Evaluating the Efficacy and Safety of Laparoscopic Heller Myotomy in Treating Achalasia

Introduction: Laparoscopic Heller myotomy (LHM) is widely recognized as the standard surgical treatment for esophageal achalasia. However, there is a lack of local data regarding the clinical characteristics of patients and the outcomes of this intervention. Methodology: This retrospective study analyzed patients who underwent LHM over an eight-year period. Demographic, operative, and postoperative variables were assessed. The Eckardt score was used to compare symptoms before and after the intervention. Continuous variables were presented as means. Results: Among the 39 patients assessed, 27 met the inclusion criteria. Of these, 51% were male, with an average age of 48 years. The average lower esophageal sphincter pressure was 36 mmHg. The mean operative time and bleeding were 133 minutes and 34 mL, respectively. The average length of the myotomy was 8.3 cm. Partial fundoplication was performed in all cases, and intraoperative endoscopy was conducted in 88% of the cases. Two intraoperative mucosal perforations occurred. The average length of hospital stay was 2.7 days. There was one medical complication but no mortality. Dysphagia significantly improved by 95%, and the mean Eckardt score decreased from 7.7 to 1.2 after surgery (p < 0.001). The average follow-up period was 24 months. Conclusion: LHM with partial fundoplication proves to be an effective and safe procedure for treating achalasia. It results in the resolution of dysphagia in 95% of cases and carries minimal morbidity. Therefore, LHM should be considered the definitive treatment of choice for achalasia.

Introducción: la miotomía de Heller laparoscópica (MHL) se considera el tratamiento quirúrgico estándar en acalasia esofágica. A nivel local se desconocen las características clínicas de los pacientes y los resultados de la intervención. Metodología: estudio retrospectivo que incluye pacientes llevados a MHL durante un periodo de 8 años. Se analizaron variables demográficas, operatorias y posoperatorias. Mediante el puntaje de Eckardt se compararon síntomas antes y después de la intervención. Las variables continuas se expresan en promedios. Resultados: 27 de 39 pacientes cumplieron los criterios de inclusión. El 51% fueron hombres y el promedio de edad fue de 48 años. La presión promedio del esfínter esofágico inferior fue de 36 mm Hg. El promedio de tiempo operatorio y sangrado fue de 133 minutos y 34 mL, respectivamente. La longitud promedio de la miotomía fue de 8,3 cm. Se adicionó funduplicatura parcial en todos los casos y en el 88% se realizó una endoscopia intraoperatoria. Se presentaron 2 perforaciones intraoperatorias de la mucosa. El promedio de estancia hospitalaria fue 2,7 días. Hubo una complicación médica y ninguna mortalidad. La disfagia mejoró en el 95% y el promedio del puntaje de Eckardt disminuyó de 7,7 a 1,2 luego de cirugía (p < 0,001). El seguimiento fue de 24 meses en promedio. Conclusión: la MHL con funduplicatura parcial es un procedimiento efectivo y seguro para el tratamiento de la acalasia. Se asocia a resolución de la disfagia en el 95% de los casos, su morbilidad es mínima y debe considerarse el tratamiento definitivo de elección.

Subcellular Localization and Activity of TRPM4 in Medial Prefrontal Cortex Layer 2/3.

TRPM4 is a Ca2+-activated non-selective cationic channel that conducts monovalent cations. TRPM4 has been proposed to contribute to burst firing and sustained activity in several brain regions, however, the cellular and subcellular pattern of TRPM4 expression in medial prefrontal cortex (mPFC) during postnatal development has not been elucidated. Here, we use multiplex immunofluorescence labeling of brain sections to characterize the postnatal developmental expression of TRPM4 in the mouse mPFC. We also performed electrophysiological recordings to correlate the expression of TRPM4 immunoreactivity with the presence of TRPM4-like currents. We found that TRPM4 is expressed from the first postnatal day, with expression increasing up to postnatal day 35. Additionally, in perforated patch clamp experiments, we found that TRPM4-like currents were active at resting membrane potentials at all postnatal ages studied. Moreover, TRPM4 is expressed in both pyramidal neurons and interneurons. TRPM4 expression is localized in the soma and proximal dendrites, but not in the axon initial segment of pyramidal neurons. This subcellular localization is consistent with a reduction in the basal current only when we locally perfused 9-Phenanthrol in the soma, but not upon perfusion in the medial or distal dendrites. Our results show a specific localization of TRPM4 expression in neurons in the mPFC and that a 9-Phenanthrol sensitive current is active at resting membrane potential, suggesting specific functional roles in mPFC neurons during postnatal development and in adulthood.

