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Clinical value of diagnostic laparoscopy with laparoscopic ultrasound in patients with cancer of the esophagus or cardia.

Accurate pretherapeutic tumor staging becomes increasingly important for the selection of therapy in patients with cancer of the upper gastrointestinal tract. We prospectively assessed the clinical value of diagnostic laparoscopy with laparoscopic ultrasound and peritoneal lavage in 127 consecutive patients with cancer of the esophagus or cardia but no evidence of hepatic metastases, peritoneal tumor dissemination, or other systemic tumor manifestations on standard staging techniques. There was no mortality or morbidity associated with diagnostic laparoscopy. Diagnostic laparoscopy with laparoscopic ultrasound showed relevant previously unknown findings, particularly in patients with locally advanced adenocarcinoma of the distal esophagus or cardia (hepatic metastases in 22% and peritoneal tumor spread or free tumor cells in the abdominal cavity in 25%), whereas the diagnostic gain was low in those with squamous cell esophageal cancer. The sensitivity and specificity of laparoscopic ultrasound in predicting positive celiac axis lymph nodes were 67% and 92%, respectively. These data indicate that diagnostic laparoscopy with laparoscopic ultrasound and peritoneal lavage is safe and frequently provides therapeutically relevant new information in patients with locally advanced adenocarcinoma of the distal esophagus or cardia, whereas the clinical value in patients with squamous cell esophageal cancer is limited.

Adenocarcinoma↗

Esophageal endoscopic aspects after forceful dilation of the gastric cardia in patients with achalasia of Chagas' disease.

The purpose of this study was to evaluate the clinical results and to observe endoscopically the distal esophagus in a series of chagasic adults with incipient megaesophagus and normal endoscopic aspect of the mucosa, who underwent forced hydrostatic dilatation of the cardia, 48 h after the procedure. Twenty patients were submitted to a careful specific pattern of forced dilatation, changing forceful and rapid standardized injection of water to slow distension of the balloon until the patient felt pain. The procedure was repeated three times with the same volume and was maintained each time for 5 min, with intervals of about 3 min. The dysphagia was practically immediately controlled and there were no severe complications or mortality in the series. Five patients complained of pyrosis, mild in two of them. The endoscopic examination revealed mucosal edema in 11 patients (55%), hyperemia in nine (45%) and superficial fissures of the mucosa in six (30%), with seven patients (35%) presenting all the signs simultaneously. These observations characterize 'traumatic esophagitis' due to forced dilatation of the cardia as being frequently asymptomatic. Extreme care with the method can produce effective dilatation of the cardia, avoiding severe complications but not some degree of mucosal injuries.

Cardia↗

Experience of endoscopic ultrasound in staging adenocarcinoma of the cardia.

AIM: The introduction of endoscopic ultrasonography (EUS) has generally resulted in a more accurate assessment of gastrointestinal regional tumour stage. Knowing the stage and the extent of oesophageal involvement is extremely important as a guide to the choice of surgical approach in cardia cancer. The aim of this study was to evaluate the ability of EUS to accurately predict depth of tumour invasion (T), node involvement (N) and the tumour's invasion length along the oesophagus. MATERIAL AND METHODS: Thirty-five patients with adenocarcinoma of the cardia were studied by EUS and the EUS pre-operative findings were compared with the pathology findings. RESULTS: The overall accuracy in T staging was 55.2% (16/29 cases). The sensitivity in evaluating T1, T2 and T3 classes was 80%, 38.5% and 70%, respectively. The sensitivity was excellent in evaluating N0 class (100%) (5 cases), but it fell to 66.7% in N1 cases. EUS correctly determined the extent of oesophagus invasion in 75.9% (22/29) of cases; moreover, it had a very high accuracy in distinguishing between tumours with an oesophageal invasion greater or lower than 2 cm (93.1%) (27/29 cases). CONCLUSION: EUS proved to be useful in pre-operative staging of cardia adenocarcinoma and, in particular, in the pre-operative identification of the extent of oesophageal invasion.

Adenocarcinoma↗

Risk of adenocarcinomas of the oesophagus and gastric cardia in patients hospitalized for asthma.

