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Background: Thoracoscopic approaches to thymectomy and anterior mediastinal mass resection has become increasingly common due to the potential for decreased blood loss and hospital length of stay. However, contralateral mediastinal and phrenic nerve visualization if often difficult from these unilateral approaches, which may affect the ability to achieve a full phrenic to phrenic dissection Herein, we present our early experience of robotic assisted minimally invasive thymectomy (RAMIT) with simultaneous bilateral thoracoscopy and contralateral phrenic nerve visualization. Methods: This was a retrospective review of all sequential patients undergoing RAMIT with simultaneous bilateral thoracoscopy from January 2015 to May 2016. This study was approved by our Institutional Review Board (PRO15080367). Individual patient consent was waived. Results: Twenty-six patients [median age 58 (range, 29–76) years] were included in this study. Sixteen operations were performed for anterior mediastinal mass, 7 for non-thymomatous myasthenia gravis, and 3 for concurrent myasthenia gravis and thymoma. Median blood loss and hospital stay were 25 mL (range, 3–150 mL) and 3 days (range, 2–8 days), respectively. Twenty-one (80.8%) patients experienced an uncomplicated hospital course. The highest graded complication by Clavien Dindo Classification was a grade III due to pleural effusion requiring drainage via pleural catheter. One patient experienced asymptomatic hemidiaphram palsy postoperatively. There were no 90-day postoperative deaths. Conclusions: RAMIT with simultaneous bilateral thoracoscopy is a feasible approach that may allow for enhanced visualization and more complete thymic resection compared to existing unilateral minimally invasive operations. Comparative studies and long-term follow up are needed to adequately assess the potential benefits of RAMIT.

Zenker's diverticulum (ZD) is a rare disorder that has a reported annual incidence of about 2 cases per 100,000. It is a pulsion (false) diverticulum that develops in an area of natural anatomic weakness called Killian's triangle. This is located between the inferior pharyngeal constrictor and the cricopharyngeus muscles. The exact etiology and pathophysiology of ZD is not known. Cricopharyngeal discoordination, spasm, or hypertension have all been implicated as underlying mechanisms leading to herniation of the hypopharyngeal mucosa and submucosa and consequently the formation of a ZD. Gastroesophageal reflux has also been implicated as a potential underlying mechanism in the development of ZD. Patients typically will present with symptoms of oropharyngeal dysphagia, food regurgitation, and in severe cases aspiration pneumonia. Cricopharyngeal myotomy is the mainstay of surgical treatment of symptomatic ZD. The traditional surgical approach to ZD includes an open cervical cricopharyngeal myotomy. However, starting with Collard's initial report of endoscopic stapling in 1993, the endoscopic approach to ZD treatment has been popularized. Since then, increasing reports have described utilizing a variety of endoscopic techniques for management of ZD. Herein we present our current preferred endoscopic approach to treatment of ZD.

Summary The prevention of pneumothorax after percutaneous lung biopsy is a major patient safety concern. The insertion of hydrogel plugs into biopsy sites to mitigate this complication is a new intervention. The histology of the plug has not been previously reported, and in this study the histologic reaction is reported in 13 cases. The hydrogel plug forms a spherical basophilic matrix pool with an adjacent foreign body giant cell reaction and patchy eosinophilia. No extension to the pleural surface is present. The potential diagnostic errors related to the presence of the plug are discussed.

Zenker diverticulum (ZD), a pulsion diverticulum of the esophagus, has been traditionally managed with an open surgical approach, but endoscopic transoral stapling has been reported with increasing frequency. The objective of this study was to evaluate the results of endoscopic repair of ZD by a thoracic surgery service.We conducted a retrospective review of patients who underwent transoral stapling repair of ZD at our institution by the thoracic surgery service. We evaluated perioperative outcomes including dysphagia (1, no dysphagia to 5, unable to swallow saliva) and failure of repair requiring surgical intervention.A total of 151 patients (median age, 78 years; 75 men, 76 women) underwent evaluation for endoscopic repair of ZD. Endoscopic stapled repair of the ZD was completed in 135. Sixteen patients underwent conversion to open repair. The perioperative mortality was 0.6% (1 patient). The median hospital stay was 2 days (range, 0-18 days). Complications occurred in 5 patients who underwent endoscopic repair. The mean preoperative dysphagia score was 2.8 and improved to 1.2 during follow-up (median, 16 months; P .001). During further follow-up (median, 52 months), 8 patients (5.3%) had failure of the endoscopic repair requiring open surgery (n = 5) or redo transoral stapling (n = 3).Endoscopic stapling repair of ZD can be performed safely with good results in experienced centers by thoracic surgeons with significant esophageal experience. Long-term follow-up is required to evaluate the durability of endoscopic repair of ZD.

