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. 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. 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. 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.

The tight junction protein claudin-18 (CLDN18), is often expressed in various cancer types including gastric (GC) and gastroesophageal adenocarcinomas (GECs). In the last years, the isoform CLDN18.2 emerged as a potential drug target in metastatic GCs, leading to the development of monoclonal antibodies against this protein. CLDN18.2 is the dominant isoform of CLDN18 in normal gastric and gastric cancer tissues. In this work, we evaluated the immunohistochemical (IHC) profile of CLDN18 and its correlation with clinical and histopathological features including p53, E-cadherin, MSH2, MSH6, MLH1, PMS2, HER2, EBER and PD-L1 combined positive score, in a large real-world and mono-institutional series of advanced GCs (n = 280) and GECs (n = 70). The association of IHC results with survival outcomes was also investigated. High membranous CLDN18 expression (2+ and 3+ intensity ≥75%) was found in 117/350 (33.4%) samples analyzed. CLDN18 expression correlated with age <70 (p = 0.0035), positive EBV status (p = 0.002), high stage (III, IV) at diagnosis (p = 0.003), peritoneal involvement (p < 0.001) and lower incidence of liver metastases (p = 0.013). CLDN18 did not correlate with overall survival. The predictive value of response of CLDN18 to targeted agents is under investigation in several clinical trials and further studies will be needed to select patients who could benefit from these therapies.