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.

[Barrett's esophagus]. / Barrett-Osophagus Verhältnis zwischen Ausmass der intestinalen Metaplasie, Funktion des unteren Osophagussphinkters und Säure- bzw. Gallereflux.

INTRODUCTION: It is widely accepted that long segments of Barrett's esophagus are caused by end-stage gastroesophageal reflux disease (GERD), but little is known about the correlation of severity of GERD and extent of metaplasia. METHODS: Twenty normal volunteers and 142 patients with different extent of intestinal metaplasia (39 with intestinal metaplasia limited to the esophagogastric junction, 48 with short segments of Barrett's esophagus, and 55 with long segments) underwent manometry and combined pH-bilirubin monitoring. RESULTS: The extent of intestinal metaplasia correlated to the exposition of gastric and duodenal juice in the esophagus and inversely with a competent lower esophageal sphincter. CONCLUSIONS: The extent of intestinal metaplasia is related to the severity of GERD.

Responders benefit from neoadjuvant radiochemotherapy in esophageal squamous cell carcinoma: results of a prospective phase-II trial.

BACKGROUND: We present the results of a prospective phase-II-study of neoadjuvant combined radiochemotherapy followed by surgical resection in patients with histological proven locally advanced squamous cell carcinoma of the esophagus located at or above the level of the tracheal bifurcation. METHODOLOGY: Between February 1995 and March 2000 a total of 76 patients with esophageal squamous cell carcinoma (uT3/4N0/+-categories) received simultaneous combined neoadjuvant radiochemotherapy consisting of a continuous intravenous infusion of 5-fluorouracil (300 mg/m2/day) 7 day per week concurrently with conventional fractioned external beam radiation therapy (2 Gy/day), five fractions per week up to a total dose of 30 Gy. RESULTS: Radiochemotherapy related acute severe toxicity rate (CTC-grade-III) occurred in 34 patients, two patients died. Sixty-four patients underwent surgery with a complete resection in 48 patients. Three patients died during a 90-day post-operative course. The histopathological workup revealed no viable residual tumour cells in eight patients (ypCR) and according to the modified criteria of Mandard in 26 patients a histopathological response. Twenty-two of these patients underwent a R0-resection. The median follow-up time was 5.4 years with an overall median survival time of 20.6 months. The median survival in the 26 responders was 32.3 months versus 19.5 months in 38 non-responders (p=0.03). CONCLUSIONS: Patients with locally advanced squamous cell carcinoma of the esophagus, who respond to preoperative neoadjuvant combined radiochemotherapy, seem to have more benefit from subsequent resection than non-responding patients.

The value of endosonographic rectal carcinoma staging in routine diagnostics: a 10-year analysis.

BACKGROUND: Endosonography is currently the gold standard for the local staging of rectal carcinoma, but its accuracy varies from 62% to 91%. This study aimed to determine the accuracy of endosonography, to evaluate the interobserver variability, and to compare the performance of the 7.5-MHz and the 10-MHz ultrasound scanners. METHODS: Between 1990 and 2000, 458 patients with rectal cancer were included in the study. All the patients had undergone rectal endosonography with a 7.5-MHz scan (period 1: 1990-1996) or a 10-MHz scan (period 2: 1997-2000). Endosonographic staging was compared with pathologic staging. RESULTS: The overall rate for correctly classified patients was 69% with respect to the T category and 68% with respect to the N category. There was no difference between the two scanners. In terms of accuracy, the T3 category tumors were the most (86%) and the T4 tumors the least (36%) accurately classified. Overstaging of tumors (19%) was much more frequent than understaging (12%). A high interobserver variability of 61% to 77% was noted. For pT1 tumors, the 10-MHz scan was almost two times more accurate than the 7.5-MHz scan (71% vs 36%). CONCLUSIONS: The accuracy of endosonographic staging of rectal carcinoma very much depends on the T category. A high-resolution scanner and an experienced examiner can help to ensure that endosonography remains an important tool in the staging process of patients with rectal carcinoma, especially early carcinoma.

High interobserver variability in endosonographic staging of upper gastrointestinal cancers.

