Christian Rizzetto

Four hundred laparoscopic myotomies for esophageal achalasia: a single centre experience.

Objective:Laparoscopic myotomy is the currently preferred treatment for achalasia. Our objectives were to assess the long-term outcome of this operation and preoperative factors influencing said outcome. Methods:Demographic and clinical characteristics and data on long-term outcome were prospectively collected on patients undergoing laparoscopic myotomy for achalasia at our institution from 1992 to 2007. Treatment failure was defined as a postoperative symptom score higher than the 10th percentile of the preoperative score (>9). Logistic regression analysis was used to identify independent preoperative factors associated with successful myotomy. Results:Four hundred seven consecutive patients (220 men, 187 women) underwent the laparoscopic Heller-Dor procedure during the study period; 89 (22%) of them had previously had endoscopic treatment(s). The mortality rate was 0; the conversion and morbidity rates were 1.5% and 1.9%, respectively. The operation failed in 10% of patients (39/407) and the 5-year actuarial probability of being asymptomatic was 87%. Most failures (25/39, 64%) occurred within 12 months of the operation and can be considered as technical failures (incomplete myotomy). Pneumatic dilation overcome the dysphagia in 75% of patients whose surgery was unsuccessful. Considering both the primary surgery and this ancillary treatment, the operation was effective in 97% of achalasia patients. The frequency of sigmoid esophagus, lower esophageal sphincter (LES) resting pressures, and chest pain scores differed statistically between patients with and without recurrences. At multivariate analysis, high preoperative LES pressures (>30 mm Hg) was an independent predictor of a good response. The presence of chest pain and of sigmoid esophagus independently predicted the failure of the procedure. Conclusion:Laparoscopic myotomy can durably relieve dysphagia symptoms. High preoperative LES pressures represent the strongest predictor of a positive outcome, probably reflecting a less severely damaged esophageal muscle.

Vagal-sparing esophagectomy: The ideal operation for intramucosal adenocarcinoma and Barrett with high-grade dysplasia

Objective:Our aim was to compare outcome of vagal-sparing esophagectomy with transhiatal and en bloc esophagectomy in patients with intramucosal adenocarcinoma or high-grade dysplasia. Summary Background Data:Intramucosal adenocarcinoma and high grade dysplasia have a low likelihood of lymphatic or systemic metastases and esophagectomy is curative in most patients. However, traditional esophagectomy is associated with significant morbidity and altered gastrointestinal function. A vagal-sparing esophagectomy offers the advantages of complete disease removal with the potential for reduced morbidity and a better functional outcome. Method:Retrospective review of outcome in patients with intramucosal adenocarcinoma or high grade dysplasia that had a vagal-sparing (n = 49), transhiatal (n = 39) or en bloc (n = 21) esophagectomy. Results:The length of hospital stay and the incidence of major complications was significantly reduced with a vagal-sparing esophagectomy compared with a transhiatal or en bloc resection. Further, postvagotomy dumping and diarrhea symptoms were significantly less common, and weight was better maintained postoperatively with a vagal-sparing esophagectomy. Recurrent cancer has developed in only 1 patient. Conclusion:Survival with intramucosal adenocarcinoma or Barretts with high-grade dysplasia is independent of the type of resection. A vagal-sparing esophagectomy is associated with significantly less perioperative morbidity and a shorter hospital stay than a transhiatal or en bloc esophagectomy. Further, late morbidity including weight loss, dumping, and diarrhea are significantly less likely after a vagal-sparing approach. Consequently a vagal-sparing esophagectomy is the preferred procedure for patients with intramucosal adenocarcinoma or high grade dysplasia.

En bloc esophagectomy reduces local recurrence and improves survival compared with transhiatal resection after neoadjuvant therapy for esophageal adenocarcinoma

OBJECTIVE Neoadjuvant therapy is commonly used for esophageal adenocarcinoma. We have reported reduced local recurrence rates and improved survival after an en bloc esophagectomy compared with a transhiatal resection as primary therapy for adenocarcinoma of the esophagus. The aim of this study was to determine whether the benefits of an en bloc resection would extend to patients after neoadjuvant therapy. METHODS The charts of all patients with esophageal adenocarcinoma that had neoadjuvant therapy and en bloc or transhiatal esophagectomy from 1992-2005 were reviewed. Patients found to have systemic metastatic disease at the time of the operation or who had an incomplete resection were excluded. RESULTS There were 58 patients: 40 had an en bloc resection and 18 had a transhiatal esophagectomy. A complete pathologic response occurred in 17 (29.3%) of 58 patients. Median follow-up was 34.1 months after en bloc resection and 18.3 months after transhiatal resection (P = .18). Overall survival at 5 years and survival in patients with residual disease after neoadjuvant therapy was significantly better with an en bloc resection (overall survival: 51% for en bloc resection and 22% for transhiatal resection [P = .04]; survival with residual disease: 48% for en bloc resection and 9% for transhiatal resection [P = .02]). Survival in patients with complete pathologic response tended to be better after an en bloc resection (en bloc, 70%; transhiatal, 43%; P = .3). CONCLUSION An en bloc resection provides a survival advantage to patients after neoadjuvant therapy compared with a transhiatal resection, particularly for those with residual disease. Similar to patients treated with primary resection, an en bloc esophagectomy is the procedure of choice after neoadjuvant therapy.