Video Video 1 Video available at: https://www.jtcvs.org/article/S2666-2507(21)00514-9/fulltext. Video 2 Video available at: https://www.jtcvs.org/article/S2666-2507(21)00514-9/fulltext. Video 3 Video available at: https://www.jtcvs.org/article/S2666-2507(21)00514-9/fulltext. Video 4 Video available at: https://www.jtcvs.org/article/S2666-2507(21)00514-9/fulltext. Video 5 Video available at: https://www.jtcvs.org/article/S2666-2507(21)00514-9/fulltext. Video 6 Video available at: https://www.jtcvs.org/article/S2666-2507(21)00514-9/fulltext. Video 7 Video available at: https://www.jtcvs.org/article/S2666-2507(21)00514-9/fulltext. Video 8 Video available at: https://www.jtcvs.org/article/S2666-2507(21)00514-9/fulltext. Video 9 Video available at: https://www.jtcvs.org/article/S2666-2507(21)00514-9/fulltext. Video 10 Video available at: https://www.jtcvs.org/article/S2666-2507(21)00514-9/fulltext. Video 11 Video available at: https://www.jtcvs.org/article/S2666-2507(21)00514-9/fulltext.

While robotic-assisted lung resection has seen a significant rise in adoption, concerns remain regarding initial programmatic outcomes and potential increased costs. We present our initial outcomes and cost analysis since initiation of a robotic lung resection program.Patients undergoing either video-assisted thoracoscopic lobectomy or segmentectomy (VATS) or robotic-assisted lobectomy or segmentectomy (RALS) between August of 2014 and January of 2017 underwent retrospective review. Patients underwent 1:1 propensity matching based on preoperative characteristics. Perioperative and 30-day outcomes were compared between groups. Detailed activity-based costing analysis was performed on individual patient encounters taking into effect direct and indirect controllable costs, including robotic operative supplies.There were no differences in 30-day mortality between RALS (n = 74) and VATS (n = 74) groups (0% vs 1.4%; P = 1). RALS patients had a decreased median length of stay (4 days vs 7 days; P.001) and decreased median chest tube duration (3 days vs 5 days, P.001). Total direct costs, including direct supply costs, were not significantly different between RALS and VATS ($6621 vs $6483; P = .784). Median total operating costs and total unit support costs, which are closely correlated to length of stay, were lower in the RALS group. Overall median controllable costs were significantly different between RALS and VATS ($16,352 vs $21,154; P = .025).A potentially cost-advantageous robotic-assisted pulmonary resection program can be initiated within the context of an existing minimally invasive thoracic surgery program while maintaining good clinical outcomes when compared with traditional VATS. Process-of-care changes associated with RALS may account for decreased costs in this setting.

Robotic lung resection for lung cancer has gained popularity over the last 10 years. As with many surgical techniques, there are improvements in outcomes associated with increased operative volume. We sought to investigate lymph-node harvest and upstaging rates for robotic lobectomies performed at hospitals with varying robotic experience. The National Cancer Data Base was queried for patients with early stage non-small cell lung cancer who received lobectomy between 2010 and 2015. Hospitals were stratified into volume categories based on the number of robotic resections performed, as a proxy for robotic experience: low at ≤ 12, low–middle 13–26, middle–high 27–52, and high volume at greater than or equal to 53. Lymph-node counts and nodal upstaging were compared among these volume categories. 8360 robotic lobectomies were performed. Mean lymph-node counts were for low, low–middle, middle–high, and high-volume robotic lobectomies were 9.8, 11.4, 12.9, and 12.6, respectively (P

The introduction of minimally invasive techniques to the field of foregut surgery has revolutionized the surgical approach to giant paraesophageal hernia repair. Laparoscopy has become the standard approach in patients with giant paraesophageal hernia because it has been shown to be safe and is associated with lower morbidity and mortality when compared with various open approaches. Specifically, it has been associated with decreased intraoperative blood loss, decreased complications, and reduced hospital length of stay. This is despite a rise in comorbid conditions associated with this patient population. This article describes our operative approach to laparoscopic giant paraesophageal hernia repair.

Background Equipoise still exists regarding routine mesh cruroplasty during laparoscopic paraesophageal hernia (PEH). We aimed to determine whether selective mesh cruroplasty is associated with differences in recurrence and patient-reported outcomes. Methods We compared symptom outcomes (n = 688) and radiographic recurrences (n = 101; at least 10% [or 2 cm] of stomach above hiatus) for 795 non-emergent PEH repair with fundoplication (n = 106 with mesh). Results Heartburn, regurgitation, epigastric pain, and anti-reflux medication use decreased significantly in both groups while postoperative dysphagia (mesh; p = 0.14), and bloating (non-mesh; p = 0.32), were unchanged. Radiographic recurrence rates were similar (15 mesh [22%] versus 86 non-mesh [17%]; p = 0.32; median 27 [IQR 14, 53] months), but was associated with surgical dissatisfaction (13% vs 4%; p = 0.007). Conclusions Selective mesh cruroplasty was not associated with differences in symptom outcomes or radiographic recurrence rates during laparoscopic PEH repair. Radiographic recurrence was associated with dissatisfaction, emphasizing the need for continued focus on reducing recurrences.

