Rat Reflux Model of Esophageal Cancer and Its Implication in Human Disease.

OBJECTIVES: The epidemiologic shift in esophageal cancer from squamous cell carcinoma to esophageal adenocarcinoma coincided with popularization of proton pump inhibitors and has focused attention on gastroesophageal reflux disease as a causative factor in this shift. The aim of this study is to review the literature on the rat reflux model in an effort to elucidate this phenomenon. METHODS: An extensive online literature review (PubMed) was carried out to identify all seminal contributions to the study of esophageal adenocarcinoma using the rat reflux model. RESULTS: The rat reflux model is a validated reproducible model for the development of Barrett's esophagus and esophageal adenocarcinoma. Esophageal reflux of an admixture of gastric acid and duodenal juice induces Barrett's esophagus followed by adenocarcinoma. A high-pH environment created by surgical gastrectomy or proton pump inhibitor therapy in combination with a high-fat diet seems to potentiate the development of Barrett's esophagus and adenocarcinoma. Early surgical intervention to prevent reflux reduces the progression toward esophageal adenocarcinoma. Anti-inflammatory, antioxidant, and nitrate-trapping agents reduce the incidence of tumorigenesis. CONCLUSIONS: As in the rat so also in humans, reflux of an admixture of gastric acid and duodenal juice in a high-pH environment induces the development of Barrett's esophagus followed by esophageal adenocarcinoma. This has led to the hypothesis that to prevent Barrett's esophagus and subsequent esophageal adenocarcinoma in humans, the reflux of an admixture of acid and bile must be controlled before the development of Barrett's esophagus by methods other than acid-suppression therapy.

The University of Chicago contribution to the treatment of gastroesophageal reflux disease and its complications: a tribute to David B. Skinner 1935-2003.

OBJECTIVE: To highlight the contributions from the University of Chicago under the leadership of Dr David B. Skinner to the understanding of gastroesophageal reflux disease (GERD) and its complications. BACKGROUND: The invention of the esophagoscope confirmed that GERD was a premorbid condition. The medical world was divided between those who believed in a morphological lower esophageal sphincter (LES) and those who did not. Those who did not believe attempted to rearrange the anatomy of the foregut organs to stop reflux with minimal success. The discovery of the LES focused attention on the sphincter as the main deterrent to reflux and the hope that measurement of a low LES pressure would mark the presence of GERD. This turned out not to be so. In July 1973, with this history of confusion, Dr Skinner at the age of 36 assumed the chair of surgery at the University of Chicago. METHODS: The publications of the University of Chicago's esophageal group were collected from private and public (PubMed) databases, reviewed, and seminal contributions selected. RESULTS: Twenty-four-hour esophageal pH monitoring led to the understanding of the LES, its contribution to GERD, and the complication of Barrett's esophagus. The relationship of Barrett's to adenocarcinoma was clarified. The rising incidence of esophageal adenocarcinoma led to contributions in the staging of esophageal cancer and its treatment with an en bloc resection. CONCLUSIONS: Ten years after the death of Dr Skinner, we can appreciate the monumental contributions to benign and malignant esophageal disease under his leadership.

High resolution manometry sub-classification of Achalasia: does it really matter? Does Achalasia sub-classification matter?

BACKGROUND: Three variants of Achalasia have been described using high-resolution esophageal manometry (HRM). While manometrically distinct, their clinical significance has yet to be established. Our objective was to compare the outcome after myotomy in patients with these Achalasia subtypes. METHODS: A retrospective chart review was performed to identify patients with Achalasia who had HRM and who underwent Heller myotomy or Per oral endoscopic myotomy (POEM). Symptoms and esophageal clearance by timed barium study were compared before and after treatment. RESULTS: We identified 49 patients, 21 males and 28 females, with a median age of 52 years. The primary symptom in all patients was dysphagia, with a median duration of 4 years (range 4 months-50 years). By HRM, ten patients (20 %) were classified as Type I, 30 (61 %) as Type II, and 9 (18 %) as Type III. At a median follow-up of 16 months after myotomy (range 1-63 months), the median Eckardt score was zero and was similar across subtypes. Relief of dysphagia was also similar across subtypes (80 % of Type I, 93 % of Type II and 89 % of Type III). On pre-treatment timed barium study, no patient had complete emptying at 1 or 5 min. After myotomy, complete emptying occurred within 1 min in 50 % (20/40) and within 5 min in 60 % (24/40) and was similar across groups. CONCLUSION: Myotomy for Achalasia results in excellent symptomatic outcome and improvement in esophageal clearance. There was no difference among the described HRM Achalasia variants. This calls into question the clinical utility of Achalasia sub-classification and affirms the benefit of myotomy for this disease.

