Value of perioperative inhaled epoprostenol with low tidal volume ventilation for complex endocarditis surgery.

BACKGROUND AND AIM: To compare outcomes of patients treated with inhaled epoprostenol and low tidal volume ventilation during cardiopulmonary bypass with those who did not receive this medication in the operating room at all, and those who received it as a rescue therapy at the end of the case. METHODS: Retrospective chart review between 2014 and 2017, follow-up included the entire hospital stay. RESULTS: Seventy-one patients were included, and mean age was 54 years. 78.9% of the patients were male. Procedures included 96% (n = 68) aortic valve replacement, 28% (n = 20) reconstruction of the intravalvular fibrosa, and 13% (n = 9) repair of an endocarditis-related intracardiac fistula. Patients who received epoprostenol (iEpo) (treatment and rescue groups), when compared with the control group had more intra-aortic balloon pump placement (23% vs 2.5%, P = .018), open chest after surgery (32% vs 7.5%, P = .012), and duration of mechanical ventilation (8.3 ± 2.7 vs. 2.4 ± 0.4 days, P = 0.01). There was no significant difference between the two groups in terms of extracorporeal circulatory support (6.5% vs 2.5%, P = .577) and hospital death (13% vs 10%, P = .72). In a subanalysis, hospital death and duration of mechanical ventilation were higher in the recue group when compared with the treatment group (P = .004 and .056, respectively). CONCLUSIONS: Prophylactic application of iEpo with low tidal volume ventilation for an anticipated complex endocarditis operation may contribute to favorable outcome when compared with postoperative epoprostenol rescue.

Novel Repair of Clamshell Thoracotomy Sternal Dehiscence after Lung Transplant: A Case Report.

Bilateral transverse thoracosternotomy, or "clamshell" thoracotomy, can be complicated by dehiscence. A 65-year-old male underwent lung transplantation via clamshell thoracotomy, with subsequent sternal dehiscence on postoperative day 11. Upon repair, the previous sternal wires had pulled through, so a Sternal Talon connected to a Recon Talon was utilized to re-approximate the inferior sternum. On follow-up at 3 months, the patient recovered well. Use of the Sternal Talon provides an effective technique for repairing transverse sternal dehiscence.

Development and validation of a universal esophageal patient-reported outcome measure: The Cleveland Clinic Esophageal Questionnaire (CEQ).

OBJECTIVE: Currently, there is no validated patient-reported outcome measure (PROM) applicable to all esophageal diseases. Our objective was to create a psychometrically robust, validated universal esophageal PROM that can also objectively assess patients' quality of life (QoL). METHODS: The pilot PROM constructed based on expert opinions, literature review, and previous unpublished institutional research had 27 items covering 8 domains. It was completed by 30 patients in the outpatient clinic followed by a structured debriefing interview, which allowed for refining the PROM. The final PROM: Cleveland Clinic Esophageal Questionnaire (CEQ) included 34 items across 6 domains (Dysphagia, Eating, Pain, Reflux & Regurgitation, Dyspepsia, Dumping), each accompanied by a corresponding QoL component. Further psychometric assessment of the PROM was conducted by evaluating (1) acceptability, (2) construct validity, (3) reliability, and (4) responsiveness. RESULTS: Five hundred forty-six unique patients (median 63.7 years [54.3-71.7], 53% male [287], 86% White) completed CEQ at >90% completion within 5 minutes. Construct validity was demonstrated by differentiating scores across esophageal cancer (n = 146), achalasia (n = 170), hiatal hernia (n = 160), and other diagnoses (n = 70). Internal reliability (Cronbach alpha 0.83-0.89), and test-retest reliability (intraclass correlation coefficients 0.63-0.85) were strong. Responsiveness was demonstrated through CEQ domains improving for 53 patients who underwent surgery for achalasia or hiatal hernia (Cohen d 0.86-2.59). CONCLUSIONS: We have constructed a psychometrically robust, universal esophageal PROM that allows concise, consistent, objective quantification of symptoms and their effect on the patient. The CEQ is valuable in prognostication and tracking of longitudinal outcomes in both benign and malignant esophageal diseases.

Clinical T2 N0 M0 Esophageal Cancer: Identifying Predictive Factors of Upstaging.

