Search

Background: A new manometric classification of esophageal achalasia has recently been proposed that also suggests a correlation with the final outcome of treatment. The aim of this study was to investigate this hypothesis in a large group of achalasia patients undergoing laparoscopic Heller-Dor myotomy.Methods: We evaluated 246 consecutive achalasia patients who underwent surgery as their first treatment from 2001 to 2009. Patients with sigmoid-shaped esophagus were excluded. Symptoms were scored and barium swallow X-ray, endoscopy, and esophageal manometry were performed before and again at 6 months after surgery. Patients were divided into three groups: (I) no distal esophageal pressurization (contraction wave amplitude <30 mmHg); (II) rapidly propagating compartmentalized pressurization (panesophageal pressurization >30 mmHg); and (III) rapidly propagating pressurization attributable to spastic contractions. Treatment failure was defined as a postoperative symptom score greater than the 10th percentile of the preoperative score (i.e., >7).Results: Type III achalasia coincided with a longer overall lower esophageal sphincter (LES) length, a lower symptom score, and a smaller esophageal diameter. Treatment failure rates differed significantly in the three groups: I = 14.6% (14/96), II = 4.7% (6/127), and III = 30.4% (7/23; p = 0.0007). At univariate analysis, the manometric pattern, a low LES resting pressure, and a high chest pain score were the only factors predicting treatment failure. At multivariate analysis, the manometric pattern and a LES resting pressure <30 mmHg predicted a negative outcome.Conclusion: This is the first study by a surgical group to assess the outcome of surgery in 3 manometric achalasia subtypes: patients with panesophageal pressurization have the best outcome after laparoscopic Heller-Dor myotomy. [ABSTRACT FROM AUTHOR]

Summary: In Barrett''s mucosa, both aneuploidy and TP53 mutations are consistently recognized as markers of an increased risk of Barrett''s adenocarcinoma. Overexpression of the mitotic kinase encoding gene (AURKA) results in chromosome instability (assessed from the micronuclei count) and ultimately in aneuploidy. Eighty-seven esophageal biopsy samples representative of all the phenotypic lesions occurring in the multistep process of Barrett''s carcinogenesis (gastric metaplasia in 25, intestinal metaplasia in 25, low-grade intraepithelial neoplasia in 16, high-grade intraepithelial neoplasia in 11, and Barrett''s adenocarcinoma in 10) were obtained from long segments of Barrett''s mucosa. Twenty-five additional biopsy samples of native esophageal mucosa were used for control purposes. In all tissue samples, the immunohistochemical expression of both AURKA and TP53 gene products was scored; and the micronuclei index was calculated. AURKA immunostaining increased progressively and significantly along with dedifferentiation of the histologic phenotype (P < .001). Nine of 10 Barrett''s adenocarcinomas showed AURKA immunostaining. AURKA expression correlated significantly with p53 expression and the micronuclei index (both Ps < .001). AURKA overexpression is significantly associated with Barrett''s mucosa progressing to Barrett''s adenocarcinoma and contributes to esophageal carcinogenesis via chromosome instability. The identification of AURKA as a novel molecular target of cancer progression in Barrett''s mucosa provides a lead for the development of new therapeutic approaches in Barrett''s mucosa patients. [Copyright &y& Elsevier]

Background: Zenker's diverticula (ZD) can be treated by transoral diverticulostomy or open surgery (upper esophageal sphincter myotomy and diverticulectomy or diverticulopexy). The aim of this study was to compare the effectiveness of a minimally invasive (group A) versus a traditional open surgical approach (group B) in the treatment of ZD.Material and Methods: Between 1993 and September 2007, 128 ZD patients underwent transoral diverticulostomy (n = 51) or cricopharyngeal myotomy and diverticulectomy or diverticulopexy (n = 77). All patients were evaluated for symptoms using a detailed questionnaire. Manometry recorded upper esophageal sphincter (UES) pressure, relaxations, and intrabolus pharyngeal pressure. The size of the pouch was measured on the barium swallow. The choice of treatment was based on the size of the diverticulum and the patients' preference. Long-term follow-up data were available for 121/128 (94.5%) patients with a median follow-up of 40 months (interquartile range, 17-83).Results: Mortality was nil. Three patients in group A (5.8%) and ten in group B (13%) had postoperative complications (p = n.s.). Hospital stays were markedly shorter for patients after diverticulostomy (p < 0.01). Postoperative manometry showed a reduction in UES pressure, improved UES relaxation, and lower intrabolus pressure in both groups (p < 0.05). Four patients in the open surgery group (5.2%) complained of severe dysphagia after surgery (three of them required endoscopic dilations). In the transoral diverticulostomy group, 11 patients (21.5%) required additional septal reduction (n = 8) or a surgical myotomy (n = 3) for persistent symptoms (p < 0.01); nine of these 11 patients had a ZD < or = 3 cm in size. After primary and complementary treatments, symptoms disappeared or improved significantly at long-term follow-up in 93.5% of patients in group A and 96% of those in group B.Conclusion: Diverticulostomy is safe, quick, and effective for most patients with medium-sized ZD, but open surgery offers better long-term results as a primary treatment and should be recommended for younger, healthy patients, especially those with small diverticula. Small ZD may represent a formal contraindication to the transoral approach because an excessively short septum prevents a complete division of the sphincter fibers. [ABSTRACT FROM AUTHOR]

