-((2-methoxy-4-methylphenyl)carbamoyl)piperidin-1-yl)-4-oxobutanoic Acid, with a Distinct Molecular Scaffold.

Lysophosphatidic acid receptor 1 (LPAR1) antagonists show promise as potentially novel antifibrotic treatments. In a human LPAR1 ß-arrestin recruitment-based high-throughput screening campaign, we identified urea 19 as a hit with a LPAR1 IC50 value of 5.0 µM. Hit-to-lead activities revealed that one of the urea nitrogen atoms can be replaced by carbon and establish the corresponding phenylacetic amide as a lead structure for further optimization. Medicinal chemistry efforts led to the discovery of piperidine 18 as a potent and selective LPAR1 antagonist with oral activity in a mouse model of LPA-induced skin vascular leakage. The molecular scaffold of 18 shares no obvious structural similarity with any other LPAR1 antagonist disclosed so far.

Discovery of the Novel, Orally Active, and Selective LPA1 Receptor Antagonist ACT-1016-0707 as a Preclinical Candidate for the Treatment of Fibrotic Diseases.

Piperidine 3 is a potent and selective lysophosphatidic acid receptor subtype 1 receptor (LPAR1) antagonist that has shown efficacy in a skin vascular leakage target engagement model in mice. However, compound 3 has very high human plasma protein binding and high clearance in rats, which could significantly hamper its clinical development. Continued lead optimization led to the potent, less protein bound, metabolically stable, and orally active azetidine 17. Rat pharmacokinetics (PK) studies revealed that 17 accumulated in the liver. In vitro studies indicated that 17 is an organic anion co-transporting polypeptide 1B1 (OATP1B1) substrate. Although analogue 24 was no longer a substrate of OATP1B1, PK studies suggested that the compound undergoes enterohepatic recirculation. Replacing the carboxylic acidic side chain by a non-acidic sulfamide moiety and further fine-tuning of the scaffold yielded the potent, orally active LPAR1 antagonist 49, which was selected for preclinical development for the treatment of fibrotic diseases.

Local ablative therapies and the effect on antitumor immune responses in pancreatic cancer - A review.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, projected to rank as the second most prevalent cause of cancer-related mortality by 2030. Despite significant progress in advances in surgical techniques and chemotherapy protocols, the overall survival (OS) remains to be less than 10 % for all stages combined. In recent years, local ablative techniques have been introduced and utilized as additional therapeutic approaches for locally advanced pancreatic cancer (LAPC), with promising results with respect to local tumor control and OS. In addition to successful cytoreduction, there is emerging evidence that local ablation induces antitumor immune activity that could prevent or even treat distant metastatic tumors. The enhancement of antitumor immune responses could potentially make ablative therapy a therapeutic option for the treatment of metastatic PDAC. In this review, we summarize current ablative techniques used in the management of LAPC and their impact on systemic immune responses.

Assessment of resectability of pancreatic cancer using novel immersive high-performance virtual reality rendering of abdominal computed tomography and magnetic resonance imaging.

PURPOSE: Virtual reality (VR) allows for an immersive and interactive analysis of imaging data such as computed tomography (CT) and magnetic resonance imaging (MRI). The aim of this study is to assess the comprehensibility of VR anatomy and its value in assessing resectability of pancreatic ductal adenocarcinoma (PDAC). METHODS: This study assesses exposure to VR anatomy and evaluates the potential role of VR in assessing resectability of PDAC. Firstly, volumetric abdominal CT and MRI data were displayed in an immersive VR environment. Volunteering physicians were asked to identify anatomical landmarks in VR. In the second stage, experienced clinicians were asked to identify vascular involvement in a total of 12 CT and MRI scans displaying PDAC (2 resectable, 2 borderline resectable, and 2 locally advanced tumours per modality). Results were compared to 2D standard PACS viewing. RESULTS: In VR visualisation of CT and MRI, the abdominal anatomical landmarks were recognised by all participants except the pancreas (30/34) in VR CT and the splenic (31/34) and common hepatic artery (18/34) in VR MRI, respectively. In VR CT, resectable, borderline resectable, and locally advanced PDAC were correctly identified in 22/24, 20/24 and 19/24 scans, respectively. Whereas, in VR MRI, resectable, borderline resectable, and locally advanced PDAC were correctly identified in 19/24, 19/24 and 21/24 scans, respectively. Interobserver agreement as measured by Fleiss κ was 0.7 for CT and 0.4 for MRI, respectively (p < 0.001). Scans were significantly assessed more accurately in VR CT than standard 2D PACS CT, with a median of 5.5 (IQR 4.75-6) and a median of 3 (IQR 2-3) correctly assessed out of 6 scans (p < 0.001). CONCLUSION: VR enhanced visualisation of abdominal CT and MRI scan data provides intuitive handling and understanding of anatomy and might allow for more accurate staging of PDAC and could thus become a valuable adjunct in PDAC resectability assessment in the future.

