Endoscopic Submucosal Dissection in North America: A Large Prospective Multicenter Study.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) in Asia has been shown to be superior to endoscopic mucosal resection (EMR) and surgery for the management of selected early gastrointestinal cancers. We aimed to evaluate technical outcomes of ESD in North America. METHODS: We conducted a multicenter prospective study on ESD across 10 centers in the United States and Canada between April 2016 and April 2020. End points included rates of en bloc resection, R0 resection, curative resection, adverse events, factors associated with failed resection, and recurrence post-R0 resection. RESULTS: Six hundred and ninety-two patients (median age, 66 years; 57.8% were men) underwent ESD (median lesion size, 40 mm; interquartile range, 25-52 mm) for lesions in the esophagus (n = 181), stomach (n = 101), duodenum (n = 11), colon (n = 211) and rectum (n = 188). En bloc, R0, and curative resection rates were 91.5%, 84.2%, and 78.3%, respectively. Bleeding and perforation were reported in 2.3% and 2.9% of the cases, respectively. Only 1 patient (0.14%) required surgery for adverse events. On multivariable analysis, severe submucosal fibrosis was associated with failed en bloc, R0, and curative resection and higher risk for adverse events. Overall recurrence was 5.8% (31 of 532) at a mean follow-up of 13.3 months (range, 1-60 months). CONCLUSIONS: In this large multicenter prospective North American experience, we demonstrate that ESD can be performed safely, effectively, and is associated with a low recurrence rate. The technical resection outcomes achieved in this study are in line with the current established consensus quality parameters and further support the implementation of ESD for the treatment of select gastrointestinal neoplasms; ClinicalTrials.gov, Number: NCT02989818.

Effect of endoscopic submucosal dissection on histologic diagnosis in Barrett's esophagus visible neoplasia.

BACKGROUND AND AIMS: Data are limited on the role of endoscopic submucosal dissection (ESD) as a potential diagnostic and staging tool in Barrett's esophagus (BE) neoplasia. We aimed to evaluate the frequency and factors associated with change of histologic diagnosis by ESD compared with pre-ESD histology. METHODS: This was a multicenter, prospective cohort study of patients who underwent ESD for BE visible neoplasia. A change in histologic diagnosis was defined as "upstaged" or "downstaged" if the ESD specimen had a higher or lower degree, respectively, of dysplasia or neoplasia when compared with pre-ESD specimens. RESULTS: Two hundred five patients (median age, 69 years; 81% men) with BE visible neoplasia underwent ESD from 2016 to 2021. Baseline histology was obtained using forceps (n = 182) or EMR (n = 23). ESD changed the histologic diagnosis in 55.1% of cases (113/205), of which 68.1% were upstaged and 31.9% downstaged. The frequency of change in diagnosis after ESD was similar whether baseline histology was obtained using forceps (55.5%) or EMR (52.2%) (P = .83). In aggregate, 23.9% of cases (49/205) were upstaged to invasive cancer on ESD histopathology. On multivariate analysis, lesions in the distal esophagus and gastroesophageal junction (odds ratio, 2.1; 95 confidence interval, 1.1-3.9; P = .02) and prior radiofrequency ablation (odds ratio, 2.5; 95% confidence interval, 1.2-5.5; P = .02) were predictors of change in histologic diagnosis. CONCLUSIONS: ESD led to a change of diagnosis in more than half of patients with BE visible neoplasia. Selective ESD can serve as a potential diagnostic and staging tool, particularly in those with suspected invasive disease. (Clinical trial registration number: NCT02989818.).

Modeling rectal cancer to advance neoadjuvant precision therapy.