P2X4 Receptor in Silico and Electrophysiological Approaches Reveal Insights of Ivermectin and Zinc Allosteric Modulation.

Protein allosteric modulation is a pillar of metabolic regulatory mechanisms; this concept has been extended to include ion channel regulation. P2XRs are ligand-gated channels activated by extracellular ATP, sensitive to trace metals and other chemicals. By combining in silico calculations with electrophysiological recordings, we investigated the molecular basis of P2X4R modulation by Zn(II) and ivermectin, an antiparasite drug currently used in veterinary medicine. To this aim, docking studies, molecular dynamics simulations and non-bonded energy calculations for the P2X4R in the apo and holo states or in the presence of ivermectin and/or Zn(II) were accomplished. Based on the crystallized Danio rerio P2X4R, the rat P2X4R, P2X2R, and P2X7R structures were modeled, to determine ivermectin binding localization. Calculations revealed that its allosteric site is restricted to transmembrane domains of the P2X4R; the role of Y42 and W46 plus S341 and non-polar residues were revealed as essential, and are not present in the homologous P2X2R or P2X7R transmembrane domains. This finding was confirmed by preferential binding conformations and electrophysiological data, revealing P2X4R modulator specificity. Zn(II) acts in the P2X4R extracellular domain neighboring the SS3 bridge. Molecular dynamics in the different P2X4R states revealed allosterism-induced stability. Pore and lateral fenestration measurements of the P2X4R showed conformational changes in the presence of both modulators compatible with a larger opening of the extracellular vestibule. Electrophysiological studies demonstrated additive effects in the ATP-gated currents by joint applications of ivermectin plus Zn(II). The C132A P2X4R mutant was insensitive to Zn(II); but IVM caused a 4.9 ± 0.7-fold increase in the ATP-evoked currents. Likewise, the simultaneous application of both modulators elicited a 7.1 ± 1.7-fold increase in the ATP-gated current. Moreover, the C126A P2X4R mutant evoked similar ATP-gated currents comparable to those of wild-type P2X4R. Finally, a P2X4/2R chimera did not respond to IVM but Zn(II) elicited a 2.7 ± 0.6-fold increase in the ATP-gated current. The application of IVM plus Zn(II) evoked a 2.7 ± 0.9-fold increase in the ATP-gated currents. In summary, allosteric modulators caused additive ATP-gated currents; consistent with lateral fenestration enlargement. Energy calculations demonstrated a favorable transition of the holo receptor state following both allosteric modulators binding, as expected for allosteric interactions.

Observed Variability in Sleeve Gastrectomy Volume and Compliance Does Not Correlate to Postoperative Outcomes.

BACKGROUND: Restrictive bariatric procedures reduce gastric capacity as a primary mechanism of action. Intraoperatively, surgeons observe variability in size and compliance of specimens. We hypothesized that higher gastric specimen volume or tissue compliance would respond better to restrictive procedures. MATERIALS AND METHODS: Consecutive patients undergoing laparoscopic sleeve gastrectomy between September 2012 and September 2013 were enrolled. Specimens were insufflated at graduated pressure points creating pressure volume curves, and compliance was calculated. Postoperative weight loss and a hunger scores were recorded. Correlations were determined by Spearman correlation. RESULTS: Eighty-four patients consented to enrollment. Mean age, weight, and body mass index (BMI) were 45 ± 12 years, 126 ± 23 kg, and 45.4 ± 6 m/kg2, respectively. The resected specimens varied in insufflated capacity from 0.3 to 1.8 (0.71 ± 0.32) L and compliance varied from 14.3 to 85.7 (36.1 ± 14.7) cc/mm Hg. Male patients had a larger greater curvature length (GCL) (P < 0.001), staple line length (SLL) (P = 0.03), gastric volume (GV) (P = 0.002), and gastric compliance (GC) (P < 0.001). Neither GV nor GC correlated to excess body weight loss (EBWL%) as hypothesized. There was an inverse correlation between hunger score and GV (P = 0.010). The mean 1-month, 3-month, 6-month, and 12-month EBWL was 17.4%, 33.2%, 43.7%, and 54.1%, respectively. Follow-up was 71.4% at 1 month, 39.3% at 3 months, 54.8% at 6 months, and 42.9% at 12 months. CONCLUSIONS: Sleeve gastrectomy specimens exhibit nearly 6-fold variability in both volume and compliance. A large GC is anticipated in male and tall subjects. These observations do not appear to be correlated to %EBWL.

