Harry Henteleff

Results of Collis gastroplasty and selective fundoplication, using a left thoracoabdominal approach, for failed antireflux surgery.

OBJECTIVE To study patterns of failure following primary antireflux surgery and to evaluate efficacy of reoperation using a left thoracoabdominal Collis gastroplasty and selective fundoplication. METHODS Thirty-one patients who underwent reoperative antireflux surgery between 1991 and 2000 were studied. Transabdominal fundoplication had been performed in 21 patients, and ten patients had a partial fundoplication by left thoracotomy, 1-33 years (mean, 15 years) previously. All patients presented with clinically disabling symptoms. Objective studies documented for all patients, a disrupted fundoplication, a short esophagus, and an associated hiatus hernia (Type I: 21 patients, 68%; Type III: ten patients, 32%), esophagitis (nine patients, 29%), and Barretts mucosa (five patients, 16%). Abnormal esophageal motility was found in nine of 26 (36%) patients studied. All patients were reoperated using a left thoracoabdominal approach, with epidural analgesia. A Collis gastroplasty was used to lengthen the esophagus, incorporating a complete (24 patients, 77%) or partial (seven patients, 23%) fundoplication based of preoperative esophageal function studies. RESULTS There was no perioperative mortality. Median length of hospitalization was 8 days, and was uncomplicated for 18 (58%) patients. Postoperative morbidity was considered minimal, and comprised left lower lobe infiltrates (six patients, 19%), atrial fibrillation (three patients, 10%), urinary tract infection (one patient, 3%), superficial wound infection (one patient, 3%), aspiration (one patient, 3%), and nausea (one patient, 3%). Median follow-up was 42 months (6-105 months), and was complete for 29 patients. Six patients (21%) had moderate-severe post-thoracotomy pain, for up to 18 months postoperatively, and five patients (17%) required esophageal dilation, ranging from two to six dilations within the first 6 months after surgery. Overall, 93% (27/29) of patients were satisfied with the results of surgery, in terms of quality of swallowing and control of preoperative symptoms. CONCLUSIONS In this series, failure of primary antireflux surgery was related to short esophagus. Intermediate-term subjective results of reoperative antireflux surgery were good for selected patients who undergo esophageal lengthening and fundoplication. The left thoracoabdominal approach was safe, generally well tolerated, and provided excellent exposure of the esophagogastric junction for complex reoperative antireflux surgery.

Evidence-based review of the surgical management of hyperhidrosis

The great majority of the currently available evidence supporting sympathectomy for primary hyperhidrosis is observational, coming from a variety of prospective and restrospective clinical series as well as comparative studies. A cumulative experience in over 6000 patients suggests that ETS is a safe, reproducible, and effective procedure, and most patients are satisfied with the results of the surgery. The currently available experimental data comes from clinical trials that compared alternative levels of sympathetic chain disruption; these trials speak only to the relative merits of one surgical technique over another and do not provide an assessment of the overall impact of surgery in the general population of patients with primary hyperhidrosis. Furthermore, it is difficult to compare series and generalizability is compromised by a lack of uniform definitions and measures at both the exposure and outcome levels. There is marked heterogeneity with respect to study population and entry criteria, with significant variability of site and severity of excess sweating as well as the degree of preoperative conservative management of hyperhidrosis before surgical referral. Also the operative approach varies widely among studies, and the optimal procedure remains elusive: unilateral versus staged nonsimultaneous bilateral versus concomitant bilateral sympathectomy; ganglionic resection versus ablation using electrocoagulation or harmonic scalpel; clipping of the chain to maintain reversibility in the event of intolerable symptoms versus permanent disruption. In addition, the lack of uniform outcome measures makes these data difficult to interpret, and standardized metrics of surgical results are necessary, such as objective quantification of sweating by gravimetry or use of the SF-36 Health Survey Questionnaire as an estimate of patient quality of life. A multicenter, adequately powered, randomized controlled trial comparing surgical to medical management of hyperhidrosis is unlikely given the current enthusiasm for same-day thoracoscopic sympathectomy among surgeons, a largely positive literature replete with encouraging results, and well-informed hyperhidrosis patients who want to be cured of a socially debilitating illness. Future clinical trials in this area will likely compare surgical techniques. For such comparisons, procedures must be standardized and outcome measures validated for both symptoms of the disease and surgical complications. Finally, the studies must have large numbers of patients and adequate long-term follow-up if they are to detect differences in results among procedures with very high technical success rates.

