What are essential laparoscopic skills these days? Results of the SAGES Fundamentals of Laparoscopic Surgery (FLS) Committee technical skills survey.

INTRODUCTION: The Fundamentals of Laparoscopic Surgery (FLS) program tests basic knowledge and skills required to perform laparoscopic surgery. Educational experiences in laparoscopic training and development of associated competencies have evolved since FLS inception, making it important to review the definition of fundamental laparoscopic skills. The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) assigned an FLS Technical Skills Working Group to characterize technical skills used in basic laparoscopic surgery in current practice contexts and their possible application to future FLS tests. METHODS: A group of subject matter experts defined an inventory of 65 laparoscopic skills using a Nominal Group Technique. From these, a survey was developed rating these items for importance, frequency of use, and priority for testing for FLS certification. This survey was distributed to SAGES members, recent recipients of FLS certification, and members of the Association of Program Directors in Surgery (APDS). Results were collected using a secure web-based survey platform. RESULTS: Complete data were available for 1742 surveys. Of these, 1143 comprised results for post-residency participants who performed advanced procedures. Seventeen competencies were identified for FLS testing prioritization by determining the proportion of respondents who identified them of highest priority, at median (50th percentile) of the maximum survey scale rating. These included basic peritoneal access, laparoscope and instrument use, tissue manipulation, and specific problem management skills. Sixteen could be used to show appropriateness of the domain construct by confirmatory factor analysis. Of these 8 could be characterized as manipulative tasks. Of these 5 mapped to current FLS tasks. CONCLUSIONS: This survey-identified competencies, some of which are currently assessed in FLS, with a high level of priority for testing. Further work is needed to determine if this should prompt consideration of changes or additions to the FLS technical skills test component.

Myotomy technique and esophageal contractility impact blown-out myotomy formation in achalasia: an in silico investigation.

We used in silico models to investigate the impact of the dimensions of myotomy, contraction pattern, the tone of the esophagogastric junction (EGJ), and musculature at the myotomy site on esophageal wall stresses potentially leading to the formation of a blown-out myotomy (BOM). We performed three sets of simulations with an in silico esophagus model, wherein the myotomy-influenced region was modeled as an elliptical section devoid of muscle fibers. These sets investigated the effects of the dimensions of myotomy, differing esophageal contraction types, and differing esophagogastric junction (EGJ) tone and wall stiffness at the myotomy affected region on esophageal wall stresses potentially leading to BOM. Longer myotomy was found to be accompanied by a higher bolus volume accumulated at the myotomy site. With respect to esophageal contractions, deformation at the myotomy site was greatest with propagated peristalsis, followed by combined peristalsis and spasm, and pan-esophageal pressurization. Stronger EGJ tone with respect to the wall stiffness at the myotomy site was found to aid in increasing deformation at the myotomy site. In addition, we found that an esophagus with a shorter myotomy performed better at emptying the bolus than that with a longer myotomy. Shorter myotomies decrease the chance of BOM formation. Propagated peristalsis with EGJ outflow obstruction has the highest chance of BOM formation. We also found that abnormal residual EGJ tone may be a co-factor in the development of BOM, whereas remnant muscle fibers at myotomy site reduce the risk of BOM formation.NEW & NOTEWORTHY Blown-out myotomy (BOM) is a complication observed after myotomy, which is performed to treat achalasia. In silico simulations were performed to identify the factors leading to BOM formation. We found that a short myotomy that is not transmural and has some structural architecture intact reduces the risk of BOM formation. In addition, we found that high esophagogastric junction tone due to fundoplication is found to increase the risk of BOM formation.

Outcomes of 100 Patients More Than 4 Years After POEM for Achalasia.