Background Postoperative infection increases cancer recurrence and worsens survival in colorectal cancer, but the relationship for esophagogastric adenocarcinoma after esophagectomy is not well defined. We aimed to determine whether recurrence and survival after minimally invasive esophagectomy for esophagogastric adenocarcinoma were influenced by postoperative infection using propensity-matched analysis. Methods We abstracted data for 810 patients (1997–2010) and defined exposure as at least 1 in-hospital or 30-day infectious complication (n = 206 [25%]). Using 29 pretreatment/intraoperative variables, patients were propensity-score matched (caliper = 0.05). Time to cancer recurrence and survival (Kaplan-Meier curves and the Breslow test), and associated factors (Cox regression with shared frailty) were assessed. Results After propensity matching (n = 167 pairs), median bias across propensity-score variables was reduced from 12.9% ( p p = 1.000). Postoperative infection was not associated with rate (n = 60 versus 63; McNemar p = 0.736) or time to recurrence in those in whom disease recurred (median, 10.7 versus 11.1 months; Wilcoxon signed-rank p = 0.455) but was associated with shorter overall survival (n = 124 versus 102 deaths; median, 26 versus 41 months; Breslow p = 0.002). After adjusting for age, body mass index, neoadjuvant therapy, sex, comorbidity score, positive resection margins, pathologic stage, R0 resection, and recurrence, postoperative infection was associated with a 44% greater hazard for death (hazard ratio, 1.44; 95% confidence interval, 1.10–1.89). Conclusions In patients with esophagogastric adenocarcinoma, infections after esophagectomy were not associated with an increased rate or earlier time to recurrence when baseline characteristics associated with infection risk were balanced using propensity-score matching. Despite this, overall survival was shorter in patients with infectious complications. After adjusting for other important survival predictors, infections after esophagectomy continued to be independently associated with worse survival.

Background Thoracic esophageal diverticula are uncommon, and controversies exist regarding their management. The objective of this study was to evaluate the outcomes of a relatively large cohort of patients with thoracic esophageal diverticula treated with minimally invasive surgical techniques. Methods We conducted a retrospective review of patients who underwent minimally invasive surgical treatment for symptomatic esophageal diverticula during a 15-year period. The primary end point was 30-day mortality. In addition, we evaluated the morbidity, improvement in dysphagia (score: 1, best to 5, worst), and quality of life (Gastroesophageal Reflux Disease–Health-Related Quality of Life score: 0, best to 50, most symptoms). Results Fifty-seven patients underwent minimally invasive surgical treatment of symptomatic thoracic esophageal diverticula. The most common symptom was dysphagia (45 of 57; 79%). A motility disorder or distal mechanical obstruction was identified in 49 patients (86%). Approaches used included video-assisted thoracoscopic surgery (n = 33), laparoscopy (n = 18), and combined video-assisted thoracoscopic surgery and laparoscopy (n = 6). The most common procedure performed was diverticulectomy and myotomy (47 of 57 patients; 82.5%). The 30-day mortality was 0%. There were 4 patients (7%) with postoperative leaks requiring reoperation. During follow-up, the median dysphagia score improved from 3 to 1 ( p Conclusions A minimally invasive surgical approach for the management of thoracic esophageal diverticula is safe and effective during intermediate-term follow-up when performed by surgeons experienced in esophageal surgery and minimally invasive techniques. Further follow-up is required to assess the durability of these results. The optimal approach and procedures performed should be determined on an individualized basis after a thorough investigation.

Objectives Prognosis for patients with locally advanced esophagogastric adenocarcinoma (EAC) is poor with surgery alone, and adjuvant therapy after open esophagectomy is frequently not tolerated. After minimally invasive esophagectomy (MIE); however, earlier return to normal function may render patients better able to receive adjuvant therapy. We examined whether primary MIE followed by adjuvant chemotherapy influenced survival compared with propensity-matched patients treated with neoadjuvant therapy. Methods Patients with stage II or higher EAC treated with MIE (N = 375) were identified. Using 30 pretreatment covariates, propensity for assignment to either neoadjuvant followed by MIE (n = 183; 54%) or MIE as primary therapy (n = 156; 46%) was calculated, generating 97 closely matched pairs. Hazard ratios were adjusted for age, sex, body mass index, smoking, comorbidity, and final pathologic stage. Results In propensity-matched pairs, adjusted hazard ratio for death did not differ significantly for primary MIE compared with neoadjuvant (hazard ratio, 0.83; 95% confidence interval, 0.60-1.16). Recurrence patterns were similar between groups and 65% of patients with IIb or greater pathologic stage received adjuvant therapy. Clinical staging was inaccurate in 37 out of 105 patients (35%) who underwent primary MIE (n = 18 upstaged and n = 19 downstaged). Conclusions Primary MIE followed by adjuvant chemotherapy guided by pathologic findings did not negatively influence survival and allowed for accurate staging compared with clinical staging. Our data suggest that primary MIE in patients with resectable EAC may be a reasonable approach, improving stage-based prognostication and potentially minimizing overtreatment in patients with early stage disease through accurate stage assignments. A randomized controlled trial testing this hypothesis is needed.

