Gregory Zuccaro

Esophageal Carcinoma: Depth of Tumor Invasion Is Predictive of Regional Lymph Node Status

BACKGROUND The depth of tumor invasion (T) and regional lymph node status (N) are two factors that define the stage of an esophageal carcinoma. However, the arrangement of staging groups assumes that these factors are independent variables. A retrospective review of 359 consecutive patients undergoing esophageal resection was conducted to define the relationship between T and N and to determine whether T is a significant predictor of regional lymph node metastasis (N1). METHODS Primary treatment was operation without preoperative therapy. There were 295 (82%) adenocarcinomas, 55 (15%) squamous cell carcinomas, and 9 (3%) adenosquamous carcinomas. T status was Tis in 29 (8%) patients, T1 in 65 (18%), T2 in 37 (10%), T3 in 219 (61%), and T4 in 9 (3%). N status was N0 in 161 (45%) patients and N1 in 198 (55%). M status was M0 in 327 (91%) patients and M1 in 32 (9%). Stage was 0 in 29 (8%) patients, I in 58 (16%), IIA in 70 (20%), IIB in 22 (6%), III in 148 (41%), and IV in 32 (9%). RESULTS The likelihood of N1 disease occurring with increasing T was tested using the trend test. The percentage of patients with N1 disease is 0% for Tis, 11% for T1, 43% for T2, 77% for T3, and 67% for T4 (p < 0.001). This relationship existed for both adenocarcinoma and squamous cell carcinoma. Multivariable analysis identified increasing T, adenocarcinoma, and lack of well-differentiated histologic features as significant predictors of N1 disease. Compared with a T1 patient, a T2 patient is 6 times more likely to have N1 disease, a T3 patient 23 times, and a T4 patient 35 times. CONCLUSIONS We conclude that for patients with esophageal carcinoma, T is an important predictor of N and this association should be included with other established factors used in clinical staging and treatment decisions.

A prospective, randomized, controlled trial of covered expandable metal stents in the palliation of malignant esophageal obstruction at the gastroesophageal junction

OBJECTIVE:Palliation of malignant esophageal obstruction is an important clinical problem. Expandable metal stents are a major advance in therapy, but many stents become obstructed because of tumor ingrowth. The aim of this study was to compare a new, membrane-covered expandable metal stent to conventional prostheses in a randomized controlled trial.METHODS:Sixty-two patients with malignant inoperable esophageal obstruction at the gastroesophageal junction participated in the study. Patients were randomly assigned to covered or uncovered stents. The principal outcome measure was the need for reintervention because of recurrent dysphagia or migration. Secondary endpoints were relief of dysphagia measured by a dysphagia score (grade 0 = no dysphagia, grade 1 = able to eat solid food, grade 2 = semisolids only, grade 3 = liquids only, grade 4 = complete dysphagia) and the rate of complications and functional status. All patients were observed at monthly intervals until death or for 6 months.RESULTS:One week after stenting the dysphagia score improved significantly in both the uncovered (n = 32, 3 ± 0.1 to 1 ± 0.1 [means ± SEMs], p < 0.001) and covered (n = 30, 3 ± 0.1 to 1 ± 0.2 [means ± SEMs], p < 0.001) stents. Obstructing tumor ingrowth was significantly more likely in the uncovered stent group (9/30) than in the covered group (1/32) (p = 0.005). Significant stent migration occurred in 2/30 patients with uncovered stents, as compared with 4/32 patients in the covered group (p = 0.44). Reinterventions for tumor ingrowth were significantly greater in the uncovered stent group (27%), as compared with 0% in the covered group (p = 0.002). Life table analysis showed similar survival in both groups.CONCLUSION:Membrane-covered stents have significantly better palliation than conventional bare metal stents because of decreased rates of tumor ingrowth that necessitate endoscopic reintervention for dysphagia.

Management of the Adult Patient With Acute Lower Gastrointestinal Bleeding

Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When data are not available that will withstand objective scrutiny, a recommendation may be made based on a consensus of experts. Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty. Guidelines are intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. Given the wide range of choices in any health care problem, the physician should select the course best suited to the individual patient and the clinical situation presented. These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee. These guidelines are also approved by the governing boards of the American Gastroenterological Association and the American Society for Gastrointestinal Endoscopy. Expert opinion is solicited from the outset for the document. Guidelines are reviewed in depth by the Committee, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time.

