Arzu Oezcelik

Obesity and gastroesophageal reflux: quantifying the association between body mass index, esophageal acid exposure, and lower esophageal sphincter status in a large series of patients with reflux symptoms.

IntroductionObesity and gastroesophageal reflux disease (GERD) are increasingly important health problems. Previous studies of the relationship between obesity and GERD focus on indirect manifestations of GERD. Little is known about the association between obesity and objectively measured esophageal acid exposure. The aim of this study is to quantify the relationship between body mass index (BMI) and 24-h esophageal pH measurements and the status of the lower esophageal sphincter (LES) in patients with reflux symptoms.MethodsData of 1,659 patients (50% male, mean age 51 ± 14) referred for assessment of GERD symptoms between 1998 and 2008 were analyzed. These subjects underwent 24-h pH monitoring off medication and esophageal manometry. The relationship of BMI to 24-h esophageal pH measurements and LES status was studied using linear regression and multiple regression analysis. The difference of each acid exposure component was also assessed among four BMI subgroups (underweight, normal weight, overweight, and obese) using analysis of variance and covariance.ResultsIncreasing BMI was positively correlated with increasing esophageal acid exposure (adjusted R2 = 0.13 for the composite pH score). The prevalence of a defective LES was higher in patients with higher BMI (p < 0.0001). Compared to patients with normal weight, obese patients are more than twice as likely to have a mechanically defective LES [OR = 2.12(1.63–2.75)].ConclusionAn increase in body mass index is associated with an increase in esophageal acid exposure, whether BMI was examined as a continuous or as a categorical variable; 13% of the variation in esophageal acid exposure may be attributable to variation in BMI.

A New Technique for Measurement of Pharyngeal pH: Normal Values and Discriminating pH Threshold

IntroductionIdentifying gastroesophageal reflux disease as the cause of respiratory and laryngeal complaints is difficult and depends largely on the measurements of increased acid exposure in the upper esophagus or ideally the pharynx. The current method of measuring pharyngeal pH environment is inaccurate and problematic due to artifacts. A newly designed pharyngeal pH probe to avoid these artifacts has been introduced. The aim of this study was to use this probe to measure the pharyngeal pH environment in normal subjects and establish pH thresholds to identify abnormality.MethodsAsymptomatic volunteers were studied to define the normal pharyngeal pH environment. All subjects underwent esophagram, esophageal manometry, upper and lower esophageal pH monitoring with a dual-channel pH catheter and pharyngeal pH monitoring with the new probe. Analyses were performed at 0.5 pH intervals between pH 4 and 6.5 to identify the best discriminating pH threshold and calculate a composite pH score to identify an abnormal pH environment.ResultsThe study population consisted of 55 normal subjects. The pattern of pharyngeal pH environment was significantly different in the upright and supine periods and required different thresholds. The calculated discriminatory pH threshold was 5.5 for upright and 5.0 for supine periods. The 95th percentile values for the composite score were 9.4 for upright and 6.8 for supine.ConclusionA new pharyngeal pH probe which detects aerosolized and liquid acid overcomes the artifacts that occur in measuring pharyngeal pH with existing catheters. Discriminating pH thresholds were selected and normal values defined to identify patients with an abnormal pharyngeal pH environment.

Recurrence after Esophagectomy for Adenocarcinoma: Defining Optimal Follow-Up Intervals and Testing

