Zane Hammoud

A modified frailty index to assess morbidity and mortality after lobectomy.

BACKGROUNDnFrailty has yet to be explored as a risk factor for thoracic surgery. We hypothesized that our modified frailty index (mFI) may be a predictor of morbidity and mortality following lobectomy.nnnMATERIALSnNational Surgical Quality Improvement Program (NSQIP) participant use files were reviewed (2005-2010). Patients undergoing lobectomy were identified based on Current Procedural Terminology code 32480. We used an mFI with 11 variables, based on mapping the Canadian Study of Health and Aging Frailty Index to the NSQIP comorbidities. Data were analyzed using χ(2) test, independent sample t-test, Jonckheere-Terpstra test, and logistic regression.nnnRESULTSnOf 1940 open lobectomy patients identified, morbidity and mortality uniformly increased as the mFI increased; 14.9% of patients (75/504) with mFI of 0 had at least one complication, compared with 32% of patients (91/284) with mFI of 0.27 (P < 0.001). An mFI of 0 was associated with a mortality rate of 1% (5/504), compared with 5.6% (16/284) for mFI of 0.27 (P < 0001). Failure to wean from the ventilator, reintubation, surgical site infections, pneumonia, and Clavien 4 and above complications occurred in 1.8% (9/504), 2.6% (13/504), 2.2% (11/504), 5.4% (27/504), and 4.2% (21/504), respectively, in patients with an mFI of 0, compared with 7.4% (21/284), 7% (22/284), 3.2% (9/284), 10.9% (31/284), and 14.4% (41/284), respectively, in patients with mFI of 0.27.nnnCONCLUSIONSnThis study demonstrates that the mFI may identify patients at higher risk for morbidity and mortality post-lobectomy. With the aging population, preoperative selection is important in minimizing morbidity and mortality and improving risk stratification for informed decision-making.

Esophageal Cancer Metabolite Biomarkers Detected by LC-MS and NMR Methods

Background Esophageal adenocarcinoma (EAC) is a rarely curable disease and is rapidly rising worldwide in incidence. Barrets esophagus (BE) and high-grade dysplasia (HGD) are considered major risk factors for invasive adenocarcinoma. In the current study, unbiased global metabolic profiling methods were applied to serum samples from patients with EAC, BE and HGD, and healthy individuals, in order to identify metabolite based biomarkers associated with the early stages of EAC with the goal of improving prognostication. Methodology/Principal Findings Serum metabolite profiles from patients with EAC (nu200a=u200a67), BE (nu200a=u200a3), HGD (nu200a=u200a9) and healthy volunteers (nu200a=u200a34) were obtained using high performance liquid chromatography-mass spectrometry (LC-MS) methods. Twelve metabolites differed significantly (p<0.05) between EAC patients and healthy controls. A partial least-squares discriminant analysis (PLS-DA) model had good accuracy with the area under the receiver operative characteristic curve (AUROC) of 0.82. However, when the results of LC-MS were combined with 8 metabolites detected by nuclear magnetic resonance (NMR) in a previous study, the combination of NMR and MS detected metabolites provided a much superior performance, with AUROCu200a=u200a0.95. Further, mean values of 12 of these metabolites varied consistently from healthy controls to the high-risk individuals (BE and HGD patients) and EAC subjects. Altered metabolic pathways including a number of amino acid pathways and energy metabolism were identified based on altered levels of numerous metabolites. Conclusions/Significance Metabolic profiles derived from the combination of LC-MS and NMR methods readily distinguish EAC patients and potentially promise important routes to understanding the carcinogenesis and detecting the cancer. Differences in the metabolic profiles between high-risk individuals and the EAC indicate the possibility of identifying the patients at risk much earlier to the development of the cancer.

Metabolomics study of esophageal adenocarcinoma

OBJECTIVEnThe objective of this study was to detect and evaluate reliable metabolite markers for screening and monitoring treatment of patients with esophageal adenocarcinoma (EAC) by studying metabolomics. The sensitivity and specificity of the study were evaluated not only for EAC but also for Barrett esophagus and high-grade dysplasia, which are widely regarded as precursors of EAC.nnnMETHODSnProfiles of metabolites in blood serum were constructed using nuclear magnetic resonance spectroscopy and statistical analysis methods. The metabolite biomarkers discovered were selected to build a predictive model that was then used to test the classifications accuracies.nnnRESULTSnEight metabolites showed significant differences in their levels in patients with cancer and in the control group on the basis of Student t test. A partial least-squares discriminant analysis model built on these metabolites provided excellent classifications of patients with cancer and the control group, with the area under the receiver operating in a characteristic curve of >0.85 for both training and validation sample sets. Evaluated by the same model, the Barrett esophagus samples were of mixed classification, and the high-grade dysplasia samples were classified primarily as cancer samples. A pathway study indicated that altered energy metabolism and changes in the trochloroacetic acid cycle were the dominant factors in the biochemistry of EAC.nnnCONCLUSIONSn1H nuclear magnetic resonance-based metabolite profiling analysis was shown to be an effective approach to differentiating between patients with EAC and healthy subjects. Good sensitivity and selectivity were shown by using the 8 metabolite markers discovered to predict the classification of samples from the healthy control group and the patients with the disease. Serum metabolic profiling may have potential for early diagnosis of EAC and may enhance our understanding of its mechanisms.