Objective A recent meta-analysis of 3 randomized controlled trials reported reduced incidence and severity of postesophagectomy anastomotic dehiscence with anastomotic omentoplasty. Unfortunately, these trials excluded neoadjuvant patients who received chemoradiation. We aimed to determine whether anastomotic omentoplasty was associated with differential postesophagectomy anastomotic complications after neoadjuvant chemoradiotherapy. Methods Data for patients who underwent minimally invasive esophagectomy following neoadjuvant chemoradiotherapy were abstracted (n = 245; 2001-2016; omentoplasty = 147 [60%]). Propensity for omentoplasty was estimated on 21 pretreatment variables, using augmented inverse probability of treatment weights, and used to determine the adjusted proportion of adverse anastomotic outcomes, major morbidity, and 30-day/in-hospital mortality. Results Overall, anastomotic leak rate was 15%; leak-associated mortality was 13% (n = 5 out of 37). Leak rates (omentoplasty n = 24 [16%] vs no omentoplasty n = 13 [13%]; P = .512) and incidence of any major complications (48% vs 48%; P = .958) were similar. Leaks requiring surgical intervention occurred in 12 patients (5% vs 5%; P = .904). Propensity weighting achieved excellent balance across all 21 pretreatment variables (before weighting, standardized differences ranged from –0.23 to 0.35; postweighting standardized differences ranged from –0.09 to 0.07). In propensity-weighted data, omentoplasty was not associated with differential adjusted risk of anastomotic leak (13.2% vs 14.3%; P = .83), major morbidity (27.9% vs 32.6%; P = .44), or mortality (6.7% vs 4.8%; P = .61). Conclusions Within the limits of our sample size and statistical approach, our study failed to find evidence that anastomotic omentoplasty during esophagectomy after neoadjuvant chemoradiation reduced anastomotic leak rate or need for leak-related reoperation.

Patients undergoing non-elective paraesophageal hernia repair (PEHR) have worse perioperative outcomes. Because they are usually older and sicker, however, these patients may be more prone to adverse events, independent of surgical urgency. Our study aimed to determine whether non-elective PEHR is associated with differential postoperative outcome compared to elective repair, using propensity-score weighting.We abstracted data for patients undergoing PEHR (n = 924; non-elective n = 171 (19 %); 1997-2010). Using boosted regression, we generated a propensity-weighted dataset. Odds of 30-day/in-hospital mortality and major complications after non-elective surgery were determined.Patients undergoing non-elective repair were significantly older, had more adverse prognostic factors, and significantly more major complications (38 versus 18 %; p 0.001) and death (8 versus 1 %; p 0.001). After propensity weighting, median absolute percentage bias across 28 propensity-score variables improved from 19 % (significant imbalance) to 5.6 % (well-balanced). After adjusting propensity-weighted data for age and comorbidity score, odds of major complications were still nearly two times greater (OR 1.67, CI 1.07-2.61) and mortality nearly three times greater (OR 2.74, CI 0.93-8.1) than for elective repair.Even after balancing significant differences in baseline characteristics, non-elective PEHR was associated with worse outcomes than elective repair. Symptomatic patients should be referred for elective repair by experienced surgeons.

Laparoscopic paraesophageal hernia repair continues to be one of the most challenging procedures facing the minimally invasive surgeon. A thorough understanding of the tenets of the operation and advanced skills in minimally invasive laparoscopy are needed for long-term freedom from symptomatic and anatomic recurrence. These include complete reduction of the hernia sac from the mediastinum back into the abdomen with careful preservation of the integrity of muscle and peritoneal lining of the crura, aggressive and complete mobilization of the esophagus to the level of the inferior pulmonary vein, vagal preservation, clear identification of the gastroesophageal junction to allow accurate assessment of the intraabdominal esophageal length, and use of Collis gastroplasty when esophageal lengthening is required for a tension-free intraabdominal repair. Liberal mobilization of the phrenosplenic and phrenogastric attachments substantially increases the mobility of the left limb of the crura, allowing for a tension-free primary closure in a large percentage of patients. The following describes our current approach to laparoscopic paraesophageal hernia repair following a decade of refinement in a high-volume center.