Encouraging results of blood conservation in neonatal open-heart surgery.

OBJECTIVE: To report early outcomes of blood conservation in neonatal open-heart surgery. METHODS: Ninety-nine patients undergoing neonatal open-heart surgery during the implementation of a blood conservation program between May 2021 and February 2023 were reviewed. Patients either received traditional blood management (blood prime, n = 43) or received blood conservation strategies (clear prime, n = 56). Baseline characteristics and outcomes were compared between groups. RESULTS: There was no difference in body weight (median, 3.2 kg vs 3.3 kg; P = .83), age at surgery (median, 5 days vs 5 days; P = .37), distribution of The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Categories categories or duration of cardiopulmonary bypass. Patients in the clear prime group had higher preoperative hematocrit (median, 41% vs 38%; P < .01), shorter postoperative mechanical ventilation time (median, 48 hours vs 92 hours; P = .02) and postoperative intensive care unit length of stay (median, 6 days vs 9 days; P < .01) than patients in the blood prime group. Fourteen patients (25%) in the clear prime group, including 1 Norwood patient, were discharged without any transfusion. Among patients within the clear prime group, hospitalizations without blood exposure were associated with higher preoperative hematocrit (median, 43% vs 40%; P = .02), shorter postoperative mechanical ventilation times (median, 22 hours vs 66 hours; P = .01) and shorter postoperative hospital stays (median, 10 days vs 15 days; P = .02). CONCLUSIONS: Bloodless surgery is possible in a significant proportion of neonates undergoing open-heart surgery, including the Norwood operation, even in the early stages of experience. Early clinical results are favorable but long-term follow-up and continued efforts are warranted to prove safety and reproducibility.

Pharyngeal pH monitoring better predicts a successful outcome for extraesophageal reflux symptoms after antireflux surgery.

BACKGROUND: Gastroesophageal reflux disease can be associated with extraesophageal symptoms (hoarseness, cough, asthma, and globus). However, these symptoms may have a multifactorial etiology. Proximal pH monitoring has been proposed as a means of identifying patients where reflux is the cause of the extraesophageal symptoms. The aim of this study was to determine whether proximal esophageal or pharyngeal pH monitoring better identified patients with extraesophageal symptoms that improved after antireflux surgery. METHODS: A retrospective chart review was performed to identify all patients who had esophageal and pharyngeal pH monitoring before an antireflux operation. A composite score was used to define an abnormal result with each test. A successful outcome was defined as improvement or resolution of extraesophageal symptoms. RESULTS: There were 20 patients identified. Antireflux surgery led to a successful outcome in 14 patients (70 %). Restech better identified patients with extraesophageal symptoms who had a successful outcome with antireflux surgery (12 of 14 [86 %] based on abnormal Restech versus 5 of 10 [50 %] based on abnormal proximal probe, p = 0.06). Comparing only the 15 patients who had both proximal esophageal and pharyngeal pH monitoring, Restech again better identified those who had a successful outcome with antireflux surgery (9 of 10 [90 %] based on abnormal Restech versus 5 of 10 [50 %] based on abnormal proximal probe, p = 0.05). The positive and negative predictive values for symptomatic improvement after a fundoplication were better for an abnormal Restech score than for an abnormal proximal esophageal score (80 vs. 71 % and 60 vs. 38 %, respectively). In two patients with a successful outcome, Restech was the only positive test. CONCLUSIONS: In patients with extraesophageal reflux symptoms, proximal esophageal pH monitoring failed to identify half of the patients who had a successful outcome after antireflux surgery. In contrast, an abnormal Restech pH test was present in 90 % of patients with a successful outcome. Further, a negative Restech study more reliably indicated the absence of reflux-induced extraesophageal symptoms. Our results indicate that Restech pharyngeal pH monitoring should be utilized in the evaluation of patients with extraesophageal symptoms that may be associated with reflux disease.

