The impact of bariatric and metabolic surgery on cancer development.

Obesity (BMI ≥ 30 kg/m2) with related comorbidities such as type 2 diabetes mellitus, cardiovascular disease, sleep apnea syndrome, and fatty liver disease is one of the most common preventable risk factors for cancer development worldwide. They are responsible for at least 40% of all newly diagnosed cancers, including colon, ovarian, uterine, breast, pancreatic, and esophageal cancer. Although various efforts are being made to reduce the incidence of obesity, its prevalence continues to spread in the Western world. Weight loss therapies such as lifestyle change, diets, drug therapies (GLP-1-receptor agonists) as well as bariatric and metabolic surgery are associated with an overall risk reduction of cancer. Therefore, these strategies should always be essential in therapeutical concepts in obese patients. This review discusses pre- and post-interventional aspects of bariatric and metabolic surgery and its potential benefit on cancer development in obese patients

Comparison of opiate activity in granulosa cells of PCOS and non-PCOS women

Aufgrund des ansteigenden Alters Erstgebärender, einer größeren gesellschaftlichen Akzeptanz gegenüber reproduktionsmedizinischen Maßnahmen sowie einem leichteren Zugang zu entsprechender ärztlicher Behandlung kann eine ansteigende Inanspruchnahme assistierter Reproduktion wie z.B. in-vitro-Fertilisation (IVF) beobachtet werden. Die schwerwiegendste, wenn auch relativ selten auftretende Nebenwirkung im Rahmen dieser Therapie ist das sogenannte ovarielle Hyperstimulationssyndrom (OHSS), bei dem es aufgrund einer massiven und überschießenden Reaktion der Ovarien auf die hormonelle Stimulation und dem iatrogen zugeführten Ovulationstrigger zu peritonealen Flüssigkeitsansammlungen mit damit verbundenen Symptomen wie Schmerzen, Übelkeit sowie in seltenen, schweren Fällen zu Hämokonzentration und Schock kommen kann. Hauptursächlich dafür wurde VEGF, ein endothelialer Wachstumsfaktor, identifiziert, der bei betroffenen Frauen in supraphysiologischen Mengen von Granulosazellen und möglicherweise auch anderen Organen und Geweben sezerniert wird und eine Erhöhung der Gefäßpermeabilität in den Ovarien bewirkt. Ein besonderer Risikofaktor für die Entwicklung des OHSS stellt das Krankheitsbild des PCOS (=Polyzystisches Ovar-Syndrom) dar, da es oft mit Insulinresistenz und reaktiver Hyperinsulinämie vergesellschaftet ist zwei Faktoren, die eine VEGF-Hypersekretion begünstigen. Da Opiatrezeptoren mit VEGF und dessen intrazelluläre Regulation in Verbindung gebracht wurden, stellten wir die Hypothese auf, dass 1) humane Granulosazellen Opiatrezeptoren exprimieren und 2)dass durch eine gezielte Blockade dieser Rezeptoren an Granulosazellen deren VEGF-Sekretion vermindert werden kann. Um dieses Projekt durchzuführen, wurden neben einer etablierten humanen Granulosazelllinie primäre Granulosazellen aus Follikelflüssigkeit von IVF-Patientinnen verwendet, die mittels eines Dichtegradienten isoliert wurden. Die unterschiedlichen Opiatrezeptoren (OPRM1, OPRD1, OPRK1) wurden in beiden Zelltypen mittels Western blot sowie Durchflusszytometrie auf Proteinebene als auch auf mRNA-Ebene mittels PCR analysiert. Für die Untersuchung des Effekts von Opiatagonisten, -antagonisten sowie deren Kombination mit Insulin auf die VEGF-Sekretion wurden sowohl die Zelllinie, als auch die primären Zellen für 72 Stunden unter standardisierten Bedingungen mit entsprechenden Substanzen inkubiert. Zugeführtes Insulin soll in diesem Zusammenhang eine in vivo Hyperinsulinämie in vitro nachahmen. VEGF-Konzentrationen im Zellkulturüberstand wurden anschließend mittels ELISA quantifiziert. Insgesamt konnten 12 gesunde Patientinnen (Tubarsterilität oder Sterilität des Partners oder eine Kombination als IVF-Indikation) für die Kontrollgruppe sowie 12 Patientinnen mit diagnostiziertem PCOS in die Studie eingeschlossen werden. Für die Aufbewahrung der Zellen konnte eine Einfrier-Auftau-Routine etabliert werden, eine Grundvoraussetzung für die logistische Realisierbarkeit des Projekts. Sowohl in der Granulosazelllinie als auch in den luteinisierten Primärzellen erbrachten den erstmaligen Nachweis von Opiatrezeptoren (OPRM1, OPRD1, OPRK1). Zellen von Frauen mit PCOS erwiesen sich als deutlich empfindlicher auf Insulinstimulation als jene der Vergleichskohorte und eine verstärkte VEGF-Sekretion konnte beobachtet werden. Die Inkubation mit einem Opiatantagonisten, sowohl alleine als auch in Kombination mit Insulin, führte zu einer signifikanten VEGF-Reduktion im Zellkulturüberstand. Auf der Suche nach einem möglichen endogenen Liganden für die Opiatrezeptoren konnten wir das Präkursor-Molekül für ß-Endorphin, POMC, ein endogener Agonist vorwiegend an OPRM1, in den