Aurora kinase A in Barrett’s carcinogenesis

In Barretts mucosa, both aneuploidy and TP53 mutations are consistently recognized as markers of an increased risk of Barretts 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 Barretts carcinogenesis (gastric metaplasia in 25, intestinal metaplasia in 25, low-grade intraepithelial neoplasia in 16, high-grade intraepithelial neoplasia in 11, and Barretts adenocarcinoma in 10) were obtained from long segments of Barretts 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 Barretts adenocarcinomas showed AURKA immunostaining. AURKA expression correlated significantly with p53 expression and the micronuclei index (both Ps < .001). AURKA overexpression is significantly associated with Barretts mucosa progressing to Barretts adenocarcinoma and contributes to esophageal carcinogenesis via chromosome instability. The identification of AURKA as a novel molecular target of cancer progression in Barretts mucosa provides a lead for the development of new therapeutic approaches in Barretts mucosa patients.

T1912 Association Between Ccttt Pentanucleotide Repeat in the Inducible Nitric Oxide Synthase Promoter Polymorphism and Achalasia

averaging successive swallows cancels out extrinsic pressure from HREPT studies, isolating the intrinsic esophageal contraction. Topographic plots of peristalsis can thus be reduced in a coordinate-specific scheme to three sequential zones: inhibition-contraction-quiescence. Consequently, motility disorders can similarly be physiologically defined as impaired inhibition (achalasia), abnormal contraction (hyper or hypotensive peristalsis) or persistent contraction (spastic nutcracker) depending on the length-time coordinates of abnormal contractile activity.

Abstract 3050: MicroRNA expression profiling of human Barrett's carcinogenesis

Barrett9s Mucosa (BM) is a metaplastic replacement of the native esophageal (squamous) epithelium (ESq) by columnar-intestinalized mucosa. BM is the main risk factor for Barrett9s adenocarcinoma (BAc). MicroRNAs (miRNAs) are a class of small non-coding RNAs that control gene expression by targeting mRNAs; miRNAs deregulation has been associated with Barrett9s oncogenesis. To explore the hypothesis that a specific miRNAs signature is associated with BM (and its associated cancer risk) a miRNA microarray analysis (OSU-CCC version 4.0; Ohio State University) compared ESq versus all the spectrum of the phenotypic lesions of the Barrett9s carcinogenesis. Specimens were collected at Department of Pathology of Padova University from 14 patients undergone esophagectomy for BAc or High-grade non-invasive neoplasia (HG-NiN). Tissues samples for the microarray study included: ESq= 14 samples; BM= 14; Low-grade non-invasive neoplasia (LG-NiN)= 7; HG-NiN= 5; BAc= 11. The miRNA-profiling study consistently disclosed increased expression of 6 miRNAs (hsa-miR-215, hsa-miR-560, hsa-miR-615-3p, hsa-miR-192, hsa-miR-326, hsa-miR-147), and decreased expression of 7 others (hsa-miR-100, hsa-miR-23a, hsa-miR-605, hsa-miR-99a, hsa-miR-205, hsa-let-7c, hsa-miR-203). Microarray results were further validated by qRT-PCR, using a different series of 10 consecutive BAc cases (Esq= 10 samples; BM= 6 samples; BAc= 10 samples). Interestingly, some of the miRNAs found deregulated in this series are already known as suitable markers of cancer progression in other models of epithelial oncogenesis (i.e.: hsa-let-7c, hsa-miR-192, hsa-miR-203, hsa-miR-205, hsa-miR-215). The results achieved by the miRNA profiling study were further validated by the immunohistochemical (IHC) analysis on a well-defined miRNA gene target (HMGA2 [hsa-let-7c]). The IHC expression of the protein product was consistent with the corresponding miRNA9s deregulation. In fact, HMGA2 IHC expression was up-regulated in HG-NiN and BAc. The achieved results confirm that specific miRNAs are involved in BM carcinogenesis and that they may represent a novel diagnostic/prognostic tool in the characterization of BAc gene targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3050.

819 Is Laparoscopic Heller Myotomy Still Indicated in Stage IV Sigmoid Megaesophagus

S A T A b st ra ct s LARS is an effective and durable treatment option for GERD. Success or failure cannot be defined in a single domain. A comprehensive analysis of outcomes requires categorization that includes symptom response, side-effects, patients perception and objective measurement of acid exposure, mucosal integrity, and the need for additional medical or surgical treatment. Only then can patients and physicians better understand the role of LARS and make informed decisions.

M1530 Accidental Mucosal Perforation During Laparoscopic Heller-Dor Myotomy Does Not Affect the Final Outcome of the Operation

as ropeway technique, because the nerves can be seen as ropeways after the completion of the dissection. Another one is new HALS method, named as double gloving method for HALS. With this method, thorough lymph node dissection of the lower mediastinum can be securely performed. RESULTS: Between April 2004 and October 2007, we had performed this procedure for 76 cases of esophageal cancer patient. After introduction of this method, the operation time has become shorter and the complication rate, especially hoarseness has decreased. CONCLUSIONS: These new two techniques, ropeway technique and double gloving method of HALS are feasible for endoscopic esophagectomy with the three-field lymph node dissection and also contribute to safer procedures.