Pyrazole derivatives as selective orexin-2 receptor antagonists (2-SORA): synthesis, structure-activity-relationship, and sleep-promoting properties in rats.

Selective orexin 2 receptor antagonists (2-SORA) such as seltorexant (15) are in clinical development for the treatment of insomnia and other conditions such as depression. Herein, we report our structure-activity-relationship (SAR) optimization efforts starting from an HTS hit (1) (N-(1-((5-acetylfuran-2-yl)methyl)-1H-pyrazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamide) that was derived from an unrelated in-house GPCR-agonist program. Medicinal chemistry efforts focused on the optimization of orexin 2 receptor (OX2R) antagonistic activity, stability in liver microsomes, time dependent CYP3A4 inhibition, and aqueous solubility. Compounds were assessed for their brain-penetrating potential in in vivo experiments to select the most promising compounds for our in vivo sleep model. Our lead optimization efforts led to the discovery of the potent, brain penetrating and orally active, 2-SORA (N-(1-(2-(5-methoxy-1H-pyrrolo[3,2-b]pyridin-3-yl)ethyl)-1H-pyrazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamide) 43 with efficacy in a sleep model in rats comparable to 15.

The short- and long-term outcome after the surgical management of common bile duct stones in a tertiary referral hospital.

BACKGROUND: The removal of common bile duct stones by endoscopic retrograde cholangiopancreatography (ERCP) shows excellent results with low complication rates and is therefore considered a gold standard. However, in case of stones non-removable by ERCP, surgical extraction is needed. The surgical approach is still controversial and clinical guidelines are missing. This study aims to analyze the outcomes of patients treated with choledochotomy or hepaticojejunostomy for common bile duct stones. METHODS: All patients who underwent choledochotomy or hepaticojejunostomy for common bile duct stones at a tertiary referral hospital over 11 years were included. The analyzed data contains basic demographics, diagnostics, surgical parameters, length of hospitalization, and morbidity and mortality. RESULTS: Over the study period, 4375 patients underwent cholecystectomy, and 655 received an ERCP with stone extraction, with 48 of these patients receiving subsequent surgical treatment. ERCP was attempted in 23/30 (77%) of the choledochotomy patients pre/intraoperatively and 11/18 (56%) in hepaticojejunostomy patients. The 30-day major complication rate (Clavien-Dindo > II) was 1/30 (3%) in the choledochotomy group and 2/18 (11%) in the hepaticojejunostomy group. Complications after 30 days occurred in 3/30 (10%) patients and 2/18 (11%), respectively, and no mortality occurred. CONCLUSION: ERCP should still be considered the gold standard, although due to low short- and long-term morbidity rates, choledochotomy and hepaticojejunostomy represent effective surgical solutions for common bile duct stones.

Machine learning in pancreas surgery, what is new? literature review.

Background: Machine learning (ML) is an inquiry domain that aims to establish methodologies that leverage information to enhance performance of various applications. In the healthcare domain, the ML concept has gained prominence over the years. As a result, the adoption of ML algorithms has become expansive. The aim of this scoping review is to evaluate the application of ML in pancreatic surgery. Methods: We integrated the preferred reporting items for systematic reviews and meta-analyses for scoping reviews. Articles that contained relevant data specializing in ML in pancreas surgery were included. Results: A search of the following four databases PubMed, Cochrane, EMBASE, and IEEE and files adopted from Google and Google Scholar was 21. The main features of included studies revolved around the year of publication, the country, and the type of article. Additionally, all the included articles were published within January 2019 to May 2022. Conclusion: The integration of ML in pancreas surgery has gained much attention in previous years. The outcomes derived from this study indicate an extensive literature gap on the topic despite efforts by various researchers. Hence, future studies exploring how pancreas surgeons can apply different learning algorithms to perform essential practices may ultimately improve patient outcomes.

