Andrea McConico

Natural Orifice Translumenal Endoscopic Surgery Used for Perforated Viscus Repair Is Feasible Using Lower Peritoneal Pressures than Laparoscopy in a Porcine Model

BACKGROUND Procedure-related complications contribute to 1-year mortality in patients with perforated ulcers. Natural orifice translumenal endoscopic surgery (NOTES) might offer a new repair approach. STUDY DESIGN Swine were randomized to laparoscopic or NOTES repair. Laparoscopic gastrotomy creation (1 cm) was followed by 4 hours soilage time. After peritoneal cavity irrigation (per group assignment), repair proceeded with a laparoscopic or NOTES approach. For NOTES repair, omentum was endoscopically grasped, pulled into the gastric lumen, and fixed with metallic clips. Feasibility; time to complete procedures; pneumoperitoneal pressures; and clinical parameters, including necropsy and peritoneal culture at 2 weeks, were recorded. RESULTS NOTES repair failed in 1 animal (technical); repair was completed laparoscopically, and data were analyzed as intention to treat. Specific NOTES repair time (minutes) was comparable with laparoscopy (36 versus 46; p = 0.2). Mean abdominal pressure (mmHg) required to complete NOTES repair was lower than in laparoscopy (4 versus 12; p < 0.001). Nineteen of 23 animals thrived until necropsy at 2 weeks. Three animals succumbed to airway compromise in recovery; 1 NOTES animal failed to thrive on postoperative day 7. No intra-abdominal cause for these deaths was found. At necropsy all repairs were intact, and peritoneal cultures revealed a small and equivalent amount of colony-forming units in each group. CONCLUSIONS Endoscopic ulcer repair appears technically feasible with similar clinical and infectious outcomes to laparoscopy. The lower required pneumoperitoneal pressures used in these NOTES techniques are recognizable different outcomes from laparoscopy and can be advantageous in critically ill patients.

A longitudinal study of whole body, tissue, and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition

The sequence of events that lead to inflammation and fibrosing nonalcoholic steatohepatitis (NASH) is incompletely understood. Hence, we investigated the chronology of whole body, tissue, and cellular events that occur during the evolution of diet-induced NASH. Male C57Bl/6 mice were assigned to a fast-food (FF; high calorie, high cholesterol, high fructose) or standard-chow (SC) diet over a period of 36 wk. Liver histology, body composition, mitochondrial respiration, metabolic rate, gene expression, and hepatic lipid content were analyzed. Insulin resistance [homeostasis model assessment-insulin resistance (HOMA-IR)] increased 10-fold after 4 wk. Fibrosing NASH was fully established by 16 wk. Total hepatic lipids increased by 4 wk and remained two- to threefold increased throughout. Hepatic triglycerides declined from sixfold increase at 8 wk to threefold increase by 36 wk. In contrast, hepatic cholesterol levels steadily increased from baseline at 8 wk to twofold by 36 wk. The hepatic immune cell population altered over time with macrophages persisting beyond 16 wk. Mitochondrial oxygen flux rates of FF mice diet were uniformly lower with all the tested substrates (13-276 pmol·s-1·ml-1 per unit citrate synthase) than SC mice (17-394 pmol·s-1·ml-1 per unit citrate synthase) and was accompanied by decreased mitochondrial:nuclear gene copy number ratios after 4 wk. Metabolic rate was lower in FF mice. Mitochondrial glutathione was significantly decreased at 24 wk in FF mice. Expression of dismutases and catalase was also decreased in FF mice. The evolution of NASH in the FF diet-induced model is multiphasic, particularly in terms of hepatic lipid composition. Insulin resistance precedes hepatic inflammation and fibrosis. Mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent. Collectively, these observations provide a unique overview of the sequence of changes that coevolve with the histological evolution of NASH.NEW & NOTEWORTHY This study demonstrates in a first of kind longitudinal analysis, the evolution of nonalcoholic steatohepatitis (NASH) on a fast-food diet-induced model. Key findings include 1) hepatic lipid composition changes in a multiphasic fashion as NASH evolves; 2) insulin resistance precedes hepatic inflammation and fibrosis, answering a longstanding chicken-and-egg question regarding the relationship of insulin resistance to liver histology in NASH; and 3) mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent.