Granulosazellen erstmalig nachweisen. Zusammenfassend konnten wir beweisen, dass humane Granulosazellen Opiatrezeptoren exprimieren und die entsprechenden Liganden selbst sezernieren, was auf eine parakrine Funktion dieses Opiatsystems schließen lässt. Durch gezielte Blockade dieser Rezeptoren konnten wir nachweisen, dass sich das VEGF-Sekretionsprofil von Granulosazellen positiv beeinflussen lässt. Dieses Projekt war der notwendige erste Schritt für eine weitergehende Untersuchung von Opiatantagonisten und deren Einfluss auf VEGF in vivo in der Prävention und Therapie von OHSS.Due to multiple factors including elective delay in childbearing, decreasing stigma about infertility treatment, and greater availability and access to treatment, an increasing demand for assisted reproduction techniques such as in vitro fertilization (IVF) has been observed. The most serious though relatively rare side effect of IVF is the ovarian hyperstimulation syndrome (OHSS), resulting from an excessive ovarian response to the hormonal stimulation and ovulation trigger administered. Peritoneal fluid accumulation leads to symptoms such as pain, nausea, and hemoconcentration with rare, isolated cases of shock and death reported. VEGF, an endothelial growth factor, was identified as the main culprit in the pathogenesis of OHSS. In affected women, VEGF is secreted from granulosa cells in supraphysiologic quantities and causes an increase in vascular permeability in the ovaries and possibly also other organs and tissues. The polycystic ovary syndrome (PCOS) represents a particular risk factor for the development of OHSS since it is often accompanied by insulin resistance with reactive hyperinsulinemia, which poses an additional risk for VEGF hypersecretion. As opiate receptors have been linked to VEGF and its intracellular regulation, we hypothesized, that 1) human granulosa cells express opiate receptors and that 2) granulosa cell VEGF secretion can be reduced by a targeted blockade of these receptors. To carry out this project, we used an established human granulosa cell line as well as primary granulosa cells isolated from follicular fluid from patients undergoing IVF by a density gradient. The presence of different opiate receptor subtypes (OPRM1, OPRD1, OPRK1) was tested in both granulosa cell types on a protein level using Western blot and flow cytometry as well on the mRNA level by PCR. To investigate the effect of opiate agonists, antagonists and their combination with insulin on VEGF secretion in granulosa cell types, COV434 and primary cells were incubated with the appropriate substances for 72 hours under standard conditions. Insulin was added in vitro to mimic in vivo hyperinsulinemia. VEGF concentrations in the cell culture supernatant were then quantitatively assessed by ELISA. A total of 12 healthy patients (IVF patients treated for either tubal factor infertility, male factor infertility or the combination) for the control group and 12 patients with confirmed PCOS were included in the study. For long-term storage of the primary cells, a cryopreservation routine could be established. This operating procedure was the basic prerequisite for the logistical feasibility of the project. In COV434 granulosa cells as well as in primary granulosa cells isolated from follicular fluid we show for the first time the presence of opiate receptors (OPRM1, OPRD1, OPRK1). Cells retrieved from women with PCOS were found to be significantly more sensitive to insulin stimulation compared to granulosa cells from the control cohort, resulting in an increased VEGF secretion. Incubation with an opiate antagonist, either alone or in combination with insulin, resulted in a significant reduction in VEGF-cell culture supernatant. In search for a locally produced endogenous ligand for opioid receptors, POMC, the precursor molecule for ß-endorphin, was discovered for the first time in granulosa cells. ß-Endorphin is the primary endogenous ligand for OPRM1. In summary, this project shows for the first time the expression of opioid receptors and the expression of an endogenous opioid precursor molecule in granulosa cells, implying a paracrine signaling function of opiates within the follicular microenvironment. Through a targeted blockade of these receptors, we could show that the granulosa VEGF secretion profile can be positively modified. This project was the necessary first step for further studies of opiate antagonists and their influence on VEGF secretion in vivo in the prevention and treatment of OHSS.Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersArbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüftInnsbruck, Med. Univ., Diss., 2016(VLID)100800

Chemoradiotherapy alone or chemoradiotherapy followed by surgery in rectal cancer

