Ermanno Ancona

The Number of Lymph Nodes Removed Predicts Survival in Esophageal Cancer: An International Study on the Impact of Extent of Surgical Resection

Objective:Surveillance, Epidemiology and End Results (SEER) data indicate that number of lymph nodes removed impacts survival in gastric cancer. Our aim was to study this relationship in esophageal cancer. Methods:The study population included 2303 esophageal cancer patients (1381 adenocarcinoma, 922 squamous) from 9 international centers that had R0 esophagectomy prior to 2002 and were followed at regular intervals for 5 years or until death. Patients treated with neoadjuvant or adjuvant therapy were excluded. Results:Operations consisted of esophagectomy with (1700) and without (603) thoracotomy. Median number of nodes removed was 17 (IQR10-29). There were 508 patients with stage I, 853 stage II, and 942 stage III. Five-year survival was 40%. Cox regression analysis showed that the number of lymph nodes removed was an independent predictor of survival (P < 0.0001). The optimal threshold predicted by Cox regression for this survival benefit was removal of a minimum of 23 nodes. Other independent predictors of survival were the number of involved nodes, depth of invasion, presence of nodal metastasis, and cell type. Conclusions:The number of lymph nodes removed is an independent predictor of survival after esophagectomy for cancer. To maximize this survival benefit a minimum of 23 regional lymph nodes must be removed.

Predicting Systemic Disease in Patients With Esophageal Cancer After Esophagectomy: A Multinational Study on the Significance of the Number of Involved Lymph Nodes

Objective:The aim of this study was to determine whether the risk of systemic disease after esophagectomy can be predicted by the number of involved lymph nodes. Summary Background Data:Primary esophagectomy is curative in some but not all patients with esophageal cancer. Identification of patients at high risk for systemic disease would allow selective use of additional systemic therapy. This study is a multinational, retrospective review of patients treated with resection alone to assess the impact of the number of involved lymph nodes on the probability of systemic disease. Methods:The study population included 1053 patients with esophageal cancer (700 adenocarcinoma, 353 squamous carcinoma) who underwent R0 esophagectomy with ≥15 lymph nodes resected at 9 international centers: Asia (1), Europe (5), and United States (3). To ensure a minimum potential follow-up of 5 years, only patients who had esophagectomy before October 2002 were included. Patients treated with neoadjuvant or adjuvant therapy were excluded. The impact of the number of involved lymph nodes on the risk of systemic disease recurrence was assessed using univariate and multivariate analyses. Results:Systemic disease occurred in 40%. The number of involved lymph nodes ranged from 0 to 26 with 55% of patients having at least 1 involved lymph node. The frequency of systemic disease after esophagectomy was 16% for those without nodal involvement and progressively increased to 93% in patients with 8 or more involved lymph nodes. Conclusions:This study shows that the number of involved lymph nodes can be used to predict the likelihood of systemic disease in patients with esophageal cancer. The probability of systemic disease exceeds 50% when 3 or more nodes are involved and approaches 100% when the number of involved nodes is 8 or more. Additional therapy is warranted in these patients with a high probability of systemic disease.

Randomized controlled trial of botulinum toxin versus laparoscopic heller myotomy for esophageal achalasia

Objective:To compare laparoscopic cardia myotomy and fundoplication with botulinum toxin (BoTx) injection in patients with esophageal achalasia. Summary Background Data:Although myotomy is thought to offer better results, recent studies have reported 80% success rates after 2 BoTx injections a month apart. No randomized controlled trials comparing the 2 treatments have been published so far. Materials and Methods:Newly diagnosed achalasia patients were randomly assigned to BoTx injection or laparoscopic myotomy. Symptoms were scored; lower esophageal sphincter resting and nadir pressures were measured by manometry; barium swallow was used to assess esophageal diameter pre- and post-treatment. Eight to one hundred units of BoTx were injected twice, a month apart, at the esophagogastric junction. Myotomy included anterior partial (Dor) or Nissen fundoplication. Results:Eighty patients were involved in the study: 40 received BoTx and 40 underwent myotomy. Mortality was nil. One surgical patient bled from the trocar site. Median hospital stay was 6 days for surgery; BoTox patients were treated as day-hospital admissions. All patients completed the follow-up. After 6 months, the results in the 2 groups were comparable, although symptom scores improved more in surgical patients (82% confidence interval [CI] 76–89 vs. 66% CI 57–75, P < 0.05). The drop in lower esophageal sphincter pressure was similar in the 2 groups; the reduction in esophageal diameter was greater after surgery (19% CI 13–26 vs. 5% CI 2–11, P < 0.05). Later on, symptoms recurred in 65% of the BoTx-treated patients and the probability of being symptom-free at 2 years was 87.5% after surgery and 34% after BoTx (P < 0.05). Conclusion:Laparoscopic myotomy is as safe as BoTx treatment and is a 1-shot treatment that cures achalasia in most patients. BoTx should be reserved for patients who are unfit for surgery or as a bridge to more effective therapies, such as surgery or endoscopic dilation.