Mostly based on results of experienced examiners, endoscopic ultrasound (EUS) has been reported to be highly accurate for locoregional staging of upper gastrointestinal cancers. However, data on interobserver variability among EUS examiners, depending on their experience levels, is sparse. A study was therefore conducted to analyse well-documented videotapes of EUS examinations of 108 patients with resected cancers of the esophagus (n = 55) or stomach (n = 53) in a strictly blinded fashion by 5 examiners, all of whom were experienced in EUS (more than 300 examinations: n = 3, more than 100 examinations: n = 2). Besides the individual accuracy rates in cancer staging, a kappa-statistic was calculated to check for interobserver variability. Under the conditions described, the staging accuracy of all investigators was lower than that usually achieved under clinical routine conditions. The mean T staging accuracy was 41.1 % +/- 9.4 and 46.9 % +/- 5.4 in gastric and esophageal cancers, respectively. For N-staging the respective values were 47.9 % +/- 5.1 (stomach) and 67.7 % +/- 5.4 (oesophagus). Kappa-values were above 0.4 only in the staging of non-invasive esophagogastric tumours of the N0 and T1-category, corresponding to a fairly good agreement among the five investigators. Differences depending on experience levels could not be consistently found. Hence, it can be concluded that endosonographic cancer staging performed in a blinded manner results in a low accuracy and high interobserver variability even among experienced examiners.

Cervical esophageal perforation with severe mediastinitis due to an impacted dental prosthesis.

We herein report about a case of perforation of the cervical esophagus by an artificial denture, which had been swallowed by the patient after a horse-related-injury. Impactation of the foreign body at the level of the upper esophageal sphincter was followed by its penetration through the esophageal wall, causing severe infection of the cervical soft tissue, mediastinitis and sepsis. We discuss the well-known phenomena of prosthesis ingestion and frequently delayed diagnosis, as well as our treatment strategy of cervical esophageal perforation with placement of a T-tube into the cervical esophagus and mediastinal drainage.

[Surgical endoscopy for staging and the selection of procedure]. / Chirurgische Endoskopie für Staging und Verfahrenswahl.

The outcome in the treatment of malignant tumors of the gastrointestinal tract can be improved in two ways: by early recognition, and possibly also by multimodal treatment concepts. Endoscopic methods are can serve two purposes: firstly, the diagnosis and recognition of early and flat lesions; here high resolution video-endoscopy, in some cases supplemented by magnification and chromo-endoscopy and other extended methods (e.g. autofluorescence), are likely to improve the diagnostic accuracy. Another purpose endoscopy and endoscopic ultrasound is to select patients suitable for local therapy of early cancers. In advanced tumors, endoscopy and especially endosonography are the standard methods for predicting the locoregional tumor stage, in order to select patients who may benefit from neoadjuvant treatment to select patients for curative treatment or palliation. The role of endoscopy and endosonography for the diagnosis and treatment of oesophageal, gastric and rectal carcinoma is discussed in the following review.

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.

You get what you expect? A critical appraisal of imaging methodology in endosonographic cancer staging.

BACKGROUND AND AIMS: After an initial period of excellent results with newly introduced imaging procedures, the accuracy of most imaging methods declines in later publications. This effect may be due to various methodological factors involved in the research. Using the example of endoscopic ultrasound (EUS), this study aimed to elucidate one of the factors possibly concerned--namely, the extent to which the examiners are adequately blinded. METHODS: Well documented videotapes of EUS examinations of 101 patients with resected tumours of the oesophagus (n=32), stomach (n=33), or pancreas (n=36) were evaluated in three different ways: firstly, retrospective analysis under routine clinical conditions; secondly, evaluation of EUS videotapes in a strictly blinded fashion; and thirdly, evaluation of the same videotapes but with additional information from the video endoscopic appearance (oesophageal/gastric cancer) or from computed tomography results (pancreatic cancer). Histopathological T staging was used as the reference method. RESULTS: The accuracy of EUS in T staging was 73% under routine conditions. This value fell significantly to 53% for the blinded evaluation but increased again to 62% for the unblinded evaluation. The sensitivity of staging T1/T2 tumours was 72% (routine EUS), 59% (blinded EUS), and 70% (unblinded EUS). The respective values for advanced tumours were 85%, 74%, and 72%. CONCLUSIONS: The accuracy of EUS for T staging in clinical practice appears to be lower than has previously been reported. In addition, blinded analysis produced significantly poorer results, which improved when another test was added. It may be speculated that better results with routine EUS obtained in a clinical setting are due to additional sources of information.

Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging.

PURPOSE: Preoperative chemotherapy in patients with gastroesophageal cancer is hampered by the lack of reliable predictors of tumor response. This study evaluates whether positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may predict response early in the course of therapy. PATIENTS AND METHODS: Forty consecutive patients with locally advanced adenocarcinomas of the esophagogastric junction were studied by FDG-PET at baseline and 14 days after initiation of cisplatin-based polychemotherapy. Clinical response (reduction of tumor length and wall thickness by > 50%) was evaluated after 3 months of therapy using endoscopy and standard imaging techniques. Patients with potentially resectable tumors underwent surgery, and tumor regression was assessed histopathologically. RESULTS: The reduction of tumor FDG uptake (mean +/- 1 SD) after 14 days of therapy was significantly different between responding (-54% +/- 17%) and nonresponding tumors (-15% +/- 21%). Optimal differentiation was achieved by a cutoff value of 35% reduction of initial FDG uptake. Applying this cutoff value as a criterion for a metabolic response predicted clinical response with a sensitivity and specificity of 93% (14 of 15 patients) and 95% (21 of 22), respectively. Histopathologically complete or subtotal tumor regression was achieved in 53% (eight of 15) of the patients with a metabolic response but only in 5% (one of 22) of the patients without a metabolic response. Patients without a metabolic response were also characterized by significantly shorter time to progression/recurrence (P =.01) and shorter overall survival (P =.04). CONCLUSION: PET imaging may differentiate responding and nonresponding tumors early in the course of therapy. By avoiding ineffective and potentially harmful treatment, this may markedly facilitate the use of preoperative therapy, especially in patients with potentially resectable tumors.

Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxorubicin, and cisplatinum. Closing results after 5 years of follow-up.

BACKGROUND: The intent to curatively treat patients with gastric carcinoma is based on complete surgical resection of the primary tumor and its lymphatic drainage. Postoperative adjuvant chemotherapy has failed to show a significant prognostic advantage for these patients. Preoperative chemotherapy, based on promising results in the treatment of patients with disease in primarily unresectable stages, is still being evaluated for those with locally advanced gastric carcinoma. Most published studies still lack adequate staging methods, and long term results of this treatment modality are not known at present. METHODS: In a Phase II study, a series of 42 patients with locally advanced gastric carcinoma (International Union Against Cancer Stages IIIA, IIIB, and IV) initially were staged with endoscopy, with endoscopic ultrasound to establish the clinical tumor classification, with computed tomography scans to rule out tumor infiltration of adjacent organs and to detect distant metastases, and with surgical laparoscopy to exclude occult peritoneal carcinomatosis. Three or four planned cycles of neoadjuvant chemotherapy with etoposide, doxorubicin, and cisplatinum were given prior to total gastrectomy. RESULTS: After a complete follow-up of at least 5 years, there was a median survival of 19.1 months for all patients. Only patients who underwent a complete surgical tumor resection appeared to have a survival benefit, with a median survival of 28.4 months. A superior survival rate was seen in patients who had a major clinical response to chemotherapy, with a median survival of 45 months. CONCLUSIONS: Phase III studies comparing results from patients who undergo neoadjuvant chemotherapy followed by surgery with results from patients who undergo surgery alone should stress the value of adequate pretherapeutic staging and must be accompanied by studies of potential methods for predicting tumor response.

Endoscopic ultrasound criteria for vascular invasion in the staging of cancer of the head of the pancreas: a blind reevaluation of videotapes.

