Can We Identify Patients Appropriate for Same-Day Discharge After Laparoscopic Fundoplication?

Background: Patients, surgeons, and payers are interested in reducing hospital length of stay. Outpatient laparoscopic fundoplication (LF) can be done safely and cost effectively. There is low acceptance of this practice due to fear of readmission and patient dissatisfaction. Our aim was to identify factors predicting failure of same-day discharge after LF. Methods and Procedures: We simulated an outpatient setting for patients who underwent LF from 2017 to 2018 and collected the data prospectively. A perioperative pain and nausea protocol was utilized. Postoperatively, patients were given a liquid diet and oral medications, observed overnight, and then discharged after standard criteria were met. Failure was defined by the need for physician intervention after 3 hours or failure to discharge. Univariate and multivariable logistic regression analyses were performed assessing factors associated with failure. Two-sample t-test and chi-squared tests were used for significance. Results: Ninety-eight patients were included. Twenty patients failed, primarily due to the need for intravenous medications. Seven were discharged on postoperative day 1 but required physician intervention after 3 hours. Thirteen patients stayed >23 hours. Two patients were readmitted within 1 week of discharge. There was one acute recurrence, requiring reoperation, and one conversion to laparotomy. We found no statistically significant patient risk factor, comorbidity, or perioperative variable that could reliably predict failure of same-day discharge. Conclusion: This study suggests that same-day discharge after LF is safe and feasible. However, 20% of patients will unpredictably fail to meet discharge criteria.

Endoscopic resection of giant fibrovascular esophageal polyps.

BACKGROUND: Giant fibrovascular esophageal polyps are rare benign intraluminal tumors that originate from the submucosa of the cervical esophagus [Owens et al. (JAMA 103: 838-842, 1994), Totten et al. (JAMA 25:606-622, 1953)]. Due to their indolent course, these tumors tend to reach enormous proportions before patients develop symptoms. Accurately diagnosing these tumors is difficult, as endoscopy may miss 25% of these lesions because these polyps exhibit normal intact esophageal mucosa [Levine et al. (JAMA 166: 781-787, 1996)]. METHODS: Surgical resection has been the treatment of choice. We present a video that illustrates the feasibility of an endoscopic approach. TECHNIQUE/CASE: A 62-year-old man presented to our clinic with a pedunculated esophageal mass. During this time, he developed progressive dysphagia to solid foods. A complete workup confirmed the presence of a giant polyp and endoscopic resection under general anesthesia was planned. Using an endoscopic snare-technique, a 16 cm × 3 cm polyp was amputated and retracted out of the oropharynx. Upon repeat endoscopy a second 7 cm × 3 cm polyp was discovered originating proximal to the larger polyp. Again, removal of this polyp was attempted using a snare-technique. Following amputation of the polyp, a broad-based component of the polyp remained. Given its proximal location in the esophagus, we were able to use a snare to pull the broad base of the remaining polyp into the oropharynx and remove it at its origin. Postoperative endoscopy and endoscopic ultrasound confirmed that the polyps were completely removed and the muscular resection bed was hemostatic. Clinically, the patient's symptoms resolved and he encountered no adverse sequela as a result of the operation. CONCLUSION: Giant fibrovascular esophageal polyps are rare benign intraluminal tumors that can lead to obstructive symptoms. Surgical resection is the treatment of choice, and may be possible with an endoscopic approach. An endoscopic snare technique can be used to resect these lesions while minimizing patient morbidity.

The bradykinin-cGMP-PKG pathway augments insulin sensitivity via upregulation of MAPK phosphatase-5 and inhibition of JNK.