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.

Etiology, Diagnosis, and Treatment of Failures After Laparoscopic Heller Myotomy for Achalasia

ObjectiveTo assess the causes of failure of laparoscopic Heller myotomy and to verify whether endoscopic pneumatic dilation is a feasible treatment.Summary Background DataLaparoscopic Heller myotomy has proved an effective treatment for esophageal achalasia, with good or excellent results in 90% of

Esophageal achalasia: Laparoscopic versus conventional open heller-dor operation

BACKGROUND The laparoscopic treatment of esophageal achalasia has recently been introduced, and the occasional reports in the literature seem to indicate considerable advantages for patients in terms of surgical trauma, postoperative discomfort, and appearance. As yet, however, no studies have directly analyzed the benefits and shortcomings of the new surgical technique by comparison with the conventional open procedure. The objective of our study was to review recent experience with the laparoscopic Heller-Dor operation (LAP-HD) at the Department of Surgery of Padua University and compare it with the traditional open Heller-Dor procedure (OPEN-HD) to assess early effectiveness in patients with primary esophageal achalasia. PATIENTS AND METHODS The records of 17 patients who had LAP-HD and a matched group of 17 patients who had OPEN-HD were retrospectively reviewed. The duration of procedures, morbidity, several aspects of the postoperative course, and hospital costs were recorded and compared. Results of clinical follow-up and of manometric and pH-monitoring studies performed 6 months postoperatively were also evaluated in both patient groups. RESULTS LAP-HD took longer than OPEN-HD (mean 178 versus 125 minutes). There was no mortality or major morbidity in either group. Postoperative pain and ileus and need for IV nutrition lasted a shorter time for LAP-HD patients (P < 0.0001). Consequently, the median postoperative hospital stay and the median interval before returning to normal activity were also shorter (4 and 14 days for the LAP-HD group versus 10 and 30 days for the OPEN-HD group, P < 0.0001). During follow-up, dysphagia recurred in 1 patient of the LAP-HD group and gastroesophageal reflux was registered in 1 patient of the OPEN-HD group. Lower esophageal sphincter pressure decreased significantly after both procedures. CONCLUSIONS Laparoscopic management of achalasia leads to short-term results comparable to those of the well-established open technique. In view of the less severe surgical trauma and lower hospital cost, the laparoscopic approach is preferable, but long-term studies are needed.

Treatment of esophageal achalasia with laparoscopic Heller myotomy and Dor partial anterior fundoplication: Prospective evaluation of 100 consecutive patients

In this article we report our experience in 100 consecutive achalasia patients who were treated with laparoscopic Heller myotomy and Dor antireflux fundoplication, with particular regard to the technical problems encountered, the learning curve, and the long-term follow-up. The operation was completed laparoscopically in 94 patients, with a median operative duration of 150 minutes, and a continuous steady reduction in the operating time from the first patients to the last. In six patients the operation was completed through “open” access. Postoperative complications were recorded in six cases. Follow-up was completed in all 100 patients, with a median follow-up of 24 months. Overall, actuarial life-table analysis showed a probability of 90% that patients would be symptom free over a S-year period. Radiologic assessment showed a significant reduction in the esophageal diameter, and manometry showed a significant reduction in the lower esophageal sphincter resting pressure and residual pressure. Twenty-four-hour pH monitoring showed postoperative reflux in 6.9% of the patients. Persistent dysphagia or chest pain was reported by eight patients, which constituted treatment failures. Seven of these eight patients were eventually treated with multiple pneumatic dilatations, which were successful in six cases. It was concluded that laparoscopic Heller myotomy with Dor fundoplication is a feasible and effective treatment for achalasia, with an actuarial success rate of 90% at 5 years.

