The effects of neoadjuvant chemoradiation on pTNM staging and its prognostic significance in esophageal cancer.

For esophageal cancer, it is not clear if pathologic TNM staging after chemoradiation and resection will have the same prognostic significance compared with patients who undergo resection only. From 1995 to 2004, prospectively collected data from 279 patients with intrathoracic squamous cell cancers were analyzed. Patients were given chemoradiation either as part of a randomized trial comparing neoadjuvant chemoradiation with surgical resection alone, or because of advanced disease at presentation. One hundred seventy patients had surgical resection only (surgery), and 109 had neoadjuvant chemoradiation (CRT plus surgery). In the surgery group, pT1, 2, 3, and 4 disease was found in 15, 17, 104, and 34 patients, respectively; their respective pN1 rates were 13.3%, 29.4%, 57.7%, and 64.7%, P < 0.01. In CRT plus surgery, pT0, T1, 2, 3, and 4 were found in 48, 12, 23, 21, and 5 patients, respectively; their respective pN1 rates were 31.3%, 16.7%, 21.7%, 52.4%, and 20%, P = 0.44. Logistic regression analysis of factors predictive of pN1 showed that pT stage correlated with pN1 status (P = 0.005) in the surgery group, but not for the CRT plus surgery group. Cox regression analysis demonstrated that in the surgery group, pT, pN, and R category, and overall pTNM stage, were independent prognostic factors, whereas pN, R category, and gender were identified as relevant for CRT plus surgery. After chemoradiation, pT and overall pTNM stage groupings were not as clearly prognostic as in patients without prior therapy. Nodal status remains an important prognostic factor.

Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications.

BACKGROUND AND AIMS: The role of clopidogrel in patients at risk for gastrointestinal complications is uncertain, although it has been recommended for patients who have gastrointestinal intolerance to aspirin. We tested the hypothesis that clopidogrel is as effective as esomeprazole and aspirin in preventing recurrences of ulcer complications. METHODS: This was a prospective, double-blind, randomized, controlled study of 170 patients who developed ulcer bleeding after the use of low-dose aspirin between November 2002 and January 2005. After healing of ulcers and eradication of Helicobacter pylori, if present, patients were assigned randomly to treatment with esomeprazole 20 mg/day and aspirin 100 mg/day (n = 86) or clopidogrel 75 mg/day (n = 84) for 52 weeks. The primary end point was recurrent ulcer complications. RESULTS: During a median follow-up period of 52 weeks, no patient in the esomeprazole group, as compared with 9 patients in the clopidogrel group, developed recurrent ulcer complications. The cumulative incidences of recurrent ulcer complications were 0% in patients receiving esomeprazole and aspirin and 13.6% in patients receiving clopidogrel (absolute difference, 13.6%; 95% confidence interval for the difference, 6.3-20.9; log-rank test, P = .0019). CONCLUSIONS: The combination of esomeprazole and aspirin is superior to clopidogrel in preventing ulcer complications in patients who have a past history of aspirin-related peptic ulcer bleeding.

The influence of technical complications on postoperative outcome and survival after esophagectomy.

BACKGROUND: The dismal survival associated with esophagectomy for cancer has led to the search for potentially correctable factors responsible for this poor prognosis. Although it is intuitive that technical complications could increase postoperative mortality, the effect on long-term survival is controversial. METHODS: From 1990 to 2002, 434 patients underwent resection for squamous cell carcinoma of the intrathoracic esophagus. Prospectively collected data were reviewed for the presence of technical complications. Patient, tumor, and operative variables, postoperative outcome, and survival were compared between patients with technical complications and those without. Prognostic factors were assessed by multivariate analysis. RESULTS: Technical complications occurred in 98 (22.6%) patients. Patients with technical complications had a higher prevalence of cardiac disease, more proximal tumors, and more cervical anastomoses. Technical complications were associated with an increased rate of pulmonary complications (37.8% vs. 10.7%; P<.001) and increased hospital mortality (9.2% vs. 3.3%; P=.025), but no difference in 30-day mortality (2% vs. 1.2%; P=.6). Poor-prognostic factors for survival included male sex, stage III/IV disease, cirrhosis, proximal tumors, and R1/R2 resection, but not technical complications. CONCLUSIONS: Although immediate postoperative outcome and hospital mortality rates were increased, no effect on long-term survival was seen in patients with complications related to errors in surgical technique.