In the first cohort study of the question we followed 92 986 (42 663 men and 50 323 women) adult patients hospitalized for asthma in Sweden from 1965 to 1994 for an average of 8.5 years to evaluate their risk of oesophageal and gastric cardia adenocarcinoma. Standardized incidence ratio (SIR) adjusted for gender, age and calendar year was used to estimate relative risk, using the Swedish nationwide cancer incidence rates as reference. Asthmatic patients overall had a moderately elevated risk for oesophageal adenocarcinoma (SIR = 1.5, 95% confidence interval CI, 0.9-2.5) and gastric cardia cancer (SIR = 1.4, 95% CI, 1.0-1.9). However, the excess risks were largely confined to asthmatic patients who also had a discharge record of gastro-oesophageal reflux (SIR = 7.5, 95% CI, 1.6-22.0 and SIR = 7.1, 95% CI, 3.1-14.0, respectively). No significant excess risk for oesophageal squamous-cell carcinoma or distal stomach cancer was observed. In conclusion, asthma is associated with a moderately elevated risk of developing oesophageal or gastric cardia adenocarcinoma. Special clinical vigilance vis-à-vis gastro-esophageal cancers seems unwarranted in asthmatic patients, but may be appropriate in those with clinically manifest gastro-oesophageal reflux.

Adenocarcinoma↗

Incidence rate of adenocarcinoma of the gastric cardia, and endoscopic classification of early cardial carcinoma in Henan Province, the People's Republic of China.

Mass surveys of 29,235 people in high-risk areas for esophageal carcinoma have been carried out, and 21,721 cases examined by gastroscopy were collected from 13 hospitals in high- and low-risk areas for esophageal carcinoma in Henan Province. During the mass surveys, it was found that the incidence rate of adenocarcinoma of the gastric cardia (AGC) was 0.19%, and the ratio of esophageal carcinoma (EC) to ACG was 3.28:1. The prevalence rate of AGC was 5.12% in the 8 hospitals in the high-risk areas for EC, in contrast to 3.57% (P less than 0.01) in the group in low-risk regions, showing that the incidence rate of AGC was also high in the populations living in the high-risk areas for EC. Most gastric cancers detected in both the high- and low-risk areas for EC have a predominantly proximal location, most being located in the gastric cardia. The endoscopic findings of 79 cases with early adenocarcinoma of the gastric cardia (EAGC) are described. It is suggested that EAGC could be divided into four types - congestive type, erosive type, plaque-like type and polypoid type.

Adenocarcinoma↗

[Secondary achalasia in non-Hodgkin's lymphoma of low malignancy and leiomyomatosis of the cardia].

A 28-year-old man had been dysphagic for 9 months with a weight loss of 4 kg. A preliminary diagnosis of primary achalasia was made on the basis of typical radiological and manometric findings. Despite balloon dilatation of the cardia the symptoms did not improve and further diagnostic tests were performed. Ultrasound demonstrated a 4 cm tumour below the cardia. But its type and possible malignancy remained uncertain even at laparotomy. But as a malignant tumour was suspected a gastrectomy and omentectomy with removal of the local and regional lymph nodes were performed. After this the symptoms regressed and postoperative food intake was without problem. Histological examination of the surgical specimen revealed leiomyomatosis of the cardia and the gastric fundus, combined with a low-malignant B-cell lymphoma of the mucosa-associated lymphatic tissue. Oesophagus manometry 4 months postoperatively gave normal results. The patient has been free of symptoms and without evidence of recurrence for by now 18 months postoperatively.

Adult↗

Application of the new classification for cancer of the cardia.

BACKGROUND: Cancer of the cardia is now topographically classified into three types: type I, with the tumor center in the distal esophagus treated with subtotal esophagectomy; type II, arising at the gastroesophageal junction and treated with distal esophagectomy and either proximal or total gastrectomy; and type III, subcardial cancer treated with extended total gastrectomy. Our objective was to review the new classifications and compare the outcomes in patients grouped and treated according to these classifications. METHODS: Seventy-four patients with cancer of the cardia--15 with type I, 30 with type II, and 29 with type III cancer--underwent surgical resection at our institution between 1992 and 1997. Postoperative complications, UICC stages, and survival (Kaplan-Meier) were compared. RESULTS: The majority of patients with type I (73%) or type II (53%) cancer had stage I or II tumors, but only 27% of patients with type III cancer had this tumor stage (P < .05). Overall 30-day mortality was 4% and morbidity was 31%. Curative resections were performed in 73% (54 of 74) of the patients with 3-year survival rates of 72% (type I), 68% (type II), and 61% (type III). CONCLUSION: The recommended therapy for the different types of cancer of the cardia results in acceptable morbidity, mortality, and survival rates.

