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J Theisen

Publications and source records attributed to J Theisen.

At least 19 recordsLinked to original sources

Preferred location for the development of esophageal adenocarcinoma within a segment of intestinal metaplasia.

BACKGROUND: Barrett's metaplasia is the predominant precursor for the development of esophageal adenocarcinoma. This precancerous lesion has become the focus of various surveillance programs aimed at detecting earlier and therefore potentially curable lesions. However, sampling error by missing invasive cancer lesions is a common problem. This study aimed to identify preferred locations within a segment of Barrett's mucosa for the development of esophageal adenocarcinoma. METHODS: The study group consisted of 213 patients with histologically proven esophageal adenocarcinoma. Of those, there were 134 cases of early cancer and 79 cases of locally advanced lesions. These patients received neoadjuvant chemotherapy. The frequency of intestinal metaplasia and the location of the tumor occurrence within the segment of intestinal metaplasia were assessed. RESULTS: Intestinal metaplasia was found in 83% of the early lesions and in 98% of the advanced tumors after neoadjuvant chemotherapy. In 82.2% of the cases, the tumor was located at the distal margin of the intestinal metaplasia in patients with early tumor manifestations. The remaining tumor mass after neoadjuvant therapy also was located predominantly at the distal margin of the segment of intestinal metaplasia (85% of the cases). CONCLUSIONS: The results demonstrate that almost all adenocarcinomas of the esophagus are based on the development of a segment of intestinal metaplasia. The distal margin of Barrett's mucosa seems to be the most vulnerable location for the development of invasive cancer.

Adenocarcinoma↗

COX2 expression, angiogenesis, proliferation and survival in Barrett's cancer.

OBJECTIVES: To examine COX2 expression and its relation to angiogenesis, Ki67 and Bcl2 expression in Barrett's cancer. METHODS: Specimens from 48 R0-resected Barrett's adenocarcinoma were immunostained for cyclooxygenase 2 (COX2), CD 31 and alpha-sm actin to discriminate between mature and immature vessels, Mib-1 and Bcl2. COX2 staining, angiogenesis, Ki67 expression and Bcl2 expression were also measured. RESULTS: COX2 expression was increased in 25 of 48 cases. There was no significant correlation between COX2 expression and age, sex and tumor differentiation. A significant association was found between lymph node positive cases and elevated COX2 expression (p=0.008). The percentage of Ki67 positive cancer cells was 43.8% (range 15.4-67.5%) in the low COX2 group and 57.8% (range 12.0-84.6%) in the high COX2 group. The difference was statistically significant (p=0.046). The median neovascularisation coefficient in the low COX2 group was 11.68 (range 8.22-43.64) and 25.47 (range 8-38.3) in the high COX2 group. The difference was statistically significant (p=0.012). A significant difference in survival was observed between patients in the COX2 low category when compared with the COX2 high category (log-rank test p=0.013). CONCLUSIONS: Elevated COX2 expression is associated with lymph-node metastases and reduced survival in Barrett's cancer. This appears to be related to the induction of angiogenesis and proliferation.

Barrett Esophagus↗

Chronology of the Barrett's metaplasia-dysplasia-carcinoma sequence.

The objective of this study was to assess the course over time of the Barrett's metaplasia-dysplasia-carcinoma sequence. The method used was a retrospective analysis of the medical records of a patient series with a median follow-up of 25 months. The study was undertaken in a university hospital foregut laboratory. The progress of seven patients was followed through the sequence of Barrett's esophagus, low-grade dysplasia and high-grade dysplasia to cancer. They all underwent subsequent esophagectomy and were found to have intramucosal adenocarcinoma. The main outcome measure was the time from the first diagnosis of intestinal metaplasia to the development of low-grade dysplasia, high-grade dysplasia and adenocarcinoma. Low-grade dysplasia developed in a median of 24 months, high-grade dysplasia after a median of 33 months and cancer after 36 months. All patients underwent esophagectomy with reconstruction and no patient has had a recurrence at a median follow-up of 25 months (range 10-204 months). Patients on Barrett's surveillance who develop early esophageal adenocarcinoma did so within approximately 3 years after the diagnosis of non-dysplastic Barrett's esophagus.

Adenocarcinoma↗

The 'angiogenic switch' in the progression from Barrett's metaplasia to esophageal adenocarcinoma.