OBJECTIVE: We aim to describe the long-term follow-up data from our institution's POEM experience. SUMMARY BACKGROUND DATA: Per-oral endoscopic myotomy (POEM) is a well-established endoscopic therapy for achalasia with excellent short-term efficacy, but long-term outcomes data are limited. METHODS: Patients older than 4 years removed from POEM for treatment of achalasia were studied. Clinical success was defined as an Eckardt Symptom (ES) score ≤3 and freedom from reintervention for achalasia. Patients underwent esophagogastroduodenoscopy (EGD), high-resolution manometry, impedance planimetry, and timed barium esophagram (TBE) preoperatively and at least 4 years postoperatively. Objective gastroesophageal reflux disease (GERD) was defined LA Grade B or worse esophagitis on EGD. RESULTS: One hundred and nineteen consecutive patients were included. Five patients died or had catastrophic events unrelated to achalasia or POEM. One hundred of the remaining patients (88%, 100/114) had long-term data available. Clinical follow-up for all patients was greater than 4 years postoperatively and the mean was 55 months. Mean current ES was significantly improved from preop (n = 100, 1 ±â€Š1 vs 7 ±â€Š2, P < 0.001). Overall clinical success was 88% and 92%. Five patients had a current ES >3 and 4 patients required procedural reintervention on the lower esophageal sphincter. Reinterventions were successful in 75% of patients (3/4), with current ES ≤3. The rate of objective GERD was 33% (15/45). Esophageal physiology was improved with a decrease in median integrated relaxation pressure (11 ±â€Š4 vs 33 ±â€Š15 mm Hg, P < 0.001), a decrease in median TBE column height (3 ±â€Š3 vs 13 ±â€Š8 cm, P < 0.001), and an increase in median distensibility index (5.1 ±â€Š2 vs 1.1 ±â€Š1 mm2/mm Hg, P < 0.001). CONCLUSIONS: POEM provides durable symptom relief and improvement in physiologic esophagogastric junction relaxation parameters over 4.5 years postoperatively. Reinterventions are rare and effective.

Comparison of preoperative, intraoperative, and follow-up functional luminal imaging probe measurements in patients undergoing myotomy for achalasia.

BACKGROUND AND AIMS: The functional luminal imaging probe (FLIP) is a novel catheter-based device that measures esophagogastric junction (EGJ) distensibility index (DI) in real time. Previous studies have demonstrated DI to be a predictor of post-treatment clinical outcomes in patients with achalasia. We sought to evaluate EGJ DI in patients with achalasia before, during, and after peroral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM) and to assess the correlation of DI with postoperative outcomes. METHODS: DI (defined as the minimum cross-sectional area at the EGJ divided by distensive pressure) was measured at 4 time points in patients undergoing surgical myotomy for achalasia: (1) during outpatient preoperative endoscopy (preoperative DI), (2) at the start of each operation after the induction of anesthesia (induction DI), (3) at the conclusion of each operation (postmyotomy DI), and (4) at routine follow-up endoscopy 12 months postoperatively (follow-up DI). Routine Eckardt symptom score, endoscopy, timed barium esophagram, and pH study were obtained 12 months postoperatively. RESULTS: Forty-six patients (35 POEM, 11 LHM) underwent FLIP measurements at all 4 time points. Preoperative and induction mean DI were similar for both groups (POEM, 1 vs .9 mm2/mm Hg; LHM, 1.7 vs 1.5 mm2/mm Hg). POEM resulted in a significant increase in DI (induction .9 vs postmyotomy 7 mm2/mm Hg, P < .001). There was a subsequent decrease in DI in the follow-up period (postmyotomy 7 vs follow-up 4.8 mm2/mm Hg, P < .01), but DI at follow-up was still significantly improved from preoperative values (P < .001). For LHM patients, DI also increased as a result of surgery (induction 1.5 vs postmyotomy 5.9 mm2/mm Hg, P < .001); however, the increase was smaller than in POEM patients (DI increase 4.4 vs 6.2 mm2/mm Hg, P < .05). After LHM, DI also decreased in the follow-up period, but this change was not statistically significant (5.9 vs 4.4 mm2/mm Hg, P = .29). LHM patients with erosive esophagitis on follow-up endoscopy had a significantly higher postmyotomy DI compared with those without esophagitis (9.3 vs 4.8 mm2/mm Hg, P < .05). CONCLUSIONS: EGJ DI improved dramatically as a result of both POEM and LHM, with POEM resulting in a larger increase. Mean DI decreased at intermediate follow-up but remained well above previously established thresholds for symptom recurrence. DI at the conclusion of LHM was predictive of erosive esophagitis in the postoperative period, which supports the potential use of FLIP for calibration of partial fundoplication construction during LHM.