Propofol Versus Traditional Sedative Agents for Gastrointestinal Endoscopy: A Meta-analysis

BACKGROUND & AIMS Even though propofol has better recovery profile than traditional agents, its use is limited because of the perception of increased complication rates. Because an adequately powered trial comparing risk of propofol with traditional agents is lacking, we performed a meta-analysis of the current literature. METHODS We searched Medline (1966-October 2004), EMBASE (1980-October 2004), and Cochrane controlled trials registry. The following 4 cardiopulmonary complications were assessed: hypoxia, hypotension, arrhythmias, and apnea. Procedures were divided into 3 groups: esophagogastroduodenoscopy group, colonoscopy group, and endoscopic retrograde cholangiopancreatography/endoscopic ultrasonography group. Pooled odds ratios for complications were calculated for all the procedures combined and then separately for the 3 groups. Random effects models were used for 2-proportion comparisons. RESULTS Of the 90 citations identified, 12 original studies qualified for this meta-analysis and included 1161 patients. Of these, 634 received propofol, and 527 received midazolam, meperidine, and/or fentanyl. Most of the included studies were randomized trials of moderate quality and nonsignificant heterogeneity (Cochran Q = 4.81, P = .90). Compared with traditional sedative agents, the pooled odds ratio with the use of propofol for developing hypoxia or hypotension for all the procedures combined was 0.74 (95% confidence interval [CI], 0.44-1.24); for EGD, 0.85 (95% CI, 0.33-2.17); for colonoscopy, 0.4 (95% CI, 0.2-0.79); and for ERCP/EUS, 1.07 (95% CI, 0.38-3.01). CONCLUSIONS Propofol sedation during colonoscopy appears to have lower odds of cardiopulmonary complications compared with traditional agents, but for other procedures, the risk of complications is similar.

Endoscopic ultrasound cannot determine suitability for esophagectomy after aggressive chemoradiotherapy for esophageal cancer.

OBJECTIVE:Endoscopic ultrasound (EUS) provides important information in the initial staging of patients with esophageal cancer. With recent modifications in chemoradiotherapy protocols, a significant number of patients have no residual tumor at esophagectomy. The high surgical morbidity and mortality might be avoided if complete response to chemoradiotherapy could be predicted. Previously published clinical trials, with relatively small patient numbers, have suggested that EUS may accurately stage esophageal cancer after chemoradiotherapy. The aim of this study was to verify the accuracy of EUS in staging esophageal cancer after effective chemoradiotherapy.METHODS:EUS staging was performed before and after concurrent cisplatin, 5-fluorouracil, and hyperfractionated radiotherapy in 59 patients with newly diagnosed esophageal cancer. All patients underwent subsequent esophagectomy and pathological staging. The accuracy of preoperative, postchemoradiotherapy EUS was evaluated in a retrospective fashion by comparison to pathological staging.RESULTS:After chemoradiotherapy, 18 patients (31%) had no residual disease at pathological staging (T0N0). However, EUS correctly predicted complete response to chemoradiotherapy (T0N0) in only three patients (17%). The accuracy of postchemoradiotherapy EUS for pathological T stage was only 37%, and its sensitivity for N1 disease was only 38%. EUS was unable to distinguish postradiation fibrosis and inflammation from residual tumor.CONCLUSION:When aggressive preoperative chemoradiotherapy is provided to patients with esophageal cancer, the predictive value of postchemoradiotherapy EUS is inadequate for use in clinical decision making.

Pathogenesis of Chronic Pancreatitis: An Evidence-Based Review of Past Theories and Recent Developments

In the past several decades, four prominent theories of chronic pancreatitis pathogenesis have emerged: the toxic-metabolic theory, the oxidative stress hypothesis, the stone and duct obstruction theory, and the necrosis-fibrosis hypothesis. Although these traditional theories are formulated based on compelling scientific observations, substantial contradictory data also exist for each. Furthermore, the basic premises of some of these theories are directly contradictory. Because of the recent scientific progress in the underlying genetic, cellular, and molecular pathophysiology, there have been substantial advances in the understanding of chronic pancreatitis pathogenesis. This paper will provide an evidence-based review and critique of the traditional pathogenic theories, followed by a discussion of the new advances in pancreatic fibrogenesis. Moreover, we will discuss plausible pathogenic sequences applied to each of the known etiologies.

Deep sedation occurs frequently during elective endoscopy with meperidine and midazolam.

BACKGROUND AND AIMS:Although moderate (conscious) sedation is intended during elective gastrointestinal endoscopy, unintended levels of deep sedation occur. The aims of this study were to prospectively evaluate the incidence and risk factors of deep sedation during elective endoscopy with meperidine and midazolam intended to maintain a level of moderate sedation.METHODS:Eighty American Society of Anesthesiology class 1-2, outpatients presenting for elective esophagogastroduodenoscopy (EGD), colonoscopy, endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasonography (EUS) were offered enrollment. Intravenous meperidine and midazolam were administered according to a standardized protocol. Hemodynamic parameters and levels of sedation were assessed and recorded by a single observer at 3-min intervals. The Modified Observers Assessment of Alertness/Sedation (MOAA/S) scale (ranging 1–5) is a subjective sedation assessment scale used to assess sedation levels. Occurrence of deep sedation, defined by MOAA/S 1–2, was recorded. Univariable and multivariable analyses were used to assess predictors of deep sedation.RESULTS:Deep sedation occurred in 54/80 (68%) patients for a total of 204/785 (26%) of total sedation assessments. The percentage of deep sedation episodes of all sedation-level observations by procedure was 26% for EGD, 11% for colonoscopy, 35% for ERCP, and 29% for EUS. Deep sedation occurred at least once in 60% of EGD, 45% of colonoscopy, 85% of ERCP, and 80% of EUS. Multivariable analysis showed that only ERCP and EUS were independent risk factors of deep sedation.CONCLUSIONS:Deep sedation occurs frequently during elective endoscopy with meperidine and midazolam used with the intent of moderate sedation. ERCP and EUS are risk factors for the occurrence of deep sedation, independent of sedation dose or length of procedure.