From laparoscopic to robotic-assisted Heller myotomy for achalasia in a single high-volume visceral surgery center: postoperative outcomes and quality of life.

BACKGROUND: Laparoscopic (LSC) Heller myotomy (HM) is considered the standard procedure for the treatment of achalasia. Robotic platforms, established over the last years, provide important advantages to surgeons, such as binocular 3-dimensional vision and improvement of fine motor control. However, whether perioperative outcomes and long-term results of robotic-assisted laparoscopic (RAL) HM are similar or even superior to LSC technique, especially concerning long-term follow-up, is still debated. Therefore, the aim of the present study was to evaluate intra- and postoperative results as well as long-term quality of life after RAL compared to LSC surgery for achalasia in a single high-volume visceral surgery center. METHODS: Between August 2007 and April 2020, 43 patients undergoing minimally invasive HM for achalasia in a single high-volume Swiss visceral surgery center, were included in the present study. Intra- and postoperative outcome parameters were collected and evaluated, and a long-term follow-up was performed using the gastroesophageal-reflux disease health-related quality of life (GERD-Hr-QuoL) questionnaire. RESULTS: A total of 11 patients undergoing RAL and 32 undergoing LSC HM were analyzed. Baseline demographics and clinical characteristics were similar. A trend (p = 0.052) towards a higher number of patients with ASA III score treated with RAL was detectable. Operation time was marginally, but significantly, shorter in LSC (140 min, IQR: 136-150) than in RAL (150 min, IQR: 150-187, p = 0.047). Postoperative complications graded Clavien-Dindo ≥ 3 were only observed in one patient in each group. Length of hospital stay was similar in both groups (LSC: 11 days, IQR: 10-13 vs. RAL: 11 days, IQR: 10-14, p = 0.712). Long-term follow-up (LSC: median 89 months, vs. RAL: median 28 months, p = 0.001) showed comparable results and patients from both groups expressed similar levels of satisfaction (p = 0.181). CONCLUSIONS: LSC and RAL HM show similar peri- and postoperative results and a high quality of life, even in long-term (> 24 months) follow-up. Prospective, randomized, controlled multicenter trials are needed to overcome difficulties associated to small sample sizes in a rare condition and to confirm the equality or demonstrate the superiority of robotic-assisted procedures for achalasia. Meanwhile, the choice of the treatment technique could be left to the operating surgeon's preferences.

Trends in pancreatic surgery in Switzerland: a survey and nationwide analysis over two decades.

BACKGROUND: Centralisation of highly specialised medicine (HSM) has changed practice and outcome in pancreatic surgery (PS) also in Switzerland. Fewer hospitals are allowed to perform pancreatic surgery according to nationally defined cut-offs. OBJECTIVE: We aimed to examine trends in PS in Switzerland. First, to assess opinions and expected trends among Swiss pancreatic surgeons in regard of PS practice and second, to assess the evolution of PS performance in Switzerland by a nationwide retrospective analysis. METHODS: First, a 26-item survey among all surgeons who performed PS in 2016 in Switzerland was performed. Then, nationwide data from 1998 to 2018 from all hospitals performing PS was analysed including centre volume, perioperative morbidity and mortality, surgical indications and utilisation of minimally invasive pancreatic surgery (MIPS). The national cut-off for regulatory accredited volume centres (AVC) was ≥ 12. Additionally, an international benchmark definition for high volume (≥ 20 surgeries/year) was used. RESULTS: Among 25 surgeons from 15 centres (response rate 51%), the survey revealed agreement that centralisation is important to improve perioperative outcomes. Respondents agreed on a minimum case load per surgeon or centre. Within the nationwide database, 8534 pancreatic resections were identified. Most resections were performed for pancreatic ductal adenocarcinoma (58.9%). There was a significant trend towards centralisation of PS with fewer non-accredited volume centres (nAVC) (36 in 1998 and 17 in 2018, p < 0.001) and more AVC (2 in 1998 and 18 in 2018, p < 0.001). A significantly higher adjusted mortality after pancreatoduodenectomy (PD) was observed in low-volume compared to high-volume hospitals (OR 1.45 [95% CI 1.15-1.84], p = 0.002) and a similar trend compared among AVC and nAVC (OR 1.25 [95% CI 0.98-1.60], p = 0.072), while mortality after distal pancreatectomy (DP) was not influenced by centre volume. CONCLUSIONS: Over the last two decades, centralisation of PS towards higher-volume centres was observed in Switzerland with a decrease of mortality after PD and low mortality after DP. Further centralisation is supported by most pancreatic surgeons. However, the ideal metric and outcome measures for the allocation of highly specialised medicine need further discussion to allow a fair and outcome-focused allocation.