Congenital diaphragmatic hernia: experience without extracoporeal membrane oxygenation

Abstract While extracorporeal membrane oxygenation (ECMO) is used in the management of congenital diaphragmatic hernia (CDH), its value is questioned. The charts of all newborn infants who presented in respiratory distress due to CDH over the past 27 years were reviewed. Inborn versus outborn, year of repair, use of ultrasound (US), and the predictive value of various parameters was evaluated. Fishers exact test and logistic regression tests were used to analyze data. There were 81 patients, 43 males and 38 females. Repair occurred after stabilization without ECMO; 65 patients survived (80%). Apgar scores at 1 min (P=0.03) and 5 min (P=0.005), best postductal PaO2 (BPDPaO2) (P=0.02), and type of repair (P=0.01) were predictive of outcome. There was no difference in survival between inborn and outborn patients or over the years of review (P=0.29). Forty-six patients had documented prenatal US scans, with no obvious impact on outcome. Thus, survival of CDH patients without ECMO is comparable to the best results reported with ECMO, suggesting that the costs and associated morbidity of ECMO may not justify its use for such patients. Apgar scores, BPDPaO2, and type of repair are good predictors of outcome.

Nodal vessels disease as a risk factor for atrial fibrillation after coronary artery bypass graft surgery.

OBJECTIVE Atrial fibrillation (AF) is common after coronary artery bypass graft (CABG) surgery. Atrial ischaemia due to diseased atrioventricular (AV) and sinoatrial (SA) arteries has been proposed as a cause of AF post-CABG. We examined if the presence of diseased nodal arteries was a significant predictor of the development of AF post-CABG. METHODS 100 consecutive cases (AF post-CABG) were compared to 100 consecutive controls (No AF post-CABG) with respect to pre-operative angiographic evidence of diseased nodal arteries. Cases and controls identified from the Society of Thoracic Surgeons database underwent detailed chart reviews to obtain data on potential risk factors. Patients were excluded if they were undergoing anything but a routine CABG procedure, were older than 65 years, or had previous AF. All angiograms were reviewed by a single radiologist blinded to outcome. The effect of grafting diseased nodal arteries on the development of AF post-CABG was also measured. A multiple logistic regression model was utilized to measure the effect of disease in each artery on the development of AF post-CABG. RESULTS Cases and controls were comparable regarding potential risk factors, with the exception that the AF group was older than the non-AF group. Significant AV artery disease was detected in 78 cases compared to 74 controls (adjusted odds ratio (OR) OR=1.04, CI, 0.51-2.12, P=0.82). Significant SA artery disease was detected in 34 cases compared to 21 controls (adjusted OR=2.093, CI: 1.06-4.09, P=0.03). Six of ten patients having revascularization of their SA nodal artery developed AF versus 28 of 45 of those who did not (OR=0.91, CI: 0.18-5.06, P=0.58). Forty-eight of 87 patients having revasacularization of their AV nodal artery developed AF versus 30 of 65 of those who did not (OR=1.44, CI: 0.72-2.88, P=0.27). CONCLUSION The presence of a diseased SA artery is significantly associated with AF post-CABG. Such association may be used to identify a subset of patients who might be targeted with prophylaxis.

