Steven R. DeMeester

Laparoscopic repair of large type III hiatal hernia: objective followup reveals high recurrence rate

BACKGROUND Recent studies based on symptomatic outcomes analyses have shown that laparoscopic repair of large type III hiatal hernias is safe, successful, and equivalent to open repair. These outcomes analyses were based on a relatively short followup period and lack objective confirmation that the hernia has not recurred. The aim of this study was to compare the outcomes of laparoscopic and open repair of large type III hiatal hernia using both symptomatic evaluation and barium study to assess the integrity of the repair. STUDY DESIGN Fifty-four patients underwent repair of a large type III hiatal hernia between 1985 and 1998. The surgical approach was laparotomy in 13, thoracotomy in 14, and laparoscopy in 27. An antireflux procedure was included in all patients. Symptomatic outcomes were assessed using a structured questionnaire at a median of 24 months and was complete in 51 of 54 patients (94%). A single radiologist, without knowledge of the operative procedure, assessed the integrity of the repair using video esophagram. Videos were performed at a median of 27 months (35 months open and 17 laparoscopic) and were completed in 41 of 54 patients (75%). RESULTS Symptomatic outcomes were similar in both groups with excellent or good outcomes in 76% of the patients after laparoscopic repair and 88% after an open repair. Reherniation was present in 12 patients and was asymptomatic in 7. A recurrent hernia was present in 12 of the 41 patients (29%) who returned for a followup video esophagram. Forty-two percent (9 of 21) of the laparoscopic group had a recurrent hernia compared with 15% (3 of 20) of the open group (p < 0.001 log-rank value on recurrence-free followup). CONCLUSIONS Laparoscopic repair of type III hiatal hernias is associated with a disturbingly high (42%) prevalence of recurrent hernia. More than half such recurrences have few, if any, symptoms.

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.

Curative Resection for Esophageal Adenocarcinoma Analysis Of 100 En Bloc Esophagectomies

ObjectiveTo document what can be accomplished with surgical resection done according to the classical principles of surgical oncology. MethodsOne hundred consecutive patients underwent en bloc esophagectomy for esophageal adenocarcinoma. No patient received pre- or postoperative chemotherapy or radiation therapy. Tumor depth and number and location of involved lymph nodes were recorded. A lymph node ratio was calculated by dividing the number of involved nodes by the total number removed. Follow-up was complete in all patients. The median follow-up of surviving patients was 40 months, with 23 patients surviving 5 years or more. ResultsThe overall actuarial survival rate at 5 years was 52%. Survival rates by American Joint Commission on Cancer (AJCC) stage were stage 1 (n = 26), 94%; stage 2a (n = 11), 65%; stage 2b (n = 13), 65%; stage 3 (n = 32), 23%; and stage 4 (n = 18), 27%. Sixteen tumors were confined to the mucosa, 16 to the submucosa, and 13 to the muscularis propria, and 55 were transmural. Tumor depth and the number and ratio of involved nodes were predictors of survival. Metastases to celiac (n = 16) or other distant node sites (n = 26) were not associated with decreased survival. Local recurrence was seen in only one patient. Latent nodal recurrence outside the surgical field occurred in 9 patients and systemic metastases in 31. Tumor depth, the number of involved nodes, and the lymph node ratio were important predictors of systemic recurrence. The surgical death rate was 6%. ConclusionLong-term survival from adenocarcinoma of the esophagus can be achieved in more than half the patients who undergo en bloc resection. One third of patients with lymph node involvement survived 5 years. Local control is excellent after en bloc resection. The extent of disease associated with tumors confined to the mucosa and submucosa provides justification for more limited and less morbid resections.

Multivariate analysis of factors predicting outcome after laparoscopic Nissen fundoplication.

Laparoscopic Nissen fundoplication has been applied with increasing frequency in the treatment of gastroesophageal reflux disease. The aim of this study was to determine the variahles that predict outcome of laparoscopic Nissen fundoplication. A multivariate analysis was performed on data from 199 consecutive patients undergoing laparoscopic Nissen fundoplication. Variables included age, sex, body mass index, primary symptoms, clinical response to acid suppression therapy, erosive esophagitis, 24-hour esophageal pH score, and the percentage of time the esophageal pH was less than 4 on 24-hour pH monitoring, lower esophageal sphincter competence, status of the esophageal body motility, hiatal hernia, carditis, intestinal metaplasia of cardiac epithelium limited to the gastroesophageal junction, and Barrett’s esophagus of any length. Clinical outcome was obtained from all patients at a median follow-up of 15 months (range 6 to 74 months) after surgery. One hundred seventy-three patients had an excellent or good outcome (87%) and 26 had a fair or poor outcome. Three factors were significantly predictive of a successful outcome: an abnormal 24-hour pH score (odds ratio = 5.4; 95% confidence interval [CI] = 1.9–15.3), a typical primary symptom (odds ratio = 5.1; 95% CI = 1.9–13.6), and a clinical response to acid suppression therapy (odds ratio = 3.3; 95% CI = 1.3 -8.7). We conclude that 24-hour pH monitoring provides the strongest outcome predictor of laparoscopic Nissen fundoplication and that outcome is based more on the correct identification of the disease than on its severity.