Previously regarded as a rare neoplasm, the incidence of esophageal adenocarcinoma has risen rapidly in recent decades. It is often discovered late in the disease process and has a dismal prognosis. Current prognostic markers including clinical, radiographic, and histopathologic findings have limited utility and do not consider the biology of this deadly disease. Genome-wide analyses have identified SMAD4 inactivation in a subset of tumors. Although Smad4 has been extensively studied in other gastrointestinal malignancies, its role in esophageal adenocarcinoma remains to be defined. Herein, we show, in a large cohort of esophageal adenocarcinomas, Smad4 loss by immunohistochemistry in 21 of 205 (10%) tumors and that Smad4 loss correlated with increased postoperative recurrence (P=0.040). Further, patients whose tumors lacked Smad4 had shorter time to recurrence (TTR) (P=0.007) and poor overall survival (OS) (P=0.011). The median TTR and OS of patients with Smad4-negative tumors was 13 and 16 months, respectively, as compared with 23 and 22 months, respectively, among patients with Smad4-positive tumors. In multivariate analyses, Smad4 loss was a prognostic factor for both TTR and OS, independent of histologic grade, lymphovascular invasion, perineural invasion, tumor stage, and lymph node status. Considering Smad4 loss correlated with postoperative locoregional and/or distant metastases, Smad4 was also assessed in a separate cohort of 5 locoregional recurrences and 43 metastatic esophageal adenocarcinomas. In contrast to primary tumors, a higher prevalence of Smad4 loss was observed in metastatic disease (44% vs. 10%). In summary, loss of Smad4 protein expression is an independent prognostic factor for TTR and OS that correlates with increased propensity for disease recurrence and poor survival in patients with esophageal adenocarcinoma after surgical resection.

Staging for esophagogastric adenocarcinoma lacked sufficient prognostic accuracy and was revised. We compared survival prognostication between American Joint Committee on Cancer (AJCC) 6th and 7th editions.We abstracted data for 836 patients who underwent minimally invasive esophagectomy for esophagogastric adenocarcinoma (n = 256 neoadjuvant). Monotonicity and strength of survival trends, by stage, were assessed (log-rank test of trend chi-square statistic) and compared using permutation testing. Overall survival (Cox regression) and model fit (Akaike Information Criterion) were determined.A greater log-rank test of trend statistic indicated stronger survival trends by stage in AJCC 7th (152.872 vs 167.623; permutation test P.001) edition. Greater Cox likelihood chi-square value (162.957 vs 173.951) and lower Akaike Information Criterion (4,831.011 vs 4,820.016) indicated better model fit. Superior performance was also shown after neoadjuvant therapy.AJCC 7th edition staging for esophagogastric adenocarcinoma provides superior prognostic stratification after minimally invasive esophagectomy, overall and after neoadjuvant therapy compared with AJCC 6th edition.

The systemic inflammatory response syndrome initiated by infection shares many features in common with the trauma-induced systemic response. The toll-like receptors (TLRs) stand at the interface of innate immune activation in the settings of both infection and sterile injury by responding to a variety of microbial and endogenous ligands alike. Recently, a body of literature has evolved describing a key role for TLRs in acute injury using rodent models of hemorrhagic shock, ischemia and reperfusion, tissue trauma and wound repair, and various toxic exposures. This review will detail the observations implicating a TLR family member, TLR4, as a key component of the initial injury response.

The receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of numerous conditions associated with excessive inflammation. To determine whether RAGE-dependent signaling is important in the development of intestinal barrier dysfunction after hemorrhagic shock and resuscitation (HS/R), C57Bl/6, rage−/−, or congenic rage+/+ mice were subjected to HS/R (mean arterial pressure of 25 mmHg for 3 h) or a sham procedure. Twenty-four hours later, bacterial translocation to mesenteric lymph nodes and ileal mucosal permeability to FITC-labeled dextran were assessed. Additionally, samples of ileum were obtained for immunofluorescence microscopy, and plasma was collected for measuring IL-6 and IL-10 levels. HS/R in C57Bl/6 mice was associated with increased bacterial translocation, ileal mucosal hyperpermeability, and high circulating levels of IL-6. All of these effects were prevented when C57Bl/6 mice were treated with recombinant human soluble RAGE (sRAGE; the extracellular ligand-binding domain of RAGE). HS/R induced bacterial translocation, ileal mucosal hyperpermeability, and high plasma IL-6 levels in rage+/+ but not rage−/− mice. Circulating IL-10 levels were higher in rage−/− compared with rage+/+ mice. These results suggest that activation of RAGE-dependent signaling is a key factor leading to gut mucosal barrier dysfunction after HS/R.

