Correlations of glycogen synthase and phosphorylase activities with glycogen concentration in human muscle biopsies. Evidence for a double-feedback mechanism regulating glycogen synthesis and breakdown.

The purpose of this study was to verify in man the relationships of muscle glycogen synthase and phosphorylase activities with glycogen concentration that were reported in animal studies. The upper level of glycogen concentration in muscle is known to be tightly controlled, and glycogen concentration was reported to have an inhibitory effect on synthase activity and a stimulatory effect on phosphorylase activity. Glycogen synthase and phosphorylase activity and glycogen concentration were measured in muscle biopsies in a group of nine normal subjects after stimulating an increase of their muscle glycogen concentration through either an intravenous glucose-insulin infusion to stimulate glycogen synthesis, or an Intralipid (Vitrum, Stockholm, Sweden) infusion in the basal state to inhibit glycogen mobilization by favoring lipid oxidation at the expense of glucose oxidation. Phosphorylase activity increased from 71.3 +/- 21.0 to 152.8 +/- 20.0 nmol/min/mg protein (P < .005) after the glucose-insulin infusion. Phosphorylase activity was positively correlated with glycogen concentration (P = .005 and P = .0001) after the glucose-insulin and Intralipid infusions, respectively. Insulin-stimulated glycogen synthase activity was significantly negatively correlated with glycogen concentration at the end of the Intralipid infusion (P < .005). In conclusion, by demonstrating a negative correlation of glycogen concentration with glycogen synthase and a positive correlation with phosphorylase, this study might confirm in man the double-feedback mechanism by which changes in glycogen concentration regulate glycogen synthase and phosphorylase activities. It suggests that this mechanism might play an important role in the regulation of glucose storage.

Patients' preferences on information and involvement in decision-making in gastrointestinal surgery

Contexte et but de l'étude: La relation médecin-patient a subi d'importants changements et l'actuelle émancipation des patients a conduit à un véritable partenariat dans la prise de décisions thérapeutiques. Notre étude a pour but de déterminer les préférences des patients pour différents aspects de la prise de décisions au cours d'un traitement et de ses potentielles complications, de même que la quantité et le type d'information souhaitée avant une intervention chirurgicale digestive. Patients et méthodes : Il s'agit d'une étude prospective non-randomisée basée sur un questionnaire donné lors de la consultation préopératoire à 254 patients consécutifs prévus pour une chirurgie gastro-intestinale élective. Résultats : Pour les potentielles complications chirurgicales et la possibilité d'un séjour aux soins intensifs, 64% des patients souhaitent participer activement aux décisions médicales, et respectivement 89% et 60% des patients aimeraient discuter d'une éventuelle réanimation cardio-pulmonaire et de limitations au traitement. Respectivement 73%, 77% et 47% des patients ont souhaité une information très détaillée, une infoimation pour une possible hospitalisation en soins intensifs ou une éventuelle réanimation cardiaque. Les patients âgés ou avec un niveau de formation bas étaient significativement moins intéressés à une prise de décision partagée (p=0.003 et 0.015) et à une information complète (p=0.03 et 0.05), De plus, l'implication des familles dans les prises de décision n'était favorisée que si le patient est en coma (74%), et significativement moins importante chez les personnes âgées et de sexe masculin (p=0.04 et 0.03 respectivement). Ni le type de chirurgie prévue (majeure ou mineure) ni la sévérité de la pathologie (cancer ou non) ne furent des facteurs statistiquement significatifs pour un désir plus élevé de partager la prise de décision, pour plus d'information ou pour impliquer d'avantage la famille. Conclusions : Notre étude démontre que la majorité des patients chirurgicaux souhaitent recevoir une information préopératoire complète concernant leur maladie et le traitement planifié. Ils considèrent également comme crucial d'être impliqués dans les prises de décisions thérapeutiques pour le traitement et pour les possibles complications. Le rôle de la famille est limité aux situations ou le patient n'est plus en mesure de participer aux décisions.

Identifying the index lesion with template prostate mapping biopsies.