Detecting performance variance in complex surgical procedures: analysis of a step-wise technique for laparoscopic right hepatectomy.

BACKGROUND: Laparoscopic right hepatectomy (LRH) is a technically challenging operation. Our aim is to evaluate a standardized technique of LRH and determine variances in performance. METHODS: The procedure was deconstructed into 7 major step-wise components. All LRH followed the same surgical sequence, and used the same devices and operating room set-up. Thirty randomly selected video recordings of the procedure underwent intraoperative time analysis. The variances measured by standard deviation of each step were calculated (mean in minutes ± standard deviation). RESULTS: Mean total operative time was 114 ± 25 min. The steps with the least variance were inferior vena cava dissection (8 ± 3) and right hepatic vein ligation (9 ± 5). The longest and also the step with the greatest variance was parenchymal transection (35 ± 12). CONCLUSIONS: LRH can be performed consistently using a standardized step-wise technique. Parenchymal transection had most variation, and this could be explained by intrinsic liver factors. Surgical performance improvement should begin with deconstructing the operation into definable steps to identify areas for change.

ATP and related purines stimulate motility, spatial congregation, and coalescence in red algal spores.

Adenosine 5'-triphosphate (ATP) is a versatile extracellular signal along the tree of life, whereas cAMP plays a major role in vertebrates as an intracellular messenger for hormones, transmitters, tastants, and odorants. Since red algal spore coalescence may be considered analogous to the congregation process of social amoeba, which is stimulated by cAMP, we ascertained whether exogenous applications of ATP, cAMP, adenine, or adenosine modified spore survival and motility, spore settlement and coalescence. Concentration-response studies were performed with carpospores of Mazzaella laminarioides (Gigartinales), incubated with and without added purines. Stirring of algal blades released ADP/ATP to the cell media in a time-dependent manner. 10-300 µM ATP significantly increased spore survival; however, 1,500 µM ATP, cAMP or adenine induced 100% mortality within less than 24 h; the exception was adenosine, which up to 3,000 µM, did not alter spore survival. ATP exposure elicited spore movement with speeds of 2.2-2.5 µm · s(-1) . 14 d after 1,000 µM ATP addition, spore abundance in the central zone of the plaques was increased 2.7-fold as compared with parallel controls. Likewise, 1-10 µM cAMP or 30-100 µM adenine also increased central zone spore abundance, albeit these purines were less efficacious than ATP; adenosine up to 3,000 µM did not influence settlement. Moreover, 1,000 µM ATP markedly accelerated coalescence, the other purines caused a variable effect. We conclude that exogenous cAMP, adenine, but particularly ATP, markedly influence red algal spore physiology; effects are compatible with the expression of one or more membrane purinoceptor(s), discarding adenosine receptor participation.

Review of robotics in foregut and bariatric surgery.