Magnetic resonance cholangiopancreatography enhanced by virtual reality as a novel tool to improve the understanding of biliary anatomy and the teaching of surgical trainees.

Objective: The novel picture archiving and communication system (PACS), compatible with virtual reality (VR) software, displays cross-sectional images in VR. VR magnetic resonance cholangiopancreatography (MRCP) was tested to improve the anatomical understanding and intraoperative performance of minimally invasive cholecystectomy (CHE) in surgical trainees. Design: We used an immersive VR environment to display volumetric MRCP data (Specto VRTM). First, we evaluated the tolerability and comprehensibility of anatomy with a validated simulator sickness questionnaire (SSQ) and examined anatomical landmarks. Second, we compared conventional MRCP and VR MRCP by matching three-dimensional (3D) printed models and identifying and measuring common bile duct stones (CBDS) using VR MRCP. Third, surgical trainees prepared for CHE with either conventional MRCP or VR MRCP, and we measured perioperative parameters and surgical performance (validated GOALS score). Setting: The study was conducted out at Clarunis, University Center for Gastrointestinal and Liver Disease, Basel, Switzerland. Participants: For the first and second study step, doctors from all specialties and years of experience could participate. In the third study step, exclusively surgical trainees were included. Of 74 participating clinicians, 34, 27, and 13 contributed data to the first, second, and third study phases, respectively. Results: All participants determined the relevant biliary structures with VR MRCP. The median SSQ score was 0.75 (IQR: 0, 3.5), indicating good tolerability. Participants selected the corresponding 3D printed model faster and more reliably when previously studying VR MRCP compared to conventional MRCP: We obtained a median of 90 s (IQR: 55, 150) and 72.7% correct answers with VR MRCP versus 150 s (IQR: 100, 208) and 49.6% correct answers with conventional MRCP, respectively (p < 0.001). CBDS was correctly identified in 90.5% of VR MRCP cases. The median GOALS score was higher after preparation with VR MRCP than with conventional MRCP for CHE: 16 (IQR: 13, 22) and 11 (IQR: 11, 18), respectively (p = 0.27). Conclusions: VR MRCP allows for a faster, more accurate understanding of displayed anatomy than conventional MRCP and potentially leads to improved surgical performance in CHE in surgical trainees.

Robotic Versus Conventional Minimal-Invasive Inguinal Hernia Repair: Study Protocol for a Prospective, Randomized and Blinded Clinical Trial.

Introduction: Inguinal hernia repairs are commonly performed procedures. The surgical techniques vary from open procedures to minimally invasive and robotic-assisted surgeries and include totally extra-peritoneal hernia repairs (TEP) and robotic transabdominal pre-peritoneal hernia repairs (rTAPP). So far, there is no randomized and blinded clinical trial comparing these two surgical approaches. Our objective is to investigate whether rTAPP is associated with a decreased postoperative level of pain. Methods: This is a prospective, single center, randomized and blinded clinical trial. Patients will receive either rTAPP or TEP for uni- or bilateral inguinal hernias. All patients and assessors of the study are blinded to the randomization. The perioperative setting is standardized, and all surgeons will perform both rTAPP and TEP to eliminate surgeons` bias. Primary endpoint is the assessment of pain while coughing 24 hours after surgery using the numeric rating scale (NRS). Secondary endpoints include the assessment of multiple pain and quality of life questionnaires at several defined times according to the study schedule. Furthermore, intra- and postoperative complications, duration until discharge, procedure time, duration of postoperative sick leave and the recurrence rate will be evaluated. Registry: The trial has been registered at ClinicalTrials.gov under the registry number NCT05216276. Highlights: Trial comparing robotic and conventional minimal-invasive inguinal hernia repairRandomized and patient/assessor blinded trialEarly postoperative pain as primary outcome (24 hours)Secondary patient outcomes include pain and quality of life scores up to one yearFurther secondary outcomes: complications, costs, surgeon's stress level.