PURPOSE: The natural history of prostate cancer might be driven by the index lesion. We determined the percent of men in whom the index lesion could be defined using transperineal template prostate mapping biopsies. MATERIALS AND METHODS: Included in study were consecutive men undergoing transperineal template prostate mapping biopsies with biopsies grouped into 20 zones. Men with clinically significant disease in only 1 prostate area were considered to have an identifiable index lesion. We evaluated the impact of using 2 definitions of clinically significant disease (Gleason grade pattern 4 and/or lesion volume 0.5 cc or greater) and 2 clustering rules (stringent and tolerant) to define the index lesion. RESULTS: Included in study were 391 men with a median age of 62 years (IQR 58-67) and a median prostate specific antigen of 6.9 ng/ml (IQR 4.8-10.0). Of the men 269 (69%) were previously diagnosed with prostate cancer. By deploying a median of 1.2 cores per ml (IQR 0.9-1.7) cancer was diagnosed in 82.9% of the men (324 of 391) with a median of 6 positive cores (IQR 2-9), a median maximum cancer core length of 5 mm (IQR 3-8) and a total cancer core length per zone of 7 mm (IQR 3-13). Insignificant disease was found in 26.3% to 42.9% of cases. When a stringent spatial relationship was used to define individual lesions, 44.4% to 54.6% of patients had 1 index lesion and 12.7% to 19.1% had more than 1 area with clinically significant disease. These proportions changed to 46.6% to 59.2% and 10.5% to 14.5%, respectively, when less stringent spatial clustering was applied. CONCLUSIONS: Transperineal template prostate mapping biopsies enable the index lesion to be localized in most men with clinically significant disease. This information may be important to select appropriate candidates for targeted therapy and to plan a tailored treatment strategy in men undergoing radical therapy.

Human cytomegalovirus induced pseudotumor of upper gastrointestinal tract mucosa: Effects of long-term chronic disease?

Human cytomegalovirus-induced lesions resembling malignancies have been described in the gastrointestinal tract and include ulcerated or exophytic large masses. The aim of this study was to review the cases registered in the databases of two academic hospitals and formulate a hypothesis concerning the pathogenic mechanisms responsible for cytomegalovirus-induced pseudotumor development. All the diagnoses of human cytomegalovirus infections of the upper gastrointestinal tract recorded from 1991 to 2013 were reviewed. Cases of mucosal alterations misdiagnosed endoscopically as malignancies were selected. Large ulcers occurring in the stomach (three cases) and an irregular exophytic mass at the gastro-jejunal anastomosis were misdiagnosed endoscopically as malignancies (4 cases out of 53). Histologically, all lesions reflected hyperplastic mucosal changes with a prevalence of epithelial and stroma infected cells, without signs of cell atypia. The hypothesis presented is that the development of human cytomegalovirus-induced pseudotumors may be the morphological expression of chronic mucosa damage underlying long-term infection.

Hémorragie par le canal de Wirsung: forme rare d'hémorragie digestive haute. A propos d'une observation [Hemorrhage through Wirsung's duct: rare form of upper gastrointestinal hemorrhage. A case report].

The case of a 41-year-old alcoholic patient who presented with massive upper gastrointestinal bleeding is reported. The diagnosis was established rapidly by endoscopy which revealed bleeding through the papilla of Vater. Selective angiography of the superior mesenteric artery opacified the pancreatic duct as well as the duodenum. CT scan showed signs of chronic pancreatitis. Because of the recurrence of bleeding and shock, an urgent operation was necessary and a Whipple procedure was performed. Recovery was complete. The clinical presentation, the etiology, the diagnostic modalities and the treatment of this particular condition are discussed. Usually, hemorrhage through the pancreatic duct presents as repeated episodes of upper gastrointestinal bleeding with no source found at endoscopy. The presence of chronic pancreatitis or of epigastric pain during bleeding should suggest the diagnosis. Upper gastrointestinal endoscopy and angiography are the principal diagnostic tools. Definitive treatment requires surgery, and resection in most of the cases.