Hemorrhagic shock and resuscitation (HS/R) activates inflammatory pathways leading to organ injury after trauma. Toll-like receptors (TLRs), such as TLR4, are required for activation of proinflammatory cellular signaling pathways in response to microbial products, but can also recognize endogenous molecules released from damaged tissues. Using mouse strains deficient in TLR4 protein or signaling, we hypothesized that TLR4 would be important for development of systemic inflammation and hepatic injury after HS/R. We sought to determine the role of lipolysaccharide through use of CD14-/- mice.TLR4-mutant (C[3H]/HeJ), TLR4-deficient (TLR4-/-), CD14-/-, TLR2-/- mice and wild-type (WT) controls were subjected to HS/R or sham procedure (Sham). At 6.5 hours, mice were euthanized for determination of serum interleukin (IL)-6, IL-10, and alanine aminotransferase concentrations. Hepatic nuclear factor-kappaB DNA-binding (electrophoretic mobility shift assay) and tumor necrosis factor, IL-10, and inducible nitric oxide synthase mRNA expression (semiquantitative reverse transcriptase-polymerase chain reaction) were determined.Relative to sham, TLR4-competent (C[3H]/HeOuJ) mice exhibited a significant increase in serum alanine aminotransferase, IL-6, and IL-10 after HS/R (p0.05). TLR4-mutant (C[3H]/HeJ) mice were protected from HS/R-induced hepatocellular injury and had lower circulating IL-6 and IL-10 levels than WT (p0.05). Similarly, TLR4-/- mice had lower circulating IL-6 and IL-10 levels than WT after HS/R (p0.05). Hepatic nuclear factor-kappaB activation and tumor necrosis factor, IL-10, and inducible nitric oxide synthase mRNA expression were lower in TLR4-mutant compared with TLR4-competent mice after HS/R. In contrast, serum ALT concentrations were comparable between CD14-/- and TLR2-/- mice and their WT counterparts after HS/R.These results suggest that TLR4, but not TLR2, signaling is required for initiation of the systemic inflammatory response and development of hepatocellular injury after HS/R. Lack of involvement of CD14 argues for a lipolysaccharide-independent role for TLR4 in this process.

Intractable gastroesophageal reflux disease (GERD) after antireflux operations presents a challenge-particularly in obese patients and patients with esophageal dysmotility-and increases the complexity of the redo operation. This study evaluated the results of Roux-en-Y near esophagojejunostomy (RNYNEJ) in the management of recurrent GERD after antireflux operations.We conducted a retrospective review of overweight patients with intractable GERD who underwent RNYNEJ for failed antireflux operations. We evaluated perioperative outcomes, dysphagia (ranging from 1 = no dysphagia to 5 = unable to swallow saliva), and quality of life (QOL) (assessed using the GERD health-related quality-of-life instrument (HRQOL).Over a 12-year period, 105 patients with body mass index (BMI) greater than 25 underwent RNYNEJ for failed antireflux operations. Most were obese (BMI30; 82 patients [78%]); esophageal dysmotility was demonstrated in more than one-third of patients. Forty-eight (46%) patients had multiple antireflux operations before RNYNEJ, and 27 patients had undergone a previous Collis gastroplasty. There was no perioperative mortality. Major complications, including anastomotic leak requiring surgical intervention (n = 3 [2.9%]), were noted in 25 patients (24%).The median length of stay was 6 days. During follow-up (mean, 23.39 months), median BMI decreased from 35 to 27.6 (p0.0001), and the mean dysphagia score decreased from 2.9 to 1.5 (p0.0001). The median GERD HRQOL score, assessed in a subset of patients, was 9 (classified as excellent).RNYNEJ for persistent GERD after antireflux operations in appropriately selected patients can be performed safely with good results in experienced centers. RNYNEJ should be considered an important option for the treatment of intractable recurrent symptoms after antireflux operations, particularly in obese patients.

Esophagectomy is an important curative treatment modality for esophageal cancer, but is a complex operation with associated risks. A minimally invasive approach to esophagectomy may decrease the risks associated with resection. Recently, an important study was published in the Lancet by Biere and colleagues that reported the results of a randomized study, with the primary endpoint of postoperative pulmonary infection, comparing minimally invasive esophagectomy versus open esophagectomy for esophageal cancer. The findings from this trial confirm the data from previous, non-randomized studies and highlight the substantial early postoperative benefits of minimally invasive esophagectomy.

Background:Esophagectomy is a complex operation and is associated with significant morbidity and mortality. In an attempt to lower morbidity, we have adopted a minimally invasive approach to esophagectomy.Objectives:Our primary objective was to evaluate the outcomes of minimally invasive esophagecto

A vagotomized, tubularized gastric conduit is the most commonly used conduit for reconstruction of the thoracic esophagus at esophagectomy. However, the gastric conduit is an imperfect esophageal replacement. The conduit has no receptive relaxation and has a reduced capacity compared with the native stomach. There is decreased antral motility, and gravity is the major determinant of conduit drainage. A pyloric drainage procedure, such as a pyloroplasty or pyloromyotomy, facilitates the emptying of the gastric conduit and may improve foregut function and quality of life after esophageal resection.1 Critics of this approach are concerned that a pyloroplasty may lead to excessive bile reflux and too rapid emptying of the stomach. At our institution, we have developed a minimally invasive Ivor Lewis esophagectomy to treat resectable cancer of the esophagus and gastroesophageal junction.2,3 To optimize conduit function and emptying, we construct a narrow, straight gastric conduit, 3-4 cm in diameter, and perform a pyloroplasty. Here, we describe a technique of minimally invasive, Heineke–Mikulicz pyloroplasty, which we routinely perform within the context of a minimally invasive, Ivor Lewis esophagectomy.