Assessment of Morbidity and Mortality After Esophagectomy Using a Modified Frailty Index

BACKGROUNDnEsophagectomy is associated withxa0significant morbidity and mortality. This retrospective study examined use of a modified frailty index as a potential predictor of morbidity and mortality in esophagectomy patients.nnnMETHODSnNational Surgical Quality Improvement Program Participant Use Files were reviewed for 2005 through 2010. Patients undergoing esophagectomy were selected based on CPT codes. A modified frailty index with 11 variables was used to determine correlation between frailty and postesophagectomy morbidity and mortality. Data were analyzed using χ(2) test and logistic regression.nnnRESULTSnA total of 2,095 patients were included in the analysis. Higher frailty scores were associated with a statistically significant increase in morbidity and mortality. A frailty score of 0, 1, 2, 3, 4, and 5 had associated morbidity rates of 17.9% (142 of 795 patients), 25.1% (178 of 710 patients), 31.4% (126 of 401 patients), 34.4% (48 of 140 patients), 44.4% (16 of 36 patients), and 61.5% (8 of 13 patients), respectively. A frailty score of 0, 1, 2, 3, 4, and 5 had associated mortality rates of 1.8% (14xa0of 795 patients), 3.8% (27 of 710 patients), 4% (16 of 401 patients), 7.1% (10 of 140 patients), 8.3% (3 of 36 patients), and 23.1% (3 of 13 patients), respectively. When using multivariate logistic regression for mortality comparing age, functional status, prealbumin, emergency surgery, wound class, American Society of Anesthesiologists score, and sex, only age and frailty were statistically significant. The odds ratio was 31.84 for frailty (pxa0= 0.015) and 1.05 (pxa0= 0.001) for age.nnnCONCLUSIONSnUsing a large national database, a modified frailty index was shown to correlate with postesophagectomy morbidity and mortality. Such an index may be used to aid in improving risk assessment and patient selection for esophagectomy.

Diffusion lung capacity for carbon monoxide (DLCO) is an independent prognostic factor for long-term survival after curative lung resection for cancer.

We examined the early and late prognostic significance of DLCO and forced expiratory volume in 1u2009sec (FEV1) in patients who underwent surgical resection of lung cancer.

Targeted serum metabolite profiling of nucleosides in esophageal adenocarcinoma

Nucleosides are indicators of the whole-body turnover of transfer RNA. Based on the activity of cancer cells these molecules could potentially be used as cancer biomarkers, and several studies have determined that the metabolic levels of nucleosides are significantly altered in cancer patients compared to control groups. Here we report a targeted metabolite investigation of serum nucleosides in esophageal adenocarcinoma specimens. We quantified eight nucleosides using high-performance liquid chromatography/triple quadrupole mass spectrometry (HPLC/TQMS) and determined that the metabolic levels of 1-methyladenosine (p <2.14u2009×u200910(-7)), N(2),N(2)-dimethylguanosine (p <2.78u2009×u200910(-7)), N(2)-methylguanosine (p <2.48u2009×u200910(-6)) and cytidine (p <6.98u2009×u200910(-4)) were significantly elevated while the concentration of uridine (p <3.74u2009×u200910(-3)) was significantly lowered in serum samples from cancer patients compared to those of control group. Our results suggest that nucleosides could potentially serve as useful biomarkers to identify esophageal adenocarcinoma.

Surgical management of pulmonary and mediastinal sequelae of histoplasmosis: a challenging spectrum.

BACKGROUNDnHistoplasmosis may result in a spectrum of complications that require thoracic surgical intervention. We reviewed our 17-year experience in the management of histoplasmosis to determine outcomes as well as gain insight into the distribution of complications requiring surgical intervention.nnnMETHODSnThe hospital records of patients who underwent surgical treatment for complications related to histoplasmosis from 1991 to 2008 were reviewed. Based on the predominant presentation, patients were categorized with complications secondary to broncholithiasis, granulomatous disease, or fibrosing mediastinitis. Patients who underwent diagnostic surgery and were found to have histoplasmosis were excluded.nnnRESULTSnOf the 49 patients who underwent surgery for histoplasmosis-related complications, 27 (55%) had granulomatous disease, 13 (27%) had broncholithiasis, and 9 (18%) had fibrosing mediastinitis. The most common clinical presentations were recurrent pneumonia (n = 16) and hemoptysis (n = 13); less common presentations included dysphagia (n = 3) and superior vena cava syndrome (n = 1). Two patients required cardiopulmonary bypass for resection; 1 of these died postoperatively (series mortality 2%). Seven patients (14%) had complications. Relief of symptoms was achieved in all surviving patients.nnnCONCLUSIONSnComplications of histoplasmosis requiring thoracic surgical intervention are diverse with pulmonary complications predominating. Although surgically challenging, excellent short- and long-term outcomes may be expected.