Early prediction of tumor recurrence after curative resection of gastric carcinoma by measuring soluble E-cadherin.

BACKGROUND: Currently, to the authors' knowledge, there is no serum marker to predict disease recurrence after patients undergo curative resection for gastric carcinoma. Previous reports have indicated that serum levels of soluble E-cadherin had prognostic value in these patients. The objective of the current study was to determine whether soluble E-cadherin levels could predict disease recurrence in patients with gastric carcinoma who underwent curative surgery. METHODS: Sixty-nine patients who underwent curative surgery for gastric carcinoma after December 1997 were followed prospectively. Venous blood samples were collected preoperatively, 1 month after surgery, and every 3 months thereafter. The blood samples were assayed for soluble E-cadherin and for carcinoembryonic antigen (CEA) using commercial enzyme-linked immunosorbent assay kits. Receiver operating characteristic (ROC) curves were used to define a cut-off level of E-cadherin for the optimal sensitivity and specificity for predicting disease recurrence. RESULTS: The median follow-up was 21 months for patients with recurrent disease (n = 17 patients) and 36 months for patients without recurrent disease (n = 52 patients; P = 0.007). The optimal cut-off level of E-cadherin was 10,000 ng/mL. The sensitivity for predicting prediction disease recurrence using this cut-off level at 3 months and at 6 months postsurgery was 47% and 59% respectively, which was significantly better compared with the sensitivity of CEA using the conventional cut-off level (6% at 3 months postsurgery and 6% at 6 months postsurgery; P = 0.004 and P < 0.0001, respectively). The median time between the elevated E-cadherin level and documented disease recurrence was 13 months (range, 3-20 months), compared with 4 months (range, 1-20 months) for CEA. CONCLUSIONS: Serum soluble E-cadherin was a good marker for predicting disease recurrence in the first 3-6 months after surgery, with a median of 13 months before clinical recurrence. The use of this marker may allow time for vigilant surveillance and consideration of adjuvant therapy.

Patients with Helicobacter pylori positive and negative duodenal ulcers have distinct clinical characteristics.

AIM: To assess the clinical characteristics of Helicobacter pylori (H pylori) negative duodenal ulcer. METHODS: Patients with an endoscopic diagnosis of duodenal ulcer between 1996 and 2002 were included in the present study. Patients were considered to be negative for H pylori, if both histological examination and rapid urease test of biopsy specimens were negative. A comparison was made between patients with H pylori positive and negative duodenal ulcers. RESULTS: A total of 1 343 patients were studied. Their mean age was 54.7+/-0.5 years. There was a male preponderance (M:F=2.5:1). Three hundred and ninety-eight patients (29.6%) did not have H pylori infection. The annual proportion of patients with H pylori negative duodenal ulcers increased progressively from 1996 to 2002. On multivariate analysis, patients with H pylori negative duodenal ulcer were more likely to be older, have concomitant medical problem, pre-existing malignancy, recent surgery, underlying sepsis, or taken non-steroidal anti-inflammatory drugs. In terms of clinical presentations, patients with H pylori negative duodenal ulcer were more likely to present with bleeding, multiple ulcers and larger ulcers. CONCLUSION: The proportion of patients with H pylori negative duodenal ulcers is on the rise because of a continued drop in incidence of H pylori positive duodenal ulcers in recent years. Such patients have distinct clinical characteristics and it is important to ascertain the H pylori status before starting eradication therapy.

A single-layer, continuous, hand-sewn method for esophageal anastomosis: prospective evaluation in 218 patients.