BACKGROUND: Inaccuracy of clinical staging renders management of clinical T2 N0 M0 (cT2 N0 M0) esophageal cancer difficult. When an underlying advanced-stage disease is understaged to cT2 N0 M0, patients miss the opportunity to gain the potential benefits of neoadjuvant therapy. This study aimed to identify preoperative factors that predict underlying advanced-stage esophageal cancer. METHODS: From 2000 to 2020, 1579 patients with esophageal cancer underwent esophagectomy. Sixty patients who underwent upfront surgery for cT2 N0 M0 esophageal cancer were included in this study. The median age was 62.5 years, and 78% (n = 47) of these patients were male. Radiologic, clinical, and endoscopic factors were evaluated as preoperative markers. The Fisher exact and the Wilcoxon rank sum tests were used for categoric and continuous variables, respectively. Random forest classification was used to identify preoperative factors for predicting upstaging and downstaging. RESULTS: Of the 60 patients, 8 (13%) were found to have pathologic T2 N0 M0 esophageal cancer. Sixteen (27%) patients had cancer that was pathologically downstaged, and 36 (60%) had upstaged disease. Seven (19%) patients had upstaged cancer on the basis of the pathologic T stage, 14 (39%) had upstaging on the basis of the pathologic N stage, and 15 (42%) had upstaging on the basis of both T and N stages. Dysphagia (P = .003) and tumor maximum standardized uptake value (P = .048) were predictors of upstaging, with a combined predictive value of up to 75%. CONCLUSIONS: The presence of dysphagia and of high maximum standardized uptake value (≥5) of the tumor is predictive of more advanced underlying disease for patients with cT2 N0 M0 esophageal cancer, and these patients should be considered for neoadjuvant therapy.

Preoperative predictors of spread through air spaces in lung cancer.

OBJECTIVE: Spread through air spaces (STAS) is a new histologic feature of invasion of non-small cell lung cancer that lacks sensitivity and specificity on frozen sections and is associated with higher recurrence and worse survival with sublobar resections. Our objective is to identify preoperative characteristics that are predictive of STAS to guide operative decisions. METHODS: From January 2018 through December 2021, 439 cT1-3N0 M0 patients with non-small cell lung cancer and a median age of 68 years, 255 (58%) women, who underwent primary surgery at our institution were included. Patients who received neoadjuvant therapy and whose STAS status was not documented were excluded. Age, sex, smoking status, tumor size, ground-glass opacities, maximum standardized uptake values, and molecular markers on preoperative biopsy were evaluated as preoperative markers. Comparisons between groups were conducted using standardized mean differences and random forest classification was used for prediction modeling. RESULTS: Of the 439 patients, 177 had at least 1 STAS-positive tumor, and 262 had no STAS-positive tumors. Overall, 179 STAS tumors and 293 non-STAS tumors were evaluated. Younger age (50 years or younger), solid tumor, size ≥2 cm, and maximum standardized uptake value ≥2.5 were independently predictive of STAS with prediction probabilities of 50%, 40%, 38%, and 40%, respectively. STAS tumors were more likely to harbor KRAS mutations and be PD-L1 negative. CONCLUSIONS: Young age (50 years or younger), larger (≥2 cm) solid tumors, high maximum standardized uptake values, and presence of KRAS mutation, are risk factors for STAS and can be considered for lobectomy. Smoking status and gender are still controversial risk factors for STAS.

Non-iatrogenic esophageal trauma: a narrative review.

Background and Objective: Non-iatrogenic esophageal trauma is a rare entity that has a high morbidity and mortality. The diagnosis can often be quite challenging, however is critical to perform in a timely manner. The workup and management of non-iatrogenic trauma continues to evolve, with new innovative approaches available for both diagnosis and treatment. The aim of this narrative review is to comprehensively describe the incidence, presentation, workup, treatment approaches and outcomes of non-iatrogenic esophageal trauma. Methods: A thorough literature review was performed using full length articles available in English via PubMed between January 1, 1960 to September 30, 2021, focusing on the epidemiology, workup and treatment of non-iatrogenic esophageal trauma, including current surgical techniques. Key Content and Findings: Injuries to the cervical esophagus are more common than injuries to the thoracic esophagus, occurring more in young males, with significant racial disparity. Penetrating trauma via gunshot wounds are the most common forms of injury, followed by stab wounds and blunt trauma. Workup is multimodal and involves a combination of plain radiographs, computed tomography (CT) scans, endoscopy and fluoroscopy depending of the stability of the patient and associated injuries. Conclusions: Workup and management of non-iatrogenic esophageal trauma depends on the location and extent of esophageal injury, and can include observation, debridement and drainage, esophageal diversion, endoscopic approaches or esophagectomy, with indications, techniques and outcomes described in further detail in this review.

Thoracoabdominal approach for traumatic diaphragmatic hernia in a hemodynamically unstable patient.