Progress in rectal cancer therapy has been hindered by the lack of effective disease-specific preclinical models that account for the unique molecular profile and biology of rectal cancer. Thus, we developed complementary patient-derived xenograft (PDX) and subsequent in vitro tumor organoid (PDTO) platforms established from preneoadjuvant therapy rectal cancer specimens to advance personalized care for rectal cancer patients. Multiple endoscopic samples were obtained from 26 Stages 2 and 3 rectal cancer patients prior to receiving 5FU/RT and implanted subcutaneously into NSG mice to generate 15 subcutaneous PDXs. Second passaged xenografts demonstrated 100% correlation with the corresponding human cancer histology with maintained mutational profiles. Individual rectal cancer PDXs reproduced the 5FU/RT response observed in the corresponding human cancers. Similarly, rectal cancer PDTOs reproduced significant heterogeneity in cellular morphology and architecture. PDTO in vitro 5FU/RT treatment response replicated the clinical 5FU/RT neoadjuvant therapy pathologic response observed in the corresponding patient tumors (p < 0.05). The addition of cetuximab to the 5FU/RT regiment was significantly more sensitive in the rectal cancer PDX and PDTOs with wild-type KRAS compared to mutated KRAS (p < 0.05). Considering the close relationship between the patient's cancer and the corresponding PDX/PDTO, rectal cancer patient-derived research platforms represent powerful translational research resources as population-based tools for biomarker discovery and experimental therapy testing. In addition, our findings suggest that cetuximab may enhance RT effectiveness by improved patient selection based on mutational profile in addition to KRAS or by developing a protocol using PDTOs to identify sensitive patients.

Race and Prevalence of Large Bowel Polyps Among the Low-Income and Uninsured in South Carolina.

BACKGROUND: Compared to whites, blacks have higher colorectal cancer incidence and mortality rates and are at greater risk for early-onset disease. The reasons for this racial disparity are poorly understood, but one contributing factor could be differences in access to high-quality screening and medical care. AIMS: The present study was carried out to assess whether a racial difference in prevalence of large bowel polyps persists within a poor and uninsured population (n = 233, 124 blacks, 91 whites, 18 other) undergoing screening colonoscopy. METHODS: Eligible patients were uninsured, asymptomatic, had no personal history of colorectal neoplasia, and were between the ages 45-64 years (blacks) or 50-64 years (whites, other). We examined the prevalence of any adenoma (conventional, serrated) and then difference in adenoma/polyp type by race and age categories. RESULTS: Prevalence for ≥1 adenoma was 37 % (95 % CI 31-43 %) for all races combined and 36 % in blacks <50 years, 38 % in blacks ≥50 years, and 35 % in whites. When stratified by race, blacks had a higher prevalence of large conventional proximal neoplasia (8 %) compared to whites (2 %) (p value = 0.06) but a lower prevalence of any serrated-like (blacks 18 %, whites 32 %; p value = 0.02) and sessile serrated adenomas/polyps (blacks 2 %, whites 8 % Chi-square p value; p = 0.05). CONCLUSIONS: Within this uninsured population, the overall prevalence of adenomas was high and nearly equal by race, but the racial differences observed between serrated and conventional polyp types emphasize the importance of taking polyp type into account in future research on this topic.

Discrimination of normal and esophageal cancer plasma proteomes by MALDI-TOF mass spectrometry.

BACKGROUND: Most patients presenting with symptoms of esophageal cancer (EC) have advanced disease. Even with resection, the cure rate is extremely low due to local recurrence and metastatic disease. Early detection and effective therapeutic intervention are essential to improve survival. AIMS: This study tested the hypothesis that the presence of EC modulates concentrations of specific plasma proteins and peptides, potentially allowing discrimination between EC and controls based on mass spectrometric analysis of the respective plasma proteomes. METHODS: Blood samples from 79 esophageal cancer patients and 40 age-matched normal subjects were processed to plasma, and protein/peptide sub-fractions were isolated using HIC8 or WAX-derivatized superparamagnetic beads. Triplicate matrix-assisted laser desorption time-of-flight mass spectra were acquired for specific plasma fractions from each subject. RESULTS: HIC8 and WAX-derivatized plasma eluates yielded 79 and 77 candidate features, respectively, and a Random Forest algorithm identified a subset of features whose peak intensities allowed discrimination between cancer patients and controls. Areas under the curve in receiver operating characteristic curves for HIC8 spectra were 0.88 and 0.83 for WAX spectra. The combined feature set discriminated EC from control plasma with 79 % sensitivity and 79 % specificity, with positive and negative test likelihood ratios of >14 and 0.17, respectively. CONCLUSIONS: These data lay the foundation for the development of a clinically useful test for esophageal cancer based on statistical analysis of proteomic spectra of patient plasma samples. This approach will be validated by analysis of larger patient cohorts, development of cancer-specific classifiers, and assessment of racial origin imbalances.

