Katie S. Nason

Outcomes After Minimally Invasive Esophagectomy Review of Over 1000 Patients

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 esophagectomy (MIE) in a large group of patients. Our secondary objective was to compare the modified McKeown minimally invasive approach (videothoracoscopic surgery, laparoscopy, neck anastomosis [MIE-neck]) with our current approach, a modified Ivor Lewis approach (laparoscopy, videothoracoscopic surgery, chest anastomosis [MIE-chest]). Methods: We reviewed 1033 consecutive patients undergoing MIE. Elective operation was performed on 1011 patients; 22 patients with nonelective operations were excluded. Patients were stratified by surgical approach and perioperative outcomes analyzed. The primary endpoint studied was 30-day mortality. Results: The MIE-neck was performed in 481 (48%) and MIE-Ivor Lewis in 530 (52%). Patients undergoing MIE-Ivor Lewis were operated in the current era. The median number of lymph nodes resected was 21. The operative mortality was 1.68%. Median length of stay (8 days) and ICU stay (2 days) were similar between the 2 approaches. Mortality rate was 0.9%, and recurrent nerve injury was less frequent in the Ivor Lewis MIE group (P < 0.001). Conclusions: MIE in our center resulted in acceptable lymph node resection, postoperative outcomes, and low mortality using either an MIE-neck or an MIE-chest approach. The MIE Ivor Lewis approach was associated with reduced recurrent laryngeal nerve injury and mortality of 0.9% and is now our preferred approach. Minimally invasive esophagectomy can be performed safely, with good results in an experienced center.

Outcomes after a Decade of Laparoscopic Giant Paraesophageal Hernia Repair

OBJECTIVE Laparoscopic repair of giant paraesophageal hernia is a complex operation requiring significant laparoscopic expertise. Our objective was to compare our current approach and outcomes for laparoscopic repair of giant paraesophageal hernia with our previous experience. METHODS A retrospective review of patients undergoing nonemergency laparoscopic repair of giant paraesophageal hernia, stratified by early versus current era (January 1997-June 2003 and July 2003-June 2008), was performed. We evaluated clinical outcomes, barium esophagogram, and quality of life. RESULTS Laparoscopic repair of giant paraesophageal hernia was performed in 662 patients (median age 70 years, range 19-92 years) with a median percentage of herniated stomach of 70% (range 30%-100%). With time, use of Collis gastroplasty decreased (86% to 53%), as did crural mesh reinforcement (17% to 12%). Current era patients were 50% more likely to have a Charlson comorbidity index score greater than 3. Thirty-day mortality was 1.7% (11/662). Mortality and complication rates were stable with time, despite increasing comorbid disease in current era. Postoperative gastroesophageal reflux disease health-related quality of life scores were available for 489 patients (30-month median follow-up), with good to excellent results in 90% (438/489). Radiographic recurrence (15.7%) was not associated with symptom recurrence. Reoperation occurred in 3.2% (21/662). CONCLUSIONS With time, we have obtained significant minimally invasive experience and refined our approach to laparoscopic repair of giant paraesophageal hernia. Perioperative morbidity and mortality remain low, despite increased comorbid disease in the current era. Laparoscopic repair provided excellent patient satisfaction and symptom improvement, even with small radiographic recurrences. Reoperation rates were comparable to the best open series.

Anatomic segmentectomy for the solitary pulmonary nodule and early-stage lung cancer.

BACKGROUND Anatomic segmentectomy is a versatile sublobar resection approach that can be both diagnostic and therapeutic in the setting of the indeterminate pulmonary nodule (IPN), metastasectomy, as well as small, peripheral cancers. We analyzed the clinical indications and perioperative outcomes after anatomic segmentectomy and explored its utility in the diagnosis and treatment of IPNs and small stage IA lung cancers. METHODS This study is a retrospective review of 785 consecutive patients undergoing anatomic segmentectomy from 2002 to 2010. Primary outcome variables include perioperative course, morbidity, mortality, recurrence patterns, and survival. RESULTS Surgical indications included IPN (62.4%), known lung cancer (27.6%), suspected metastasis (4.1%), bullous disease (3.7%), or other (2.2%). Video-assisted thoracic surgery was employed in 468 (59.6%) and open thoracotomy in 317 (40.4%) patients. Median length of stay was 6 days. Overall complication rate was 34.9%. Thirty-day mortality was 1.1%. Among 490 patients with an IPN, 381 (77.7%) were found to have lung cancer, 41 (8.4%) metastatic cancer, and 68 (13.9%) benign disease. Among patients with pathologic stage IA lung cancer, there was no difference in recurrence rates (14.5% vs 13.9%) or 5-year freedom from recurrence estimates (78% in each group, p=0.738) when comparing segmentectomy and lobectomy. CONCLUSIONS Anatomic segmentectomy provides acceptable morbidity and mortality when approaching the IPN. Cancer is identified in 86% of lesions. Complete surgical resection can be achieved with generous parenchymal margins and thorough nodal staging for small, peripheral stage IA non-small cell lung cancer. The use of anatomic segmentectomy should be considered in this era of competing image-guided diagnostic and therapeutic approaches to peripheral lung pathology.