A Double-Blinded Randomized Trial to Compare the Effectiveness of Minimally Invasive Procedures Using Patient-Reported Outcomes

BACKGROUND The Institute of Medicine has included the comparison of minimally invasive surgical techniques in its research agenda. This study seeks to evaluate a model for the comparison of minimally invasive procedures using patient-reported outcomes. STUDY DESIGN A double-blinded randomized controlled trial (NCT01489436) was conducted. Baseline data were obtained, standardized anesthesia was induced, and patients were randomized to single-port (SP) or 4-port (FP) laparoscopic cholecystectomy. Perioperative care was standardized. The outcomes were pain (Visual Analog Scale) on postoperative day 1 (primary) and quality of life (Patient-Reported Outcomes Measures Information System and Linear Analog Self-Assessment), serum cytokines, and heart rate variability (secondary). Analysis was intention to treat. Using identical occlusive dressings, patients and the outcomes assessor remained blinded until postoperative day 2. RESULTS Fifty-five patients were randomized to each arm. There was no difference in demographics. Visual Analog Scale pain score on postoperative day 1 was significantly different from baseline in each group (SP: 1.6 ± 1.9 to 4.2 ± 2.4 vs FP: 1.8 ± 2.3 to 4.2 ± 2.2), but not different from each other (p = 0.83). Patients in the FP arm reported significantly less fatigue on postoperative day 7 than patients in the SP group (3.1 ± 2.1 vs 4.2 ± 2.2; p = 0.009). Fewer patients in the FP group required postoperative oral narcotics before discharge (40% vs 60%; p = 0.056). Cytokines levels and heart rate variability were similar between arms. In patients followed for >1 year, no difference in umbilical hernia rates was noted. CONCLUSIONS Early postoperative quality of life data captured differences in fatigue, indicating improved recovery after FP within a controlled trial. Physiologic measures were similar, suggesting that the differences between SP and FP are minimal.

In utero cell transfer between porcine littermates

Trafficking of cells between mother and fetus during the course of normal pregnancy is well documented. Similarly, cells are known to travel between twins that share either a placenta (i.e. monozygotic) or associated chorion (i.e. monochorionic). Transferred cells are thought to be channelled via the vessels of the placenta or vascular connections established via the chorion and the long-term presence of these cells (i.e. microchimerism) can have important consequences for immune system function and reparative capacity of the host. Whether cells can be transferred between twins with separate placentas and separate chorions (i.e. no vascular connections between placentas) has not been investigated nor have the biological consequences of such a transfer. In the present study, we tested the possibility of this type of cell transfer by injecting human cord blood-derived cells into a portion of the littermates of swine and probing for human cells in the blood and tissues of unmanipulated littermates. Human cells were detected in the blood of 78% of unmanipulated littermates. Human cells were also detected in various tissues of the unmanipulated littermates, including kidney (56%), spleen (33%), thymus (11%) and heart (22%). Human cells were maintained in the blood until the piglets were sacrificed (8 months after birth), suggesting the establishment of long-term microchimerism. Our findings show that the transfer of cells between fetuses with separate placentas and separate chorions is significant and thus such twins may be subject to the same consequences of microchimerism as monozygotic or monochorionic counterparts.