Addressing the gap in laparoscopic common bile duct exploration training for rural surgeons: imparting procedural ability is not enough.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is an underutilized therapy for choledocholithiasis. The driving factors of this practice gap are poorly defined. We sought to evaluate the attitudes and practice patterns of surgeons who underwent training courses using an LCBDE simulator. METHODS: Surgeons completed a half-day simulator-based LCBDE curriculum at national courses, including the American College of Surgeons Advanced Skills Training for Rural Surgeons and the Society of American Gastrointestinal and Endoscopic Surgeons annual meeting. Attitudes were assessed with Likert surveys immediately before and after curriculum completion. Follow-up surveys were distributed electronically. RESULTS: 159 surgeons completed training during six courses. Surgeon attitudes regarding the overall superiority of LCBDE vs. ERCP shifted towards favoring LCBDE after course participation (4.0 vs 3.3; Likert scale 1-5, p < 0.001). 44% of surgeons completed follow-up surveys at a mean of 3 years post-course. Surgeons remained confident in their ability to perform LCBDE, with only 14% rating their skill as a significant barrier to practice, as compared with 43% prior to course participation (p < 0.01). However, only 28% of surgeons saw an increase in LCBDE volume. Deficiencies in operating room (OR) staff knowledge and instrument availability were the most significant barriers to post-course practice implementation and were inversely correlated with LCBDE case volume (ρ = - 0.44 and - 0.47, both p < 0.01). Surgeons for whom OR staff knowledge of LCBDE was not a significant barrier performed nearly 4 times more LCBDE than those who rated staff knowledge as a moderate, strong, or complete barrier. CONCLUSIONS: Surgeons trained at an LCBDE course retained long-term confidence in their procedural ability. Practice implementation was hindered by deficiencies in OR staff knowledge and instrument availability. Surgeons with knowledgeable operating room staff performed significantly more LCBDEs than those with less capable assistance. These barriers should be addressed in future curricula to improve procedural adoption.

Blown-out myotomy: an adverse event of laparoscopic Heller myotomy and peroral endoscopic myotomy for achalasia.

BACKGROUND AND AIMS: Although laparoscopic Heller myotomy (LHM) or peroral endoscopic myotomy (POEM) is highly effective, 10% to 20% of patients with achalasia remain symptomatic after treatment. In evaluating such patients, we have observed a pattern of failure associated with a pseudodiverticulum, or blown-out myotomy (BOM), in the distal esophagus. We aimed to assess risk factors and patient-reported outcomes associated with a BOM. METHODS: We reviewed our manometry database for patients with achalasia previously treated with LHM or POEM. We included patients who had a post-treatment esophagram within 1 year of their follow-up manometry. A BOM was defined radiographically as a wide-mouthed outpouching (>50% increase in esophageal diameter) in the area of the myotomy. RESULTS: One hundred twenty-nine patients with achalasia who underwent treatment were included; 23 (17.8%) had a BOM. Comparing patients with a BOM with those without, post-treatment Eckardt scores were significantly greater (5 vs 2, P = .002), type III achalasia was more common (39.1% vs 14.2%, P = .005), and LHM was more common than POEM (73.9% vs 26.1%, P = .013). The integrated relaxation pressure was also significantly greater in the BOM group (15.0 mm Hg vs 11.0 mm Hg, P = .025). CONCLUSIONS: BOM is a common adverse event after myotomy for achalasia but is not seen after pneumatic dilation. Pretreatment type III achalasia, LHM as opposed to POEM, and a greater post-treatment integrated relaxation pressure were risk factors for developing a BOM. We speculate that esophageal wall strain in the area weakened by myotomy, whether from residual spastic contractility or continued esophageal outflow obstruction, may be the underlying mechanism of BOM development.