BOB CAT: a Large-Scale Review and Delphi Consensus for Management of Barrett’s Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia

OBJECTIVES:Barrett’s esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD).METHODS:We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations.RESULTS:In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients.CONCLUSIONS:In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research.

Postesophagectomy chylothorax: Incidence, risk factors and outcomes

BACKGROUND Chylothorax is a rare but potentially lethal complication of esophagectomy. This study evaluated the rate of postesophagectomy chylothorax, identified associated risk factors, and compared postoperative outcomes in patients with and without chylothorax. METHODS We reviewed 892 consecutive patients who underwent esophagectomy (1997 to 2008). Preoperative, operative, and postoperative details, including adverse outcomes and mortality, were analyzed. RESULTS Postesophagectomy chylothorax occurred in 34 patients (3.8%). Chylothorax was significantly associated with 30-day major complications (85% vs 46%; p<0.001), including an increased likelihood of sepsis (p=0.001), pneumonia (p=0.009), reintubation (p=0.002) or reoperation (p<0.001), and death (17.7% vs 3.9%, p<0.001). Median length of stay was 17 vs 8 days (p=0.005). Median time to chylothorax diagnosis was 5 days. Thoracic duct ligation was performed in 21 (62%) at a median 13 days after esophagectomy. Two patients required repeat duct ligation for persistent chylothorax. Squamous cell cancer histology (9 of 34; 26%) was an independent predictor of postoperative chylothorax (odds ratio, 4.18; 95% confidence interval, 1.39 to 12.6). Odds of chylothorax were 36 times greater with average daily chest tube output exceeding 400 mL in the first 6 postoperative days (odds ratio, 35.9; 95% confidence interval, 8.2 to 157.8). CONCLUSIONS Postoperative chylothorax is associated with significant postoperative morbidity and mortality. Patients with squamous cell cancer may be at increased risk. In addition, average daily chest tube output exceeding 400 mL in the early postoperative period should prompt fluid analysis for chylothorax to facilitate early diagnosis and consideration of thoracic duct ligation.

Thymic Carcinoma: A Multivariate Analysis of Factors Predictive of Survival in 290 Patients

BACKGROUND Thymic carcinoma is a rare, aggressive disease with low 5-year survivals. We undertook this study to identify factors that impact prognosis and to better define the relationship between survival and surgical intervention. METHODS We queried the Surveillance, Epidemiology, and End Results cancer database and identified patients with thymic carcinoma. We performed univariate and multivariate analyses to identify factors prognostic for survival, focusing on demographic, tumor, and treatment variables. RESULTS For 290 patients with thymic carcinoma, the median survival was 48 months with 5-year survival of 30%. In multivariate analysis, type of surgical therapy (none, incomplete excision, complete thymic excision, debulking), Masaoka stage, and sex were important determinants of survival. Patients who underwent complete thymic excision had a significantly longer median survival than those who did not receive surgical therapy (105 versus 29 months; p < 0.001). In patients who underwent complete thymic excision, Masaoka stage and race were important determinants of survival in multivariate analysis. CONCLUSIONS Complete thymic excision is the preferred primary treatment for thymic carcinoma. Masaoka stage has significant prognostic implications for all patients, including those who undergo complete thymic excision.

Increased Levels of Tumor-Infiltrating Lymphocytes are Associated with Improved Recurrence-Free Survival in Stage 1A Non-Small-Cell Lung Cancer

BACKGROUND Tumor-infiltrating lymphocytes (TILs) have been found to increase survival in many forms of cancer, including, endometrial, bile ductal, colonic, esophageal, and urothelial cancers, as well as melanoma and follicular lymphoma. The relevance of TILs in the prognosis of non-small-cell lung cancer (NSCLC), however, still remains controversial. We compared the outcomes of stage 1A NSCLC with and without tumor infiltrating lymphocytes to evaluate the effects of TILs on recurrence and survival patterns. MATERIALS AND METHODS From 2000 to 2009, 273 anatomic segmentectomies and lobectomies were performed on stage 1A NSCLC. Patients were stratified into TIL- and TIL+ cohorts based on pathologic evaluation. Further investigation was conducted on the effects of TILs in patients with and without angiolymphatic invasion. Variables analyzed include overall survival, recurrence-free survival, and type of recurrence. RESULTS Overall 5-y survival was not affected by TIL status (65% versus 60%, P = 0.469). Five-year recurrence-free survival (RFS) was significantly increased in the TIL+ group versus the TIL- group (87% versus 73%, P = 0.011), most significantly in women (P = 0.016). The presence of angiolymphatic invasion (ALI) was associated with decreased 5-y RFS versus patients without ALI (61% versus 85%, P < 0.001). Interestingly, in the ALI negative group, TIL+ patients experienced a significantly increased 5-y recurrence-free survival versus TIL- patients (93% versus 80%, P = 0.036). CONCLUSIONS High levels of intratumoral TILs are associated with improved recurrence-free survival in stage 1A NSCLC patients as well as a reduced likelihood of systemic recurrence. When angiolymphatic invasion is not present, the beneficial effects of TILs become even more profound.