Introduction: The natural history of esophageal epiphrenic diverticula (ED) is not entirely clear; the decision whether to operate or not is often based on the personal preference of the physician and patient. The aim of this study was to evaluate the long-term fate of operated and unoperated patients with ED.Materials and Methods: Clinical, radiological, and motility findings, and operative morbidity and long-term outcome of 41 patients with ED (January 1993 to December 2005) were analyzed. All patients were reviewed at the outpatient clinic or interviewed over the phone. A symptom score was calculated using a standard questionnaire and subjective patient assessment. The radiological maximum diameter of the ED was measured.Results: Twenty-two patients (12M:10F; median age, 60 years) were operated. One underwent surgery for spontaneous rupture of a large diverticulum. Operative mortality was nil; postoperative morbidity was 22.7%, the most severe complication being suture leakage (4 patients, all managed conservatively); median follow-up was 53 months. Nineteen patients (9M, 10F; median age 70 years) were not operated: 3 received pneumatic dilations; median follow-up was 46 months. None of the patients in either group died for reasons related to their ED. Symptoms decreased in all operated patients and, to a lesser extent, also in unoperated patients. ED recurrence was observed in one operated patient. Four patients had GERD symptoms with esophagitis and/or positive pH-metry after surgery and 3 patients had persistent dysphagia/regurgitation and were dissatisfied with the outcome of surgery.Discussion: Surgery is an effective treatment for ED, but carries a significant morbidity related mainly to suture leakage. Even in the long-term, unoperated patients do not die of their ED, though a better subjective symptom outcome is reported by operated patients. A non-interventional policy can safely be adopted in cases of small, mildly symptomatic ED. [ABSTRACT FROM AUTHOR]

Most papers report excellent results of laparoscopic fundoplication but with relatively short follow-up. Only few studies have a follow-up longer than 5 years. We prospectively collected data of 399 consecutive patients with gastroesophageal reflux disease (GERD) or large paraesophageal/mixed hiatal hernia who underwent laparoscopic fundoplication between January 1992 and June 2005. Preoperative workup included symptoms questionnaire, videoesophagogram, upper endoscopy, manometry, and pH-metry. Postoperative clinical/functional studies were performed at 1, 6, 12 months, and thereafter every other year. Patients were divided into four groups: GERD with nonerosive esophagitis, erosive esophagitis, Barrett's esophagus, and large paraesophageal/mixed hiatal hernia. Surgical failures were considered as follows: (1) recurrence of GERD symptoms or abnormal 24-h pH monitoring; (2) recurrence of endoscopic esophagitis; (3) recurrence of hiatal hernia/slipped fundoplication on endoscopy/barium swallow; (4) postoperative onset of dysphagia; (5) postoperative onset of gas bloating. One hundred and forty-five patients (87 M:58 F) were operated between January 1992 and June 1999: 80 nonerosive esophagitis, 29 erosive esophagitis, 17 Barrett's esophagus, and 19 large paraesophageal/mixed hiatal hernias. At a median follow-up of 97 months, the success rate was 74% for surgery only and 86% for primary surgery and 'complementary' treatments (21 patients: 13 redo surgery and eight endoscopic dilations). Dysphagia and recurrence of reflux were the most frequent causes of failure for nonerosive esophagitis patients; recurrence of hernia was prevalent among patients with large paraesophageal/mixed hiatal hernia. Gas bloating (causing failure) was reported by nonerosive esophagitis patients only. At last follow-up, 115 patients were off 'proton-pump inhibitors'; 30 were still on medications (eight for causes unrelated to GERD). Conclusion confirms that laparoscopic fundoplication provides effective, long-term treatment of gastroesophageal reflux disease. Hernia recurrence and dysphagia are its weak points. [ABSTRACT FROM AUTHOR]