BACKGROUND: It has been claimed in several prospective studies that endoscopic ultrasonography (EUS) is highly accurate in the locoregional staging of pancreatic cancer. However, the value of the EUS criteria for the diagnosis of vascular involvement is less well established. To totally exclude potential bias introduced by the availability of prior information, a completely blinded analysis of videotapes of patients with cancer of the pancreatic head was therefore conducted. METHODS: Videotape sequences of 75 patients with cancer of the head of the pancreas with surgical confirmation or unequivocally positive angiography demonstrating vascular invasion were reevaluated without any clinical data or information from other imaging studies. Involvement of the vascular system (portal vein with confluence, superior mesenteric vein, celiac axis) was assessed on EUS with special emphasis on EUS parameters of the tumor-vessel relationship. RESULTS: The overall sensitivity and specificity of EUS in the diagnosis of venous invasion were 43% and 91%, respectively, when using predetermined parameters (visualization of tumor in the lumen, complete obstruction, or collateral vessels). If the parameter "irregular tumor-vessel relationship" had been added to these criteria, the sensitivity would have risen to 62%, but the specificity would have fallen to 79%. The only vascular system that could be properly visualized by EUS was the portal vein/confluence area. The positive and negative predictive values for the single parameters chosen to diagnose portal venous involvement were as follows: 42% and 33% for irregular tumor-vessel relationship, 36% and 34% for visualization of tumor in the vascular lumen, 80% and 28% for complete vascular obstruction, and 88% and 18% for collateral vessels. CONCLUSIONS: In a completely blinded evaluation of the EUS diagnosis of vascular invasion by cancer of the head of the pancreas it was not possible to find suitable morphologic parameters with clinically useful sensitivity and specificity values (over 80%).

P53 mutational status improves estimation of prognosis in patients with curatively resected adenocarcinoma in Barrett's esophagus.

The incidence of adenocarcinomas in Barrett's esophagus has been rising in the last two decades in the United States and Western Europe for yet unknown reasons. We reported previously a large multi-institutional trial implicating p53 mutations as being involved in the pathogenesis of Barrett's cancer and representing an early marker for the malignant potential of Barrett's epithelium. A prospective study was performed to evaluate the prognostic impact of p53 mutations on survival in 59 patients with Barrett's cancer. Tissue for DNA analysis was obtained by endoscopic biopsy or immediately after surgical resections from the tumor, Barrett's epithelium, and normal stomach and esophagus. p53 mutation analysis was performed by PCR-single strand conformational polymorphism screening of exons 5-9 and DNA sequencing to unequivocally prove the presence of a mutation. p53 mutations were identified in 30 of 59 (50.8%) patients. The presence of a p53 mutation in the tumor had a significant impact on survival after curative resections (RO-resections) with cumulative 5-year survival probabilities of 68.8+/-9.7% for mutation-negative tumors and 24.3+/-9.9% for mutation-positive tumors (log rank: P < 0.001). By Cox proportional hazard analysis, including the parameters of gender, age, Union International Contre Cancer tumor stage, grading, and p53 mutation status, only Union International Contre Cancer tumor stage (P < 0.0001) and p53 mutation status (P < 0.02) were of significant independent prognostic importance. p53 mutation analysis by DNA sequencing is of significant independent prognostic importance next to histopathological tumor stage in patients with curatively resected (RO-resection) Barrett's cancer. It appears that p53 mutational status is a valuable parameter to define low-risk (p53 mutation-negative) and high-risk (p53 mutation-positive) groups for treatment failure after curative resections.

Fibrovascular esophageal polyp as a diagnostic challenge.

Fibrovascular polyps are rare benign esophageal tumors that usually arise from the proximal third of the esophagus. We present the case of a 48-year-old man with a history of dysphagia and 7-kg weight loss over a period of 2 months. A barium swallow showed a distended esophagus with a tumor extending from the upper esophageal sphincter to the cardia. On a thoracic computed tomographic scan, a homogeneous intramural mass with a density of 22 Hounsfield units was seen, which extended throughout the entire esophagus. Fiberoptic endoscopy confirmed the presence an intramural tumor beginning at the upper esophageal sphincter and reaching to the cardia. The tumor was completely covered with mucosa, except for an ulcerated area at its distal end, which herniated into the stomach. On endoscopic ultrasound, the tumor appeared to grow submucosally and to respect the muscularis propria. Endoscopic biopsies from the ulcerated distal aspect of the tumor suggested a leiomyoma. None of the imaging modalities used revealed evidence of a polyp or intraluminal esophageal tumor. Rather, a potentially malignant extensive intramural tumor was suspected, and an esophagectomy was performed. Only at the time of removal of the specimen did it become evident that the tumor mass was located intraluminally with a pedicle in the region of the upper esophageal sphincter. The final pathological diagnosis was a giant fibrovascular polyp of the esophagus.

Radical transhiatal esophagectomy with two-field lymphadenectomy and endodissection for distal esophageal adenocarcinoma.