Intraoperative use of FLIP is associated with clinical success following POEM for achalasia.

BACKGROUND: Esophagogastric junction distensibility index (DI), measured using the functional luminal imaging probe (FLIP), correlates with symptomatic outcomes after interventions for achalasia. The objective of this study was to determine if the intraoperative measurement of DI using FLIP was associated with improved clinical outcomes following per-oral endoscopic myotomy (POEM) for achalasia when compared with procedures in which FLIP was not utilized. METHODS: Patients undergoing POEM from 2012 to 2017 at a single institution by a single surgeon were studied. Use of FLIP during this time period was based on catheter and technician availability, resulting in two patient cohorts. In patients in whom FLIP was used, operative video recordings were reviewed to determine when DI measurements led to the performance of additional myotomy. Postoperative Eckardt symptom scores (ES) at 12 months and postoperative physiologic studies were compared between patients with and without intraoperative FLIP. Associations were assessed using Mann-Whitney U and Chi-square tests. RESULTS: 143 patients were included in the analysis (61 with intraoperative FLIP and 82 without FLIP). Video recordings were available for 85% of the FLIP cohort. Review of these operative recordings revealed that 65% of patients who underwent FLIP had additional myotomy performed following the initial postmyotomy FLIP measurement. At 12 months after POEM, the FLIP cohort had significantly more clinical successes (defined as ES ≤ 3) than patients in whom FLIP was not used (93% vs. 81%, p < 0.05). CONCLUSIONS: Use of intraoperative FLIP during POEM resulted in the surgeon performing additional myotomy in over half of cases and was associated with improved clinical outcomes. This study demonstrates the potential for a FLIP-tailored myotomy to improve outcomes in patients undergoing surgical myotomy for achalasia.

Intraoperative FLIP distensibility during POEM varies according to achalasia subtype.

BACKGROUND: The functional luminal imaging probe (FLIP) can be used to measure the esophagogastric junction distensibility index (DI) during myotomy for achalasia and increased DI has been shown to predict superior clinical outcomes. The objective of this study was to determine if the intraoperative DI and the changes produced by per oral endoscopic myotomy (POEM) differed between achalasia subtypes. METHODS: FLIP measurements were performed during POEM for achalasia at a single institution. DI (defined as the minimum cross-sectional area (CSA) at the EGJ divided by distensive pressure) was measured at three time points: after induction of anesthesia, after submucosal tunneling, and after myotomy. Measurements were reported at the 40 mL fill volume for the 8 cm FLIP (EF-325) and at the 60 mL fill volume for the 16 cm FLIP (EF-322). Measurements were compared using chi-square and Kruskal-Wallis tests. RESULTS: 142 patients had intraoperative FLIP performed during POEM for achalasia between 2012 and 2019 (30 type I, 68 type II, 27 type III, and 17 variant). Patients with type I achalasia had a significantly higher induction DI (median 1.7 mm2/mmHg) than type II (0.8 mm2/mmHg), type III (0.9 mm2/mmHg), and variants (1.1 mm2/mmHg; p < 0.001). These differences persisted after submucosal tunneling and final DI after myotomy was also significantly higher in type I patients (median 8.0 mm2/mmHg) compared to type II (5.8 mm2/mmHg), type III (3.9 mm2/mmHg), and variants (5.4 mm2/mmHg; p < 0.001). Achalasia subtypes were found to have similar CSA at all time points, whereas pressure differed with type I having the lowest pressure and type III the highest. CONCLUSION: The DI at each operative step during POEM was found to differ significantly between achalasia subtypes. These differences in DI were due to pressure, as CSA was similar between subtypes. Achalasia subtype should be accounted for when using FLIP as an intraoperative calibration tool and in future studies examining the relationship between DI and clinical outcomes.

Intraoperative assessment of esophageal motility using FLIP during myotomy for achalasia.