HYPOTHESIS: A 1-layer, continuous technique for esophageal anastomosis after esophagectomy has been in routine use at the University of Hong Kong Medical Centre since 1996. This study aims to document the results of this method and examine factors that may predispose patients to complications associated with esophageal anastomosis. DESIGN: Retrospective study. SETTING: University academic surgical center. PATIENTS AND METHODS: We studied 218 consecutive patients who had an esophageal anastomosis constructed with a 1-layer, continuous technique. Data were prospectively collected. MAIN OUTCOME MEASURES: Morbidity and mortality rates, anastomotic leaks, stricture, and recurrences. RESULTS: Anastomotic leaks affected 7 patients (3.2%), of whom 3 required surgical reexploration and none died. The hospital mortality rate was 0.9% (2 patients), attributed to myocardial infarction and malignancy. Anastomotic strictures developed in 24 patients (11.1%). Multivariate analysis in those with gastric conduits showed that a cervical anastomosis (intrathoracic vs cervical; odds ratio, 0.27; 95% confidence interval, 0.08-0.87; P = .03) and use of the distal stomach (distal stomach vs whole stomach; odds ratio, 5.25; 95% confidence interval, 1.65-16.66; P = .005) were predictive of benign anastomotic stricture formation. Eleven patients (17.5%) who had a cervical anastomosis developed strictures compared with 13 (8.6%) in those who had intrathoracic anastomoses. Strictures developed in 12 patients (7.4%) with a whole stomach conduit and in 9 patients (19.6%) with a distal stomach conduit. Anastomotic recurrence occurred in 8 patients (3.7%); none had a histologically involved resection margin. CONCLUSIONS: The single-layer, continuous, hand-sewn technique for esophageal anastomosis is safe and effective. Cervical anastomosis and use of the distal stomach were associated with more benign strictures.

Predictive factors for postoperative pulmonary complications and mortality after esophagectomy for cancer.

OBJECTIVE: This study aimed at: (1) documenting the evolution of surgical results of esophagectomy in a high-volume center, (2) identifying predictive factors of pulmonary complications and mortality, and (3) examining whether preoperative chemoradiation therapy would complicate postoperative recovery. SUMMARY BACKGROUND DATA: Pulmonary complications and mortality rate after esophagectomy remain substantial, and factors responsible have not been adequately studied. Neoadjuvant chemoradiation is widely used; it is hypothesized that this may lead to adverse postoperative outcome. METHODS: Prospectively collected data were used to analyze outcome in 421 patients with intrathoracic squamous cell esophageal cancer who underwent resection. Logistic regression analyses determined independent predictors of pulmonary complications and death. Two time periods were compared: period I (January 1990 to June 1995) and period II (July 1995 to December 2001). In the later period, neoadjuvant chemoradiation therapy was introduced. RESULTS: Transthoracic resections were carried out in 83% of patients. Neoadjuvant chemoradiation was given to 42% of patients in period II. Major pulmonary complications occurred in 15.9%, and were primarily responsible for 55% of hospital deaths. Thirty-day and hospital mortality rates were 1.4% and 4.8%, respectively. Logistic regression analysis identified age, operation duration, and proximal tumor location as risk factors for pulmonary complications, whereas advanced age and higher blood loss were predictive of mortality. Chemoradiation did not lead to worse outcome. When period I and II were compared, hospital mortality rate reduced from 7.8% to 1.1%, P = 0.001, with correspondingly less blood loss (median blood loss was 700 ml (range: 200-2700 (period I) and 450 ml (range: 100-7000) (period II), P < 0.01). CONCLUSION: A 1.1% mortality rate was achieved in the last 6 years of the study period. Preoperative chemoradiation did not result in worse outcome. Reduction in mortality rate correlated with decreased blood loss.

Pleural drainage after transthoracic esophagectomy: experience with a vacuum system.

Conventional pleural cavity drainage after esophagectomy involves one to two large-bore drainage tubes connected to underwater bottles. The purpose of this study is to evaluate the use of a small mobile vacuum drainage system. Out of 173 patients who underwent transthoracic esophagectomy, 167 (97%) had the vacuum drain successfully placed at the end of the operation. Of those, use of the vacuum drain was uneventful for 131 until its removal (78%). Air leaks necessitating connection to underwater drainage occurred in 34 patients (20%), but in 26 of them this was only temporary. Overall success was therefore achieved in 157 patients (94%). Median in-situ placement of the vacuum drain was 4 days, and 85% of patients had their drains removed by the seventh postoperative day. The presence of lung adhesions significantly increased the need for underwater drainage. Postoperative outcomes were no different from a historical cohort with conventional underwater drainage. No drain-related complications were reported. The vacuum drain is an alternative to the conventional, large-bore, chest tube system after transthoracic esophagectomy.

A prospective evaluation of catheter probe EUS for the detection of ascites in patients with gastric carcinoma.