Diaphragmatic relaxing incisions during laparoscopic paraesophageal hernia repair.

BACKGROUND: Laparoscopic paraesophageal hernia (PEH) repair is associated with an objective recurrence rate exceeding 50% at 5 years. Minimizing tension is a critical factor in preventing hernia recurrence. This study aimed to evaluate the outcomes of crural relaxing incisions in patients undergoing PEH repair. METHODS: Records were reviewed to identify patients who received a relaxing incision during laparoscopic PEH repair. The patients were followed by chest X-ray and videoesophagram at 3 months and then annually. RESULTS: From November 2010 to March 2013, 58 patients underwent PEH repair, and 15 patients received a relaxing incision to accomplish crural closure. The median age of the patients was 72 years (range 58-84 years). The relaxing incision was right-sided in 13 patients, left-sided in one patient, and bilateral in one patient. All the procedures were completed laparoscopically and included a fundoplication. Collis gastroplasty for a short esophagus was performed for 40% of the patients. No major complications occurred. During a median follow-up period of 4 months, one patient had an asymptomatic mildly elevated left hemidiaphragm, and one patient had a trivial recurrent hernia, as shown on esophagogastroduodenoscopy (EGD). CONCLUSION: Crural tension likely contributes to the high recurrence rate noted with laparoscopic PEH repair. Relaxing incisions are safe and allow crural approximation. Advanced laparoscopic surgeons should be aware of this option when faced with a large hiatus in a patient with PEH.

Surgical Considerations in Shone Complex.

Shone complex is defined by 4 anomalies: parachute mitral valve, supravalvar mitral ring, subaortic stenosis, and coarctation of the aorta. Establishing a clear definition is one of the principal challenges in the study of Shone complex as not all patients have all lesions. The essential feature of Shone complex is multilevel left-sided obstruction involving both the left ventricular inflow and outflow. This anatomic variability is reflected in the clinical presentation as signs of left ventricular inflow obstruction are often masked by outflow obstruction and the multilevel nature of the condition is thus underappreciated. Surgical treatment is often stepwise addressing the outflow obstruction first. In this review, geared to the pediatric cardiac anesthesiologist, we review the pathophysiology, diagnosis, treatment, and outcomes of Shone complex.

The Yasui operation: A single institutional experience over 30 years.

Objective: The Yasui operation was introduced in 1987 for patients with 2 adequate ventricles, a ventricular septal defect, and aortic atresia or interrupted aortic arch. Despite promising early outcomes, left ventricular outflow tract obstruction (LVOTO) remains a long-term concern. The purpose of this study is to report our institutional experience with the Yasui operation. Methods: We retrospectively reviewed all patients undergoing the Yasui operation between 1989 and 2021. Results are reported as median with interquartile range (IQR). Results: Twenty-five patients underwent a Yasui operation (19 primary), at 11 days (IQR, 7-218 days) of life and weight of 3 kg (IQR, 2.8-4.1 days). Fundamental diagnosis was ventricular septal defect/interrupted aortic arch in 11 patients and ventricular septal defect/aortic atresia in 14. Follow-up was 96% (24 out of 25) at 5 years (IQR, 1.4-14.7) with 92% survival. Freedom from LVOTO reoperation was 91% at late follow-up with 2 patients requiring baffle revision at 6 and 9 years. Latest echocardiogram showed 100% of patients had normal biventricular function and 87% (20 out of 23) less than mild LVOTO at 5 years (IQR, 2.3-14.9). Diagnosis, aortic valve morphology, and material used were not predictors of LVOTO. Freedom from right ventricle-to-pulmonary artery conduit reoperation was 48% at a median of 5 years (IQR, 1.4-14.7). Conduit type was not a predictor of reintervention. Conclusions: The Yasui operation can be performed with low morbidity and mortality in patients with 2 acceptable-size ventricles and aortic atresia or interrupted aortic arch with severe LVOTO. Despite some burden of reoperation, midterm reoperation for LVOTO is not common and ventricular function is preserved.

Transcriptional Profiling of Normal, Stenotic, and Regurgitant Human Aortic Valves.