BACKGROUND To determine the optimal follow-up strategy after esophagectomy for adenocarcinoma of the esophagus or gastroesophageal junction by evaluating the timing of recurrence and the method that first detected the recurrence. STUDY DESIGN Between 1991 and 2007, 590 patients had an esophagectomy for adenocarcinoma. Recurrence occurred in 233 (40%) and, of those, 174 had complete follow-up at our center with a protocol that consisted of an office visit with CT scans and laboratory studies every 3 months for 3 years, every 6 months for 2 years, and then annually. A subset of patients had PET annually. RESULTS Recurrence in the 174 patients with complete follow-up was systemic in 104 (60%), locoregional/nodal in 51 (30%), and both in 19 (10%). Recurrence was first suspected by symptoms and/or physical examination in 29 patients (17%), by CT scan in 105 (60%), PET in 32 (18%), and by elevated CEA in 8 (5%). Recurrence was detected at a median of 11 months (range 3 to 72 months) and occurred later after esophagectomy alone compared with patients who received neoadjuvant therapy (12 versus 8 months; p = 0.01), but the pattern of recurrence was similar. More than 90% of recurrences were detected within 2 years after neoadjuvant therapy, compared with 3 years after esophagectomy alone. Median survival after recurrence was 7 months and was significantly longer in patients treated for the recurrence (9 versus 3 months; p = 0.001). CONCLUSIONS Frequent early follow-up is appropriate after esophagectomy for adenocarcinoma because >90% of recurrences will occur by 3 years after esophagectomy alone and by 2 years following neoadjuvant therapy. Beyond these time periods, 2% to 3% of recurrences were detected each year, suggesting that annual follow-up is adequate. Survival after recurrence was improved with therapy, confirming the use of careful follow-up in these patients.

Clinical characteristics, biologic behavior, and survival after esophagectomy are similar for adenocarcinoma of the gastroesophageal junction and the distal esophagus

OBJECTIVE The Siewert classification system differentiates between adenocarcinoma of the gastroesophageal junction and that of the distal esophagus. The purpose of this study was to evaluate whether there were differences in the location and prevalence of lymph node metastases, type of recurrence, and survival with these tumors that warrant distinguishing between them in clinical practice. METHODS Records of all patients who underwent resection for adenocarcinoma of the distal esophagus or gastroesophageal junction from 1987 to 2007 were retrospectively reviewed. Based on the endoscopic location of the epicenter of the tumor in relation to the gastroesophageal junction, tumors were categorized in 301 patients as being of the distal esophagus and in 208 as being of the gastroesophageal junction. RESULTS There were no significant differences in age, sex, or body mass index between patients with adenocarcinoma of the distal esophagus or gastroesophageal junction. Patients with adenocarcinoma of the distal esophagus were more likely to have reflux symptoms (75% vs 53%, P < .0001) and peritumoral intestinal metaplasia (73% vs 51%, P < .0001) and be in a surveillance program (54% vs 9%, P = .0005) compared with patients with adenocarcinoma of the gastroesophageal junction. However, the prevalence and location of nodal metastases was similar, and in node-positive patients mediastinal node involvement was present in more than 40% of the patients in each group (distal esophageal adenocarcinoma, 47%; gastroesophageal junction adenocarcinoma, 41%). Survival was similar (5 years: distal esophageal adenocarcinoma, 45%; gastroesophageal junction adenocarcinoma, 38%; P = .14), as was the prevalence and type of recurrence. CONCLUSION The prevalence and distribution of lymph node metastases in patients with adenocarcinoma of the distal esophagus and gastroesophageal junction were similar, and after esophagectomy, there was no difference in overall survival or recurrence. Efforts to differentiate between these tumors are unnecessary, and both are effectively treated with esophagectomy.

Genetic variations in angiogenesis pathway genes predict tumor recurrence in localized adenocarcinoma of the esophagus.