Robot-Assisted Minimally Invasive Ivor Lewis Esophagectomy With Real-Time Perfusion Assessment

BACKGROUNDnSurgical resection is viewed as the most effective way to ensure both locoregional control and long-term survival in esophageal cancer. Although minimally invasive esophagectomy has been widely accepted as an alternative to open surgery, the role of robotic assistance has yet to be elucidated. We report our institutional experience with robotic-assisted Ivor Lewis esophagectomy using real-time perfusion assessment and demonstrate this as a safe and technically feasible alternative to traditional open Ivor Lewis esophagectomy.nnnMETHODSnA retrospective chart review of all patients undergoing robotic-assisted Ivor Lewis esophagectomy at a single institution from 2011 to 2014 was performed. Operative and postoperative outcomes were recorded.nnnRESULTSnFifty-four patients underwent robotic-assisted Ivor Lewis esophagectomy during the study period. Indication for surgery was cancer in 49 patients, 38 of whom underwent neoadjuvant chemoradiation therapy. The average operative time was 6 hours 2 minutes, and the average blood loss was 74 mL. There was 1 postoperative mortality (1.9%). Three (5.5%) patients experienced an anastomotic leak. The average number of lymph nodes harvested in cancer patients was 16.2 (range, 3 to 35). The average length of stay was 12.9 days.nnnCONCLUSIONSnOur study demonstrates that robotic-assisted Ivor Lewis esophagectomy using real-time perfusion assessment is a safe and technically feasible alternative to traditional open Ivor Lewis esophagectomy. It allows for R0 resection with adequate lymph node harvesting and a short hospital stay.

Clinical Utility of a Plasma Protein Classifier for Indeterminate Lung Nodules

Evaluation of indeterminate pulmonary nodules is a complex challenge. Most are benign but frequently undergo invasive and costly procedures to rule out malignancy. A plasma protein classifier was developed that identifies likely benign nodules that can be triaged to CT surveillance to avoid unnecessary invasive procedures. The clinical utility of this classifier was assessed in a prospective–retrospective analysis of a study enrolling 475 patients with nodules 8–30xa0mm in diameter who had an invasive procedure to confirm diagnosis at 12 sites. Using this classifier, 32.0xa0% (CI 19.5–46.7) of surgeries and 31.8xa0% (CI 20.9–44.4) of invasive procedures (biopsy and/or surgery) on benign nodules could have been avoided. Patients with malignancy triaged to CT surveillance by the classifier would have been 24.0xa0% (CI 19.2–29.4). This rate is similar to that described in clinical practices (24.5xa0% CI 16.2–34.4). This study demonstrates the clinical utility of a non-invasive blood test for pulmonary nodules.

Barrett's Esophagus After Resection of the Gastroesophageal Junction: Effects of Concomitant Fundoplication

BackgroundBarrett’s metaplasia has been known to occur after esophagectomy or gastrectomy in which the gastroesophageal junction with its associated lower esophageal sphincter has been resected. It is thought to be secondary to the refluxogenic nature of the operation. The present study was based on the hypothesis that patients who undergo a fundoplication with the resection would have a lower incidence of the development of postoperative Barrett’s metaplasia.MethodsAll patients who underwent any type of esophagectomy or proximal gastrectomy in which the gastroesophageal junction was resected and an esophagogastrostomy performed were eligible for the study. Data gathered included age, gender, preoperative diagnosis, operation, postoperative pathology, occurrence and timing of postoperative upper endoscopy, and presence of Barrett’s metaplasia on postoperative endoscopy. Statistical analysis was done with Fisher’s exact test.ResultsOf the 179 patients who underwent resection, 151 had follow-up endoscopy documenting the presence or absence of Barrett’s esophagus. Follow-up ranged from 6xa0months to 10xa0years. Of the 53 patients without fundoplications, 8 (18%) had Barrett’s esophagus on follow-up upper endoscopy. Of the 98 patients with fundoplications, 5 (6%) had Barrett’s esophagus (Pxa0=xa00.04).ConclusionsThe present study suggests that concomitant fundoplication with resection of the gastroesophageal junction may have some protective effect against the development of Barrett’s esophagus. A randomized trial will be required to prove this assertion. Also, it is still unclear as to the consequences of the development of post-resection Barrett’s esophagus.