Background: Diaphragmatic hernias with strangulated contents are a surgical challenge. Thoracoabdominal incisions are commonly used for a variety of thoracic and vascular cases, although rarely used for diaphragmatic hernias, which are typically repaired with laparotomy, thoracotomy, or minimally invasive approaches. Case report: We present the unique case of a 60-year-old, critically ill unstable patient with severe heart failure with a reduced ejection fraction (15-25%) and severe valve disease presenting with a left-sided diaphragmatic hernia containing strangulated small intestine and requiring urgent surgical exploration. This was safely and efficiently repaired via a thoracoabdominal approach at the index surgery, with intestines left in discontinuity and placement of temporary chest and abdominal closure. At the second planned operation, good continuity was successfully restored. Results: The patient had early extubation, gradual diet advancement with full recovery, and discharge home on postoperative day 17. Conclusion: A thoracoabdominal incision can safely be used in large strangulated diaphragmatic hernias, including in critically unstable patients. This approach provides rapid access to both the chest and abdomen with excellent, speedy, and safe exposure, which can save a life in extreme conditions.

Modified Ravitch Procedure for Pectus Excavatum Combined With Complex Cardiac Surgery.

Pectus excavatum is common in patients with connective tissue disorders or congenital heart disease undergoing cardiac surgery, and is occasionally severe enough to warrant repair. The optimal surgical strategy is currently debated. We report our experience with simultaneous repair. From January 2012 to January 2020, 11 patients (median age of 35 ± 18 years, range 12-74) underwent a modified Ravitch procedure for severe pectus excavatum performed by a single thoracic surgeon at the time of simultaneous complex cardiac surgery. Eight patients (73%) had a confirmed connective tissue disorder and 2 patients (18%) had recurrent pectus excavatum following a failed Nuss procedure in adolescence. The mean Haller index was 7.3 ± 3.2 (range 3.8-13). The most common concomitant cardiac procedures were valve-preserving aortic root replacement (n=7, 64%) and mitral valve repair (n = 4, 36%). Patients are presented as a case series with descriptive analysis. The median total operative and cardiopulmonary bypass times were 400 minutes (±109 minutes) and 168 minutes (± 43 minutes), respectively. No deaths occurred in-hospital or during follow-up. There were no reoperations for bleeding, tamponade or other indications. No deep or superficial sternal wound infections occurred. Postoperative analgesia regimens were multimodal to facilitate early mobilization and pulmonary hygiene. None of the patients required prolonged ventilation or reintubation for respiratory failure. The mean stay in the intensive care unit was 82 hours (±56 hours) and the mean hospital stay was 9.1 days (2.4 days). Concurrent pectus excavatum repair at the time of cardiac surgery using a modified Ravitch technique can be safely performed by a multi-disciplinary team and should be considered for patients with multiple indications for operation.

Recent advancements in the minimally invasive management of esophageal perforation, leaks, and fistulae.

INTRODUCTION: Historically, the gold standard management of esophageal perforations, leaks, and fistulae has been traditional open surgery, but it is associated with significant morbidity and mortality. Minimally invasive approaches offer alternatives to surgery in treating hemodynamically stable patients with such defects. In this review article, we will discuss the recent advancements in the minimally invasive management of esophageal perforations, leaks, and fistulas. AREAS COVERED: This review includes information from case reports, case series, and clinical trials on minimally invasive management of esophageal perforations, leaks, and fistulas. The focus is on the devices, outcomes, and application of the technology. EXPERT COMMENTARY: Minimally invasive treatment represents significant progress in the management of esophageal perforations, leaks, and fistulas. Based on current evidence, it seems safe and effective but it is evolving and more studies are needed to help draw definitive conclusions.

Reintervention After Heller Myotomy for Achalasia: Is It Inevitable?

BACKGROUND: Few studies of reintervention after Heller myotomy for achalasia set patients' expectations, assist therapeutic decision making, and direct follow-up. Therefore, we investigated the frequency and type of symptoms and reinterventions after myotomy based on achalasia type. METHODS: From January 2006 to March 2013, 248 patients who had preoperative high-resolution manometry and a timed barium esophagram (TBE) underwent Heller myotomy, 62 (25%) for type I, 162 (65%) for type II, and 24 (10%) for type III achalasia. Postoperative surveillance, including TBE, was performed at 8 weeks, then annually. Median follow-up was 36 months. End points were all symptom types and modes of reintervention, endoscopic or surgical. Reintervention was based on both symptoms and objective TBE measurements. RESULTS: Eventually most patients (169 of 218; 69%) experienced at least one symptom after myotomy. Fifty patients underwent 85 reinterventions, 41 endoscopic only, 4 surgical only, and 5 both. Five-year freedom from reintervention was 62% for type I, 74% for type II, and 87% for type III, most occurring within 6 months, although later in type III. At 5 years, number of reinterventions per 100 patients was 72 for type I, 51 for type II, and 13 for type III. After each reintervention, there was approximately a 50% chance of another within 2 years. CONCLUSIONS: Patients' expectations when undergoing Heller myotomy for achalasia must be that symptoms will only be palliated, and patients who have worse esophageal function-achalasia type I-may require one or more postoperative reinterventions. Thus, we recommend that patients with achalasia have lifelong annual surveillance after Heller myotomy that includes TBE.

Devices for ex vivo heart and lung perfusion.