Distal adenocarcinoma of the esophagus is defined as a tumor originating from an endobrachyesophagus or a tumor with its main tumor mass (more than two-thirds) located in the distal tubular esophagus. Controversy exists about the optimal mode of surgical resection. Some favor transthoracic esophagectomy, whereas others prefer transhiatal (blunt) esophagectomy. A radical transhiatal esophagectomy (RTE) combined with two-field lymphadenectomy and mediastinoscopic dissection of the upper thoracic esophagus (endodissection) is described herein. We assessed the short- and long-term results of this technique and compared them to a historical group of patients undergoing conventional transhiatal esophagectomy (THE) for adenocarcinoma of the distal esophagus. Altogether 124 patients underwent transmediastinal esophagectomy because of adenocarcinoma of the distal esophagus in our department between January 1986 and May 1995. Thirteen of these patients were excluded from this analysis because of preoperative chemotherapy. The remaining 109 patients were divided into two groups: 62 patients who underwent THE between January 1986 and March 1991 (51 men, 11 women; mean age 65.3 years, range 31-83 years) and 47 patients who had RTE between April 1991 and May 1995 (44 men, 3 women; mean age 63.4 years, range 41-84 years). To compare the long-term results of RTE and THE, we used a matched-pairs analysis considering tumor stage and age. The hospital (30-day) mortality was marginally lower in the RTE group (4.3% versus 6.4%), resulting in an overall mortality of 5.5%. The rate of pulmonary complications was insignificantly lower in the RTE group [19.1% RTE versus 25.8% THE; not significant (NS), and the rate of postoperative cardiac abnormalities significantly decreased after RTE (2.6% RTE versus 19.3% THE; p < 0.05). The overall rate of R0 resections was 87.2% (82.2% RTE, 87.1% THE). Overall survival was similar within the two study groups. Complete tumor removal, T and N stages, and the lymph node ratio were identified as prognostic factors for long-term survival. Overall survival was better after RTE than after conventional THE in patients with involved lymph nodes. The mean number of resected lymph nodes per patient in the RTE group was 26.7. Positive lymph nodes were most common in the paracardial region and at the lesser curvature (72%/10.8% of all invaded abdominal nodes). In the mediastinum positive nodes were most common in the paraesophageal and paraaortal region (48%/27% of all mediastinal nodes). Patients with positive abdominal and mediastinal lymph nodes had a poor long-term prognosis. Distal adenocarcinoma of the esophagus can be safely resected by RTE with two-field lymphadenectomy and endodissection. This technique allows radical "enbloc" resection of the tumor-bearing distal third of the esophagus, which includes the primary area of lymph node metastasis of adenocarcinoma of the distal esophagus: the lower mediastinum and paracardial region. The analysis showed that RTE incurred fewer cardiac complications and a better overall survival in N1-positive patients when compared retrospectively to THE. Intraoperative mediastinoscopy allows controlled dissection of the upper mediastinum and biopsy of several mediastinal lymph nodes, with the advantage of providing additional staging information.

Endosonographic differentiation of benign and malignant stromal cell tumors.

BACKGROUND: Endosonography (EUS) is a valuable technique for diagnosing gastrointestinal stromal cell tumors. However, EUS features that are predictive of malignancy in these tumors have not been defined. METHODS: Videotapes and photographs of EUS examinations performed prior to surgical resection of 35 stromal cell tumors (9 malignant) were blindly reviewed by a single examiner. EUS features associated with malignancy were determined. Interobserver agreement in interpreting these features was then measured among a panel of five expert endosonographers who judged EUS videotapes of 35 resected stromal cell tumors (10 malignant). RESULTS: Stepwise logistic regression analysis demonstrated that tumor size (diameter > 4 cm), irregular extraluminal border, echogenic foci, and cystic spaces were independently associated with malignancy in stromal cell tumors (p < 0.05). Interobserver agreement for irregular extraluminal border, echogenic foci, and cystic spaces, as measured by mean kappa statistic, was 0.43, 0.39, and 0.28, respectively. For the five experts, the sensitivity for detecting malignancy ranged between 80% to 100% when at least two of the three features were judged to be present. The likelihood of finding malignancy ranged between 0% to 11% for the experts when all three features were judged absent. CONCLUSIONS: Tumor size and certain EUS features are useful for predicting malignancy in stromal cell tumors. Absence of these features indicates benign disease. Agreement among experts in interpreting these EUS features is fair to moderate.