Over the past decade, our technique of MIE has evolved considerably. In the incipient phase of our experience, we used a totally laparoscopic approach similar to that described in the initial reports from DePaula and colleagues and Swanstrom and Hansen. However, it was soon apparent that there were several critical disadvantages to a purely laparoscopic approach. Laparoscopic transhiatal mobilization of the esophagus offers suboptimal visualization of important periesophageal structures, including the inferior pulmonary vein and the left mainstem bronchus. Moreover, decreased visibility hindered hemostatic division of periesophageal vessels and negatively impacted the completeness of the mediastinal lymph node dissection. These problems are further exacerbated in taller patients. In light of these considerations, we soon transitioned to a laparoscopic-thoracoscopic McKeown approach (thoracoscopic mobilization of the intrathoracic esophagus, laparoscopic gastric tube creation, cervical anastomosis). To this date, the great majority of our minimally invasive esophagectomies (>500 cases) have been performed with this 3-field technique. Indeed, the procedure has been the mainstay of our experience in the past 10 years with reduced perioperative morbidity and mortality compared with many other open series. In our experience, perhaps the most significant technical concern with this operation is the cervical dissection. Recurrent laryngeal nerve injuries, perturbations in pharyngeal transit, and swallowing dysfunction even in the absence of recurrent nerve injury are not infrequent. Moreover, as described in open series using a cervical anastomosis, anastomotic stricture and leak have been shown to occur with increased frequency [35]. In short, there is a significant learning curve with the cervical dissection. Out of these concerns emerged our more recent experience with completely thoracoscopic-laparoscopic Ivor Lewis esophagectomy. However, we did first evolve through a transition phase whereby a mini-thoracotomy (hybrid approach) was performed for creation of the intrathoracic anastomosis. We believe that the experience with totally thoracoscopic-laparoscopic Ivor Lewis esophagectomy will ultimately reproduce the low morbidity and mortality we have previously published with our established MIE technique. The omission of a cervical dissection has reduced our recurrent nerve injury rate to zero. From a theoretical standpoint, one would presume that pharyngeal transit problems and oropharyngeal swallowing dysfunction should be reduced as well with a chest anastomosis. It should be emphasized that there is a steep operator learning curve associated with this approach. Indeed, thoracoscopic port placement is critical, as poorly positioned trocars can result in difficulty maneuvering instruments through the rigid chest wall. Additionally, both blood and lung can obscure visualization of the esophagus, which lies at the dependent aspect of the operative field. Prone positioning has been described as an alternative approach that may facilitate operative exposure and address such technical concerns. Low rates of anastomotic leak (3%), low mortality (1.5%), and equivalent stage-specific survival compared with open series have been shown with this thoracoscopic prone approach [36]. In conclusion, our technique of MIE has evolved such that laparoscopic-thoracoscopic Ivor Lewis esophagectomy has become our preferred approach. Although somewhat early in our experience, we are convinced that this operative technique is feasible with reproducible results. Perioperative morbidity and mortality are comparable with our previously established MIE with cervical anastomosis while essentially eliminating recurrent nerve injury, limiting the length of the gastric conduit required, and allowing a more aggressive gastric resection margin. Recent data from other publications also suggests that lymph node yields may be improved, although insufficient data exist at this time to comment on oncologic results or outcomes with this technique.

Intestinal barrier dysfunction occurs following hemorrhagic shock and resuscitation (HS/R). High-mobility group B1 (HMGB1) has been shown to increase the permeability of Caco-2 human enterocyte-like epithelial monolayers in vitro. In this study, we found that serum concentrations of HMGB1 were higher in blood samples obtained from 25 trauma victims with hemorrhagic shock than in 9 normal volunteers. We also studied whether treatment with anti-HMGB1 antibody can ameliorate HS/R-induced gut barrier dysfunction in mice. Animals were shocked by withdrawal of blood to maintain mean arterial pressure at 25 to 30 mmHg for 2 h. After resuscitation with shed blood plus Ringer’s lactate solution, the mice were treated with either anti-HMGB1 antibody or nonimmune rabbit IgG. Serum HMGB1 concentrations were significantly higher in trauma victims than control mice. Treatment with anti-HMGB1 antibody improved survival at 24 h and ameliorated the development of ileal mucosal hyperpermeability to FITC-labeled dextran. At 24 h after HS/R, treatment with anti-HMGB1 antibody decreased bacterial translocation to mesenteric lymph nodes and was associated with lower circulating concentrations of IL-6 and IL-10. These data support the notion that HMGB1 is a mediator of HS/R-induced gut barrier dysfunction and suggest that anti-HMGB1 antibodies warrant further evaluation as a therapeutic to ameliorate the morbidity of HS/R in trauma patients.