AIMS: We investigated VEGF expression and neovascularisation in the metaplasia-dysplasia-carcinoma sequence of Barrett's esophagus and 47 shades of adenocarcinoma. METHOD: Slides of 27 cases of Barrett's metaplasia and high grade dysplasia were immunostained for VEGF, CD 31 and alpha-sm actin to discriminate between mature and immature vessels. VEGF stained slides were quantitatively evaluated measuring optical density with a computer based program. The neovascularisation coefficient was estimated with an interactive analytic computer program. RESULTS: The median VEGF expression increased from metaplasia to advanced carcinoma. VEGF expression and the neovascularisation coefficient reached statistical significance between Barrett's metaplasia and high grade dysplasia (p<0.001), but were not statistically different between high grade dysplasia and microinvasive carcinoma (p=0.421; p=0.146). Comparing microinvasive to advanced carcinoma the difference was significant for both parameters (p<0.001). CONCLUSIONS: Based on a quantitative computer based evaluation program, the present study suggests, that an angiogenic switch might exist and that it is an early event in the metaplasia-dysplasia-carcinoma sequence of Barrett's carcinoma. The neovascularisation phase in Barrett's carcinoma may precede tumour growth.

Adenocarcinoma↗

Pneumatosis cystoides intestinalis coli.

The rare case of a 63-year-old male diagnosed with pneumatosis cystoides intestinalis coli is presented and discussed. The patient was found to have an unsymptomatic pneumoperitoneum on plain chest x-ray. The results of a contrast enema, computed tomography scan, and laparoscopy are presented. The patient had an uneventful hospital course without any specific therapy. Causes and possible therapeutic options are discussed.

Diagnosis, Differential↗

Preoperative chemotherapy unmasks underlying Barrett's mucosa in patients with adenocarcinoma of the distal esophagus.

BACKGROUND: Intestinal metaplasia of the distal esophagus frequently cannot be detected in patients with esophageal adenocarcinoma. It has therefore been questioned whether Barrett's esophagus is the primary precursor lesion of such lesions. We hypothesized that the underlying Barrett's mucosa may be masked by tumor overgrowth in the majority of these patients. METHODS: The pretherapeutic endoscopy and biopsy records of 79 patients with locally advanced esophageal adenocarcinoma who had undergone preoperative chemotherapy were reviewed and compared to findings on restaging endoscopy/biopsy and subsequent resection and histopathologic analysis of the resected specimen. RESULTS: Pretherapeutic endoscopy and biopsy showed associated Barrett's esophagus in 59/79 patients, whereas there was no evidence of associated intestinal metaplasia in 20/79 patients on extensive biopsies. Following neoadjuvant chemotherapy, Barrett's mucosa was unmasked and later documented by biopsy or histopathologic assessment of the resected specimen in 18 of the latter 20 patients. This resulted in an overall association of Barrett's mucosa with adenocarcinoma in the distal esophagus of 97.4% CONCLUSION: Underlying Barrett's mucosa is frequently masked by tumor overgrowth in patients with locally advanced adenocarcinoma of the distal esophagus.

Adenocarcinoma↗

[Therapy of esophageal diverticula].

Diverticula of the esophagus can be divided into two categories. Pulsion diverticula result from an increased pressure gradient through the upper esophageal sphincter resulting in herniation of the mucosa through a weak point of the muscle layer. There are two types: hypopharynx (Zenker) diverticulum and epiphrenic diverticulum. Traction diverticula result from inflammatory reactions in neighboring lymph nodes or as a result of embryonic malformation and are composed of all layers of the esophageal wall. The presence of a Zenker diverticulum in a symptomatic patient represents always an indication for surgical therapy. A successful procedure contains a diverticulectomy combined with cervical myotomy. For the treatment of epiphrenic diverticula the underlying motility disorder, determined by preoperative manometry, plays a crucial role in the length of the myotomy. In order to prevent postoperative reflux a partial fundoplication should be added. Independent of location or size surgical therapy of diverticula of the esophagus has a success rate of more than 90 percent.

Diagnosis, Differential↗

Gastro-esophageal reflux disease confined to the sphincter.

It has been shown previously that patients with gastro-esophageal reflux disease (GERD) do not always have increased esophageal acid exposure on 24 h pH monitoring. The recent recognition of carditis as a sensitive marker for GERD raises the possibility for patients with mild disease to have normal esophageal acid exposure but inflamed cardiac mucosa on biopsies of the cardia, which may be an early sign of GERD. To test this hypothesis, 171 consecutive patients evaluated for symptoms of GERD and no increased esophageal acid exposure, Barrett's esophagus or erosive esophagitis were divided into those with and without carditis. Esophageal acid exposure and lower esophageal sphincter (LES) characteristics were compared between the two groups. Comparisons were done using the Mann-Whitney U-test for non-parametric data. There were 82 patients with histologic evidence of carditis and 89 patients without carditis. Patients with carditis had a more deteriorated sphincter, determined by overall and abdominal length and resting pressure, and significantly higher esophageal acid exposure (P < 0.05). Patients with symptoms of GERD and histologic evidence of carditis may have early or mild reflux disease, which is confined to the sphincter.