Continuously sutured versus linear-stapled anastomosis in robot-assisted hybrid Ivor Lewis esophageal surgery following neoadjuvant chemoradiotherapy: a single-center cohort study.

BACKGROUND: Esophageal cancer surgery is technically highly demanding. During the past decade robot-assisted surgery has successfully been introduced in esophageal cancer treatment. Various techniques are being evaluated in different centers. In particular, advantages and disadvantages of continuously sutured (COSU) or linear-stapled (LIST) gastroesophageal anastomoses are debated. Here, we comparatively analyzed perioperative morbidities and short-term outcomes in patients undergoing hybrid robot-assisted esophageal surgery following neoadjuvant chemoradiotherapy (nCRT), with COSU or LIST anastomoses in a single center. METHODS: Following standardized, effective, nCRT, 53 patients underwent a hybrid Ivor Lewis robot-assisted esophagectomy with COSU (n = 32) or LIST (n = 21) gastroesophageal anastomoses. Study endpoints were intra- and postoperative complications, in-hospital morbidity and mortality. Duration of operation, intensive care unit (ICU) and overall hospital stay were also evaluated. Furthermore, rates of rehospitalization, endoscopies, anastomotic stenosis and recurrence were assessed in a 90-day follow-up. RESULTS: Demographics, ASA scores and tumor characteristics were comparable in the two groups. Median duration of operation was similar in patients with COSU and LIST anastomosis (467 vs. 453 min, IQR 420-521 vs. 416-469, p = 0.0611). Major complications were observed in 4/32 (12.5%) and 4/21 (19%) patients with COSU or LIST anastomosis, respectively (p = 0.697). Anastomotic leakage was observed in 3/32 (9.3%) and 2/21 (9.5%) (p = 1.0) patients with COSU or LIST anastomosis, respectively. Pleural empyema occurred in 1/32 (3.1%) and 2/21 (9.5%) (p = 0.555) patients, respectively. Mortality was similar in the two groups (1/32, 3.1% and 1/21, 4.7%, p = 1.0). Median ICU stay did not differ in patients with COSU or LIST anastomosis (p = 0.255), whereas a slightly, but significantly (p = 0.0393) shorter overall hospital stay was observed for COSU, as compared to LIST cohort (median: 20 vs. 21 days, IQR 17-22 vs. 18-28). CONCLUSIONS: COSU is not inferior to LIST in the performance of gastroesophageal anastomosis in hybrid Ivor Lewis operations following nCRT.

Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells.

Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial-mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk.

From open Ivor Lewis esophagectomy to a hybrid robotic-assisted thoracoscopic approach: a single-center experience over two decades.

PURPOSE: Robotic-assisted procedures are increasingly used in esophageal cancer surgery. We compared postoperative complications and early oncological outcomes following hybrid robotic-assisted thoracoscopic esophagectomy (Rob-E) and open Ivor Lewis esophagectomy (Open-E), performed in a single mid-volume center, in the context of evolving preoperative patient and tumor characteristics over two decades. METHODS: We evaluated prospectively collected data from a single center from 1999 to 2020 including 321 patients that underwent Ivor Lewis esophagectomy, 76 underwent Rob-E, and 245 Open-E. To compare perioperative outcomes, a 1:1 case-matched analysis was performed. Endpoints included postoperative morbidity and 30-day mortality. RESULTS: Preoperative characteristics revealed increased rates of adenocarcinomas and wider use of neoadjuvant treatment over time. A larger number of patients with higher ASA grades were operated with Rob-E. In case-matched cohorts, there were no differences in the overall morbidity (69.7% in Rob-E, 60.5% in Open-E, p value 0.307), highest Clavien-Dindo grade per patient (43.4% vs. 38.2% grade I or II, p value 0.321), comprehensive complication index (median 20.9 in both groups, p value 0.401), and 30-day mortality (2.6% in Rob-E, 3.9% in Open-E, p value 1.000). Similar median numbers of lymph nodes were harvested (24.5 in Rob-E, 23 in Open-E, p value 0.204), and comparable rates of R0-status (96.1% vs. 93.4%, p value 0.463) and distribution of postoperative UICC stages (overall p value 0.616) were observed. CONCLUSIONS: Our study demonstrates similar postoperative complications and early oncological outcomes after Rob-E and Open-E. However, the selection criteria for Rob-E appeared to be less restrictive than those of Open-E surgery.