Objective:The aim of this study was to determine whether the risk of systemic disease after esophagectomy could be predicted by angiogenesis-related gene polymorphisms. Summary Background Data:Systemic tumor recurrence after curative resection continues to impose a significant problem in the management of patients with localized esophageal adenocarcinoma (EA). The identification of molecular markers of prognosis will help to better define tumor stage, indicate disease progression, identify novel therapeutic targets, and monitor response to therapy. Proteinase-activated-receptor 1 (PAR-1) and epidermal growth factor (EGF) have been shown to mediate the regulation of local and early-onset angiogenesis, and in turn may impact the process of tumor growth and disease progression. Methods:We investigated tissue samples from 239 patients with localized EA treated with surgery alone. DNA was isolated from formalin-fixed paraffin-embedded normal esophageal tissue samples and polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism and 5′-end [&ggr;-33P] ATP-labeled polymerase chain reaction methods. Results:PAR-1 −506 ins/del (adjusted P value = 0.011) and EGF +61 A>G (adjusted P value = 0.035) showed to be adverse prognostic markers, in both univariate and multivariable analyses. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of PAR-1 −506 ins/del (any insertion allele) and EGF +61 A>G (A/A) were associated with a higher likelihood of developing tumor recurrence (adjusted P value <0.001). Conclusion:This study supports the role of functional PAR-1 and EGF polymorphisms as independent prognostic markers in localized EA and may therefore help to identify patient subgroups at high risk for tumor recurrence.

Ten-year survival of esophageal cancer after an en-bloc esophagectomy

Esophagectomy with gastric pull‐up is the optimal treatment for patients with resectable esophageal cancer. Although the morbidity and mortality of an esophagectomy is reduced, the long‐term outcome remains poor. The aim of this study was to evaluate the 10‐year survival of a standardized multidisciplinary therapy concept for esophageal cancer.

Proximal esophageal pH monitoring: improved definition of normal values and determination of a composite pH score.

BACKGROUND Patients with respiratory and laryngeal symptoms are commonly referred for evaluation of reflux disease as a potential cause. Dual-probe pH monitoring is often performed, although data on normal acid exposure in the proximal esophagus are limited because of the small number of normal subjects and inconsistent placement of the proximal pH sensor in relation to the upper esophageal sphincter. We measured proximal esophageal acid exposure using dual-probe pH and calculated a composite pH score in a large number of asymptomatic volunteers to better define normal values. STUDY DESIGN Eighty-one normal subjects free of reflux, laryngeal, or respiratory symptoms were recruited. All had video esophagraphy to exclude hiatal hernia. Esophageal pH monitoring was performed using 1 of 3 different dual-probe catheters with sensors spaced 10, 15, or 18 cm apart. The standard components of esophageal acid exposure were measured, excluding meal periods. A composite pH score for the proximal esophagus was calculated using these components. RESULTS The final study population consisted of 59 (49% male) subjects, with a median age of 27 years. All had normal distal esophageal acid exposure and no hiatal hernia. The 95(th) percentile values for the percent time the pH was < 4 for the total, upright, and supine periods were 0.9%, 1.2%, and 0.4%, respectively. The 95(th) percentile for the number of reflux episodes was 24 and for the calculated proximal esophageal composite pH score was 16.4. CONCLUSIONS In a large population of normal subjects, we have defined the normal values and calculated a composite pH score for proximal esophageal acid exposure. The total percent time pH < 4 was similar to previously published normal values, but the number of reflux episodes was greater.

Esophagectomy for cancer in octogenarians.

Because of changes in life expectancy, there is an increasing number of elderly patients with esophageal cancer. The aim of this study was to assess the outcome of esophagectomy for cancer in patients 80 years or older. A retrospective review was performed of the records of all patients who underwent esophagectomy for cancer from 1992 to 2007. A cardiac and pulmonary evaluation was obtained on an individual basis in the younger patients and in all octogenarians. Among 560 patients with esophagectomy for cancer, 47 patients (8%) were octogenarians. The median age of the younger group (n= 513) was 63 years (interquartile range 56-71). Octogenarians had significantly more stage III disease (49% vs 31%, P= 0.02) but received less neoadjuvant therapy than younger patients (2% vs 21%, P= 0.0004). In octogenarians, the transhiatal resection was more common than in the younger group (79% vs 36%, P < 0.0001). Weight loss prior to surgery was similar in both groups, but body mass index was significantly lower in octogenarians (25 vs 28 kg/m(2) , P= 0.0002). Major complications occurred in 26% in octogenarians and 31% in the younger group (P= 0.51). Hospital mortality was similar (9% for octogenarians vs 4% in the younger group, P= 0.13). The median postoperative hospital stay was similar at 16 days (P= 0.69). There was no difference in cancer-related survival (median survival 48.9 vs 59.3 months, P= 0.31 log-rank test). Esophagectomy can be performed safely in carefully selected octogenarians with good cardiac and pulmonary function. Patients should not be denied an esophagectomy based only on their age.

