Serum Pancreatic Stone Protein Reference Values in Healthy Pregnant Women: A Prospective Cohort Study

Background: In non-pregnant populations, pancreatic stone protein (PSP) has been reported to have a higher diagnostic performance for identifying severe inflammatory and infectious disease than other established biomarkers. Objective: To generate reference values for serum PSP in pregnancy and compare them to the values of the general healthy population. Design: A prospective cohort study. Setting: A single center. Population: Healthy women with singleton and multiple pregnancies. Methods: This is a prospective single-center cohort study. Between 2013 and 2021, samples of 5 mL peripheral blood were drawn from 440 healthy pregnant women. Therein, 393 cases were singletons and 47 were multiple pregnancies. Serum PSP levels were measured by specific enzyme-linked immunosorbent assay. The main outcome measures were serum PSP level (ng/mL) reference values in healthy pregnant women. Results: The mean PSP reference values in women with singleton pregnancies were 7.9 ± 2.6 ng/mL (95% CI; 2.69–13.03 ng/mL). The PSP values in women with multiple pregnancies (9.17 ± 3.06 ng/mL (95% CI; 3.05–15.28 ng/mL)) were significantly higher (p = 0.001). The PSP values in the first trimester (6.94 ± 2.53 ng/mL) were lower compared to the second (7.42 ± 2.21 ng/mL) and third trimesters (8.33 ± 2.68 ng/mL, p = 0.0001). Subgroup analyses in singletons revealed no correlations between PSP values, maternal characteristics, and pre-existing medical conditions. Conclusion: The PSP values in healthy pregnant women (4–12 ng/mL) were in the range of the reference values of the general healthy population (8–16 ng/mL). This insight blazes a trail for further clinical studies on the use of PSP as a potential novel biomarker for the early detection of pregnancy-related diseases such as chorioamnionitis

The Role of Pancreatic Stone Protein (PSP) as a Biomarker of Pregnancy-Related Diseases

Background: Pancreatic stone protein (PSP) is a biochemical serum marker that contains levels that are elevated in various inflammatory and infectious diseases. The role of PSP in the diagnosis of these diseases seems to be more important compared to clinically established biochemical serum markers in discriminating the severity of the same diseases. Standard values for PSP in pregnant women in relation to gestational age have been reported recently. Additionally, increased PSP levels have been observed to be associated with renal dysfunction in pregnant women. The aim of this study is to evaluate the diagnostic role of PSP in pregnancy-related diseases, such as pre-eclampsia (PE), hemolysis-elevated liver enzymes, and low platelet (HELLP) syndrome. In addition, the study aims to assess its diagnostic role in inflammation-triggered diseases as preterm premature rupture of membranes (PPROM) or COVID-19-positive pregnant women. Materials and Methods: In this single-centred prospective study performed at a tertiary university hospital between 2013 and 2021, we included 152 pregnant women who were diagnosed with either PE, HELLP syndrome, or PPROM. In December 2020, in the context of the COVID-19 pandemic, the Independent Ethics Committee (IEC) approved an amendment to the study protocol. Depending on the underlying disease, single or serial-serum PSP measurements were assessed. These PSP values were compared to PSP levels of women with normal pregnancies. Results: Pregnant women diagnosed with pre-eclampsia or HELLP syndrome had significantly increased PSP values (mean 9.8 ng/mL, SD 2.6) compared to healthy singleton pregnant women (mean 7.9 ng/mL, SD 2.6, p ≤ 0.001). There was no difference in serum PSP in pregnant women with PPROM compared to women with uncomplicated singleton pregnancies (mean in PPROM: 7.9 ng/mL; SD 2.9 versus mean in healthy pregnancies: 7.9 ng/mL; SD 2.6, p = 0.98). Furthermore, no difference in the PSP values in women with or without intra-amniotic infection was observed (infection: mean 7.9 ng/mL; SD 2.8 versus no infection: mean 7.8 ng/mL; SD 3, p = 0.85). The mean value of PSP in COVID-19-infected women during pregnancy (8.5 ng/mL, SD 2.3) was comparable to healthy singleton pregnancies (mean 7.9 ng/mL, SD 2.6), p = 0.24. Conclusions: The novel serum biomarker PSP is significantly upregulated in pregnant women with pre-eclampsia and HELLP syndrome. Our observations call for the further evaluation of PSP in randomized controlled clinical trials to demonstrate the actual role of PSP in pregnancy-related diseases and whether it may provide new approaches for the management and discrimination of the severity of these gestational conditions