A Randomized, Placebo-controlled Trial of Preemptive Antifungal Therapy for the Prevention of Invasive Candidiasis Following Gastrointestinal Surgery for Intra-abdominal Infections.

BACKGROUND: Patients undergoing emergency gastrointestinal surgery for intra-abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy. METHODS: This exploratory, randomized, double-blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra-abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression. RESULTS: The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-β-d-glucan (ßDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result. CONCLUSIONS: This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using ßDG to identify patients at high risk of IC. CLINICAL TRIALS REGISTRATION: NCT01122368.

Preparation and management of complications in prostate biopsies

Transrectal ultrasonography-guided biopsy plays a key role in prostate sampling for cancer detection. Among interventional procedures, it is one of the most frequent procedures performed by radiologists. Despite the safety and low morbidity of such procedure, possible complications should be promptly assessed and treated. The standardization of protocols and of preprocedural preparation is aimed at minimizing complications as well as expediting their management. The authors have made a literature review describing the possible complications related to transrectal ultrasonography-guided prostate biopsy, and discuss their management and guidance to reduce the incidence of such complications.

Future development of gastrointestinal cancer incidence and mortality rates in Switzerland: a tumour registry- and population-based projection up to 2030.

QUESTIONS UNDER STUDY: Since tumour burden consumes substantial healthcare resources, precise cancer incidence estimations are pivotal to define future needs of national healthcare. This study aimed to estimate incidence and mortality rates of oesophageal, gastric, pancreatic, hepatic and colorectal cancers up to 2030 in Switzerland. METHODS: Swiss Statistics provides national incidences and mortality rates of various cancers, and models of future developments of the Swiss population. Cancer incidences and mortality rates from 1985 to 2009 were analysed to estimate trends and to predict incidence and mortality rates up to 2029. Linear regressions and Joinpoint analyses were performed to estimate the future trends of incidences and mortality rates. RESULTS: Crude incidences of oesophageal, pancreas, liver and colorectal cancers have steadily increased since 1985, and will continue to increase. Gastric cancer incidence and mortality rates reveal an ongoing decrease. Pancreatic and liver cancer crude mortality rates will keep increasing, whereas colorectal cancer mortality on the contrary will fall. Mortality from oesophageal cancer will plateau or minimally increase. If we consider European population-standardised incidence rates, oesophageal, pancreatic and colorectal cancer incidences are steady. Gastric cancers are diminishing and liver cancers will follow an increasing trend. Standardised mortality rates show a diminution for all but liver cancer. CONCLUSIONS: The oncological burden of gastrointestinal cancer will significantly increase in Switzerland during the next two decades. The crude mortality rates globally show an ongoing increase except for gastric and colorectal cancers. Enlarged healthcare resources to take care of these complex patient groups properly will be needed.

Biopsies de la prostate en 2015: quelle biopsie pour quel patient [Prostate biopsy: which strategy for which patient?].

L'adoption de l'IRM dans le parcours diagnostique a déterminé la transition des biopsies aléatoires aux biopsies ciblées vers les lésions visibles à l'imagerie. L'utilisation de logiciels rendant possible la fusion d'images IRM et échographiques permet d'améliorer significativement la précision diagnostique de ces biopsies. De plus, pour déterminer l'éligibilité d'un patient à une thérapie focale, davantage de précision diagnostique est requise au niveau de toute la glande ; par conséquent, des biopsies avec une densité d'échantillonnage plus élevée par voie transpérinéale peuvent être proposées.Les nouvelles techniques de biopsie de la prostate permettent une prise en charge personnalisée grâce à une meilleure caractérisation de l'agressivité et de l'extension locale du cancer de la prostate. The adoption of multiparametric MRI within the diagnostic pathway has allowed urologists to move from random biopsy to targeted biopsy directed towards MR-visible lesions. The use of software for MR to TRUS fusion may enhance the diagnostic accuracy of targeted biopsy. To determine the eligibility for tissue-preserving approaches, further precision is required, and template prostate mapping biopsy may be offered. The employment of novel biopsy techniques provide better characterisation of the disease, and allows a tailored approach to a single subject.