Bradykinin (BK) promotes insulin sensitivity and glucose uptake in adipocytes and other cell types. We demonstrated that in rat adipocytes BK enhances insulin-stimulated glucose transport via endothelial nitric oxide synthase, nitric oxide (NO) generation, and decreased activity of the mitogen-activated protein kinase (MAPK) JNK (c-Jun NH2-terminal kinase). In endothelial cells, NO increases soluble guanylate cyclase (sGC) activity, which, in turn, activates protein kinase G (PKG) by increasing cGMP levels. In this study, we investigated whether BK acts via the sGC-cGMP-PKG pathway to inhibit the negative effects of JNK on insulin signaling and glucose uptake in rat adipocytes. BK augmented cGMP concentrations. The BK-induced enhancement of insulin-stimulated glucose uptake was mimicked by the sGC activator YC-1 and a cell-permeable cGMP analog, CPT-cGMP, and inhibited by the sGC inhibitor ODQ and the PKG inhibitor KT 5823. Transfection of dominant-negative PKG reduced the BK augmentation of insulin-induced Akt phosphorylation. The activation of JNK and ERK1/2 by insulin was attenuated by BK, which was mediated by the sGC-cGMP-PKG pathway. Whereas insulin-stimulated phosphorylation of upstream activators of JNK and ERK, i.e., MKK4 and MEK1/2, was unaffected, BK augmented insulin-mediated induction of MKP-5 mRNA and protein levels. Furthermore, zaprinast, a phosphodiesterase inhibitor, enhanced cGMP and MKP-5 and prolonged the action of BK. These data indicate that BK enhances insulin action by inhibition of negative feedback by JNK and ERK via upregulation of MKP-5, mediated by the sGC-cGMP-PKG signaling pathway.

Comprehensive Analysis of Adverse Events Associated With Per Oral Endoscopic Myotomy in 1826 Patients: An International Multicenter Study.

OBJECTIVES: The safety of peroral endoscopic myotomy (POEM) is still debated since comprehensive analysis of adverse events (AEs) associated with the procedure in large multicenter cohort studies has not been performed. To study (1) the prevalence of AEs and (2) factors associated with occurrence of AEs in patients undergoing POEM. METHODS: Patients who underwent POEM at 12 tertiary-care centers between 2009 and 2015 were included in this case-control study. Cases were defined by the occurrence of any AE related to the POEM procedure. Control patients were selected for each AE case by matching for age, gender, and disease classification (achalasia type I and II vs. type III/spastic esophageal disorders). RESULTS: A total of 1,826 patients underwent POEM. Overall, 156 AEs occurred in 137 patients (7.5%). A total of 51 (2.8%) inadvertent mucosotomies occurred. Mild, moderate, and severe AEs had a frequency of 116 (6.4%), 31 (1.7%), and 9 (0.5%), respectively. Multivariate analysis demonstrated that sigmoid-type esophagus (odds ratio (OR) 2.28, P=0.05), endoscopist experience <20 cases (OR 1.98, P=0.04), use of a triangular tip knife (OR 3.22, P=0.05), and use of an electrosurgical current different than spray coagulation (OR 3.09, P=0.02) were significantly associated with the occurrence of AEs. CONCLUSIONS: This large study comprehensively assessed the safety of POEM and highly suggests POEM as a relatively safe procedure when performed by experts at tertiary centers with an overall 7.5% prevalence of AEs. Severe AEs are rare. Sigmoid-type esophagus, endoscopist experience, type of knife, and current used can be considered as predictive factors of AE occurrence.

Interprovincial differences in the achievement of K/DOQI targets of mineral metabolism in Canada.