Exercise Improves Outcomes of Surgery on Fatty Liver in Mice: A Novel Effect Mediated by the AMPK Pathway.

OBJECTIVE To investigate whether exercise improves outcomes of surgery on fatty liver, and whether pharmacological approaches can substitute exercising programs. SUMMARY OF BACKGROUND DATA Steatosis is the hepatic manifestation of the metabolic syndrome, and decreases the liver's ability to handle inflammatory stress or to regenerate after tissue loss. Exercise activates adenosine monophosphate-activated kinase (AMPK) and mitigates steatosis; however, its impact on ischemia-reperfusion injury and regeneration is unknown. METHODS We used a mouse model of simple, diet-induced steatosis and assessed the impact of exercise on metabolic parameters, ischemia-reperfusion injury and regeneration after hepatectomy. The same parameters were evaluated after treatment of mice with the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Mice on a control diet served as age-matched controls. RESULTS A 4-week-exercising program reversed steatosis, lowered insulin levels, and improved glucose tolerance. Exercise markedly enhanced the ischemic tolerance and the regenerative capacity of fatty liver. Replacing exercise with AICAR was sufficient to replicate the above benefits. Both exercise and AICAR improved survival after extended hepatectomy in mice challenged with a Western diet, indicating protection from resection-induced liver failure. CONCLUSIONS Exercise efficiently counteracts the metabolic, ischemic, and regenerative deficits of fatty liver. AICAR acts as an exercise mimetic in settings of fatty liver disease, an important finding given the compliance issues associated with exercise. Exercising, or its substitution through AICAR, may provide a feasible strategy to negate the hepatic consequences of energy-rich diet, and has the potential to extend the application of liver surgery if confirmed in humans

Parastomal gallbladder herniation: A case report and review of the literature

Introduction: Parastomal hernia is a common complication of patients living with an enterostomy. However, a parastomal hernia involving the gallbladder is a rare condition with only eight cases documented in the literature.Presentation of case: We report the case of a 69-year old female who underwent an open right hemicolectomy with creation of a colostomy and terminal ileostomy. She presented with parastomal swelling and pain 16 months later. A computed tomography scan revealed a parastomal herniation of the gallbladder. We elected to proceed with a cholecystectomy and hernia repair, the patient was asymptomatic at her last follow-up.Discussion: A systematic search of the literature found eight previously published cases. This condition primarily affects elderly females. Five patients were treated surgically and three conservatively, all with a favorable outcome. In frail patients without complicating factors, a conservative treatment approach with surveillance may be safe. We chose a surgical approach due to the symptomatic nature of the presentation and the gallstone containing hernia. This is the first case of a parastomal gallbladder herniation containing a large gallstone.Conclusion: This report should help broadening the physician's differential diagnosis in dealing with patients with symptomatic parastomal hernias and provide an example for diagnosis and management of this complication.</p