Laparoscopic versus robotic-assisted, left-sided colectomies: intra- and postoperative outcomes of 683 patients.

BACKGROUND: Robotic-assisted colorectal surgery has gained more and more popularity over the last years. It seems to be advantageous to laparoscopic surgery in selected situations, especially in confined regions like a narrow male pelvis in rectal surgery. Whether robotic-assisted, left-sided colectomies can serve as safe training operations for less frequent, low anterior resections for rectal cancer is still under debate. Therefore, the aim of this study was to evaluate intra- and postoperative results of robotic-assisted laparoscopy (RAL) compared to laparoscopic (LSC) surgery in left-sided colectomies. METHODS: Between June 2015 and December 2019, 683 patients undergoing minimally invasive left-sided colectomies in two Swiss, high-volume colorectal centers were included. Intra- and postoperative outcome parameters were collected and analyzed. RESULTS: A total of 179 patients undergoing RAL and 504 patients undergoing LSC were analyzed. Baseline characteristics showed similar results. Intraoperative complications occurred in 0.6% of RAL and 2.0% of LSC patients (p = 0.193). Differences in postoperative complications graded Dindo ≥ 3 were not statistically significant (RAL 3.9% vs. LSC 6.3%, p = 0.227). Occurrence of anastomotic leakages showed no statistically significant difference [RAL n = 2 (1.1%), LSC n = 8 (1.6%), p = 0.653]. Length of hospital stay was similar in both groups. Conversions to open surgery were significantly higher in the LSC group (6.2% vs.1.7%, p = 0.018), while stoma formation was similar in both groups [RAL n = 1 (0.6%), LSC n = 5 (1.0%), p = 0.594]. Operative time was longer in the RAL group (300 vs. 210.0 min, p < 0.001). CONCLUSION: Robotic-assisted, left-sided colectomies are safe and feasible compared to laparoscopic resections. Intra- and postoperative complications are similar in both groups. Most notably, the rate of anastomotic leakages is similar. Compared to laparoscopic resections, the analyzed robotic-assisted resections have longer operative times but less conversion rates. Further prospective studies are needed to confirm the safety of robotic-assisted, left-sided colectomies as training procedures for low anterior resections.

Robotic versus laparoscopic low anterior resection following neoadjuvant chemoradiation therapy for stage II-III locally advanced rectal cancer: a single-centre cohort study.

Neoadjuvant chemo-radiotherapy (nCRT) of locally advanced rectal cancer is associated with challenging surgical treatment and increased postoperative morbidity. Robotic technology overcomes laparoscopy limitations by enlarged 3D view, improved anatomical transection accuracy, and physiologic tremor reduction. Patients with UICC stage II-III rectal cancer, consecutively referred to our institution between March 2015 and June 2020 (n = 102) were treated with robotic (Rob-G, n = 38) or laparoscopic (Lap-G, n = 64) low anterior resection (LAR) for total meso-rectal excision (TME) following highly standardized and successful nCRT treatment. Feasibility, conversion rates, stoma creation, morbidity and clinical/pathological outcome were comparatively analysed. Sex, age, BMI, ASA scores, cTN stages and tumour distance from dentate line were comparable in the two groups. Robotic resection was always feasible without conversion to open surgery, which was necessary in 11/64 (17%) Lap-G operations (p = 0.006). Primary or secondary stomata were created in 17/38 (45%) Rob-G and 52/64 (81%) Lap-G patients (p < 0.001). Major morbidity occurred in 7/38 (18.4%) Rob-G and 6/64 (9.3%) Lap-G patients (p = 0.225). Although median operation time was longer in Rob-G compared with Lap-G (376; IQR: 330-417 min vs. 300; IQR: 270-358 min; p < 0.001), the difference was not significant in patients (Rob-G, n = 6; Lap-G, n = 10) with ≥30 BMI (p = 0.106). Number of resected lymph nodes, ypTN staging and circumferential resection margins (CRM) were comparable. Resection was complete in 87% of Rob-G and 89% of Lap-G patients (p = 0.750). Robotic LAR is not inferior to laparoscopic LAR following nCRT. Larger, randomized studies are needed to confirm lower conversion in robotic, compared to laparoscopic resection.