Endoscopic mucosal resection versus esophagectomy for intramucosal adenocarcinoma in the setting of barrett’s esophagus

BackgroundEsophagectomy has been the standard of care for patients with intramucosal adenocarcinoma (IMC) in the setting of Barrett’s esophagus. It is, however, associated with significant post-operative morbidity and mortality. Endoscopic mucosal resection (EMR) offers a minimally invasive approach with lesser morbidity. This study investigates the transition from esophagectomy to EMR for IMC with respect to eradication rates, post-operative morbidity, and long-term survival.MethodsPatients diagnosed with IMC from 2005 to 2013 were identified retrospectively. Beginning in 2009, preferred initial therapy for IMC transitioned from esophagectomy to EMR. Esophagectomy was performed either through a transthoracic or transhiatal technique. EMR was repeated until resolution of IMC on pathology or progression of disease. Continuous data are expressed as mean (SD) and analyzed using Student’s t test. Categorical data are presented as number (%) and analyzed using Fisher’s exact test.ResultsWe identified 23 patients; 12 patients underwent esophagectomy and 11 patients underwent EMR as initial therapy. Patients were similar with respects to age, gender, and comorbidity index. Most tumors arose from short segment (vs long segment) Barrett’s (esophagectomy: 9 (75%) vs. EMR: 10 (91%), p = 0.59) and one patient in each group had superficial invasion into the submucosa (T1sm1), the remainder having mucosal disease. Esophagectomy was associated with 7 (58%) minor complications and 2 (17%) major complications (respiratory failure, anastomotic leak), whereas there were no complications related to EMR (p < 0.01). EMR successfully eradicated IMC in 10 patients (91%) with one progressing to esophagectomy. Patients required 2 (1) endoscopies to achieve eradication. There was one mortality in each group on long-term follow-up (log-rank test, p = 0.62).ConclusionsEMR was successful in eradicating IMC in 10/11 patients with similar long-term recurrence and mortality to esophagectomy patients. Patients with IMC may benefit from EMR as initial therapy by obviating the need for a complex and morbid operation.

Abstract B21: Investigating targeted driver mutations and PD-L1 expression for improved therapy of non-small cell lung cancer

Most lung cancer patients are diagnosed at an advanced stage, limiting their treatment options to chemotherapies that have very low response rate. New therapies that target driver gene mutations (e.g., EGFR, ALK, ROS1, BRAF) are being used to treat patients who have tumors with these mutations. In addition, a type of immunotherapy called immune checkpoint inhibitor is being used to treat lung cancer patients. For instance, patients with tumors that express PD-L1 are responsive to anti-PD-1/PD-L1 therapy. Thus, being able to identify the presence of driver mutations and PD-L1 will help patients to benefit from different therapies. A total of 844 cases of non-small cell lung cancer samples have been profiled for the presence of EGFR, KRAS, BRAF, PIK3CA, and HER2 mutations by SNaPshot/sizing genotyping. Immunohistochemistry (IHC) was used to identify the protein expression of ALK and PD-L1. Histologic examination was performed to determine the pathologic type, grade, and lymphatic/vascular invasion. Statistical analysis revealed a number of correlations between the presence of the mutations, PD-L1 expression and the patient pathologic data. Specifically, it was determined that women had lung tumors with a significantly greater number of EGFR mutations than men (p value = 0.001). Examining the presence of ALK, EGFR, KRAS, BRAF, PIK3CA, and HER2 mutations against the presence of pleural invasions yielded a p-value of 0.071, which implies evidence that different mutations are not associated with pleural invasion. However, EGFR mutations were associated with the absence of vascular and lymphatic invasions in lung cancer patients (p value = 0.001, 0.002 respectively). In addition, while the expression of PD-L1 does not associate with the patients who express KRAS mutation, it is associated with lung cancer patients who express EGFR mutation (p value = 0.002). Knowing the mutational and PD-L1 status in lung cancer patients will help patients benefit from targeted therapies and/or checkpoint inhibitors. Citation Format: Akram Alwithenani, Marika Forsythe, Mathieu Castonguay, Wenda Greer, Gorden Flowerdew, Drew Bethune, Harry Henteleff, Madelaine Plourde, Aneil Mujoomdar, Daniel French, Micheal Johnston, Paola Marcato, Zhaolin Xu. Investigating targeted driver mutations and PD-L1 expression for improved therapy of non-small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B21.