BACKGROUND: In the last decade, the robotic platform has been used in different surgical fields. However, the field of foregut and bariatric surgery is still evolving. Most surgeons still prefer laparoscopic techniques because it has proven clinical benefits, does not require complex setups, and does not have high costs compared with that of robotics. The aim of this article is to review the outcomes of foregut and bariatric surgery and its potential clinical advantages. METHODS: We performed a search on PUBMED for the most relevant articles published in the field of robotic bariatric and foregut surgery in the last 15 years. More than 40 articles were selected and included on this review. Several systematic reviews were also included. Very few randomized clinical trials are available. RESULTS: For the most part, robotic procedures were associated with better ergonomics for the surgeon, better visualization of the anatomy, easier fine dissection (i.e., lymphadenectomy) when required, and higher costs. In foregut surgery, the robotic system is associated with a significant lower rate of mucosal perforation in Heller myotomy compared to laparoscopy. In bariatric surgery, the clinical advantages have not been well documented yet; however, it seems robotics shortens the learning curve of Roux-en-Y gastric bypass (RYGB). CONCLUSION: Foregut and bariatric robotic surgery is a surgical field still in development. For the vast majority of the procedures in this area, the clinical outcomes of robotic surgery are the same of standard laparoscopy. However, the use of robots in selected cases may have specific advantages and may overcome the limitations of laparoscopic surgery. More research is needed, especially large and well-designed randomized clinical trials, to elucidate more accurate conclusions.

Combining laparoscopic giant paraesophageal hernia repair with sleeve gastrectomy in obese patients.

BACKGROUND: Surgical treatment for giant paraesophageal hernias (PEH) in morbidly obese patients (BMI > 35) continues to be a difficult problem. Prior studies have demonstrated recurrence rates of up to 40% with higher rates in morbidly obese patients. Reports have shown success combining repair with a bariatric procedure to decrease recurrence rates while achieving weight loss. We report mid-term results from a larger series with combining laparoscopic giant PEH repair with sleeve gastrectomy (SG). METHODS: We reviewed all combined cases of PEH repairs with SG done at a single institution from 2008 to 2013. The surgical technique was standardized and absorbable bio-prosthetic buttress crural closure reinforcement was used selectively. Yearly upper gastrointestinal radiographic (UGI) studies and postoperative Gastroesophageal Reflux Disease Health-Related Quality of Life questionnaires were completed. 33 patients were enrolled; 18 patients (55%) completed the study RESULTS: No 30-day morbidity or mortality occurred. 16 patients were female; the average age was 55.3 ± 11.4 years (30-72) with follow-up from surgery of 19.9 ± 16.7 months (6-66). The average weight loss was 23.5 ± 12.7 kg (8-57); excess body weight loss was 46 ± 25.8% (18-112). Based on the UGIs, 9/18 (50%) had no evidence of hernia recurrence, while 6/18 (33%) demonstrated a small (<2 cm) recurrence. 3/18 (17%) patients had evidence of moderate recurrence (3-5 cm). Postoperative GERD-HRQL scores revealed an average score of 10 ± 7 (2-26). All patients reported being "satisfied" with their operation and weight loss and also had a significant improvement in foregut symptoms. No patient has required surgical revision and residual symptoms responded to conservative management. CONCLUSIONS: PEH in morbidly obese patients remain a complex surgical problem. Our case series shows that combination with SG may decrease recurrence rates but more importantly leads to lower rates of reoperation for symptomatic recurrence. Patients also garner the added medical benefits of weight loss.

Postoperative complications in bariatric surgery using age and BMI stratification: a study using ACS-NSQIP data.