Methodological differences account for inconsistencies in reported free VEGF concentrations in pregnant rats

Free vascular endothelial growth factor (VEGF) is undetectable in plasma during human pregnancy. However, studies examining pregnant rats have reported both low (8-29 pg/ml) and high (527-1,030 pg/ml) free VEGF. These discrepancies cast uncertainty over the use of rat models to study angiogenic factors in pregnancy and preeclampsia. This study investigates methodological factors that may explain these discrepancies. Plasma VEGF in nonpregnant, day 7 pregnant, and day 19 pregnant rats was measured using rat and mouse ELISAs (R&D Systems). The rat ELISA detected VEGF in plasma from nonpregnant rats but not in plasma from day 19 pregnant rats. The mouse ELISA detected higher VEGF concentrations than the rat ELISA in every sample tested. This discrepancy was greater in day 19 pregnant rats (median: 2,273 vs. 0 pg/ml) than in nonpregnant (97 vs. 20 pg/ml) and day 7 pregnant (66 vs. 2 pg/ml) rats. Recovery of recombinant rat VEGF (rrVEGF) spiked into plasma from nonpregnant and day 7 pregnant rats was high for the rat ELISA (82-105%) but low for the mouse ELISA (17-22%). The rat ELISA did not recover rrVEGF in plasma from day 19 pregnant rats, suggesting that this ELISA measures free VEGF. The use of the rat versus mouse ELISA likely explains the differences in reported VEGF concentrations in pregnant rats. While the rat ELISA appears to measure free VEGF, plasma concentrations in nonpregnant and pregnant rats are below the assay sensitivity limit. As most previous studies of pregnant rats used the mouse VEGF ELISA, these data should be interpreted cautiously.

Success of elective cholecystectomy treatment plans after emergency department visit

BACKGROUND Differentiation between patients with acute cholecystitis and patients with severe biliary colic can be challenging. Patients with undiagnosed acute cholecystitis can incur repeat emergency department (ED) visits, which is resource intensive. METHODS Billing records from 2000-2013 of all adults who visited the ED in the 30 d preceding their cholecystectomy were analyzed. Patients who were discharged from the ED and underwent elective cholecystectomy were compared with those who were discharged and returned to the ED within 30 d. T-tests, chi-square tests, and multivariable analysis were used as appropriate. RESULTS From 2000-2013, 3138 patients (34%) presented to the ED within 30 d before surgery, 63% were women, mean age 51 y, and of those 1625 were directly admitted from the ED for cholecystectomy, whereas 1513 patients left the ED to return for an elective cholecystectomy. Patients who were discharged were younger (mean age 49 versus 54 y, P < 0.001) and had shorter ED stays (5.9 versus 7.2 h, P < 0.001) than the patients admitted immediately. Of the discharged patients, 303 (20%) returned to the ED within 30 d to undergo urgent cholecystectomy. Compared with patients with successful elective cholecystectomy after the ED visit, those who failed the pathway were more likely to have an American Society of Anesthesiologists score ≥3 and were <40 or ≥60 compared with the successful group. CONCLUSIONS One in five patients failed the elective cholecystectomy pathway after ED discharge, leading to additional patient distress and use of resources. Further risk factor assessment may help design efficient care pathways.

Surgical team workload comparison for 4-port and single-port laparoscopic cholecystectomy procedures

Advanced minimally invasive procedures may cause postural constraints and increased workload and stress for providers. This study compared workload and stress across surgical team roles for 48 laparoscopic cholecystectomies (4-port vs single-port) using a task load index (NASA-TLX), a procedural difficulty question, and salivary stress hormones. Statistical analyses were performed based on the presence intra-cluster correlation within team roles, at α=0.05. The single-port technique resulted in an 89% increase in physical workload for the surgeon and 63% increase for the assistant (both p<0.05). The surgeon had significantly higher salivary stress hormones during single-port surgeries. The degree of procedural difficulty was positively correlated between the surgeon and most roles: resident (r=0.67), assistant (r=0.81), and technician (r=0.81). There was a statistically significant positive correlation between the surgeon and assistant for all selfreported workload measures (p<0.05). The single-port technique requires further improvement to balance surgical team workload for optimal patient safety and satisfaction.