Surgical Resection Should Be Considered for Stage I and II Small Cell Carcinoma of the Lung

BACKGROUND Small cell lung carcinoma (SCLC) is rarely treated with resection, either alone or combined with other modalities. This study evaluated the role of surgical resection in the treatment of stage I and II SCLC. METHODS We queried the Surveillance, Epidemiology, and End Results (SEER) database for patients from 1988 to 2007 with SCLC. Survival was determined by Kaplan-Meier analysis and compared using the log-rank test. A Cox proportional hazard model identified relevant survival variables. RESULTS We identified 3,566 patients with stage I or II SCLC. Lung resection was performed in 895 (25.1%), wedge resection in 251 (28.0%), lobectomy or pneumonectomy in 637 (71.2%), and lung resection not otherwise specified in 7 (0.78%). Median survival was 34.0 months (95% confidence interval [CI], 29.0 to 39.0 months) vs 16.0 months (95% CI, 15.3 to 16.7; p<0.001) in nonsurgical patients. Median survival after lobectomy or pneumonectomy was 39.0 months (95% CI, 30.7 to 40.3) and significantly longer than after wedge resection (28.0 months; 95% CI, 23.2 to 32.8; p=0.001). However, survival after wedge resection was still significantly longer than survival in nonsurgical patients (p<0.001). Sex (p=0.013), age, stage at diagnosis, radiotherapy, and operation (all p<0.001) significantly affected survival. In the surgical patients, sex (p=0.001), age (p<0.001), final stage (p<0.001), and type of resection (p=0.01) were important determinants of survival. CONCLUSIONS Surgical resection as a component of treatment for stage I or II SCLC is associated with significantly improved survival and should be considered in the management of early-stage SCLC.

Three-Gene Immunohistochemical Panel Adds to Clinical Staging Algorithms to Predict Prognosis for Patients With Esophageal Adenocarcinoma

PURPOSE Esophageal adenocarcinoma (EAC) is a highly aggressive disease with poor long-term survival. Despite growing knowledge of its biology, no molecular biomarkers are currently used in routine clinical practice to determine prognosis or aid clinical decision making. Hence, this study set out to identify and validate a small, clinically applicable immunohistochemistry (IHC) panel for prognostication in patients with EAC. PATIENTS AND METHODS We recently identified eight molecular prognostic biomarkers using two different genomic platforms. IHC scores of these biomarkers from a UK multicenter cohort (N = 374) were used in univariate Cox regression analysis to determine the smallest biomarker panel with the greatest prognostic power with potential therapeutic relevance. This new panel was validated in two independent cohorts of patients with EAC who had undergone curative esophagectomy from the United States and Europe (N = 666). RESULTS Three of the eight previously identified prognostic molecular biomarkers (epidermal growth factor receptor [EGFR], tripartite motif-containing 44 [TRIM44], and sirtuin 2 [SIRT2]) had the strongest correlation with long-term survival in patients with EAC. Applying these three biomarkers as an IHC panel to the validation cohort segregated patients into two different prognostic groups (P < .01). Adjusting for known survival covariates, including clinical staging criteria, the IHC panel remained an independent predictor, with incremental adverse overall survival (OS) for each positive biomarker (hazard ratio, 1.20; 95% CI, 1.03 to 1.40 per biomarker; P = .02). CONCLUSION We identified and validated a clinically applicable IHC biomarker panel, consisting of EGFR, TRIM44, and SIRT2, that is independently associated with OS and provides additional prognostic information to current survival predictors such as stage.

How Much Pharyngeal Exposure Is “Normal”? Normative Data for Laryngopharyngeal Reflux Events Using Hypopharyngeal Multichannel Intraluminal Impedance (HMII)

BackgroundLaryngopharyngeal reflux (LPR) can cause atypical symptoms, asthma, and pulmonary fibrosis. The aim of this study was to establish the normative data for LPR using hypopharyngeal multichannel intraluminal impedance-pH (HMII).MethodsAsymptomatic subjects underwent endoscopy followed by 24-h HMII using a specialized impedance catheter configured to detect LPR before and after a 2-week course of proton pump inhibitors (PPI). Subjects were excluded if they had esophageal pathology or a positive DeMeester score. A cohort of 24 LPR patients who had a complete response to treatment was used for comparison with the normative data.ResultsForty subjects were enrolled. Thirty-four subjects completed one, and 25 completed both HMII testing periods off and on PPI. There was no difference in the total number of reflux events between off and on PPI [22 (8–32) and 24 (10–28), respectively, p = 0.89]. The 95th percentiles of LPR off and on PPI were 0 and 1, respectively. All patients with treatment responsive LPR had pre-treatment HMII values of LPR greater than the 95th percentile.ConclusionLPR events are rare in an asymptomatic population. One or more LPR events should be considered abnormal in patients with LPR symptoms regardless of whether there is a positive DeMeester score.