BACKGROUND: The functional luminal imaging probe (FLIP) can evaluate esophagogastric junction (EGJ) distensibility and esophageal peristalsis in real time. FLIP measurements performed during diagnostic endoscopy can accurately discriminate between healthy controls and patients with achalasia based on EGJ-distensibility and distinct motility patterns termed repetitive antegrade contractions (RACs) and repetitive retrograde contractions (RRCs). We sought to evaluate real-time motility changes in patients undergoing surgical myotomy for achalasia. METHODS: FLIP measurements using a stepwise volumetric distention protocol were performed at three time points during assessment and performance of laparoscopic Heller myotomy and POEM: (1) During preoperative outpatient endoscopy, (2) Intraoperatively following induction of anesthesia, and (3) Intraoperatively after myotomy completion. EGJ-distensibility, contractility, RACs, and RRCs were measured. RESULTS: FLIP measurements were performed in 32 patients. The EGJ-distensibility index was similar between the preoperative and initial operative measurements (1.1 vs 1.4 mm2/mmHg, p = NS). There was a significant increase in distensibility following surgical myotomy (1.4 to 4.7 mm2/mmHg, p < 0.01). Intraoperative contractile patterns varied between achalasia subtypes. Contractility was seen in < 20% of assessments in patients with types I and II achalasia. Type III patients demonstrated contractility in 100% of assessments, with 70% exhibiting RRCs and 60% RACs. There was a reduction in the frequency of RRC presence (70% to 20%), and contractile vigor (80% to 0% of patients with lumen occluding contractions) in type III patients following surgical myotomy. CONCLUSIONS: This first report of real-time intraoperative measurement of esophageal motility using FLIP demonstrates the feasibility of such assessments during surgical myotomy for achalasia. Patients with type I and II achalasia exhibited rare intraoperative contractility, while the presence of motility was the norm in those with type III. Patients with type III achalasia demonstrated an immediate reduction in repetitive contraction motility patterns and contractile vigor following myotomy.

Esophagogastric Junction Distensibility on Functional Lumen Imaging Probe Topography Predicts Treatment Response in Achalasia-Anatomy Matters!

INTRODUCTION: To compare the utility of the distensibility index (DI) on functional lumen imaging probe (FLIP) topography to other esophagogastric junction (EGJ) metrics in assessing treatment response in achalasia in the context of esophageal anatomy. METHODS: We prospectively evaluated 79 patients (at ages 17-81 years; 47% female patients) with achalasia during follow-up after pneumatic dilation, Heller myotomy, or per-oral endoscopic myotomy with timed barium esophagram, high-resolution impedance manometry, and FLIP. Anatomic deformities were identified based on consensus expert opinion. Patients were classified based on anatomy and EGJ opening to determine the association with radiographic outcome and Eckardt score (ES). RESULTS: Twenty-seven patients (34.1%) had an anatomic deformity-10 pseudodiverticula at myotomy, 7 epiphrenic diverticula, 5 sigmoid, and 5 sinktrap. A 5-minute column area of >5 cm was best associated with an ES of >3, with a sensitivity of 84% (P = 0.0013). Area under the curve for EGJ metrics in association with retention was as follows: DI, 0.90; maximal EGJ diameter, 0.76; integrated relaxation pressure, 0.64; and basal esophagogastric junction pressure, 0.53. Only FLIP metrics were associated with retention given normal anatomy (DI 2.4 vs 5.2 mm/mm Hg and maximal EGJ diameter 13.1 vs 16.6 mm in patients with and without retention, respectively; P values < 0.0001 and 0.002). Using a DI cutoff of <2.8 as abnormal, 40 of 45 patients with retention (P = 0.0001) and 23 of 25 patients with an ES of >3 (P = 0.02) had a low DI and/or anatomic deformity. With normal anatomy, 21 of 22 patients with retention had a low or borderline low DI. DISCUSSION: The FLIP DI is most useful metric for assessing the effect of achalasia treatment on EGJ opening. However, abnormal anatomy is an important mediator of outcome and treatment success will be modulated by anatomic defects that impede bolus emptying.