The genetic mechanisms underlying aortic stenosis (AS) and aortic insufficiency (AI) disease progression remain unclear. We hypothesized that normal aortic valves and those with AS or AI all exhibit unique transcriptional profiles. Normal control (NC) aortic valves were collected from non-matched donor hearts that were otherwise acceptable for transplantation (n = 5). Valves with AS or AI (n = 5, each) were collected from patients undergoing surgical aortic valve replacement. High-throughput sequencing of total RNA revealed 6438 differentially expressed genes (DEGs) for AS vs. NC, 4994 DEGs for AI vs. NC, and 2771 DEGs for AS vs. AI. Among 21 DEGs of interest, APCDD1L, CDH6, COL10A1, HBB, IBSP, KRT14, PLEKHS1, PRSS35, and TDO2 were upregulated in both AS and AI compared to NC, whereas ALDH1L1, EPHB1, GPX3, HIF3A, and KCNT1 were downregulated in both AS and AI (p < 0.05). COL11A1, H19, HIF1A, KCNJ6, PRND, and SPP1 were upregulated only in AS, and NPY was downregulated only in AS (p < 0.05). The functional network for AS clustered around ion regulation, immune regulation, and lipid homeostasis, and that for AI clustered around ERK1/2 regulation. Overall, we report transcriptional profiling data for normal human aortic valves from non-matched donor hearts that were acceptable for transplantation and demonstrated that valves with AS and AI possess unique genetic signatures. These data create a roadmap for the development of novel therapeutics to treat AS and AI.

Spontaneous Bleeding From Multiple Intercostal Arteries in a Patient With Coarctation of the Aorta.

A 59-year-old man with a history of coarctation repair, mechanical aortic valve, and warfarin therapy presented with right flank pain. Computed tomography showed a large hematoma encircling an intact descending thoracic aorta. Computed tomography angiography demonstrated multiple areas of intercostal artery extravasation. An interventional radiologist performed angiography and embolization. The patient's course was complicated by an effusion and hypoxia, but no further bleeding was noted. We hypothesize that coarctation associated aneurysms and potential vessel wall weakness are the causes of hematoma in our case. We present this case with history of repaired coarctation with multiple spontaneous intercostal artery aneurysmal rupture.

Lecompte Procedure for Relief of Severe Airway Compression in Children With Congenital Heart Disease.

PURPOSE: Children with congenital heart disease may present with severe airway compression prior to any surgical procedure or may develop airway compression following their surgical procedure. This combination of congenital heart defect and airway compression poses a significant management challenge. The purpose of this study was to review our experience with the Lecompte procedure for relief of severe airway compression. METHODS: This was a retrospective review of ten patients who underwent a Lecompte procedure for relief of severe airway compression over the past nine years (2010-2018). Three patients with absent pulmonary valve syndrome presented with severe symptoms prior to any surgical procedure. Seven patients presented with symptoms of airway compression following repair of their congenital heart defects (one with absent pulmonary valve syndrome, three patients had repair of pulmonary atresia with ventricular septal defect, and three patients had undergone aortic arch surgery). The median age at presentation was two years (range: one day to seven years). RESULTS: The ten patients underwent a Lecompte procedure without any significant complications or operative mortality. The median interval between the surgical procedure and extubation was 9.5 days. No patients have required any further interventions for relief of airway obstruction. CONCLUSIONS: The Lecompte procedure is a surgical option for young children who present with severe airway compression. The patients in this series responded well to the Lecompte procedure as evidenced by clinical relief of airway compression.

Impact of Phrenic Nerve Palsy and Need for Diaphragm Plication Following Surgery for Pulmonary Atresia With Ventricular Septal Defect and Major Aortopulmonary Collaterals.