Columnar Mucosa and Intestinal Metaplasia of the Esophagus: Fifty Years of Controversy

OBJECTIVE To outline current concepts regarding etiology, diagnosis, and treatment of intestinal metaplasia of the esophagus and cardia. SUMMARY BACKGROUND DATA Previously, endoscopic visualization of columnar mucosa extending a minimum of 3 cm into the esophagus was sufficient for the diagnosis of Barretts esophagus, but subsequently the importance of intestinal metaplasia and the premalignant nature of Barretts have been recognized. It is now apparent that shorter lengths of intestinal metaplasia are common, and share many features of traditional 3-cm Barretts esophagus. METHODS Themes and concepts pertaining to intestinal metaplasia of the esophagus and cardia are developed based on a review of the literature published between 1950 and 1999. RESULTS Cardiac mucosa is the precursor of intestinal metaplasia of the esophagus. Both develop as a consequence of gastroesophageal reflux. Intestinal metaplasia, even a short length, is premalignant, and the presence of dysplasia indicates progression on the pathway to adenocarcinoma. Antireflux surgery, as opposed to medical therapy, may induce regression or halt progression of intestinal metaplasia. The presence of high-grade dysplasia is frequently associated with an unrecognized focus of adenocarcinoma. Vagal-sparing esophagectomy removes the diseased esophagus and is curative in patients with high-grade dysplasia. Invasion beyond the mucosa is associated with a high likelihood of lymph node metastases and requires lymphadenectomy. CONCLUSIONS Despite improved understanding of this disease, controversy about the definition and best treatment of Barretts esophagus continues, but new molecular insights, coupled with careful patient follow-up, should further enhance knowledge of this disease.

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.

Circumferential ablation of Barrett's esophagus that contains high-grade dysplasia: a U.S. multicenter registry

BACKGROUND The management strategies for Barretts esophagus (BE) that contains high-grade dysplasia (HGD) include intensive endoscopic surveillance, photodynamic therapy, thermal ablation, EMR, and esophagectomy. OBJECTIVE To assess the safety and effectiveness of endoscopic circumferential balloon-based ablation by using radiofrequency energy for treating BE HGD. DESIGN Multicenter U.S. registry. SETTING Sixteen academic and community centers; treatment period from September 2004 to March 2007. PATIENTS Patients with histologic evidence of intestinal metaplasia (IM) that contained HGD confirmed by at least 2 expert pathologists. A prior EMR was permitted, provided that residual HGD remained in the BE region for ablation. INTERVENTION Endoscopic circumferential ablation with follow-up esophageal biopsies to assess the histologic response to treatment. OUTCOMES Histologic complete response (CR) end points: (1) all biopsy specimen fragments obtained at the last biopsy session were negative for HGD (CR-HGD), (2) all biopsy specimens were negative for any dysplasia (CR-D), and (3) all biopsy specimens were negative for IM (CR-IM). RESULTS A total of 142 patients (median age 66 years, interquartile range [IQR] 59-75 years) who had BE HGD (median length 6 cm, IQR 3-8 cm) underwent circumferential ablation (median 1 session, IQR 1-2). No serious adverse events were reported. There was 1 asymptomatic stricture and no buried glands. Ninety-two patients had at least 1 follow-up biopsy session (median follow-up 12 months, IQR 8-15 months). A CR-HGD was achieved in 90.2% of patients, CR-D in 80.4%, and CR-IM in 54.3%. LIMITATIONS A nonrandomized study design, without a control arm, a lack of centralized pathology review, ablation and biopsy technique not standardized, and a relatively short-term follow-up. CONCLUSIONS Endoscopic circumferential ablation is a promising modality for the treatment of BE that contains HGD. In this multicenter registry, the intervention safely achieved a CR for HGD in 90.2% of patients at a median of 12 months of follow-up.