Treatment of Idiopathic Achalasia with Per-Oral Esophageal Myotomy.

Achalasia is a rare esophageal motility disorder that necessitates the disruption of the lower esophageal sphincter. Patients with achalasia should be evaluated in a systematic, multidisciplinary fashion. Workup should include upper endoscopy, esophagography, and high-resolution manometry. The gold standard for surgical treatment is laparoscopic Heller myotomy with partial fundoplication. Per-oral esophageal myotomy is a novel endoscopic technique that has gained considerable traction over the past decade. The procedure includes the creation of a submucosal tunnel and a selective circular myotomy of the lower esophageal sphincter. Common intra-operative hazards include bleeding within the submucosal tunnel and capnoperitoneum. Significant complications are rare. Patients experience excellent dysphagia relief that is on par with laparoscopic Heller myotomy at moderate-term follow up. Post-operative gastroesophageal reflux disease occurs in greater than one-third of patients, and the vast majority of cases are readily controlled with an anti-secretory medication. Although data is sparse, there is a growing body of literature that supports the long-term durability of per-oral esophageal myotomy.

Successful heart transplantation using a donor heart afflicted by takotsubo cardiomyopathy.

Takotsubo cardiomyopathy, also known as apical ballooning syndrome, stress cardiomyopathy, or broken heart syndrome, is a disease characterized by transient ventricular dysfunction in the absence of obstructive coronary artery disease. Herein, we present a case in which a heart with mild takotsubo cardiomyopathy was utilized as the donor organ for an orthotopic heart transplant.

Distinct cellular and therapeutic effects of obatoclax in rituximab-sensitive and -resistant lymphomas.

Bcl-2 proteins represent a rheostat that controls cellular viability. Obatoclax, a BH3-mimetic, has been designed to specifically target and counteract anti-apoptotic Bcl-2 proteins. We evaluated the biological effects of obatoclax on the anti-tumour activity of rituximab and chemotherapy agents. Obatoclax induced cell death of rituximab/chemotherapy-sensitive (RSCL), -resistant cell lines (RRCL) and primary tumour-cells derived from patients with B-cell lymphomas (N=39). Obatoclax also enhanced the activity of rituximab and had synergistic activity when combined with chemotherapy agents. The ability of Obatoclax to induce PARP cleavage varied between patient samples and was not observed in some RRCL. Inhibition of caspase activity did not affect obatoclax activity, suggesting the existence of caspase-independent death pathways. Autophagy was detected by LC3 conversion and/or electron microscopy in RRCL and in patient-derived tumour cells. Moreover, obatoclax activity was inhibited by Beclin-1 knockdown. In summary, obatoclax is an active Bcl-2 inhibitor that potentiates the activity of chemotherapy agents and, to a lesser degree, rituximab. Defining the molecular events triggered by obatoclax is necessary to further its clinical development and identify potential biomarkers that are predictive of response.

Improvement of RNA secondary structure prediction using RNase H cleavage and randomized oligonucleotides.

RNA secondary structure prediction using free energy minimization is one method to gain an approximation of structure. Constraints generated by enzymatic mapping or chemical modification can improve the accuracy of secondary structure prediction. We report a facile method that identifies single-stranded regions in RNA using short, randomized DNA oligonucleotides and RNase H cleavage. These regions are then used as constraints in secondary structure prediction. This method was used to improve the secondary structure prediction of Escherichia coli 5S rRNA. The lowest free energy structure without constraints has only 27% of the base pairs present in the phylogenetic structure. The addition of constraints from RNase H cleavage improves the prediction to 100% of base pairs. The same method was used to generate secondary structure constraints for yeast tRNA(Phe), which is accurately predicted in the absence of constraints (95%). Although RNase H mapping does not improve secondary structure prediction, it does eliminate all other suboptimal structures predicted within 10% of the lowest free energy structure. The method is advantageous over other single-stranded nucleases since RNase H is functional in physiological conditions. Moreover, it can be used for any RNA to identify accessible binding sites for oligonucleotides or small molecules.