Multimodale Therapiekonzepte beim Rektumkarzinom

Das kolorektale Karzinom (KRK) ist in der Schweiz das dritthäufigste Malignom bezüglich der Sterblichkeitsrate bei Männern und Frauen. Beim Kolonkarzinom ist weiterhin die primäre chirurgische Resektion der Goldstandard der Therapie. Beim Rektumkarzinom hingegen kommt ein differenziertes, stadienadaptiertes multimodales Therapiekonzept zur Anwendung. Frühe Tumoren (Stadium I + II ohne Lymphknotenbefall) können mit exzellenten Langzeitergebnissen alleinig chirurgisch behandelt werden. Fortgeschrittene Rektumkarzinome (Stadium III) im unteren und mittleren Rektumdrittel erfordern eine multimodale Therapie aus neoadjuvanter Behandlung (Radiotherapie, Radiochemotherapie, Chemotherapie), gefolgt von Resektion und ggf. adjuvanter Chemotherapie. Die totale neoadjuvante Therapie (TNT) erreicht durch Intensivierung der Vorbehandlung (sequenziell neoadjuvante Radio[chemo]therapie und neoadjuvante Chemotherapie) ein verbessertes Ansprechen und progressionsfreies Überleben. Nach komplettem Ansprechen auf neoadjuvante Therapie kann ein „Watch-and-wait-Konzept“ die chirurgische Resektion ersetzen. Dieser Übersichtsartikel befasst sich mit den aktuellen Standards der multimodalen Behandlungsschemata beim Rektumkarzinom. = Le cancer colorectal (CCR) est la troisième tumeur maligne la plus fréquente en termes de mortalité en Suisse chez les hommes et les femmes. Pour le cancer du côlon, la résection chirurgicale primaire reste lʼétalon-or du traitement. Pour le cancer du rectum, par contre, un concept thérapeutique différencié et adapté au stade est appliqué. Les tumeurs précoces (stades I + II sans atteinte des ganglions lymphatiques) peuvent être traitées par la chirurgie seule avec d’excellents résultats à long terme. Les cancers avancés situés dans les tiers moyen et inférieur du rectum (stade III) exigent un traitement multimodal comprenant un traitement néoadjuvant (radiothérapie, radiochimiothérapie, chimiothérapie) suivi d’une résection et éventuellement d’une chimiothérapie adjuvante. Le traitement néoadjuvant total (TNT), avec son intensification du traitement préliminaire (radio(chimio)thérapie néoadjuvante séquentielle et chimiothérapie néoadjuvante), permet d’atteindre une meilleure réponse et une meilleure survie sans progression. Après une réponse complète au traitement néoadjuvant, un concept de «watch and wait» peut remplacer la résection chirurgicale. Cet article d’aperçu discute les standards actuels des schémas thérapeutiques multimodaux lors de cancers du rectum. = Il carcinoma colorettale (“colorectal cancer”, CRC) è il tumore maligno più diffuso in Svizzera ed è al terzo posto nelle statistiche di mortalità tra uomini e donne. Nel carcinoma del colon, la resezione chirurgica primaria rimane il gold standard terapeutico. Nel carcinoma rettale, invece, si applica un approccio terapeutico multimodale differenziato e adattato allo stadio. I tumori precoci (stadio I + II senza coinvolgimento linfonodale) possono essere trattati solo chirurgicamente con ottimi risultati nel lungo periodo. Il carcinoma rettale avanzato (stadio III) nel terzo inferiore e medio del retto richiede una terapia multimodale costituita da un trattamento neoadiuvante (radioterapia, radiochemioterapia, chemioterapia), seguito da resezione e, se necessario, da chemioterapia adiuvante. La terapia neoadiuvante totale (“total neoadjuvant therapy”, TNT) attraverso l’intensificazione del pre-trattamento (radio[chemio]terapia neoadiuvante sequenziale e chemioterapia neoadiuvante) riesce a migliorare la risposta e la sopravvivenza libera da progressione. Dopo una risposta completa alla terapia neoadiuvante, un approccio “watch and wait” può sostituire la resezione chirurgica. Questo articolo presenta una panoramica degli attuali standard dei protocolli di trattamento multimodale nel carcinoma rettale

Internal retraction in single-port laparoscopic cholecystectomy: Initial experience and learning curve