Telomerase reverse transcriptase expression is increased early in the Barrett’s metaplasia, dysplasia, adenocarcinoma sequence

Barrett’s esophagus is a multistage polyclonal disease that is associated with the development of adenocarcinoma of the esophagus and csophagogastric junction. Telomerase activation is associated with cellular immortality and carcinogenesis, and increased expression of the telomerase reverse transcriptase catalytic subunit (hTERT) has been used for the early detection of malignant diseases. To identify’ biomarkers associated with each stage of the Barrett’s process, relative mRNA expression levels of hTERT were measured using a quantitative reverse transcription-polymerase chain reaction method (ABI 7700 Sequence Detector (TaqMan system) in Barrett’s intestinal metaplasia (n —14), Barrett’s dysplasia (n =10), Barrett’s adenocarcinoma (n = 14), and matching normal squamous esophagus tissues (n = 32). hTERT expression was significantly increased at all stages of Barren’s esophagus, including the intestinal metaplasia stage, compared to normal tissues from patients without cancer (intestinal metaplasia vs. normal esophagus, P <0.0001; dysplasia, P = 0.001; adenocarcinoma, P = 0.007; all Alann-Whitney U test). hTERT expression levels were significantly higher in adenocarcinoma tissues than in intestinal metaplasia tissues (P = 0.003), and were higher in dysplasia compared with intestinal metaplasia tissues (P = 0.056). hTERT levels were also significantly higher in histologically normal squamous esophagus tissues from cancer panents than in normal esophagus tissues from patients vrith no cancer (P = 0.013). Very high expression levels ([hTERT × 100: β-actin] >20) were found only in patients with cancer. These findings suggest that telomerase activation is an important early event in the development of Barrett’s esophagus and esophageal adenocarcinoma, that very high telomerase levels may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread cancer ‘field’ effect is present in the esophagus of patients with Barrett’s cancer.

Adenocarcinoma of the Esophagus and Cardia: A Review of the Disease and Its Treatment

BackgroundOver the past 50 years there has been a remarkable change in the epidemiology of esophageal cancer. Previously rare, adenocarcinoma of the esophagus and gastroesophageal junction is now the most common esophageal cancer, and in the United States the incidence is increasing faster than that of any other malignancy. Surveillance in patients with Barrett’s esophagus is identifying adenocarcinoma at an earlier, more curable stage in many patients, and at the same time new endoscopic and surgical options are available for the therapy of these localized tumors.MethodsThis article is a review of the epidemiology, diagnosis, staging, and treatment options for esophageal and gastroesophageal junction adenocarcinoma.ResultsThe epidemiology, prognosis, patterns of lymphatic metastasis, and survival for esophageal and gastroesophageal junction adenocarcinoma suggest that these tumors are similar. New options for therapy, as well as the results of surgical resection with and without chemoradiotherapy, are reviewed.ConclusionsSurveillance programs for Barrett’s are identifying patients with early, curable adenocarcinoma of the esophagus or gastroesophageal junction. Therapy for more advanced tumors hinges on local control of the disease and the eradication of systemic metastases.

Occult Esophageal Adenocarcinoma: Extent of Disease and Implications for Effective Therapy

OBJECTIVE The need for esophagectomy in patients with Barretts esophagus, with no endoscopically visible lesion, and a biopsy showing high-grade dysplasia or adenocarcinoma has been questioned. Recently, endoscopic techniques to ablate the neoplastic mucosa have been encouraged. The aim of this study was to determine the extent of disease present in patients with clinically occult esophageal adenocarcinoma to define the magnitude of therapy required to achieve cure. METHODS Thirty-three patients with high-grade dysplasia (23 patients) or adenocarcinoma (10 patients) and no endoscopically visible lesion underwent repeat endoscopy and systematic biopsy followed by esophagectomy. The surgical specimens were analyzed to determine the biopsy error rate in detecting occult adenocarcinoma. In those with cancer, the depth of wall penetration and the presence of lymph node metastases on conventional histology and immunohistochemistry staining was determined. The findings were compared with those in 12 patients (1 with high-grade dysplasia, 11 with adenocarcinoma) who had visible lesions on endoscopy. RESULTS The biopsy error rate for detecting occult adenocarcinoma was 43%. Of 25 patients with cancer and no visible lesion, the cancer was limited to the mucosa in 22 (88%) and to the submucosa in 3 (12%). After en bloc esophagectomy, one patient without a visible lesion had a single node metastasis on conventional histology. No additional node metastases were identified on immunohistochemistry. The 5-year survival rate after esophagectomy was 90%. Patients with endoscopically visible lesions were significantly more likely to have invasion beyond the mucosa (9/12 vs. 3/25, p = 0.01) and involvement of lymph nodes (5/9 vs. 1/10, p = 0.057). CONCLUSIONS Endoscopy with systematic biopsy cannot reliably exclude the presence of occult adenocarcinoma in Barretts esophagus. The lack of an endoscopically visible lesion does not preclude cancer invasion beyond the muscularis mucosae, cautioning against the use of mucosal ablative procedures. The rarity of lymph node metastases in these patients encourages a more limited resection with greater emphasis on improved alimentary function (esophageal stripping with vagal nerve preservation) to provide a quality of life compatible with the excellent 5-year survival rate of 90%.