Alberto Ruol

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.

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.

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.

Role of macronutrients, vitamins and minerals in the aetiology of squamous-cell carcinoma of the oesophagus.

Between 1992 and 1997 we conducted a case‐control study of oesophageal cancer in 3 areas of northern Italy. Cases were 304 patients (29 women), ages 39–77 years (median age 60 years), with a first incident squamous‐cell carcinoma (SCC) of the oesophagus. Controls were 743 patients (150 women), ages 35–77 years (median age 60 years), admitted for acute illnesses, unrelated to tobacco and alcohol, to major hospitals of the areas under surveillance. We derived estimates of daily dietary intake of 6 macronutrients, cholesterol, and 20 micronutrients or minerals from a validated food‐frequency questionnaire, including 78 food groups and recipes and 15 questions on individual eating patterns. After allowance for age, gender, area of residence, education, body mass index, physical activity, smoking habit, alcohol consumption and energy intake, most micronutrients were inversely associated with oesophageal SCC risk. Highly significant associations emerged for monounsaturated fatty acids [odds ratio (OR) in highest vs. lowest intake quintile = 0.5]; carotene (OR = 0.3); lutein + zeaxanthin (OR = 0.4); vitamin C (OR = 0.4); and niacin (OR = 0.5). Only retinol appeared to be positively related to risk (OR = 1.9). The effect of the above nutrients, expressed as ORs, appeared to be similar in non‐smokers and smokers, and non/light drinkers and heavy drinkers. Int. J. Cancer 86:626–631, 2000.

Trends in management and prognosis for esophageal cancer surgery: twenty-five years of experience at a single institution.

OBJECTIVE To investigate trends in results of esophagectomies to treat esophageal cancer at a single high-volume institution during the past 25 years. DESIGN AND SETTING Retrospective cohort study in a university tertiary referral center. PATIENTS AND METHODS Patients with cancer of the thoracic esophagus or esophagogastric junction seen from 1980 through 2004 were included (N = 3493). Three time periods were defined: 1980-1987, 1988-1995, and 1996-2004. MAIN OUTCOME MEASURES Clinical presentation, tumor characteristics, and morbidity, mortality, and survival rates among patients with esophageal cancer undergoing esophagectomy. RESULTS The ratio of squamous cell carcinoma to adenocarcinoma decreased from 3.3 to 1.7 (P <.001) during the study period, in parallel with an increase in the number of patients with tumors in the lower esophagus/esophagogastric junction. An increasing proportion of patients who underwent resection received neoadjuvant treatment (chemotherapy/chemoradiotherapy), and 1978 patients underwent esophagectomy. The R0 resection rate increased from 74.5% to 90.1% (P <.001). In addition, an increasing proportion of patients had early-stage tumor in the resected specimen. In-hospital postoperative mortality decreased from 8.2% to 2.6% (P <.001), and the 5-year survival rate significantly improved from 18.8% to 42.3% (P <.001) for all patients who underwent resection. Pathological tumor stage, completeness of the resection, time period, sex, tumor histological type, and tumor location influenced the prognosis of patients with esophageal cancer undergoing esophagectomy. CONCLUSIONS A change in location and histological type of esophageal cancer has occurred during the past 25 years. Earlier diagnosis, a multidisciplinary approach, and refinements in surgical technique and perioperative care have led to a significant reduction in postoperative mortality rate and improved long-term survival among patients with cancer of the thoracic esophagus or esophagogastric junction.

The laparoscopic Heller-Dor operation remains an effective treatment for esophageal achalasia at a minimum 6-year follow-up

BackgroundThe aim of this study was to investigate the long-term clinical outcome of the laparoscopic Heller Dor procedure for esophageal achalasia.MethodsA total of 71 consecutive patients with a minimum 6 year follow-up were evaluated. These patients were seen at 1 and 6 months after the operation (at which time barium swallow, endoscopy, manometry, and pH monitoring were performed), and annually thereafter. A dedicated symptom score, that combined severity and frequency of symptoms was used.ResultsThe median symptom score decreased from 22 (range, 9-29) preoperatively to 4 (range, 0-16) at last follow-up, (p< 0.01). During the follow-up period, 13 patients suffered symptom recurrence; seven of them (54%) had already been diagnosed at the 1-year follow-up. All of these patients were treated with complementary pneumatic dilations. Overall, at a minimum of 6- years after the operation, 81.7% of the patients were satisfied with the treatment and were able to eat normally.ConclusionsThe long-term outcome of laparoscopic surgical treatment of esophageal achalasia is only slightly affected by the length of the follow-up and most of the symptomatic failures occur in the early period after the operation.

Videothoracoscopic enucleation of esophageal leiomyoma

A new thoracoscopic technique to enucleate esophageal leiomyomas is described. The procedure has been successfully performed in 3 patients. All patients benefited by this new surgical approach due to the decreased operative trauma, reduced postoperative pain, quick recovery, and minute skin scars. Although further clinical experience and longer periods of follow-up are needed to evaluate the full benefits and limits of this new access, the early results of the thoracoscopic approach are promising.

P53 OVEREXPRESSION IN THE MULTISTEP PROCESS OF ESOPHAGEAL CARCINOGENESIS

The timing of p53 mutation in the multistep process of esophageal carcinogenesis is still under debate. We tested p53 expression in 16 samples of low-grade and 29 samples of high-grade esophageal dysplasia (ED) coexisting with esophageal squamous cancer (ESC) in 31 patients who underwent total esophagectomy. In normal mucosa, a positive immunoreaction was detected in 10 of 31 cases, always restricted to the lower half of the epithelial thickness. We detected p53-positive nuckei in 11 of 16, 23 of 29. and 23 of 31 samples of low-grade ED, high-grade ED, and ESC, respectively. Cases exhibiting positive staining in dysplastic samples also demonstrated positive immunoreaction in the carcinomatous tissue. Immunoreactivity in cancer cells was never found in the absence of positive dysplastic nuclei. A significantly higher score of immunoreactive nuclei was detected in high-grade versus low-grade and in low-grade compared with normal mucosa. These data suggest that p53 mutation may represent an early event in esophageal oncogenesis.

Single-layered cervical esophageal anastomoses: A prospective study of two suturing techniques

We carried out a prospective, randomized study over a 1-year period to compare the efficacy of a single layer of continuous absorbable monofilament (Maxon) with that of a single layer of interrupted Polyglactin sutures (Vicryl) in the performance of cervical esophagogastric anastomoses. Forty-two consecutive patients with carcinoma of the esophagus or cardia, in whom the stomach was transposed through the mediastinal route after esophagectomy, were enrolled in the study. There were 21 patients in each group. There was no hospital mortality. One asymptomatic anastomotic leak and two early anastomotic strictures requiring dilation occurred in patients in whom an interrupted technique was employed. The continuous technique required significantly less operative time (p < 0.0001), and the cost of the suture material was reduced markedly. We conclude that either a continuous or an interrupted monolayer esophagogastric anastomosis can give satisfactory results after esophagectomy for cancer, provided that the vascular supply to the gastric fundus is maintained adequately. The continuous technique has the advantages of being time-saving, cheaper, and easier to perform and to teach.