Adenocarcinoma↗

Metastases to the para-aortic lymph nodes in adenocarcinoma of the cardia.

OBJECTIVE: To find out the extent of involvement of the para-aortic nodes in patients with adenocarcinoma of the gastric cardia. DESIGN: Open prospective study. SETTING: Teaching hospital, Italy. SUBJECTS: 23 patients with advanced adenocarcinoma of the cardia (type II, n = 10, and type III, n = 13) who were treated by total gastrectomy with resection of the distal oesophagus and extended lymphadenectomy (D4) between January 1997 and June 1999. These were compared with 21 patients with advanced carcinoma of the proximal third of the stomach who had total gastrectomy with D4 lymphadenectomy during the same period. Lymph nodes were retrieved immediately postoperatively and assigned to the appropriate station according to the classification of the Japanese Research Society for Gastric Cancer. MAIN OUTCOME MEASURES: Number of para-aortic and other nodes involved. RESULTS: 22 of the 23 patients had lymph node metastases, and in 5 the para-aortic nodes were involved (N4). N3 lymph nodes were involved in only 1 patient, despite involvement of para-aortic nodes. Among the 5 patients with N4 metastases, 1 had only N1 metastases in addition, with no involvement of N2 or N3 nodes. Patients with involved N4 nodes had more nodes involved overall than those who did not (mean (SD) 17 (5) compared with 8 (12)). CONCLUSIONS: 5/23 patients with advanced carcinoma of the cardia had involved para-aortic nodes. This may have some prognostic value, but larger studies of D4 lymphadenectomy specimens is required.

Adenocarcinoma↗

Endoesophageal pull through. A technique for the treatment of cancers of the cardia and lower esophagus.

Transthoracic and extrathoracic approaches to cancers of the lower esophagus and cardia each have advantages and drawbacks; the trauma of thoracotomy must be balanced against that of blunt mediastinal extraction of the esophagus. A different surgical approach is proposed in this paper, avoiding both thoracotomy and encroachment upon thoracic mediastinal structures. This technique is based on the removal of the tumor and the esophageal mucosa above it as a distinct anatomic layer by blunt dissection through separate abdominal and neck incisions. This is followed by pulling upward a segment of stomach (or colon) through the esophageal muscular tunnel into the neck for a cervical anastomosis. This endoesophageal pull through (EEPT) approach has been used in the surgical treatment of a total of ten patients, six with adenocarcinomas of the cardia and four with squamous cell carcinomas of the lower esophagus. In nine patients the stomach, and in one patient the left colon, was brought to the neck to reestablish gastrointestinal (GI) continuity. The operation was well tolerated. There was no excessive intraoperative or postoperative bleeding, and there was no in-hospital mortality up to 30 days. The major postoperative complication was cervical anastomotic leakage seen in four patients. The EEPT technique is a palliative approach for cancers of the lower esophagus and cardia, comparing favorably with the standard extrathoracic or transthoracic transhiatal procedures.

Anastomosis, Surgical↗

The impact of an antireflux procedure on intestinal metaplasia of the cardia.

