Carolyn E. Jones

Are endoscopic therapies appropriate for superficial submucosal esophageal adenocarcinoma? An analysis of esophagectomy specimens.

BACKGROUND Endoscopic resection and ablation have advanced the treatment of intramucosal esophageal adenocarcinoma and have been promoted as definitive therapy for selected superficial submucosal tumors. Controversy exists regarding the prevalence of nodal metastases at various depths of mucosal and submucosal invasion. Our aim was to clarify this prevalence and identify predictors of nodal spread. STUDY DESIGN An expert gastrointestinal pathologist retrospectively reviewed 54 T1 adenocarcinomas from 258 esophagectomy specimens (2000 to 2008). Tumors were classified as intramucosal or submucosal, the latter being subclassified as SM1 (upper third), SM2 (middle third), or SM3 (lower third) based on the depth of tumor invasion. The depth of invasion was correlated with the prevalence of positive nodes. Fishers exact test and univariate and multivariate logistic regression were used to identify variables predicting nodal disease. RESULTS Nodal metastases were present in 0% (0 of 25) of intramucosal, 21% (3 of 14) of SM1, 36% (4 of 11) of SM2, and 50% (2 of 4) of SM3 tumors. The differences were significant between intramucosal and submucosal tumors (p < 0.0001), although not between the various subclassifications of submucosal tumors (p = 0.503). Univariate logistic regression identified poor differentiation (p = 0.024), lymphovascular invasion (p = 0.049), and number of harvested lymph nodes (p = 0.037) as significantly correlated with nodal disease. Multivariate logistic regression did not identify any of the tested variables as independent predictors of the prevalence of positive lymph nodes. CONCLUSIONS All depths of submucosal invasion of esophageal adenocarcinoma were associated with an unacceptably high prevalence of nodal metastases and a marked increase relative to intramucosal cancer. Accurate predictors of nodal spread, independent of tumor depth, are currently lacking and will be necessary before recommending endoscopic resection with or without concomitant ablation as curative treatment for even superficial submucosal neoplasia.

Perioperative Risk of Laparoscopic Fundoplication: Safer than Previously Reported—Analysis of the American College of Surgeons National Surgical Quality Improvement Program 2005 to 2009

BACKGROUND Several prospective randomized controlled trials show equal effectiveness of surgical fundoplication and proton pump inhibitor therapy for the treatment of gastroesophageal reflux disease. Despite this compelling evidence of its efficacy, surgical antireflux therapy is underused, occurring in a very small proportion of patients with gastroesophageal reflux disease. An important reason for this is the perceived morbidity and mortality associated with surgical intervention. Published data report perioperative morbidity between 3% and 21% and mortality of 0.2% and 0.5%, and current data are uncommon, largely from previous decades, and almost exclusively single institutional. STUDY DESIGN The study population included all patients in the American College of Surgeons National Surgical Quality Improvement Program database from 2005 through 2009 who underwent laparoscopic fundoplication with or without related postoperative ICD-9 codes. Comorbidities, intraoperative occurrences, and 30-day postoperative outcomes were collected and logged into statistical software for appropriate analysis. Postoperative occurrences were divided into overall and serious morbidity. RESULTS A total of 7,531 fundoplications were identified. Thirty-five percent of patients were younger than 50 years old, 47.1% were 50 to 69 years old, and 16.8% were older than 69 years old. Overall, 30-day mortality was 0.19% and morbidity was 3.8%. Thirty-day mortality was rare in patients younger than age 70 years, occurring in 5 of 10,000 (0.05%). Mortality increased to 8 of 1,000 (0.8%) in patients older than 70 years (p < 0.0001). Complications occurred in 2.2% of patients younger than 50 years, 3.8% of those 50 to 69 years, and 7.3% of patients older than 69 years. Serious complications occurred in 8 of 1,000 (0.8%) patients younger than 50 years, 1.8% in patients 50 to 69 years, and 3.9% of those older than 69 years. CONCLUSIONS Analysis of this large cohort demonstrates remarkably low 30-day morbidity and mortality of laparoscopic fundoplication. This is particularly true in patients younger than 70 years, who are likely undergoing fundoplication for gastroesophageal reflux disease. These data suggest that surgical therapy carries an acceptable risk profile.