Laparoscopic Heller myotomy has recently emerged as the treatment of choice for esophageal achalasia. Previous unsuccessful treatments (pneumatic dilations or botulinum toxin [BT] injections) can make surgery more difficult, causing a higher risk of mucosal perforation and jeopardizing the outcome. The study goal was to evaluate the effects of prior endoscopic treatments on laparoscopic Heller myotomy. Between January 1992 and February 2005, 248 patients (130 males and 118 females; median age, 43 years) underwent a laparoscopic Heller-Dor operation for achalasia: 203 underwent primary surgery (group A), 19 had been previously treated with pneumatic dilations (group B), and 26 had BT injections (alone [22] or with dilations [4] (group C)). Median duration of the operation and rate of intraoperative mucosal lesions were not different in the three groups. Median follow-up was 41 months. The 5-year actuarial of control of dysphagia was similar in groups A (86%) and B (94%), whereas only 75% of group C patients were symptom free at 5 years (P = 0.02). On logistic regression analysis, prior treatment with two BT injections or BT combined with dilation was associated with poor outcome of surgery. Further, dilations for surgical failure patients were effective in 80% of group A but in only 33% of group B or C patients. Heller-Dor surgery is safe and effective as a primary or a second-line treatment (after pneumatic dilations or BT injections) for achalasia. However, long-term results seem less satisfactory in patients previously treated with BT. [ABSTRACT FROM AUTHOR]

Barrett''s epithelium (BE), defined as endoscopically visible, histologically proved intestinal-type epithelium in the esophagus, is considered the ultimate consequence of long-standing gastro(duodeno)esophageal reflux disease (GERD). Recent reports suggest that effective antireflux therapy may promote the regression of this metaplastic process. This study aimed to establish whether antireflux surgery (laparoscopic fundoplication) can induce any endoscopic and/or histologic changes in BE. Thirty-five consecutive cases of BE (11 short-segment [SBE] and 24 long-segment [LBE]) were considered. All patients underwent extensive biopsy sampling before and after surgery (mean follow-up, 28 months; range, 12–99 mo). In all cases, (a) intestinal metaplasia (IM) extension (H&E), (b) IM phenotype (high-iron diamine [HID]), and (c) Cdx2 immunohistochemical expression were histologically scored in the biopsy material obtained before and after fundoplication. After surgery, a significant decrease in IM extension and a shift from incomplete- to complete-type IM were documented in SBE. No significant changes occurred in the LBE group in terms of IM extension or histochemical phenotype. A drop in the immunohistochemical expression of Cdx2 protein was also only documented in the SBE group. Antireflux surgery significantly modifies the histologic phenotype of SBE, but not of LBE. [Copyright &y& Elsevier]

The aims of this study were to assess the efficacy and safety of botulinum toxin (BoTox) injection in the cricopharyngeus muscle (CP) and CP myotomy in patients with oropharyngeal dysphagia (OPD) and to identify factors predicting the outcome of these treatments. The study involved patients with persistent OPD despite 2–6 months of rehabilitation, who all underwent clinical evaluation, esophageal manometry, upper gastrointestinal endoscopy, and videofluoroscopy (VFS). Patients received 5–10 BoTox units injections in the CP, identified by electromyography. Surgical myotomy of the upper esophageal sphincter was performed when dysphagia persisted after two BoTox injections. After treatment, patients were reevaluated with clinical interviews and VFS. The study population included 21 patients (15 mean and 6 women; median age, 68 years), classified into three groups, based on the etiology of their OPD: eight (38%) had central nervous system abnormalities, five (24%) had peripheral nerve disease, and eight (38%) were classified as idiopathic. The median time since the onset of dysphagia was 18 months. Thirteen of 21 patients (62%) needed supplemental/total gastrostomy feeding, and 5 of 21 (24%) had tracheostomy. One patient died, on posttreatment day 7, due to massive aspiration. No other BoTox-related complications were observed. After BoTox injection, dysphagia improved in 9 of 21 (43%) patients. Severely altered VFS findings and CP incoordination or low activity predicted BoTox failure at multivariate analysis. Dysphagia improved in 8 of 11 (72.7%) patients who failed to respond to BoTox and underwent myotomy. A mild impairment of VFS findings and a higher pressure of pharyngeal contractions best predicted response to BoTox with or without myotomy. BoTox injection can be used as the first therapeutic option in patients with OPD: it is safe and simple and relieves dysphagia in 43% of cases. If BoTox fails, CP myotomy can be offered to patients with preserved oral and tongue activity at VFS and an intact bolus propulsion ability on manometry. [Copyright &y& Elsevier]