OBJECTIVE: The aim of this study was to determine whether antireflux surgery is more effective in producing loss of intestinal metaplasia located only at the gastroesophageal junction than it has been in patients with intestinal metaplasia extending up into the distal esophagus. SUMMARY BACKGROUND DATA: Biopsies of a normal appearing gastroesophageal junction will demonstrate cardiac mucosa containing goblet cells--the hallmark of intestinal metaplasia--in 10% to 15% of patients who are evaluated for symptoms of gastroesophageal reflux. The incidence of adenocarcinoma of the esophagus and cardia is rising faster than any other cancer in America, and most of these cancers are found adjacent to areas of intestinal metaplasia. Antireflux surgery in patients with Barrett's esophagus may provide protection from progression to dysplasia and cancer; however, it does not reliably cause regression of the intestinal metaplasia. Less is known about the potential for intestinal metaplasia limited to the cardia (CIM) to regress. METHODS: Sixty patients with intestinal metaplasia of the esophagus or cardia had antireflux surgery. Patients in the intestinal (CIM) group (n = 15) had no endoscopically visible segment of columnar epithelium. Patients in the Barrett's group (n = 45) had columnar epithelium visible within the esophagus. Median follow-up was 25 months in each group. RESULTS: Postoperative biopsies showed complete loss of intestinal metaplasia in 73% of the patients with CIM compared with 4.4% of the patients with Barrett's. Low-grade dysplasia, present in 10 patients preoperatively, regressed in 7 patients (70%). No patient progressed to high-grade dysplasia or cancer. CONCLUSIONS: Loss of intestinal metaplasia after antireflux surgery is rare in patients with Barrett's, but occurred in most patients with CIM. This suggests that cardiac epithelium is dynamic and that microscopic areas of intestinal metaplasia are able to regress much more frequently than longer, visible segments of intestinal metaplasia.

Adult↗

The rising trend in oesophageal adenocarcinoma and gastric cardia.

The incidence of cancer of the oesophagus and stomach in the West Midlands region of England have been analysed for the 25 years 1962-86. Overall, cancer of the oesophagus is increasing (from 3.45 per 100,000 in 1962-66 to 4.37 in 1982-86) and stomach cancer is decreasing (19.22 and 16.54 respectively). However, when analysed by histological type and subsite the picture is very different. In oesophagus, squamous cell carcinoma shows only a slight increase whereas for adenocarcinoma the increase is highly significant (from 0.14 to 0.76). In stomach, cardia shows a very similar pattern to adenocarcinoma of oesophagus (increasing from 0.75 to 2.96) but pyloric antrum is decreasing (from 2.63 to 2.32). The rapid changes in investigative procedures over the period have resulted in increasing numbers with histological confirmation and subsite specification but despite these confounding factors, comparative analyses still indicate a real increase in adenocarcinoma of oesophagus and cardia. Although the incidence of both are greater in men than in women, the proportional rates of increase, particularly for cardia, are very similar in both sexes, indicating a common aetiological factor or factors. Analysis by social-economic group reveals that the increases observed are not uniform throughout the population but are relatively higher in professional classes (1 and 2).

Adenocarcinoma↗

Occupational risk factors for cancer of the gastric cardia. Analysis of death certificates from 24 US states.

We evaluated the risk of gastric cardia cancer by occupation and industry in a case-control study using information from death certificates for 24 US states in 1984-1992. One thousand fifty-six cases of gastric cardia cancer were identified among men aged 20 years or more, including 1,023 whites and 33 blacks. Controls were 5,280 subjects who died of nonmalignant diseases, 5:1 matched to cases by geographic region, race, gender, and 5-year age group. Among white men, occupations with elevated risk included financial managers (odds ratio [OR] = 6.1; 95% confidence interval [CI], 1.3-28.8), janitors and cleaners (OR = 1.7; 95% CI, 1.0-2.9), production inspectors (OR = 3.2; 95% CI, 1.5-6.9), and truck drivers (OR = 1.5; 95% CI, 1.0-2.2). Industries with elevated risk included pulp and paper mills (OR = 2.0; 95% CI, 1.0-37), newspaper publishing and printing (OR = 2.6; 95% CI, 1.0-6.3), industrial and miscellaneous chemicals (OR = 2.0; 95% CI, 1.0-3.9), water supply and irrigation (OR = 5.6; 95% CI, 1.6-19.9). Among black men, risks were nonsignificantly increased for subjects employed in railroads (3 cases, 2 controls) and for carpenters (3 cases, 0 controls). We created job-exposure matrices for asbestos, inorganic dust, metal dust, lead, polycyclic aromatic hydrocarbons, nitrogen oxides, nitrosamines, sulfuric acid, fertilizers, herbicides, other pesticides, and wood dust. Among white men, a consistent pattern of risk increase by level and probability of exposure was observed only for sulfuric acid mists, with a twofold excess (95% CI, 0.6-7.3) associated with high probability of high intensity exposure. A significant 30% increase in risk was observed for those subjects with a high probability of exposure (all levels combined) to lead, and a 60% increase was observed for subjects with high-level exposure to lead (all probabilities combined). However, crosstabulation of gastric cardia cancer risk by probability and level of exposure to lead did not show consistent trends. Asbestos exposure also showed an overall 50% increase but no consistent trends among white men. None of the 12 occupational hazards showed an association with risk for black men.