Injury to the phrenic nerves may occur during surgery for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA-VSD and MAPCAs). These patients may develop respiratory failure and require diaphragm plication. The purpose of this study was to evaluate the impact of phrenic nerve palsy on recovery following surgery for PA-VSD and MAPCAs. Between 2007 and 2016, approximately 500 patients underwent surgery for PA-VSD and MAPCAs at our institution. Twenty-four patients (4.8%) subsequently had evidence of new phrenic nerve palsy. Sixteen patients were undergoing their first surgical procedure, whereas 8 were undergoing reoperations. All 24 patients underwent diaphragm plication. A cohort of matched controls was identified based on identical diagnosis and procedures but did not sustain a phrenic nerve palsy. Eighteen of the 24 patients (75%) had clinical improvement following diaphragm plication as evidenced by the ability to undergo successful extubation (5 ± 2 days), transition out of the intensive care unit (32 ± 16 days), and discharge from the hospital (42 ± 19 days). In contrast, there were 6 patients (25%) who did not demonstrate a temporal improvement following diaphragm plication, as evidenced by intervals of 61 ± 38, 106 ± 45, and 108 ± 46 days, respectively (P < 0.05 for all 3 comparisons). The 6 patients who failed to improve following diaphragm plication had a significantly greater number of comorbidities compared to the 18 patients who demonstrated improvement (2.2 vs 0.6 per patient, P < 0.05). When compared with the control group, patients who improved following diaphragm plication spent an additional 22 days and patients who failed to improve an additional 90 days in the hospital. The data demonstrate a bifurcation of clinical outcome in patients undergoing diaphragm plication following surgery for PA-VSD and MAPCAs. This bifurcation appears to be linked to the presence or absence of other comorbidities.

Successful Operative Repair of Delayed Left Ventricle Rupture From Blunt Trauma.

A 21-year-old female was found to have an enlarging pericardial effusion 10 days after a 40-foot fall. Initial cardiac evaluation was negative. Ten days after presentation she developed hemodynamic compromise and chest computed tomography was concerning for cardiac rupture. The patient was taken to the operating room where the ruptured posterior ventricle was repaired, perforation in the P1 leaflet was identified and the mitral valve was replaced. The patient survived. To our knowledge, this is the first report of survival after delayed presentation of atrioventricular rupture at the level of the mitral valve.

Emerging Concepts for the Endoscopic Management of Superficial Esophageal Adenocarcinoma.

INTRODUCTION: Endoscopic therapy has revolutionized the treatment of Barrett's esophagus with high-grade dysplasia (HGD) or intramucosal adenocarcinoma by allowing preservation of the esophagus in many patients who would previously have had an esophagectomy. This paradigm shift initially occurred at high-volume centers in North America and Europe but now is becoming mainstream therapy. There is a lack of uniform guidelines and algorithms for the management of these patients. Our aim was to review important concepts and pitfalls in the endoscopic management of superficial esophageal adenocarcinoma. METHODS: A small group colloquium consisting of gastroenterologists, surgeons, and pathologists reviewed published data and discussed personal and institutional experiences with endotherapy for HGD and superficial esophageal adenocarcinoma. RESULTS: The group reviewed data and provided recommendations and management algorithms for seven areas pertaining to endoscopic therapy for Barrett's HGD and superficial adenocarcinoma: (1) patient selection and evaluation; (2) imaging and biopsy techniques; (3) devices; (4) indications for resection versus ablation; (5) ER specimen handling, processing, and pathologic evaluation; (6) patient care and follow-up after endoscopic therapy; and (7) complications of endoscopic therapy and treatment options. CONCLUSIONS: Endoscopic therapy is preferred over esophagectomy for most patients with HGD or intramucosal adenocarcinoma, and may be applicable to select patients with submucosal tumors. Clear guidelines and management algorithms will aid physicians and centers embarking on endoscopic therapy and enable a standardized approach to the management of these patients that is applicable internationally.

Pressurized Cadaver Model in Cardiothoracic Surgical Simulation.

Simulation is increasingly recognized as an integral aspect of thoracic surgery education. A number of simulators have been introduced to teach component cardiothoracic skills; however, no good model exists for numerous essential skills including redo sternotomy and internal mammary artery takedown. These procedures are often relegated to thoracic surgery residents but have significant negative implications if performed incorrectly. Fresh tissue dissection is recognized as the gold standard for surgical simulation, but the lack of circulating blood volume limits surgical realism. Our aim is to describe the technique of the pressurized cadaver for use in cardiothoracic surgical procedures, focusing on internal mammary artery takedown.

Long-Term Outcome of the Treatment of Zenker's Diverticulum.

