Minimally invasive pancreatic surgery—will robotic surgery be the future?

Due to the complexity of the procedures and the texture of the organ itself, pancreatic surgery remains a challenge in the field of visceral surgery. During the past decade, a minimally invasive approach to pancreatic surgery has gained distribution in clinical routine, extending from left-sided procedures to pancreatic head resections. While a laparoscopic approach has proven beneficial for many patients with left-sided pancreatic pathologies, the complex reconstruction in pancreas head resections remains worrisome with the laparoscopic approach. The robotic technique was established to overcome such technical constraints while preserving the advantages of the laparoscopic approach. Even though robotic systems are still in development, especially in pancreatoduodenectomy, the current literature demonstrates the feasibility of this approach and stable clinical and oncological outcomes compared to the open technique, albeit only under the condition of such operations being performed by specialist teams in a high-volume setting (>20 robotic pancreaticoduodenectomies per year). The aim of this review is to analyze the current evidence regarding a minimally invasive approach to pancreatic surgery and to review the potential of a robotic approach. Presently, there is still a scarcity of sound evidence and long-term oncological data regarding the role of minimally invasive and robotic pancreatic surgery in the literature, especially in the setting of pancreaticoduodenectomy

Comparison of QG-Induced Dispersion with Standard Physics Effects

One of the predictions of quantum gravity phenomenology is that, in situations where Planck-scale physics and the notion of a quantum spacetime are relevant, field propagation will be described by a modified set of laws. Descriptions of the underlying mechanism differ from model to model, but a general feature is that electromagnetic waves will have non-trivial dispersion relations. A physical phenomenon that offers the possibility of experimentally testing these ideas in the foreseeable future is the propagation of high-energy gamma rays from GRB's at cosmological distances. With the observation of non-standard dispersion relations within experimental reach, it is thus important to find out whether there are competing effects that could either mask or be mistaken for this one. In this letter, we consider possible effects from standard physics, due to electromagnetic interactions, classical as well as quantum, and coupling to classical geometry. Our results indicate that, for currently observed gamma-ray energies and estimates of cosmological parameter values, those effects are much smaller than the quantum gravity one if the latter is first-order in the energy; some corrections are comparable in magnitude with the second-order quantum gravity ones, but they have a very different energy dependence.Comment: 8 pages; Version to be published in CQG as a letter; Includes some new comments and references, but no changes in the result

Safety of transanal ileal pouch-anal anastomosis for ulcerative colitis: a retrospective observational cohort study

Background: Colectomy with transanal ileal pouch-anal anastomosis (taIPAA) is a surgical technique that can be used to treat benign colorectal disease. Ulcerative colitis is the most frequent inflammatory bowel disease (IBD) and although pharmacological therapy has improved, colectomy rates reach up to 15%. The objective of this study was to determine anastomotic leakage rates and treatment after taIPAA as well as short- and long-term pouch function. Methods: We conducted a retrospective analysis of a prospective database of all patients undergoing taIPAA at an academic tertiary referral center in Germany, between 01/03/2015 and 31/08/2019. Patients with indications other than ulcerative colitis or with adjuvant chemotherapy following colectomy for colorectal carcinoma were excluded for short- and long-term follow up due to diverging postoperative care yet considered for evaluation of anastomotic leakage. Results: A total of 22 patients undergoing taIPAA during the study time-window were included in analysis. Median age at the time of surgery was 32 +/- 12.5 (14-54) years. Two patients developed an anastomotic leakage at 11 days (early anastomotic leakage) and 9 months (late anastomotic leakage) after surgery, respectively. In both patients, pouches could be preserved with a multimodal approach. Twenty patients out of 22 met the inclusion criteria for short and long term follow-up. Data on short-term pouch function could be obtained in 14 patients and showed satisfactory pouch function with only four patients reporting intermittent incontinence at a median stool frequency of 9-10 times per day. In the long-term we observed an inflammation or "pouchitis" in 11 patients and a pouch failure in one patient. Conclusion: Postoperative complication rates in patients with benign colorectal disease remain an area of concern for surgical patient safety. In this pilot study on 22 selected patients, taIPAA was associated with two patients developing anastomotic leakage. Future large-scale validation studies are required to determine the safety and feasibility of taIPAA in patients with ulcerative colitis

The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development

Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD. We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme. To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics. Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community's chances of successfully bringing new rare disease drugs to registration and ultimately to marke

The risk of stroke recurrence in patients with atrial fibrillation and reduced ejection fraction