Adult↗

Relationship between diabetes mellitus and adenocarcinoma of the oesophagus and gastric cardia.

BACKGROUND: Obesity is a risk factor for adenocarcinomas of the oesophagus and gastric cardia. Diabetes mellitus might mediate that association. AIM: To estimate the risk of diabetes mellitus on the development of adenocarcinoma of distal oesophagus and gastric cardia beyond that of gastro-oesophageal reflux disease. METHODS: A case-control study was performed using a national administrative database of the Veterans Administration. RESULTS: A total of 311 cases of cancer and 10,154 controls were identified. Gender, age, and race were risks for cancer. Diabetes was diagnosed in 36% of cases, and 32% of controls (P = 0.15). Diabetic complications were diagnosed in 14% of cases and 13% of controls (P = 0.60). Multiple logistic regression confirmed the absence of an association between cancer and diabetes (odds ratio 1.1, 95% confidence interval 0.8-1.5) or diabetic complications (odds ratio 0.8, 95% confidence interval 0.6-1.3), adjusting for age, gender, and race. CONCLUSIONS: Within the limitations of this case-control study, there is no evidence of an association between diabetes and adenocarcinoma of the oesophagus or gastric cardia among US veterans with gastro-oesophageal reflux disease.

Adenocarcinoma↗

Exploratory laparotomy alone in carcinoma of the oesophagus and gastric cardia.

A retrospective analysis of 453 patients with carcinoma of the oesophagus and gastric cardia was carried out in order to identify the incidence, operative findings, and outcome of patients who underwent laparotomy only without a definitive procedure. Of 343 patients who underwent surgery, 81% had their tumours resected and 15% had a bypass procedure. The remaining 14 patients (4%) had an exploratory laparotomy alone. The incidence of performing a laparotomy only was 1.5% for patients with carcinoma of the thoracic oesophagus but was 14% for patients with tumour of the gastric cardia (P less than 0.001). The reasons for exploration alone in these 14 patients were advanced local disease (12), bilobar liver metastases (seven), extensive abdominal lymph node metastases (seven), peritoneal seedlings (six) and malignant ascites (four). All except one patient had more than one feature which led to the decision of exploration only. As the overall incidence of exploratory laparotomy was low, it would not be appropriate for all patients to undergo exhaustive and expensive investigations. Surgical exploration continues to be the only reliable method to determine the actual extent of disease and whether a definitive procedure is possible. However, patients with cancer of the cardia with clinical features of advanced disease might warrant additional evaluations as the incidence of exploratory laparotomy alone with minimal prior investigation is relatively high.

Adenocarcinoma↗

Detection of unsuspected left hepatic lobe metastases during EUS staging of cancer of the esophagus and cardia.

BACKGROUND: High resolution imaging of the left hepatic lobe can be obtained via endoscopic ultrasound (EUS), allowing for detection of unsuspected metastatic disease during cancer staging. The frequency at which occult liver metastases are detected during EUS staging of cancer of the esophagus and cardia is unknown. METHODS: Over an 18-month period, 98 patients underwent EUS staging for a new diagnosis of cancer of the esophagus and cardia. Wire-guided dilation was performed if necessary. Standard radial examination was followed by curvilinear evaluation with attention to the left hepatic lobe. All suspicious liver lesions were aspirated under EUS guidance. RESULTS: The radial and curvilinear echoendoscope were successfully passed to the antrum in 86% and 81% of cases, respectively, without complication. Thirty-two percent of patients required dilation. Lesions suspicious for left hepatic lobe metastases were found in 7% of cases that could be completely evaluated by EUS, all of which underwent EUS-guided fine needle aspiration. All lesions were proven metastases: four true-positive and one false-negative cytologic result. CONCLUSION: Curvilinear EUS examination of the left hepatic lobe in addition to standard radial EUS examination can be performed safely when staging cancer of the esophagus and cardia. Dedicated left hepatic lobe examination should be performed as it avoids unnecessary surgery in a subset of these patients by detection of occult liver metastases.