BACKGROUND: Abnormalities in mineral metabolism in chronic kidney disease are associated with increased morbidity and mortality. The Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines were established in 2003 to address issues in the management of mineral and bone metabolism. The goal of this study was to compare (i) mineral metabolism control among Canadian haemodialysis (HD) patients with K/DOQI-defined targets and Dialysis Outcomes and Practice Patterns Study II (DOPPS II) data and (ii) the effect of different treatment strategies. METHODS: A cross-sectional study of 2215 HD patients was conducted. Phosphorus (P), calcium (Ca), intact parathyroid hormone (iPTH) and calcium-phosphate product (CaXP) were analysed. In addition, management was compared between provinces with more or less restricted access to the phosphate binder sevelamer. RESULTS: K/DOQI targets for P, Ca, iPTH and CaXP K/DOQI targets were met by 59.7%, 58.6%, 29.7% and 83.3%, respectively. A greater proportion of patients were within target compared with those in DOPPS II (2002-2004). Targets were more likely to be reached by patients residing in provinces with formularies allowing less restricted access to sevelamer: P: 61.8% vs 55.7% (P = 0.01); CaXP: 85.5% vs 79.1% (P = 0.0006). As expected, patients in provinces with more restrictive formularies were more often receiving doses of elemental calcium > 1.5 g/day than those with more open listings (62.1% vs 14.0%, P < 0.0001) and were less likely to receive sevelamer (14.1% vs 42.4%, P = 0.0001). CONCLUSION: Mineral metabolism parameters were more frequently within the target range amongst (i) patients in the current study compared with those in the DOPPS II era and (ii) patients in provinces with less restricted access to sevelamer.

Bradykinin augments insulin-stimulated glucose transport in rat adipocytes via endothelial nitric oxide synthase-mediated inhibition of Jun NH2-terminal kinase.

An increase in bradykinin has been suggested to contribute to the enhanced insulin sensitivity observed in the presence of ACE inhibitors. To investigate a potential direct, nonvascular effect on an insulin target tissue, the effect of bradykinin on glucose uptake and insulin signaling was studied in primary rat adipocytes. Whereas basal glucose uptake was not altered, bradykinin augmented insulin-stimulated glucose uptake twofold, which was blocked by HOE-140, a bradykinin B2 receptor antagonist. The bradykinin effect on glucose uptake was nitric oxide (NO) dependent, mimicked by NO donors and absent in adipocytes from endothelial NO synthase-/- mice. Investigation of insulin signaling revealed that bradykinin enhanced insulin receptor substrate-1 (IRS-1) Tyr phosphorylation, Akt/protein kinase B phosphorylation, and GLUT4 translocation. In contrast, insulin-stimulated extracellular signal-regulated kinase1/2 and Jun NH2-terminal kinase (JNK) activation were decreased in the presence of bradykinin, accompanied by decreased IRS-1 Ser307 phosphorylation. Furthermore, bradykinin did not enhance insulin action in the presence of the JNK inhibitor, SP-600125, or in adipocytes from JNK1-/- mice. These data indicate that bradykinin enhances insulin sensitivity in adipocytes via an NO-dependent pathway that acts by modulating the feedback inhibition of insulin signaling at the level of IRS-1.

Metabolism, not autoxidation, plays a role in alpha-oxoaldehyde- and reducing sugar-induced erythrocyte GSH depletion: relevance for diabetes mellitus.

Erythrocyte and lens reduced glutathione (GSH) levels are often lower in patients with diabetes whereas erythrocyte dicarbonyl levels are often higher. We hypothesise that high plasma carbohydrates may be metabolised by glycolytic and pentose phosphate pathways to form alpha-oxoaldehydes, which deplete cellular GSH. Our aims were: (1) to compare the effectiveness of various carbohydrates or metabolites at depleting erythrocyte GSH, (2) to determine if GSH loss is related to the autoxidation or metabolism of carbohydrates. It was found that erythrocyte GSH was depleted by 50% (ED-50) at t = 2.5 h when erythrocytes were incubated with the following: methylglyoxal (MG) 23 microM, glyoxal 75 microM, DL-glyceraldehyde 299 microM, deoxyribose 606 microM, xylitol 626 microM, and ribose 2 mM. The glycolytic inhibitors, sodium arsenate and KF prevented ribose, deoxyribose, xylitol and MG-induced GSH depletion in erythrocytes over 2 h. However, the antioxidant trolox and the ferric chelator detapac did not affect MG-induced GSH depletion. These data suggest that the carbohydrates or glyceraldehyde were metabolised to form carbonyls such as MG which depleted erythrocyte GSH as a result of catalysis by glyoxalase I. None of the carbohydrates were autoxidised to carbonyls over this time period. We speculate that as a result of GSH depletion, subsequent glycoxidative stress affects erythrocyte function and contributes to diabetic complications.