Abstract Introduction: We report our experience and learning curve in single-port laparoscopic cholecystectomy (SPLC) using an internal anchored retraction system. Methods: Usefulness of the retraction system was analysed in 18 SPLC. The first eight, the following ten SPLC and 20 consecutive four-port laparoscopic cholecystectomies (4PLC) were compared. Duration of operation, burns on nontarget tissue and gallbladder perforations were assessed by reviewing videotapes recorded during the procedures. Results: Use of the retraction system failed in three out of five patients (60%) with intraoperative signs of chronic inflammation and in one out of 13 (7.1%) without such signs (p = 0.0441). Median operation time was 90 (45-120) in the first eight and 55 (40-180) minutes in the following ten SPLC (p = 0.0361). Whereas the first eight SPLC lasted longer compared to 4PLC (70 (40-140) minutes, p = 0.0435) the difference disappeared after eight procedures (p = 0.2076). Median number of burns to nontarget tissue was seven (1-16) in the first eight and one (0-8) in the following ten SPLC (p = 0.0049). There was no difference in perforation of the gallbladder. Discussion: Internal retraction enables a safe exposure of the Calot triangle avoiding bile spillage in cholecystectomies without intraoperative signs of inflammation. Familiarisation with SPLC was rapidly achieved. Operation time and dexterity were equal to 4PLC after eight SPLC

Pancreatic cancer- a curable disease

Pancreatic cancer is the seventh most common cancer in Switzerland associated with a dismal prognosis. Its natural course is fatal with a 3-year survival rate below 3%. Advances in diagnostic tools, tumor staging and multimodal treatment strategies resulted in an improved 5-year survival rate of over 20%. Patients presenting with pancreatic cancer significantly benefit from a multi-disciplinary treatment strategy in an experienced hepato-pancreato-biliary center. Following a comprehensive tumor staging, surgical resection associated with adjuvant chemotherapy is still the only curative therapy option. The role of neoadjuvant chemotherapy is currently investigated in clinical trials. Patients presenting with advanced pancreatic cancer not eligible for curative treatment might benefit from inclusion into innovative clinical trials with novel treatment concepts

Novel Benefits of Remote Ischemic Preconditioning Through VEGF-dependent Protection From Resection-induced Liver Failure in the Mouse

OBJECTIVE To investigate the impact of remote ischemic preconditioning (RIPC) on liver regeneration after major hepatectomy. SUMMARY BACKGROUND DATA RIPC is a strategy applied at remote sites to mitigate ischemic injury. Unlike other preconditioning approaches, RIPC spares target organs as it acts via systemic VEGF elevations. In the liver, however, VEGF is an important driver of regeneration following resection. Therefore, RIPC may have pro-regenerative effects. METHODS RIPC was applied to C57BL/6 mice through intermittent clamping of the femoral vessels prior to standard 68%-hepatectomy or extended 86%-hepatectomy, with the latter causing liver failure and impaired survival. Liver regeneration was assessed through weight gain, proliferative markers (Ki67, pH3, mitoses), cell cycle-associated molecules, and survival. The role of the VEGF-ID1-WNT2 signaling axis was assessed through WIF1 (a WNT antagonist) and recombinant WNT2 injected prior to hepatectomy. RESULTS RIPC did not affect regeneration after 68%-hepatectomy, but improved liver weight gain and hepatocyte mitoses after 86%-hepatectomy. Importantly, RIPC raised survival from 40% to 80% after 86%-hepatectomy, indicating the promotion of functional recovery. Mechanistically, the RIPC-induced elevations in VEGF were accompanied by increases in the endothelial transcription factor Id1, its target WNT2, and its hepatocellular effector β-catenin. WIF1 injection prior to 86%-hepatectomy abrogated the RIPC benefits, while recombinant WNT2 had pro-regenerative effects akin to RIPC. CONCLUSION RIPC improves the regenerative capacity of marginal liver remnants in a VEGF-dependent way. If confirmed in patients, RIPC may become the preconditioning strategy of choice in the setting of extended liver resections