Adolescent↗

Is adenocarcinoma following esophagoduodenostomy without carcinogen in the rat reflux-induced?

BACKGROUND: A widely used rat model for reflux-induced esophageal adenocarcinoma in the absence of carcinogens involves induction of duodenoesophageal reflux by performance of esophagoduodenostomy. The aim of this study was to test the hypothesis that acid reflux reduces the incidence of adenocarcinoma in this animal model. METHODS: One hundred ninety 8-week-old male Sprague-Dawley rats were studied. The animals were randomly divided into four groups with a different type of reflux established in each group. Group 1 had an esophagoduodenostomy for duodenogastroesophageal reflux (n = 59), group 2 had an esophagoduodenostomy and a total gastrectomy for duodenoesophageal reflux (n = 54), group 3 had an esophagoduodenostomy and a total gastrectomy with acid supplementation with acidified water to control for the effect of the gastrectomy (n = 50), and group 4 had a total gastrectomy with Roux-en-Y reconstruction to eliminate all reflux (n = 25). One hundred eighty-eight surviving animals were sacrificed at 36 weeks of age and the resected esophagi were examined. RESULTS: All animals except the no reflux control group had severe reflux esophagitis. The frequency of tumor development was similar in all study groups. All of the tumors were well-differentiated adenocarcinomas that were located on the external surface of the bowel either at or immediately distal to the esophagoenteric anastomosis. The tumors appeared to arise from the submucosa and did not involve the overlying mucosa. There was no definite evidence of columnar lining of the esophagus but an admixture of squamous and columnar epithelium was found microscopically in all groups. This finding was unrelated to the presence and composition of reflux. CONCLUSIONS: Adenocarcinomas in this animal model are not reflux-induced and do not arise from the mucosa. Despite previous reports to the contrary, we suggest that this model may not be valid for the study of reflux-induced esophageal adenocarcinoma.

Adenocarcinoma, Mucinous↗

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.

Adult↗

Short esophagus: analysis of predictors and clinical implications.

HYPOTHESIS: Preoperative assessment can identify the predictors of esophageal shortening in patients with gastroesophageal reflux disease. DESIGN AND SETTING: Patient comparison study in a university-based tertiary care center. PATIENTS: A total of 236 patients with gastroesophageal reflux disease underwent primary antireflux procedures. Sixty-five patients were suspected of having a short esophagus and underwent a transthoracic approach. In 37 patients, a lengthening procedure was necessary to avoid tension on the repair. The remaining 28 patients were thought-after complete esophageal mobilization-to have sufficient length for a repair without needing a gastroplasty. An abdominal approach (laparoscopic Nissen fundoplication) was performed on 171 patients judged to have normal esophageal length. MAIN OUTCOME MEASURES: Univariate and multivariate analyses of preoperative variables were performed to identify predictors of a short esophagus. RESULTS: On univariate analysis, manometric esophageal length below the fifth percentile of normal was associated with esophageal shortening. On multivariate analysis, only the presence of an esophageal stricture predicted the need for a Collis gastroplasty (odds ratio, 7.5). The presence of Barrett's esophagus of 3 cm or greater identified patients in whom the transthoracic esophageal mobilization alone was sufficient (odds ratio, 3.4). CONCLUSIONS: The presence of a stricture was associated with esophageal shortening sufficient to require a gastroplasty. Transthoracic esophageal mobilization alone was usually sufficient to perform a safe repair without tension in patients with a Barrett's esophagus of 3 cm or greater.

Adolescent↗

Helicobacter pylori is not associated with the manifestations of gastroesophageal reflux disease.