This study was designed to test the hypothesis that mononuclear cells in the myenteric plexus of patients with achalasia may be activated by herpes simplex virus type 1 (HSV-1). Strips of esophageal muscle were obtained from patients with achalasia and multiorgan transplant donors who served as control subjects. After muscle digestion, mononuclear cells were purified through a Percoll gradient and cultured in medium, either alone or containing ultraviolet-inactivated HSV-1 or poliovirus (multiplicity of infection 1:1.5). As an indicator of HSV-1–induced lymphocyte activation, we determined T-cell proliferation by means of 3H-thymidine incorporation and interferon gamma release. DNA was extracted from esophageal muscle of achalasia patients and control subjects, and used as a template for PCR analysis using primer pairs specific for HSV-1. Circulating anti–HSV-1 and HSV-2 antibodies were detected by enzyme-linked immunosorbent assay on serum samples. Fifteen patients with naive achalasia and eight control subjects were studied. The prevalence of circulating anti–HSV-1 and HSV-2 antibodies proved similar in the two groups, and no HSV-1 DNA was detected by polyermase chain reaction in the esophageal muscle samples. The proliferative index in mononuclear cells from achalasia patients stimulated with HSV-1 showed a 3.4-fold increase in comparison with control subjects (P<0.01). In addition, a 1.4-fold increase in interferon gamma release after incubation with HSV-1 was observed in cells from achalasia patients but not control subjects. The results of this study indicate that HSV-1–reactive immune cells are present in lower esophageal sphincter muscles of patients with achalasia. We hypothesize that the HSV-1–reactive lymphocytes in lower esophageal sphincter muscles of achalasia patients may contribute to damage of the neurons in the myenteric plexus and lead to the motor dysfunction. [Copyright &y& Elsevier]

Background: Mucosal ablation and endoscopic mucosal resection have been proposed as alternatives to surgical resection as therapy for intramucosal adenocarcinoma (IMC) of the esophagus. Acceptance of these alternative therapies requires an understanding of the clinical biology of IMC and the results of surgical resection modified for treatment of early disease. Study design: Retrospective review of 78 patients (65 men, 13 women; median age 66 years) with IMC who were treated with progressively less-extensive surgical resections (ie, en bloc, transhiatal, and vagal-sparing esophagectomy) from 1987 to 2005. Results: The tumor was located in a visible segment of Barrett’s esophagus in 65 (83%) and in cardia intestinal metaplasia in 13 (17%). A visible lesion was present in 53 (68%) and in all but 4 the lesion was cancer. In those patients with visible Barrett’s, the tumor was within 3 cm of the gastroesophageal junction in 66% and within 1 cm in 37%. Esophagectomy was en bloc in 23, transhiatal in 31, vagal-sparing in 20, and transthoracic in 4. Operative mortality was 2.6%. Vagal-sparing esophagectomy had less morbidity, a shorter hospital stay, and no mortality. Of the patients who had en bloc resection, a median of 41 nodes were removed. One patient had one lymph node metastasis on hematoxylin and eosin staining and two others, normal on hematoxylin and eosin staining, had micrometastases on immunohistochemistry. Actuarial survival at 5 years was 88% and was similar for all types of resections. Two patients died from systemic metastases and seven from noncancer causes. Conclusions: IMC occurred in cardia intestinal metaplasia and in Barrett’s esophagus. Two-thirds of patients with IMC had a visible lesion. Most tumors occurred near the gastroesophageal junction. Node metastases were uncommon, questioning the need for lymphadenectomy. A vagal-sparing technique had less morbidity than other forms of resection and no mortality. Survival after all types of resection was similar. Outcomes of endoscopic techniques should be compared with this benchmark. [Copyright &y& Elsevier]