Does Paclitaxel Improve the Chemoradiotherapy of Locoregionally Advanced Esophageal Cancer? A Nonrandomized Comparison With Fluorouracil-Based Therapy

PURPOSE A phase II trial of accelerated fractionation radiation with concurrent cisplatin and paclitaxel chemotherapy was performed to investigate the role of the paclitaxel, when substituted for fluorouracil (5-FU), in the chemoradiotherapy of esophageal cancer. PATIENTS AND METHODS Patients with an esophageal ultrasound stage of T(3) or N(1) or M(1) (nodal) esophageal cancer were treated with two courses of a cisplatin infusion (20 mg/m(2)/d for 4 days) and paclitaxel (175 mg/m(2) over 24 hours) concurrent with a split course of accelerated fractionation radiation (1.5 Gy bid to a total dose of 45 Gy). Surgical resection was performed 4 to 6 weeks later followed by a single identical postoperative course of chemoradiotherapy (24 Gy) in patients with significant residual tumor at surgery. Toxicity and results of this treatment were retrospectively compared with our previous 5-FU and cisplatin chemoradiotherapy experience. RESULTS Between September 1995 and July 1997, 40 patients were entered onto this study. Although dysphagia proved worse in our 5-FU-treated patients, profound leukopenia and a need for unplanned hospitalization were significantly more common in the paclitaxel group. Thirty-seven patients (93%) proved resectable for cure. The 3-year projected overall survival is 30%, locoregional control is 81%, and distant metastatic disease control is 44%. When compared with a similarly staged cohort of 5-FU-treated patients, there was no advantage for any survival function studied. CONCLUSION This paclitaxel-based treatment regimen for locoregionally advanced esophageal cancer produced increased toxicity with no improvement in results when compared with our previous 5-FU experience. Paclitaxel-based treatments must be carefully and prospectively studied before their incorporation into the standard management of esophageal cancer.

Optical Coherence Tomography of the Esophagus and Proximal Stomach in Health and Disease

OBJECTIVE: Surveillance of Barrett’s esophagus is problematic, as high-grade dysplasia cannot be recognized endoscopically. Endoscopic ultrasound lacks the resolution to detect high-grade dysplasia. Optical coherence tomography (OCT) employs infrared light reflectance to provide in vivo tissue images at resolution far superior to endoscopic ultrasound, nearly at the level of histology. We have developed a catheter-based system well suited for study of the GI tract. The purpose of this study was to test this catheter-based OCT system and characterize the OCT appearance of normal squamous mucosa, gastric cardia, Barrett’s esophagus, and carcinoma. METHODS: The OCT catheter was passed through the operating channel of the endoscope and placed in contact with the esophageal mucosa. Image acquisition occurred in approximately 3 s. OCT images were correlated with biopsy and/or resection specimens. RESULTS: OCT was used to construct 477 images of the esophagus and stomach in 69 patients. There were unique, distinct OCT appearances of squamous mucosa, gastric cardia, Barrett’s esophagus, and carcinoma. Further, these OCT images were accurately recognized by observers unaware of their site of origin. CONCLUSIONS: OCT provides a highly detailed view of the GI wall, with clear delineation of a multiple layered structure. It is able to distinguish squamous mucosa, gastric cardia, Barrett’s esophagus, and cancer. This technique holds great potential as an adjunct to the surveillance of patients with Barrett’s esophagus, ulcerative pancolitis, and other premalignant conditions.

A randomized, double blind study of interleukin 10 for the prevention of ERCP-induced pancreatitis

OBJECTIVES: Inflammatory cytokines are released during acute pancreatitis. Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine with immunosuppressive and anti-inflammatory activities. IL-10 has been shown to attenuate pancreatitis in an animal model. A double blind, placebo-controlled pilot study was conducted to evaluate the safety and efficacy of low dose IL-10 for the prevention of ERCP-induced pancreatitis. METHODS: Patients were randomized to receive a single i.v. dose of recombinant human IL-10 (8 μg/kg) or a placebo i.v. bolus injection 15 min before the procedure. Pancreatitis was defined as abdominal pain radiating to the back associated with elevated amylase or lipase two or more times the upper limit of normal requiring hospitalization for ≥2 days. Severity of pancreatitis was based on days of hospitalization. RESULTS: Two hundred patients were enrolled (101 IL-10, 99 placebo). No difference in age, gender, degree of pancreatic duct filling, therapeutic intervention, or complication was detected between the two groups. Eleven patients in the IL-10 group and nine patients in the placebo group had pancreatitis (p = 0.65). The median length of hospitalization was 4 days in the IL-10 group and 3 days in the placebo group (p = 0.75). CONCLUSIONS: IL-10 at the 8-μg/kg i.v. dose was not effective in reducing the incidence or severity of ERCP-induced pancreatitis. Further investigations are necessary to determine if manipulation of the cytokine pathway can prevent ERCP-induced pancreatitis.