BACKGROUND: Bariatric surgery results in long-term weight loss and significant morbidity reduction. Morbidity and mortality following bariatric surgery remain low and acceptable. This study looks to define the trend of morbidity and mortality as it relates to increasing age and body mass index (BMI) in patients undergoing bariatric surgery. METHODS: We queried the ACS/NSQIP 2010-2011 Public Use File for patients who underwent elective laparoscopic adjustable banding (LAGB), sleeve gastrectomy (LSG) and gastric bypass (LGBP). Total morbidity and 30-day mortality were evaluated. Logistic regression models were created to estimate the effect of increasing age and BMI on morbidity for these bariatric procedures. RESULTS: A total of 20,308 laparoscopic bariatric procedures were reviewed (11617 LGBP, 3069 LSG and 5622 LAGB). Overall mortality and morbidity rates were 0.11 and 3.84%, respectively. The odds of postoperative complications increased by 2% with each additional year of age (OR 1.02, 95% CI 1.02-1.03) and every point increase in BMI (OR 1.02, 95% CI 1.01-1.03). Multiple logistic regression identified COPD, Diabetes, Hypertension, and Dyspnea as major risk factors for postoperative morbidity. Postoperative complications were three times more likely after LGBP (OR 2.87, 95% CI 2.31-3.57) and two times more likely after LSG (OR 2.06, 95% CI 1.57-2.72) when compared to patients undergoing LAGB. CONCLUSION: Morbidity and mortality increase on a predictable trend with increasing age and BMI. There is increased risk of morbidity for stapling procedures when compared to gastric banding, but this must be considered in context of surgical efficacy when choosing a bariatric procedure. These data can be used in preoperative counseling and evaluation of surgical candidacy of bariatric surgical patients.

Association of radiographic morphology with early gastroesophageal reflux disease and satiety control after sleeve gastrectomy.

BACKGROUND: Variable gastric morphology has been identified on routine upper gastrointestinal series after laparoscopic sleeve gastrectomy. This test might give us useful information beyond the presence of leak and obstruction. The aim of this study is to standardize a morphologic classification of gastric sleeve based on water-soluble contrast upper gastrointestinal series, and to determine possible clinical implications. STUDY DESIGN: One hundred morbidly obese patients underwent laparoscopic sleeve gastrectomy and had routine upper gastrointestinal on postoperative day 1 or 2. Images were reviewed by 4 radiologists who were blinded to outcomes, and sleeve shape was classified as upper pouch, lower pouch, tubular, or dumbbell. Inter-observer agreement was calculated. Clinical outcomes including weight loss, satiety control, and reflux symptoms were recorded. Comparisons were determined by 1-way ANOVA and t-test. RESULTS: Mean age was 46 ± 12 years and mean BMI was 45.1 ± 6 kg/m(2). Overall inter-observer agreement level for the sleeve shape classification was 76.3%. Sleeve shapes were tubular in 37%, dumbbell in 32%, lower pouch in 22%, and upper pouch in 8%. Mean excess body weight loss at 1, 3, and 6 months was 16.8%, 29.9%, and 39.1%, respectively. Excess body weight loss was not associated with sleeve shape. Mean hunger score was 213 ± 97, and patients with dumbbell shape had higher hunger scores (p = 0.003). Mean reflux score was 5.7 ± 8. Upper pouch shape was associated with greater severity of reflux symptoms (p = 0.02). CONCLUSIONS: This study suggests a standardized radiographic classification of gastric sleeve morphology. Although sleeve shape is not correlated with weight loss, gastric sleeves with retained fundus result in lower satiety control and higher severity of reflux symptoms. An adequate resection of the gastric fundus might avoid this potential complication.

Efficacy of laparoscopic pyloroplasty for the treatment of gastroparesis.

BACKGROUND: The modest results of nonoperative modalities for the treatment of gastroparesis necessitate greater consideration of surgical therapies. However, the role of surgery is not well defined. The aim of this study is to present our experience with laparoscopic pyloroplasty as early treatment for gastroparesis. STUDY DESIGN: Fifty patients with refractory gastroparesis underwent laparoscopic pyloroplasty (hand-sewn Heineke-Mikulicz configuration) from 2006 to 2013 at our institution. Preoperative and postoperative symptom data, gastric emptying scintigraphy, and technical outcomes of the procedure were reviewed. A single-factor ANOVA was performed for the comparison of continuous variables. Results are reported as mean ± SD or median absolute deviation. RESULTS: Thirty-four of 50 (68%) patients had previous foregut procedures and/or cholecystectomy. Thirty-two of 50 (64%) patients underwent concomitant procedures (ie, paraesophageal hernia repair and gastrostomy takedown) along with the pyloroplasty. Operative time, including combined procedures, blood loss, and length of stay were 175 ± 56 minutes, 64 ± 50 mL, 2.5 ± 2.7 days, respectively. There were no conversions to open technique or intraoperative complications. There were no suture-line leaks. The readmission rate was 14%. All patients had symptom follow-up and 33 (66%) had postoperative gastric emptying scintigraphy. Postoperative symptom improvement was reported by 82% of the patients (p < 0.001). Median preoperative T1/2 was 180 ± 73 minutes and postoperative T1/2 was 60 ± 23 minutes (p < 0.001). Five patients (10%), who had normalized postoperative T1/2 times, required other gastric emptying procedures; distal gastrectomy (n = 2), duodenojejunostomy (n = 2), and gastric stimulator placement (n = 1). CONCLUSIONS: Laparoscopic pyloroplasty is an effective early-treatment modality for selected cases of gastroparesis, with substantial improvement in objective gastric emptying times and low morbidity. The laparoscopic approach does not preclude subsequent procedures when necessary.