Delayed Esophagogastrostomy: A Safe Strategy for Management of Patients with Ischemic Gastric Conduit at Time of Esophagectomy

BACKGROUND Ischemia of the gastric conduit remains an important complication of esophagectomy and is associated with an increased risk of anastomotic leak and sepsis. We report a group of patients with multiple comorbid conditions and an ischemic gastric conduit that was successfully managed by a delayed esophagogastrostomy. STUDY DESIGN Between 2000 and 2007, esophagectomy with gastric pullup was performed in 554 patients. In 37 patients (7%), the combination of an ischemic graft and substantial comorbid conditions prompted delayed reconstruction to avoid an immediate esophagogastrostomy. In these patients, the gastric conduit was brought up and secured in the neck, and a cervical esophagostomy was constructed. Subsequently, a delayed esophagogastrostomy was performed through neck incision. Outcomes were analyzed at a median of 22 months (interquartile range [IQR], 13 to 30 months). RESULTS There were 29 male and 8 female patients, with a median age of 65 years (IQR, 58 to 75 years). Thirty-one patients had malignant disease; 12 received neoadjuvant therapy. All 37 patients recovered from their esophagectomy without evidence of ischemic necrosis or fistula from their gastric conduit. In 35 patients, a delayed esophagogastrostomy was performed at a median of 98 days (IQR, 89 to 110 days). At the time of reconstruction, all had well-perfused gastric conduits, and the anastomoses healed without leak, wound infection, or sepsis. A stricture developed in three patients and was treated with dilation. Delayed esophagogastrostomy was never performed in two patients because of development of recurrent malignant disease. CONCLUSIONS Delayed esophagogastrostomy is a safe strategy for management of patients with comorbidities and an ischemic gastric conduit at the time of esophagectomy.

Survival in Lymph Node Negative Adenocarcinoma of the Esophagus after R0 Resection With and Without Neoadjuvant Therapy: Evidence for Downstaging of N Status

BACKGROUND After esophagectomy, many patients who received neoadjuvant therapy have no evidence of lymph node involvement (N0 disease). Whether lymph nodes were initially involved and eradicated by the neoadjuvant therapy (down-staged) or if the nodes were never involved is a subject of debate. To address this issue, we compared clinical outcomes in N0 patients treated with neoadjuvant therapy with outcomes in patients treated with surgery alone. STUDY DESIGN We reviewed records of 100 consecutive patients who underwent R0 esophagectomy for adenocarcinoma with pathologic N0 status. Seventy-five patients were treated by operation alone and 25 received neoadjuvant therapy. Tumor characteristics including length, depth, lymphovascular invasion, and degree of differentiation were compared and longterm survival was assessed by Kaplan-Meier analysis at a median of 46 months (interquartile range 26 to 77 months). RESULTS Tumor characteristics were similar between groups. Recurrence was more common in patients who received neoadjuvant therapy compared with those treated with surgery alone (10 of 25 versus 10 of 75, p=0.0063). Patients with N0 disease after neoadjuvant therapy had a significantly worse survival than patients treated by surgery alone (49% versus 85%, p=0.005). CONCLUSIONS Although neoadjuvant therapy may eradicate lymph node metastases, it does not result in the same outcomes as those achieved in patients with N0 disease treated with surgery alone. The poor clinical outcomes observed in N0 patients after neoadjuvant therapy suggest that they initially had node involvement and were downstaged by eradication of lymph node disease.