BACKGROUND: Treatment of Zenker's diverticulum can be accomplished by use of a transcervical myotomy (TCM) with diverticulopexy/diverticulectomy or by the transoral endoscopic stapling (TOS) approach. Our aim was to evaluate the short-term and long-term outcomes of these two techniques. METHODS: A retrospective review was performed to identify all patients who had received either treatment for Zenker's diverticulum from July 1998 to August 2013. Telephone interviews were attempted of all surviving patients to assess long-term outcome. RESULTS: There were 77 patients, with a median age of 71 years (range, 37 to 97 years). All patients had dysphagia, and 33 (43%) had regurgitation. TCM was performed in 68 patients, and TOS was done in nine. The median size of the diverticulum was 2.5 cm in the TCM group and 4 cm in the TOS group (p = 0.13). The operation was primary in 66 patients (86%) and a reoperation in 11 patients. The median hospital stay was 1 day for TOS and 3 for TCM (p = 0.0005). The median time to oral intake for both groups was 1 day. There were three adverse events in the TCM group and none in the TOS group. Early outcome was assessed in all 77 patients at a median of 4 months (interquartile range [IQR], 1 to 13.5 months). Symptomatic improvement occurred in all patients, with 55 patients (71%) reporting complete resolution. Long-term symptoms were assessed at a median of 54 months (IQR, 34 to 77 months) in 38 of 59 (64%) surviving patients. CONCLUSIONS: Cricopharyngeal myotomy with diverticulopexy/diverticulectomy and TOS are both safe and effective treatments for Zenker's diverticulum. All patients reported improvement in symptoms, with complete resolution in the majority of patients.

The surgeon's perspective on oesophageal disease, and what it means to pathologists.

GERD and its potential complications of Barrett's oesophagus and oesophageal adenocarcinoma are now the most important disease processes for oesophageal surgeons. A major impact on this disease will likely come from the development of cost-effective screening and diagnostic modalities which identify patients who are at risk for developing oesophageal cancer. The surgical approach to Barrett's oesophagus and oesophageal adenocarcinoma will continue to evolve in response to advances in ablative therapy and ER. The role of the pathologist, with expertise in the diagnosis of Barrett's oesophagus, will become more prominent as we better define the histological predictors of oesophageal adenocarcinoma. A collaborative effort between pathologists and surgeons is essential in determining the timing and best approach for interventional therapy.

Endoscopic ultrasound staging of stenotic esophageal cancers may be unnecessary to determine the need for neoadjuvant therapy.

INTRODUCTION: Endoscopic ultrasound (EUS) is an essential component of preoperative staging for esophageal cancer and is used to determine which patients should proceed to primary surgical resection or receive neoadjuvant therapy prior to surgery. However, when the EUS scope cannot traverse a tumor, the role of pre-dilatation is controversial due to the risk of perforation. METHODS: A retrospective review was conducted of all patients with esophageal tumor stenosis that could not accommodate the EUS scope who then proceeded with primary esophagectomy. The pathology results were classified based on the revised seventh edition American Joint Committee on Cancer staging system. RESULTS: A total of 27 patients met inclusion criteria. The majority of tumors were T3 (24/27, 89 %). There were no stage I tumors, 15 % (4/27) were stage II, 81 % (22/27) were stage III, and 4 % (1/27) were stage IV due to a resected solitary lung metastasis. CONCLUSION: Tumors that cannot be assessed with an EUS scope due to tumor stenosis will have locally advanced disease in the majority of cases. In these situations, pre-dilatation of the tumor with EUS staging should be omitted when considering the risk of potential esophageal perforation and the patients should be referred for neoadjuvant therapy.

Acute esophageal necrosis: a case series and long-term follow-up.

Acute esophageal necrosis (AEN) is a rare condition characterized by circumferential necrosis of varying lengths in the intrathoracic esophagus. Endoscopically, this process is manifested as a black esophagus. To date, limited case series exist describing AEN, and none report long-term follow-up. Our objective was to report 3 patients with AEN, all diagnosed within 1 year at a tertiary academic medical center, describing early and long-term outcomes of this rare disease. In the absence of perforation, patients can be managed conservatively with serial esophagogastroduodenoscopy (EGD). Long-term strictures may occur that require dilation.