Intramural pseudodiverticulosis of the esophagus: a case series.

Intramural pseudodiverticulosis of the esophagus is a rare benign disease of the esophageal wall, with dilation of the submucosal glands, and the predominant symptom is dysphagia. In the literature, 191 cases have been described so far. Along with a short review of the literature, the present report describes six cases of this disorder, including a patient in whom intramural pseudodiverticulosis of the esophagus was secondary to laser therapy and endoluminal afterloading of an esophageal squamous-cell carcinoma.

Adenocarcinoma of the gastro-esophageal junction: CT for monitoring during neoadjuvant chemotherapy.

OBJECTIVE: A clinical study was performed to assess the diagnostic value of spiral CT for evaluation of response during neoadjuvant chemotherapy (CTx) in patients with adenocarcinoma of the gastro-esophageal-junction (GEJ). Results were compared to those of endoscopy. METHODS AND MATERIAL: Twenty-five patients with histologically proven adenocarcinoma of the GEJ scheduled to undergo neoadjuvant CTx were studied. Before CT examination, 1200 ml of a vanilla flavoured paraffin emulsion were applied orally to the fasting patients and 40 mg BuscopanR or 2 mg glucagon were injected i.v. for hypotonia. Iodine (100 ml) was injected automatically (3 ml/s) and the CT scan was started 10 s after complete administration of CM. For response evaluation to CTx, four standardized parameters were measured by two experienced, blinded radiologists. The results were categorized according to the WHO classification of 1981 and compared to those of endoscopy. RESULTS: In 24 of 25 patients endoscopic and computed tomographic response evaluation showed a close correlation (r = 0.96). CONCLUSION: Spiral CT with negative oral contrast agent is a suitable technique for monitoring of GEJ masses. In combination with standardized metric parameters it offers a quantitative response evaluation in patients with GEJ masses during neoadjuvant CTx.

Mutations of p53 in Barrett's esophagus and Barrett's cancer: a prospective study of ninety-eight cases.

We had previously identified p53 mutations in Barrett's esophagus and therefore began a multiinstitutional study to determine their significance as a marker for malignancy. Ninety-eight patients from four institutions were studied. Forty-eight patients (37 men and 11 women, mean age 56.2 years) had Barrett's esophagus with metaplasia or dysplasia but no evidence of malignancy at a mean follow-up of 2.2 years. Barrett's esophagus was classified as metaplasia with no evidence of dysplasia in 32 patients, as low-grade dysplasia in 13, and as high-grade dysplasia in three. The other 50 patients (46 men and four women, mean age 60.2 years) had adenocarcinoma arising in Barrett's esophagus. Tissues from normal stomach or esophagus, tumor, and Barrett's esophagus were obtained for deoxyribonucleic acid analysis by endoscopic biopsy from patients with Barrett's esophagus or cancer or during operations on some patients with Barrett's cancer. Exons 5 through 9 of the p53 gene were studied for mutations by single-strand conformational polymorphism analysis after polymerase chain reaction amplification. Mutations detected by single-strand conformational polymorphism analysis were confirmed by deoxyribonucleic acid sequencing. None of the tissue samples from patients with Barrett's esophagus alone and no dysplasia or low-grade dysplasia had any p53 mutations, but one of the three patients with high-grade dysplasia and no evidence of invasive malignancy did have a p53 mutation. Of the 50 patients with Barrett's cancer, however, 23 (46%) had p53 mutations in Barrett's epithelium, tumors, or both. Twenty of these patients had p53 mutations in the tumor only (n = 16) or in both tumor and Barrett's epithelium (n = 4), suggesting that the mutation plays a direct role in carcinogenesis. Mutations in Barrett's epithelium were found in one patient in the group without malignancy and in seven patients with cancer (one with no dysplasia, two with low-grade dysplasia, and five with high-grade dysplasia). In three patients with cancer, mutations occurred only in Barrett's epithelium, suggesting that such mutations may also be a marker for genomic instability. Mutations were predominantly found in exons 5, 7, and 8, and transitions from guanine to adenine were the most frequent changes. Mutations of p53 are clearly involved in the pathogenesis of Barrett's cancer for a subset of patients (46%), and the fact that we could detect mutations in premalignant Barrett's epithelium supports the hypothesis that p53 mutations may be a useful marker for patients at increased risk for development of invasive cancer.