In locally advanced rectal cancer, neoadjuvant chemoradiotherapy provides a significant benefit to local cancer control in addition to total mesorectal excision. However, in 10–40% of all patients, a complete clinical remission can be detected after completion of chemoradiotherapy. Recent studies have shown that those patients omitting radical surgery after successful neoadjuvant pretreatment can be safely managed within a close follow-up network without compromising short-term overall and disease-free survival. However, available data suggest that 20–30% of all patients assigned to a watch and wait regimen will eventually have to be transferred to surgical management due to local recurrence. Careful patient selection is key for a successful watch and wait approach and the choice of non-operative management should not be made after completion of staging but rather after neoadjuvant chemoradiotherapy. Selected patients need to be thoroughly informed that there is still no standardized follow-up protocol and no predefined follow-up period

Organizing a COVID-19 triage unit: a Swiss perspective

Background: With the rapid global spread of the acute respiratory syndrome coronavirus 2, urgent health-care measures have been implemented. We describe the organizational process in setting up a coronavirus disease 2019 triage unit in a Swiss tertiary care hospital. Methods: Our triage unit was set-up outside of the main hospital building and consists of three areas: 1. Pre-triage, 2. Triage, and 3. Triage plus. The Pre-triage check-points identify any potential COVID-19-infected patients and re-direct them to the main Triage area where trained medical staff screen which patients undergo diagnostic testing. If testing is indicated, nasopharyngeal swabs are performed. If patients require further investigations, they are referred to Triage plus. At this stage, patients are then discharged home after additional testing or admitted to the hospital for management. Observations: A total of 1265 patients were screened between 10 March 2020 and 12 April 2020 at our Triage unit. Of these, 112 (8.9%) tested positive. 73 (65%) of the positively-tested patients were female and 39 (35%) were male. The mean age for all patients was 43.8 years (SD 16.3 years). Distinguishing between genders, mean age for females was 41.1 (SD 16.5) and mean age for males was 48.6 (SD 14.9), with females being significantly younger than males (p < 0.001). Conclusion: Our triage unit was set-up as part of a large-scale restructuring process. Current challenges include low sensitivity for test results as well as limited staff and resources. We hope that our experience will help other health care institutions develop similar triage systems

Improved adipocyte viability in autologous fat grafting with ascorbic acid-supplemented tumescent solution

In reconstructive surgery, fat volume augmentation is often necessary for esthetic or functional reasons. As an alternative to synthetic and xenogeneic materials, autologous fat grafting (AFG) based on liposuction is gaining popularity, yet successful transplantation and long-term volume maintenance are difficult. Standard tumescent solution formulations neglect adipocyte and stromal vascular fraction (SVF) cell survival during extraction, as well as SVF differentiation into adipocytes thereafter, all of which are crucial for the success of AFG. Here we hypothesized that addition of ascorbic acid (AA) to the tumescent solution could prevent liposuction-induced cell damage

Association of a prehabilitation program with anxiety and depression before colorectal surgery: a post hoc analysis of the pERACS randomized controlled trial.

PURPOSE Hospital-associated anxiety and depression are major preoperative stressors and common in colorectal cancer surgery and major abdominal surgery. The prehabilitation Enhanced Recovery After Colorectal Surgery (pERACS) study is a single-center, single-blinded randomized controlled trial (RCT) evaluating the effect of a structured prehabilitation program. We evaluate within this RCT the association of a prehabilitation program with anxiety and depression before colorectal surgery. METHODS Treatment allocation randomized and single-blinded. Regardless of group allocation, patients were treated according to our institutional Enhanced Recovery After Surgery (ERAS) protocol. Inclusion criteria consisted of adult patients suffering from colorectal disease requiring surgical treatment and who were treated according to the ERAS protocol. Anxiety and depression scores were assessed at baseline and at admission according to the Hospital Anxiety and Depression Scale (HADS), with its subcomponents for depression (HADS-D) and for anxiety (HADS-A). RESULTS A total of 23 patients randomized to prehabilitation (mean age: 64.8±11.5 years) and 25 patients randomized to the control group (64.0±11.9 years) were included. There was no statistically significant difference in HADS-Anxiety improvement (Prehabilitation: -1.7±2.8 points vs. control: -0.4±3.4 points, p=0.132). Similarly, the difference in HADS-Depression improvement among the prehabilitation (1.0±2.4 points) and control (-0.3 ± 4.0 points) groups (p = 0.543) was non-significant. Clinically meaningful improvement in anxiety (60.9%/40.0%, p=0.149) and depression (34.8%/20.0%, p=0.250) was similar among the groups. CONCLUSION In a post hoc analysis of a randomized trial, prehabilitation had no effect on preoperative reduction of anxiety and depression measures. TRIAL REGISTRATION NUMBER Clinicaltrials.gov NCT02746731. Date of registration: April 21, 2016

Open versus laparoscopic pyloromyotomy for pyloric stenosis.