Pathogenesis of Barrett’s esophagus: Bile acids inhibit the Notch signaling pathway with induction of CDX2 gene expression in human esophageal cells

BACKGROUND Barretts esophagus (BE) is the predominant risk factor for the development of esophageal adenocarcinoma. BE is characterized by intestinal metaplasia with goblet cells. Reflux of bile acids is known to induce intestinal metaplasia, but the mechanisms are unclear. Inhibition of Notch signaling accompanied by increased Hath1 and induction of caudal homeobox 2 (CDX2) may be involved in development of intestinal goblet cells. METHODS Esophageal adenocarcinoma cell lines OE19 and OE33 were exposed for up to 8 hours to DCA (100-300 microM), and for up to 24 hours with and without the gamma-secretase inhibitor, DAPT (20 microM). Notch signaling components and CDX2 levels were measured by real-time PCR (for mRNA) and by Western blot analysis (for proteins). RESULTS DCA induced a time and concentration dependent decrease in Notch pathway components mRNAs in OE33 and in the proteins in both cell lines. CDX2 mRNA and Hath1 protein were increased in OE19 by 3-fold. Inhibition of Notch pathway by DAPT decreased downstream Notch signaling mRNAs and proteins in both cell lines and increased Hath1 and CDX2 proteins only in OE19. CONCLUSION Bile acid inhibition of Notch signaling in esophageal cells is correlated with an increase in Hath1 and CDX2 and may be one of the key processes contributing to the formation of BE.

Six-year integrated cardiothoracic surgery residency applicants: Characteristics, expectations, and concerns

OBJECTIVE During the past 5 years, 6-year integrated cardiothoracic surgery residency programs have increased in number and popularity. METHODS To understand the background and motivation of the applicants for 6-year integrated programs, we surveyed 80 candidates interviewing for Accreditation Council for Graduate Medical Education-accredited 6-year integrated cardiothoracic surgery residency programs for the 2012 match season, with 36 respondents completing the survey. RESULTS The applicants interviewed for 6-year integrated programs had peer-reviewed publications (91.7%) and were interested in academic careers (91.4%), dedicated research time (58.3%), and cardiac surgery (66.7%). The time saved in training was considered an advantage of the 6-year integrated cardiothoracic surgery residency programs, although concern was present about the development of the mature, well-rounded cardiothoracic surgeon. CONCLUSIONS We found that most of the candidates for 6-year integrated cardiothoracic surgery residency were young, high-achieving individuals oriented toward academic careers with a significant interest in dedicated research time and cardiac surgery.

Eliminating a Need for Esophagectomy: Endoscopic Treatment of Barrett Esophagus With Early Esophageal Neoplasia