INTRODUCTION: The number of organs available for heart and lung transplantation is far short of the number that is needed to meet demand. Perfusion and ventilation of donor organs after procurement has led to exciting advances in the field of cardiothoracic transplantation. The clinical implications of this technology allows for techniques to evaluate the quality of an organ, active rehabilitation of organs after procurement and prior to implantation, and increased time between organ procurement and implantation. This ex-vivo perfusion technique has also been referred to in the lay press as the 'heart in a box' or 'lung in a box.' AREAS COVERED: This review includes information from case reports, case series, and clinical trials on ex vivo heart and lung perfusion. The focus is on the devices, ventilation and perfusion techniques, outcomes, and application of the technology. EXPERT COMMENTARY: Ex vivo perfusion of donor hearts and lungs prior to transplantation has proven to be a viable alternative to standard cold-preservation strategies. Its use has allowed for ongoing expansion of the donor pool. The biggest barriers to expansion of this technology are access, cost, and lack of evidence which clearly supports superior outcomes.

Mechanical circulatory support in pediatrics.

End-stage heart failure affects thousands of children yearly and mechanical circulatory support is used at many points in their care. Extracorporeal membrane oxygenation supports both the failing heart and lungs, which has led to its use as an adjunct to cardiopulmonary resuscitation as well as in post-operative cardiogenic shock. Continuous-flow ventricular assist devices (VAD) have replaced pulsatile-flow devices in adults and early studies have shown promising results in children. The Berlin paracorporeal pulsatile VAD recently gained U.S. Food and Drug Administration approval and remains the only VAD approved in pediatrics. Failing univentricular hearts and other congenitally corrected lesions are new areas for mechanical support. Finding novel uses, improving durability, and minimizing complications are areas of growth in pediatric mechanical circulatory support.

Myocardial inflammation in experimental acute right ventricular failure: Effects of prostacyclin therapy.

BACKGROUND: Acute transient pulmonary hypertension may induce a state of persistent right ventricular (RV) failure. We hypothesized that this could be related to an activation of inflammatory processes and reduced by prostacyclin therapy. METHODS: Sixteen dogs were assigned to a 90-minute pulmonary artery banding (n = 8), or to a sham operation (n = 8). Hemodynamic variables were measured 30 minutes after banding release. This was repeated in 7 dogs with pulmonary artery banding-induced RV failure, followed by a 60-minute epoprostenol infusion. After euthanasia of the animals, myocardial tissue was sampled. RESULTS: Persistent RV failure was associated with increased myocardial expression of interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein 1, pro-inflammatory IL-6/IL-10, and neutrophil and macrophage infiltration, whereas heme oxygenase 1 expression was decreased. These changes were observed in RV and to a lesser extent in the left ventricle (LV). In the RV only, expressions of prostacyclin synthase and anti-inflammatory IL-10 and IL-33 decreased and vascular cell adhesion molecule expression increased, whereas macrophage inflammatory protein-1α and intercellular adhesion molecule 1 expressions remained unchanged. After epoprostenol infusion, there was decreased expression of IL-1ß, macrophage inflammatory protein-1α, and vascular cell adhesion molecule 1 and increased IL-10 expression in the RV and the LV, whereas monocyte chemoattractant protein-1 decreased in the RV only. Epoprostenol infusion resulted in decreased RV IL-6/IL-10 and pro-apoptotic Bax/Bcl-2, together with decreased RV neutrophil and RV and LV macrophage infiltration. The RV ratio of end systolic-to-pulmonary arterial elastances was inversely correlated to RV IL-6/IL-10, macrophage, and neutrophil infiltration, and to RV heme oxygenase-1 and IL-33 expression. CONCLUSIONS: Acute afterload-induced persistent RV failure is associated with an activation of inflammatory processes, which are limited by epoprostenol.

Wild-type p53 protects normal cells against apoptosis induced by thiostrepton.

Cancer cells are generally more sensitive to anticancer drugs than normal cells. This provides the rationale for using anticancer drugs specifically against tumor cells, but the explanation for the specificity is often elusive. In this study, we compared the sensitivity of normal BJ human fibroblasts, BJ fibroblasts with p53 knockdown and corresponding BJ immortal/oncogenic cell lines with inactivated p53 to anticancer drug-induced apoptosis. We found that only normal cells that have wild-type p53 were resistant to the thiazole antibiotic, thiostrepton, suggesting that p53 plays an antiapoptotic role in normal cells. In this case p53 status, but not the transformation of cells per se determines their sensitivity to thiostrepton and possibly to other anticancer drugs. Since p53 is mutated in 50% of human cancers, thiostrepton may selectively kill cancer, but not normal cells. These data imply that wild-type p53 can protect normal cells from anticancer drug-induced cell death and its mutations may sensitize cancer cells to anti-neoplastic agents.