Adenocarcinoma↗

Preventive role of dietary fiber in gastric cardia cancers.

The incidence of adenocarcinoma of the esophagus and gastric cardia is increasing. Many factors are presumed to be associated: symptoms of gastroesophageal reflux disease, tobacco use, alcohol consumption, dietary factors, and obesity. A recent large population-based case-control study evaluated the association between dietary fiber intake and cancers of the gastric cardia and esophagus. This interesting study indicated that high intake of cereal fiber may significantly decrease the risk of gastric cardia cancer. More research is needed on this topic in the hope that dietary intake may decrease the incidence of these cancers.

Adenocarcinoma↗

Dietary patterns and risk of squamous-cell carcinoma and adenocarcinoma of the esophagus and adenocarcinoma of the gastric cardia: a population-based case-control study in Sweden.

We conducted a large population-based case-control study in Sweden to examine the association of dietary patterns and the development of cancers from the esophagus or gastroesophageal junction. In total 185 patients with esophageal adenocarcinoma, 165 with esophageal squamous-cell carcinoma, 258 with gastric cardia adenocarcinoma, and 815 randomly selected population controls underwent face-to-face interviews. Exploratory factor analysis was used to identify possible dietary patterns. Multivariate logistic regression with adjustments for age, sex, years of education, body mass index, physical activity, symptomatic gastroesophageal reflux, smoking, and total energy intake was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). We identified three major dietary patterns in this population, for example, "healthy diet" (high in vegetables, tomato, fruits, fish, and poultry), "Western diet" (high in processed meat, red meat, sweets, high-fat dairy, and high-fat gravy), and "alcohol drinker" (high in intakes of beer, liquor, and French fries). We found that a healthy diet tended to moderately decrease the risk of all three cancers under study, although none of the associations was statistically significant. A high score of Western diet was associated with increased risks of gastric cardia adenocarcinoma (high 3rd tertile vs. low 1st quartile, OR = 1.8, 95% CI = 1.1-2.9, P for trend = 0.04) and esophageal adenocarcinoma (high 3rd tertile vs. low 1st tertile, OR = 1.6, 95% CI = 0.9-3.1, P for trend = 0.13), whereas a dietary pattern characterized by high beer and liquor intake (alcohol drinker) significantly increased the risk of squamous-cell carcinoma of the esophagus (3rd tertile vs. low 1st tertile, OR = 3.5, 95% CI = 1.9-6.3, P for trend < 0.0001). Our study confirms the important role of diet in the carcinogenesis of esophageal and cardia cancer.

Adenocarcinoma↗

A phase II trial of docetaxel and CPT-11 in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and gastric cardia.

PURPOSE: The incidence of adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia has been rising in the face of limited treatment options for patients with metastatic disease. With the emergence of data to suggest that single agent docetaxel and irinotecan carry antineoplastic effects in this setting, we determined the response rate of these agents when given in combination. PATIENTS AND METHODS: Forty-six patients with metastatic adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia were evaluated. Patients received docetaxel 50 mg/m2/d and irinotecan 130 mg/m2/d intravenously at 21-d intervals with a tumor assessment after 2 cycles. Because of unacceptable toxicity among the first 13 patients, dosing was reduced to docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d intravenously at 21-d intervals. RESULTS: The response rate for the entire cohort was 26% (95% confidence interval: 14%, 41%) with 12 confirmed partial responses. Five of these 12 responses were observed in patients treated at the higher chemotherapy dose. However, because 8 of 13 patients suffered grade 4 neutropenia and fevers, a dose reduction was incorporated into the protocol, and the remainder of the cohort was treated at the lower dose. All except 4 of the 15 observed grade 4 toxicities occurred at the higher dose, and these toxicities included nausea and vomiting, dyspnea, hypotension, dysrhythmias, and diarrhea in addition to neutropenia and fevers. There were no grade 5 toxicities. The median survival for the entire cohort was 7.3 mo. CONCLUSION: The combination of docetaxel and irinotecan provides modest antineoplastic activity among patients with adenocarcinoma of the esophagus, esophagogastric junction, and gastric cardia. Doses of docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d at 21-d intervals provide an acceptable safety profile, but higher doses appear to result in unacceptable toxicity.

Adenocarcinoma↗