Abstract Background: Atrial fibrillation (AF) and congestive heart failure often coexist due to their shared risk factors leading to potential worse outcome, particularly cerebrovascular events. The aims of this study were to calculate the rates of ischemic and severe bleeding events in ischemic stroke patients having both AF and reduced ejection fraction (rEF) (⩽40%), compared to ischemic stroke patients with AF but without rEF. Methods: We performed a retrospective analysis that drew data from prospective studies. The primary outcome was the composite of either ischemic (stroke or systemic embolism), or hemorrhagic events (symptomatic intracranial bleeding and severe extracranial bleeding). Results: The cohort for this analysis comprised 3477 patients with ischemic stroke and AF, of which, 643 (18.3%) had also rEF. After a mean follow-up of 7.5 ± 9.1 months, 375 (10.8%) patients had 382 recorded outcome events, for an annual rate of 18.0%. While the number of primary outcome events in patients with rEF was 86 (13.4%), compared to 289 (10.2%) for the patients without rEF; on multivariable analysis rEF was not associated with the primary outcome (OR 1.25; 95% CI 0.84–1.88). At the end of follow-up, 321 (49.9%) patients with rEF were deceased or disabled (mRS ⩾3), compared with 1145 (40.4%) of those without rEF; on multivariable analysis, rEF was correlated with mortality or disability (OR 1.35; 95% CI 1.03–1.77). Conclusions: In patients with ischemic stroke and AF, the presence of rEF was not associated with the composite outcome of ischemic or hemorrhagic events over short-term follow-up but was associated with increased mortality or disability

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial

PURPOSE: This randomized, open -label trial compared the efficacy and safety of adjuvant nabpaclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430). METHODS: We assigned 866 treatment -naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m(2)) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28 -day cycles. The primary end point was independently assessed disease -free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS: Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nabpaclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 (nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P =.18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P=.02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P =.045). At a 16 -month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 (nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P =.0232). At the 5 -year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P =.0091). Eighty-six percent (nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade >= 3 treatment -emergent adverse events. Two patients per study arm died of treatment -emergent adverse events. CONCLUSION: The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Effects of tobacco exposure on the postoperative risk of marginal ulcer after laparoscopic Roux-en-Y gastric bypass

Der laparoskopische Roux-en-Y Magenbypass (LRYGB) ist weltweit eine der am häufigsten durchgeführten Operationen zur Therapie der Adipositas. Die Entstehung eines Ulkus an der Gastrojejunostomie nach erfolgtem LRYGB ist eine der wichtigsten postoperativen Komplikationen und wird durch zahlreiche Risikofaktoren beeinflusst. Der Konsum von Tabak und tabakähnlichen Produkten zeigt einen bedeutenden Einfluss in der Entwicklung eines Anastomosenulkus. Wir führten die Datenanalyse dieser Studie in Hinblick auf die Auswirkung der Quantität der Tabakexposition auf die Entstehung eines Anastomosenulkus durch. In diese retrospektiven Single-center Studie wurden 249 Patienten eingeschlossen. Alle Patienten erhielten zwischen 2010 und 2015 einen LRYGB. Weiteres Einschlusskriterium war ein Follow-up von mindestens zwei Jahren. Das Hauptaugenmerk dieser Datenanalyse lag auf der Auswertung möglicher Risikofaktoren und dem zeitlichen Auftreten von Anastomosenulzerationen nach LRYGB. Insgesamt wurden bei 27 (10,8%) Patienten ein postoperatives Anastomosenulkus diagnostiziert. Der Nikotinkonsum erwies sich als statistisch signifikanter, unabhängiger Risikofaktor verglichen mit Nicht-Rauchern (4,6-fach erhöhtes Risiko) (p=0,003). Insgesamt waren 22 (81,5%) der 27 Patienten bei denen ein Anastomosenulkus diagnostiziert wurden Raucher. Es zeigte sich eine vergleichbare Rate der Inzidenz eines Anastomosenulkus in den Gruppen der leichten, moderaten und schweren Rauchern (17,4% vs. 17,1% vs. 17,9%), gemessen am täglichen Zigarettenkonsum. Patienten in der Subgruppe der leichten Raucher mit weniger als 10 Zigaretten pro Tag zeigten ein signifikant erhöhtes Risiko für die Entstehung eines Ulkus im Vergleich zu Nicht-Rauchern (17,4% vs. 4,2%; p=0,027). Es konnte kein signifikanter Risikounterschied für Anastomosenulzerationen zwischen ehemaligen und aktuellen Rauchern festgestellt werden (13,3% vs. 17,5%; p=0,685). Tabakkonsum ist, unabhängig von der täglichen oder lebenslangen Tabakexposition, in dieser Studie der einzige wesentliche Risikofaktor in der Entstehung eines Anastomosenulkus. Die Raucherentwöhnung sollte präoperativ, zur Vermeidung dieser Komplikationen nach LRYGB dringend empfohlen werden.BACKGROUND: The laparoscopic Roux-en-Y gastric bypass (LRYGB) is worldwide one of the most common surgical therapies for obesity. Various extrinsic and intrinsic factors seem to favour the development of marginal ulcers (MUs) at the gastrojejunal anastomosis which is one of the most common postoperative complication after LRYGB. Especially smoking seems to have an major impact on the development of MUs. OBJECTIVE: Literature is missing data on how much smoking influences the risk. We therefore reviewed our patients in particular regarding the quantity of their smoking behavior and the development of MUs after LRYGB. METHODS: This study included 249 patients who underwent LRYGB surgery between 2010 and 2015. At least 2 years of follow-up were obligatory for inclusion. This retrospective analysis was performed in a primary care and a university hospital. It focused on the development of marginal ulcers after LRYGB, the time of appearance, and possible risk factors. RESULTS: A total of 27 (10.8%) patients in this study developed postoperatively MUs. In total 22 (81,5%) of the 27 patients with MU were known to smoke at the time of diagnosis. Tobacco is an independent and statistically significant predictor of the development of MUs with a 4.6-fold greater risk (P = .003). The same rate of MU development was observed between light, moderate, and heavy daily smokers (17.4% versus 17.1% versus 17.9%, respectively). Compared to nonsmokers light smokers with <10 cigarettes per day show a higher rate of MUs (17.4% versus 4.2%, respectively; P = .027). No significant differences of risk for MUs were found between former and current smokers (13.3% versus 17.5%, respectively; P = .685). CONCLUSION: MU are one of the most important and frequent complications after LRYGB. In this study the use of tobacco is shown to be the only substantial risk factor. Smoking, regardless of its intensity, is associated with an exceptional risk of MU formation after LRYGB and therefore we strongly recommend smoking cessation before bariatric surgery