Chylothorax complicating esophagectomy for cancer: A plea for early thoracic duct ligation

OBJECTIVE Postoperative chylothorax remains an uncommon but potentially life-threatening complication of esophagectomy for cancer, and the ideal management is still controversial. The aim of the study was to compare the outcomes of patients treated nonoperatively with those of patients promptly undergoing reoperation. METHODS From 1980 to 1998, 1787 esophagectomies for esophageal or cardia cancer were performed, and 19 (1.1%) patients had postoperative chylothorax. We analyzed type of operation, surgical approach, delay of diagnosis of chylothorax, daily chest tube output, type of management, major complications, death, hospital stay, and final outcome. RESULTS Of the 19 patients with chylothorax, 11 were initially managed nonoperatively (group A): 4 (36%) patients had spontaneous resolution of chylothorax, and the other 7 required reoperation for the persistence of a high-volume output. There were three infectious complications and one postoperative death in this group. No reliable predictive criteria of successful versus unsuccessful nonoperative management could be found. The 8 most recent patients underwent early reoperation (group B). All patients recovered, and no major complications possibly related to chylothorax or hospital deaths were observed. They were discharged after a median of 22 days (range, 12-85 days) compared with a median of 36 days (range, 21-64 days) for patients of group A. CONCLUSIONS Early thoracic duct ligation is the treatment of choice for chylothorax occurring after esophagectomy. Reoperation should be performed immediately after the diagnosis is made to avoid the complications related to nutritional and immunologic depletion caused by prolonged nonoperative treatment.

Altered esophageal pain threshold in irritable bowel syndrome

Gut motility disorders and altered pain perception were reported in patients with irritable bowel syndrome (IBS). To verify foregut involvement in IBS, we studied 30 patients using esophageal manometry and 24-hr pH monitoring of the distal esophagus. Two subgroups of patients underwent esophageal provocative tests (bethanechol 50 μg/kg subcutaneously and esophageal balloon distension test). Twelve healthy volunteers formed a control group. A pain threshold on esophageal distension significantly lower than in healthy subjects (11.5±1 ml vs 22.2±1.7 ml,P<0.01) was found in IBS patients. On the other hand, no differences between patients and controls were detected in lower esophageal sphincter pressure and length, esophageal body motility, or GER pattern; furthermore, bethanechol stimulation elicited similar esophageal body motility changes. Our study could confirm no detectable basal or bethanechol-induced esophageal motility disorders in IBS patients, nor enhanced GER. Esophageal involvement in IBS consists of a lower pain threshold on esophageal distension, possibly reflecting an altered visceral receptor sensitivity or modulation throughout the gut.

MicroRNA expression profiling in human Barrett's carcinogenesis.

Barretts esophagus (BE) is characterized by the native stratified squamous epithelium (N) lining the esophagus being replaced by a columnar epithelium with intestinal differentiation (Barretts mucosa; BM). BM is considered as the main risk factor for esophageal adenocarcinoma (Barretts adenocarcinoma; BAc). MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting messenger RNAs and they are reportedly dysregulated in BM. To test the hypothesis that a specific miRNA expression signature characterizes BM development and progression, we performed miRNA microarray analysis comparing native esophageal mucosa with all the phenotypic lesions seen in the Barretts carcinogenic process. Specimens were collected from 14 BE patients who had undergone esophagectomy, including: 14 with N, 14 with BM, 7 with low‐grade intraepithelial neoplasia, 5 with high‐grade intra‐epithelial neoplasia and 11 with BAc. Microarray findings were further validated by quantitive real‐time polymerase chain reaction and in situ hybridization analyses using a different series of consecutive cases (162 biopsy samples and 5 esophagectomies) of histologically proven, long‐segment BE. We identified a miRNA signature of Barretts carcinogenesis consisting of an increased expression of 6 miRNAs and a reduced expression of 7 miRNAs. To further support these results, we investigated target gene expression using the Oncomine database and/or immunohistochemical analysis. We found that target gene expression correlated significantly with miRNA dysregulation. Specific miRNAs are directly involved in BE progression to cancer. miRNA profiling significantly expands current knowledge on the molecular history of Barretts carcinogenesis, also identifying molecular markers of cancer progression.