BACKGROUND: Gastric carcinoma is known for its propensity to spread to the peritoneum. This study assessed the value of EUS in the detection of ascites not visible on CT in patients with gastric carcinoma. METHODS: A total of 402 consecutive patients with histopathologically confirmed gastric adenocarcinoma underwent catheter-probe EUS. The accuracy of catheter-probe EUS in the detection of ascites was compared with subsequent findings at laparoscopy or laparotomy. RESULTS: There was a slight predominance of men in the study population (M:F=1.6:1). Mean patient age was 65.4+/-0.7 years. Ascites was noted by catheter-probe EUS in 36 patients (9.0%). There was no procedure-related morbidity or mortality. Ascites and peritoneal seeding subsequently were found in, respectively, 56 (13.9%) and 66 (16.4%) patients. The finding of ascites by EUS was significantly related to the presence of peritoneal seeding (p<0.001). The sensitivity, specificity, and positive and negative predictive values of EUS in the detection of ascites were, respectively, 60.7%, 99.4%, 94.4%, and 94.0%. The positive and negative likelihood ratios were, respectively, 105.0: 95% CI[26, 425] and 0.40: 95% CI[0.29, 0.55]. CONCLUSIONS: EUS is useful for the detection of ascites in patients with gastric carcinoma.

Improvement in treatment results and long-term survival of patients with esophageal cancer: impact of chemoradiation and change in treatment strategy.

OBJECTIVE: To identify prognostic factors and reasons for improved survival over time in patients with esophageal cancer. SUMMARY BACKGROUND DATA: Management strategies for esophageal cancer have evolved with time. The impact of chemoradiation in the overall treatment results has not been adequately studied. METHODS: From 1990 to 2000, 399 (62.4%) of 639 patients with intrathoracic squamous cancers underwent resection. Two study periods were analyzed: period I (01/1990-06/1995), and period II (07/1995-12/2000); during period II, chemoradiation was introduced. Prognostic factors were identified by multivariate analysis and the 2 periods compared. RESULTS: Hospital mortality rate after resection decreased from 7.8% to 1.2%, P = 0.002. Five favorable prognostic factors were identified: female gender (female vs. male, HR = 0.66), infracarinal tumor location (infra vs. supra-carinal, HR = 0.63), low pTNM stage (III/IV vs. 0/I/II/T0N1, HR = 1.76), pM0 stage (M1a/b vs. M0, HR = 1.56), and R0 category (R1/2 vs. R0, HR = 2.49). Median survival was 15.8 and 25.6 months in periods I and II, respectively, P = 0.02. More R0 resections were evident in period II, being possible in 63% (period I) and 79% (period II) of patients, P = 0.001. This was attributed to tumor downstaging by chemoradiation and more stringent patient selection for resection in period II. Performing less R1/2 resections in period II coincided with using primary chemoradiation in treating advanced tumors. In patients treated without resection, survival also improved from 3 (period I) to 5.8 months (period II), P < 0.01. CONCLUSIONS: Survival has improved; chemoradiation enabled better patient selection for curative resections and also resulted in more R0 resections by tumor downstaging. This treatment strategy led to overall better outcome for the whole patient cohort, even in those treated by nonsurgical means.

Soluble E-cadherin is an independent pretherapeutic factor for long-term survival in gastric cancer.

PURPOSE: To evaluate whether pretherapeutic serum soluble E-cadherin is an independent factor predicting long-term survival in gastric cancer. Gastric cancer remains the second leading cause of cancer-related deaths in the world, but a satisfactory tumor marker is currently unavailable for gastric cancer. Soluble E-cadherin has recently been found to have prognostic value in gastric cancer. PATIENTS AND METHODS: One hundred sixteen patients with histologically proven gastric adenocarcinoma were included in the trial. Pretherapeutic serum was collected, and soluble E-cadherin was assayed using a commercially available enzyme-linked immunosorbent assay kit. The patients were followed up prospectively at the outpatient clinic. RESULTS: There were 75 men and 41 women, with a mean (+/- SD) age of 66 +/- 14 years. Forty-eight percent of tumors were located in the gastric antrum. The median survival time was 11 months. The mean pretherapeutic value of soluble E-cadherin was 9,159 ng/mL (range, 6,002 to 10,025 ng/mL), and the mean pretherapeutic level of carcinoembryonic antigen was 11 ng/mL (range, 0.3 to 4,895 ng/mL). On multivariate analysis, soluble E-cadherin is an independent factor predicting long-term survival. Ninety percent of patients with a serum level of E-cadherin greater than 10,000 ng/mL had a survival time of less than 3 years (P =.009). CONCLUSION: Soluble E-cadherin is a potentially valuable pretherapeutic prognostic factor in patients with gastric cancer.