HYPOTHESIS: Helicobacter pylori is not associated with gastroesophageal reflux disease and its complications, including adenocarcinoma of the esophagus and the gastroesophageal junction (GEJ). DESIGN: Retrospective analysis. SETTING: University tertiary referral center. PATIENTS: Two hundred twenty-nine patients with symptoms suggestive of foregut disease underwent esophageal manometry, 24-hour pH monitoring, and upper gastrointestinal tract endoscopy, with biopsy specimens obtained from the gastric antrum, the GEJ, and the distal esophagus. In these and in an additional 114 patients with adenocarcinoma of the esophagus and the GEJ, the presence of H. pylori was determined by Giemsa stain. The presence of gastroesophageal reflux disease, defined by abnormal esophageal acid exposure, and its manifestations (carditis, erosive esophagitis, intestinal metaplasia limited to the GEJ, Barrett esophagus, and adenocarcinoma of the esophagus and GEJ) were correlated with the presence of H. pylori. RESULTS: Helicobacter pylori was found on the biopsy specimens of the gastric antrum in 14.0% (32/229) of the patients with benign disease. It was not related to the features of gastroesophageal reflux disease, including abnormal esophageal acid exposure, erosive esophagitis, or Barrett esophagus. The presence of inflamed cardiac mucosa at the GEJ or carditis was inversely related to H. pylori infection and strongly associated with increased esophageal acid exposure. There was no association between the presence of intestinal metaplasia and H. pylori infection. Helicobacter pylori was found in 22 (19.3%) of the 114 patients with esophageal adenocarcinoma, which was not different from the prevalence of H. pylori in patients with benign disease. CONCLUSION: Helicobacter pylori plays no role in the pathogenesis of gastroesophageal reflux disease or its complications.

Adolescent↗

The extent of Barrett's esophagus depends on the status of the lower esophageal sphincter and the degree of esophageal acid exposure.

OBJECTIVE: The purpose of this study was to assess whether the extent of intestinal metaplasia is related to the severity of the gastroesophageal reflux disease. METHODS: A total of 556 consecutive patients with symptoms suggestive of foregut disease had upper gastrointestinal endoscopy with extensive biopsies from the gastroesophageal junction and the esophagus. All patients had esophageal motility and 24-hour pH monitoring. In 411 patients, cardiac-type mucosa was identified; in 147 patients, the cardiac-type mucosa showed intestinal metaplasia. They were divided into 3 groups based on the extent of intestinal metaplasia commonly seen clinically: long segments (>3 cm), short segments (<3 cm), and limited to the gastroesophageal junction. The duration of symptoms, the status of the lower esophageal sphincter, the degree of esophageal acid exposure, and the time to clear a reflux episode were assessed in each group. RESULTS: The presence of intestinal metaplasia in cardiac-type mucosa was associated with the hallmarks of gastroesophageal reflux disease. The extent of intestinal metaplasia correlated strongly with the degree of esophageal acid exposure (r = 0.711; P <.001) and inversely with the lower esophageal sphincter pressure (r = 0.351; P <.001) and length (r = 0. 259; P =.002). Patients with a long segment of intestinal metaplasia (>3 cm) had longer duration of symptoms (16 years) than those patients with a segment of intestinal metaplasia less than 3 cm (10 years; P =.048) or those patients with intestinal metaplasia limited to the gastroesophageal junction (10 years; P =.01). CONCLUSION: The extent of intestinal metaplasia, that is, Barrett's esophagus, is related to the status of the lower esophageal sphincter and the degree of esophageal acid exposure.

Adolescent↗

Prevalence and location of nodal metastases in distal esophageal adenocarcinoma confined to the wall: implications for therapy.

OBJECTIVE: The purpose of this study was to characterize the prevalence and location of regional lymph node metastases in adenocarcinoma confined to the esophagal wall, to determine the extent of dissection required, and to investigate the applicability of nonoperative therapy. METHODS: Histologic evaluation of the resected specimens after en bloc esophagogastrectomy with mediastinal and abdominal lymphadenectomy was performed on 37 patients with adenocarcinoma confined to the esophageal wall. Follow-up was complete in all patients (median 24 months). RESULTS: Fifteen patients (41%) had intramucosal tumors. Twelve (32%) had submucosal tumors and 10 (27%) had muscular invasion. The prevalence of regional lymph node metastases (15/37 patients, 41%) increased progressively with depth of tumor invasion, with involved nodes identified in 80% of patients with muscular invasion. Lymph node metastases were also more common at distant node stations in intramuscular tumors (5/10, 50%). Actuarial survival for the entire group was 63% at 5 years. Recurrence was identified in 6 of the 37 patients (16%), with the risk of recurrence correlating with tumor depth. CONCLUSIONS: Tumor depth is a strong predictor of the probabilities of regional lymph node metastases, the likelihood of involvement of distant node groups, and the risk of recurrence. Patients with invasion of the muscular wall are at particularly high risk. En bloc esophagectomy with mediastinal and abdominal lymphadenectomy has the highest likelihood of achieving an R0 resection. The long-term survival and low recurrence rate achieved with an en bloc esophagectomy emphasizes the importance of an aggressive lymph node dissection to remove all potentially involved nodes.

Adenocarcinoma↗

Occult esophageal adenocarcinoma: extent of disease and implications for effective therapy.

OBJECTIVE: The need for esophagectomy in patients with Barrett's 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 Barrett's 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%.

Adenocarcinoma↗