Endoscopic mucosal resection for high-grade dysplasia and intramucosal carcinoma: a Canadian experience

Background Endoscopic mucosal resection (EMR) is increasingly being used as a first-line treatment for Barrett esophagus (BE) with high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC). We reviewed our experience with endoscopic treatment of BE with HGD and IMC at our institution with respect to eradication rates, complications and long-term recurrence. Methods We performed a single-centre retrospective review of all patients referred between October 2010 and August 2014 for EMR with dysplastic BE or IMC. We performed EMR using a cap-fitted endoscope, and the procedure was repeated every 3 months until eradication or progression of disease. Results A total of 28 patients were identified: 16 with dysplastic BE (14 HGD, 1 low-grade dysplasia, 1 intermediate dysplasia) and 12 with IMC. Complete eradication of HGD was achieved in 11 of 14 (79%) patients. Three of 12 (25%) patients initially referred with suspected IMC were found to have invasive adenocarcinoma on EMR. Eradication was successful in 8 of 9 (89%) patients with true IMC, with 1 patient progressing to salvage esophagectomy. Complications occurred in 2 of 28 (7%) patients; both had esophageal strictures managed with dilatation. Median duration of follow-up was 371 days. Conclusion Our experience supports the safety of EMR as a first-line treatment for patients with BE with dysplasia and IMC in early short-term follow-up.

CAGS and ACS evidence based reviews in surgery. Guidelines for the management of Barrett esophagus with high-grade dysplasia?

Objective: To address the role of esophageal resection and other approaches that are becoming increasingly adopted for the management of Barrett esophagus with high-grade dysplasia (HGD). Data sources: MEDLINE, Cochrane Library and the Trip databases were searched for the terms “Barrett’s or high-grade dysplasia” and “surgery,” “photo-dynamic therapy,” (PDT) “radiofrequency ablation” (RFA) or a combination of these. Study selection: Studies were selected based on the best evidence supporting these commonly used strategies for HGD. Data extraction: The guideline was divided into 4 major components: endoscopic surveillance, mucosal ablation, endoscopic mucosal resection (EMR) and esophagectomy. Main results: Regarding endoscopic surveillance, HGD is an entity distinct and distinguishable from intramucosal carcinoma, and it does not invariably progress to carcinoma. If there is progression, it can be reliably detected at an early, curable stage. Patients undergoing surveillance are reliable for follow-up and are candidates for further therapy if progression is diagnosed. Regarding mucosal ablation, several methods have been reported for HGD; of these, PDT is the most widely used. Radiofrequency ablation has been introduced into practice and is being studied in many of the same centres that have advocated for PDT (RFA is useful for high-risk surgical patients and typically requires multiple endoscopic sessions for therapy and follow-up.) The EMR method has been used to excise discrete esophageal mucosal nodules that were small, flat or poly-poid in nature and that did not invade deeper than the sub-mucosa. Owing to the frequent multifocality of Barrett esophagus, a concomitant mucosal ablative procedure is often required to assure complete eradication of disease (EMR can evaluate and treat discrete mucosal nodules in the esophagus). Most cancers found incidentally in patients with HGD are cured by esophagectomy. It can be performed safely with an operative mortality approaching 1% (it remains the standard of care for patients deemed to have good operative risk). Conclusion: Given the complexities in decision-making in the management of HGD, the nuances in diagnosis and therapy, and the risks associated with either over- or undertreatment, Barrett esophagus with HGD is best managed in a centre of excellence, preferably with input from experienced surgeons, gastroenterologists and pathologists with a focused interest in treating this disorder.