4038 Background: AJCC esophageal staging assigns prognostic groups based on tumor, node, and metastasis classifications. In 2010, AJCC 7th ed. separated adenocarcinoma from squamous cell histology ...

e17681 Background: The landmark ToGA study demonstrated a significant overall survival benefit in HER2-positive gastric cancer patients with the addition of trastuzumab to chemotherapy with cisplat...

92 Background: AJCC esophageal staging assigns prognostic groups based on tumor, node, and metastasis classifications. In 2010, AJCC 7th ed. separated adenocarcinoma from squamous cell histology and added tumor grade and number of involved regional nodes. Our study aim was to compare survival prognostication for esophagogastric adenocarcinoma between AJCC 7 and AJCC 6thed. stage groupings. Methods: We abstracted pathology and survival for surgically-resected esophagogastric adenocarcinoma patients (n=836; 1997 to 2011); 256 received induction therapy. AJCC stage was assigned; overall survival in months (esophagectomy to death or most recent alive contact) was analyzed. Discriminatory ability and homogeneity, by stage, was assessed with Kaplan-Meier (KM) curves. Monotonicity comparisons were evaluated with linear trend chi-squared tests. Overall survival was compared using Cox regression and Akaike Information Criterion (AIC) was used to assess model fit. Results: Compared to AJCC 6, AJCC 7 restaged 165 patients. (Table) KM log-rank statistic indicated stronger differentiation in AJCC 7 curves compared to AJCC 6 (166.128 vs 185.523 overall). Cox likelihood ratio (162.957 vs. 173.951 overall) and AIC (4,831.011 vs 4,820.016 overall) indicated better model fit to the survival data for AJCC 7 versus AJCC 6, overall and for induction subgroups (data not shown). As stage group increases, stronger linear trends for survival were observed at 24, 36 and 60 months using AJCC7 stage groupings, overall and for induction subgroups, compared to AJCC 6. Conclusions: AJCC 7 stage groupings demonstrate superior homogeneity, discriminatory ability and monotonicity compared to AJCC 6. Incorporating the extent of nodal disease, and tumor grade into the revised AJCC 7 stage classification improves prognostic stratification of surgically resected esophagogastric adenocarcinoma patients, including patients who received induction therapy. [Table: see text]

4103 Background: Historically, the AJCC esophageal staging system separated patients into prognostic groups based on tumor, node, and metastasis (TNM) classifications. In 2010, the 7th edition (AJCC 7) significantly modified esophageal squamous cell cancer (ESCC) staging by separating ESCC from adenocarcinoma, incorporating tumor grade and location for node negative cancers, and stratifying by the number of involved regional nodes for node positive cancers. Our study aim was to determine whether AJCC 7 stage groupings provide improved survival prognostication compared to 6th edition (AJCC 6). Methods: We abstracted pathology and survival for 150 consecutive ESCC patients who underwent esophagectomy (1994-2012); 44 patients received induction therapy. AJCC 6 and AJCC 7 stages were assigned and overall survival analyzed from esophagectomy to death or most recent alive contact and censored at 60 months. Discriminatory ability and homogeneity within subgroups was assessed with Kaplan-Meier curves and monotonicity comparisons were evaluated with linear trend chi-squared tests. Overall survival was compared using Cox regression and Akaike Information Criterion (AIC) used to assess model fit. Results: Compared to AJCC 6, AJCC 7 upstaged 32 patients from IIa to IIb and 1 patient from IIb to IIIa and downstaged 3 patients from stage IIa to Ib. AJCC 7 subclassified 42 AJCC 6 stage III patients (17 IIIa, 10 IIIb and 15 IIIC). Median overall survival was 19 months. Kaplan-Meier log-rank statistic indicated stronger differentiation in AJCC 7 (19.8 vs 29.7). Cox regression likelihood (19.5 vs 26.1), AIC (618.1 vs 611.6), and linear trend chi-squared at 24- (17.5 vs 24.3) and 60-months (13.3 vs 17.3), were all superior for AJCC 7 stage groupings (AJCC 6 vs AJCC 7, respectively). Conclusions: AJCC 7 stage groupings demonstrate superior homogeneity, discriminatory ability and monotonicity compared to AJCC 6. Incorporating the extent of nodal disease, tumor location and tumor grade into the revised AJCC 7 stage classification improves prognostic stratification of surgically resected ESCC patients, including patients who received induction therapy.

whereas a 10-fold increase in k2 results in similar primary and secondary signaling peaks. Conclusions: Our simulations suggest that a simplified model of LPS/TLR4 signaling can account for complex preconditioning phenomena without invoking a specific signaling inhibition mechanism, but rather based on the dynamics of the signaling response itself, as well as the timing and magnitude of the LPS stimuli.