Over the past several years, endoscopic ablation and resection have become a new standard of care in the management of Barrett esophagus (BE) with high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC). Risk factors for failure of endoscopic therapy and the need for subsequent esophagectomy have not been well elucidated. The aims of this study were to determine the efficacy of radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) in the management of BE with HGD or IMC, to discern factors predictive of endoscopic treatment failure, and to assess the effect of endoscopic therapies on esophagectomy volume at our institution. Data were obtained retrospectively for all patients who underwent endoscopic therapies or esophagectomy for a diagnosis of BE with HGD or IMC in our department between January 1, 2004, and December 31, 2012. Complete remission (CR) of BE or HGD or IMC was defined as 2 consecutive biopsy sessions without BE or HGD or IMC and no subsequent recurrence. Recurrence was defined by the return of BE or HGD or IMC after initial remission. Progression was defined as worsening of HGD to IMC or worsening of IMC to submucosal neoplasia or beyond. Overall, 57 patients underwent RFA with or without EMR for BE with HGD (n = 45) or IMC (n = 12) between 2007 and 2012, with a median follow-up duration of 35.4 months (range: 18.5-52.0 months). The 57 patients underwent 181 ablation sessions and more than half (61%) of patients underwent EMR as a component of treatment. There were no major procedural complications or deaths, with only 2 minor complications including 1 symptomatic stricture requiring dilation. Multifocal HGD or IMC was present in 43% (25/57) of patients. CR of IMC was achieved in 100% (12/12) at a median of 6.1 months, CR of dysplasia was achieved in 79% (45/57) at a median of 11.5 months, and CR of BE was achieved in 49% (28/57) at a median of 18.4 months. Following initial remission, 28% of patients (16/57) had recurrence of dysplasia (n = 12) or BE (n = 4). Progression to IMC occurred in 7% (4/57). All patients without CR continue endoscopic treatment. No patient required esophagectomy or developed metastatic disease. Overall, 6 patients died during the follow-up interval, none from esophageal cancer. Factors associated with failure to achieve CR of BE included increasing length of BE (6.0 ± 0.6 vs 4.0 ± 0.6cm, P = 0.03) and shorter duration of follow-up (28.5 ± 3.8 months vs 49.0 ± 5.8 months, P = 0.004). Shorter surveillance duration (17.8 ± 7.6 months vs 63.9 ± 14.4 months, P = 0.009) and shorter follow-up (21.1 ± 6.1 months vs 43.2 ± 4.1 months) were the only significant factors associated with failure to eradicate dysplasia. Our use of esophagectomy as primary therapy for BE with HGD or IMC has diminished since we began using endoscopic therapies in 2007. From a maximum of 16 esophagectomies per year for early Barrett neoplasia in 2006, we performed only 3 esophageal resections for such early disease in 2012, all for IMC, and we have not performed an esophagectomy for HGD since 2008. Although recurrence of BE or dysplasia/IMC was not uncommon, RFA with or without EMR ultimately resulted in CR of IMC in all patients, CR of HGD in the majority (79%), and CR of BE in nearly half (49%). No patient treated endoscopically for HGD or IMC subsequently required esophagectomy. In patients with BE with HGD or IMC, RFA and EMR are safe and highly effective. The use of endoscopic therapies appears justified as the new standard of care in most cases of BE with early esophageal neoplasia.

Anastomotic Leakage Following Esophagectomy

Anastomotic leaks remain a significant clinical challenge following esophagectomy with foregut reconstruction. Despite an increasing understanding of the multiple contributing factors, advancements in perioperative optimization of modifiable risks, and improvements in surgical, endoscopic, and percutaneous management techniques, leaks remain a source of major morbidity associated with esophageal resection. The surgeon should be well versed in the principles underlying the cause of leaks, and strategies to minimize their occurrence. Appropriately diagnosed and managed, most anastomotic leaks following esophagectomy can be brought to a successful resolution.

Intrathoracic Migration of a Silicone Breast Implant After Video-Assisted Thoracoscopic Surgery

© 2013 by The Society of Thoracic Surgeons Published by Elsevier Inc underwent video-assisted thoracoscopic right middle lobectomy with use of a camera port, an instrument port, and a 1.5-cm access incision in the axilla with no rib spreading. The pathologic appearance was consistent with a carcinoid tumor. Six months later the patient noticed that her “right breast was gone.” Computed tomography of the chest revealed intrathoracic migration of the right breast implant with suspected rupture (Fig 2, asterisk). The patient was taken back to the operating room and underwent video-assisted thoracoscopic removal of the breast implant (Fig 3). The Remaining free silicone was removed with iced saline-soaked sponges. The axillary defect was identified as the site of implant herniation and was closed with a prosthetic mesh. The patient had an unremarkable recovery. Intrathoracic herniation of a breast implant has been reported in association with open thoracotomy [1]. To our knowledge, this is the first reported case after a videoassisted thoracoscopic surgical procedure. Closing the intercostal defect can be considered to prevent such a complication.