Minimally invasive pancreatic surgery—will robotic surgery be the future?

&lt;jats:title&gt;Summary&lt;/jats:title&gt;&lt;jats:p&gt;Due to the complexity of the procedures and the texture of the organ itself, pancreatic surgery remains a challenge in the field of visceral surgery. During the past decade, a minimally invasive approach to pancreatic surgery has gained distribution in clinical routine, extending from left-sided procedures to pancreatic head resections. While a laparoscopic approach has proven beneficial for many patients with left-sided pancreatic pathologies, the complex reconstruction in pancreas head resections remains worrisome with the laparoscopic approach. The robotic technique was established to overcome such technical constraints while preserving the advantages of the laparoscopic approach. Even though robotic systems are still in development, especially in pancreatoduodenectomy, the current literature demonstrates the feasibility of this approach and stable clinical and oncological outcomes compared to the open technique, albeit only under the condition of such operations being performed by specialist teams in a high-volume setting (&amp;gt;20 robotic pancreaticoduodenectomies per year). The aim of this review is to analyze the current evidence regarding a minimally invasive approach to pancreatic surgery and to review the potential of a robotic approach. Presently, there is still a scarcity of sound evidence and long-term oncological data regarding the role of minimally invasive and robotic pancreatic surgery in the literature, especially in the setting of pancreaticoduodenectomy.&lt;/jats:p&gt

Initial Experience with the Safe Implementation of Transanal Total Mesorectal Excision (TaTME) as a Standardized Procedure for Low Rectal Cancer

Introduction: The laparoscopic approach for TME is proven to be non-inferior in oncological outcome compared to open surgery. Anatomical limitations in the male and obese pelvis with resulting pathological shortcomings and high conversion rates were stimuli for alternative approaches. The transanal approach for TME (TaTME) was introduced to overcome these limitations. The aim of this study was to evaluate the outcomes of TaTME for mid and low rectal cancer at our center. Methods: TaTME is a hybrid procedure of simultaneously laparoscopic and transanal mesorectal excision. A retrospective analysis of all consecutive TaTME procedures performed at our center for mid and low rectal cancer between December 2014 and January 2020 was conducted. Results: A total of 157 patients underwent TaTME, with 72.6% receiving neoadjuvant chemoradiation. Mean tumor height was 6.1 &plusmn; 2.3 cm from the anal verge, 72.6% of patients had undergone neoadjuvant chemoradiotherapy, and 34.2% of patients presented with a threatened CRM upon pretherapeutic MRI. Abdominal conversion rate was 5.7% with no conversion for the transanal dissection. Early anastomotic leakage occurred in 7.0% of the patients. Mesorectum specimen was complete in 87.3%, R1 resection rate was 4.5% (involved distal resection margin) and in 7.6%, the CRM was positive. The three-year local recurrence rate of 58 patients with a follow-up &ge; 36 months was 3.4%. Overall survival was 92.0% after 12 months, and 82.2% after 36 months. Conclusion: TaTME can be performed safely with acceptable long-term oncological outcome. Low rectal cancer can be well addressed by TaTME, which is an appropriate alternative with low conversion, local recurrence, adequate mesorectal quality and CRM positivity rates