BACKGROUND Infantile hypertrophic pyloric stenosis (IHPS) is a disorder of young children (aged one year or less) and can be treated by laparoscopic (LP) or open (OP) longitudinal myotomy of the pylorus. Since the first description in 1990, LP is being performed more often worldwide. OBJECTIVES To compare the efficacy and safety of open versus laparoscopic pyloromyotomy for IHPS. SEARCH METHODS We conducted a literature search on 04 February 2021 to identify all randomised controlled trials (RCTs), without any language restrictions. We searched the following electronic databases: MEDLINE (1990 to February 2021), Embase (1990 to February 2021), and the Cochrane Central Register of Controlled Trials (CENTRAL). We also searched the Internet using the Google Search engine (www.google.com) and Google Scholar (scholar.google.com) to identify grey literature not indexed in databases. SELECTION CRITERIA We included RCTs and quasi-randomised trials comparing LP with OP for hypertrophic pyloric stenosis. DATA COLLECTION AND ANALYSIS Two review authors independently screened references and extracted data from trial reports. Where outcomes or study details were not reported, we requested missing data from the corresponding authors of the primary RCTs. We used a random-effects model to calculate risk ratios (RRs) for binary outcomes, and mean differences (MDs) for continuous outcomes. Two review authors independently assessed risks of bias. We used GRADE to assess the certainty of the evidence for all outcomes. MAIN RESULTS The electronic database search resulted in a total of 434 records. After de-duplication, we screened 410 independent publications, and ultimately included seven RCTs (reported in 8 reports) in quantitative analysis. The seven included RCTs enrolled 720 participants (357 with open pyloromyotomy and 363 with laparoscopic pyloromyotomy). One study was a multi-country trial, three were carried out in the USA, and one study each was carried out in France, Japan, and Bangladesh. The evidence suggests that LP may result in a small increase in mucosal perforation compared with OP (RR 1.60, 95% CI 0.49 to 5.26; 7 studies, 720 participants; low-certainty evidence). LP may result in up to 5 extra instances of mucosal perforation per 1,000 participants; however, the confidence interval ranges from 4 fewer to 44 more per 1,000 participants. Four RCTs with 502 participants reported on incomplete pyloromyotomy. They indicate that LP may increase the risk of incomplete pyloromyotomy compared with OP, but the confidence interval crosses the line of no effect (RR 7.37, 95% CI 0.92 to 59.11; 4 studies, 502 participants; low-certainty evidence). In the LP groups, 6 cases of incomplete pyloromyotomy were reported in 247 participants while no cases of incomplete pyloromyotomy were reported in the OP groups (from 255 participants). All included studies (720 participants) reported on postoperative wound infections or abscess formations. The evidence is very uncertain about the effect of LP on postoperative wound infection or abscess formation compared with OP (RR 0.59, 95% CI 0.24 to 1.45; 7 studies, 720 participants; very low-certainty evidence). The evidence is also very uncertain about the effect of LP on postoperative incisional hernia compared with OP (RR 1.01, 95% CI 0.11 to 9.53; 4 studies, 382 participants; very low-certainty evidence). Length of hospital stay was assessed by five RCTs, including 562 participants. The evidence is very uncertain about the effect of LP compared to OP (mean difference -3.01 hours, 95% CI -8.39 to 2.37 hours; very low-certainty evidence). Time to full feeds was assessed by six studies, including 622 participants. The evidence is very uncertain about the effect of LP on time to full feeds compared with OP (mean difference -5.86 hours, 95% CI -15.95 to 4.24 hours; very low-certainty evidence). The evidence is also very uncertain about the effect of LP on operating time compared with OP (mean difference 0.53 minutes, 95% CI -3.53 to 4.59 minutes; 6 studies, 622 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS Laparoscopic pyloromyotomy may result in a small increase in mucosal perforation when compared with open pyloromyotomy for IHPS. There may be an increased risk of incomplete pyloromyotomy following LP compared with OP, but the effect estimate is imprecise and includes the possibility of no difference. We do not know about the effect of LP compared with OP on the need for re-operation, postoperative wound infections or abscess formation, postoperative haematoma or seroma formation, incisional hernia occurrence, length of postoperative stay, time to full feeds, or operating time because the certainty of the evidence was very low for these outcomes. We downgraded the certainty of the evidence for most outcomes due to limitations in the study design (most outcomes were susceptible to detection bias) and imprecision. There is limited evidence available comparing LP with OP for IHPS. The included studies did not provide sufficient information to determine the effect of training, experience, or surgeon preferences on the outcomes assessed