Can we become better robot surgeons through simulator practice?

INTRODUCTION: There is significant growth in the use of the robotic surgery platform in the general surgery community. Current pre-requisites for robot surgery training include performing basic tasks on a simulator and achieving a minimum overall score for each task. However, there is limited information about these tasks related to performance and time required to become proficient. We focused on critical tasks that have the highest potential for preventing inadvertent injuries, and constructed models to predict how many attempts would be needed to master the tasks depending on the user's initial attempt. METHODS AND PROCEDURES: This study was conducted using de-identified data collected over 12 months from the dV-Trainers® simulator at our institution. We analyzed tasks used in institutional surgical robot credentialing that focused on camera manipulation and energy use. Data were extracted from the Camera Targeting, Energy Dissection, and Energy Switching exercises focusing on individual metrics such as Time to Complete Exercise, Economy of Motion, Misapplied Energy Time, and Blood Volume Loss. Mixed linear models looking at sequential attempts and specific performance metrics were constructed using IBM SPSS Statistics version 20. RESULTS: Over 26,000 overall minutes of recorded use was logged in our simulator by more than 30 unique users across all exercises. An average of 15 users performed each of the analyzed exercises, with an average of eight attempts per exercise. Based on our models, on average most users would need four to five attempts to achieve 80 % proficiency for any given metric. CONCLUSION: Virtual reality robotic simulators such as the dv-Trainer® can be used by general surgeons to become better robotic surgeons. Our data suggests that it can be used by a surgeon to predict how much time and effort one would need to spend on the simulator in order to become proficient with the robot, especially in critical metrics such as camera manipulation and energy application. Surgeons who require more attempts to successfully complete tasks may want to consider additional training methods, such as proctoring or hands-on laboratories, to improve robot surgery proficiency.

Sex-linked differences in the vasorelaxant effects of anandamide in vascular mesenteric beds: role of oestrogens.

Anandamide (0.01 to 10 microM) caused greater concentration-dependent reductions of the contractile-induced responses to noradrenaline in female than in male mesenteric vascular beds isolated from adult Sprague-Dawley rats. Greater relaxant responses in females were also induced by the vanilloid TRPV1 receptor agonist capsaicin (0.01 to 10 microM), whereas no sex differences were observed for the relaxations caused by either acetylcholine or sodium nitroprusside. The effect of anandamide in either sex was reduced by the vanilloid TRPV1 receptor antagonist capsazepine but not by the cannabinoid CB1 receptor antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR141716A). In males, the anandamide-induced relaxations were potentiated by in vitro exposure during 5 min to 0.5 microM 17beta-oestradiol and unmodified by the protein synthesis inhibitor cycloheximide. The vasorelaxant effects of anandamide in female rats were decreased by ovariectomy. This decrease was prevented by in vivo treatment with 17beta-oestradiol-3-benzoate (450 microg/kg i.m., once a week during 3 weeks) and counteracted by in vitro exposure to oestrogen. In vivo treatment with 17beta-oestradiol also potentiated anandamide-induced responses in males. In conclusion, this study shows an oestrogen-dependent sensitivity to the vanilloid TRPV1 receptor-mediated vasorelaxant effects of anandamide in the mesenteric vasculature of Sprague-Dawley rats, that could be mediated by both genomic and non-genomic mechanisms.