Patients' short-term knowledge of personal polyp history inadequate despite systematic notification of results after polypectomy.

OBJECTIVES: Patients' memories of personal polyp characteristics have been shown to be inadequate when compared with the medical record. An accurate polyp history is necessary to adhere to guidelines. We sought to determine whether systematically informing patients of the results of their colonoscopy and pathology in a multifaceted manner could increase their knowledge of their personal polyp history. METHODS: We conducted a prospective pilot study of 240 consecutive patients undergoing screening colonoscopy with polypectomy by a single endoscopist (B.J.H.) at a tertiary care center. All of the patients were provided with a verbal report of findings immediately after the procedure, an endoscopy report specifying polyp size and number, and a mailed letter specifying the pathology results of their polyps. Telephone contact was attempted for all of the patients. Patients were asked to recall the size, number, and histology of their polyps. RESULTS: One hundred (42%) of the patients completed the telephone survey. Forty patients remembered the polyp number; five remembered their polyp histology, and one recalled the polyp size. None of the patients recalled all three factors, although patients who recalled telling a family member the results of the colonoscopy were more likely to recall at least one polyp descriptor (relative risk 2.62 [95% confidence interval 1.01-6.83]). No other variables were associated with polyp recall. CONCLUSIONS: Patients' knowledge of personal polyp characteristics, even after systematic notification, does not seem adequate for determining the best guideline-based colonoscopy surveillance interval. Discussing results with family members may help.

Radiofrequency ablation in Barrett's esophagus with dysplasia.

BACKGROUND: Barrett's esophagus, a condition of intestinal metaplasia of the esophagus, is associated with an increased risk of esophageal adenocarcinoma. We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barrett's esophagus and decrease the rate of neoplastic progression. METHODS: In a multicenter, sham-controlled trial, we randomly assigned 127 patients with dysplastic Barrett's esophagus in a 2:1 ratio to receive either radiofrequency ablation (ablation group) or a sham procedure (control group). Randomization was stratified according to the grade of dysplasia and the length of Barrett's esophagus. Primary outcomes at 12 months included the complete eradication of dysplasia and intestinal metaplasia. RESULTS: In the intention-to-treat analyses, among patients with low-grade dysplasia, complete eradication of dysplasia occurred in 90.5% of those in the ablation group, as compared with 22.7% of those in the control group (P<0.001). Among patients with high-grade dysplasia, complete eradication occurred in 81.0% of those in the ablation group, as compared with 19.0% of those in the control group (P<0.001). Overall, 77.4% of patients in the ablation group had complete eradication of intestinal metaplasia, as compared with 2.3% of those in the control group (P<0.001). Patients in the ablation group had less disease progression (3.6% vs. 16.3%, P=0.03) and fewer cancers (1.2% vs. 9.3%, P=0.045). Patients reported having more chest pain after the ablation procedure than after the sham procedure. In the ablation group, one patient had upper gastrointestinal hemorrhage, and five patients (6.0%) had esophageal stricture. CONCLUSIONS: In patients with dysplastic Barrett's esophagus, radiofrequency ablation was associated with a high rate of complete eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression. (ClinicalTrials.gov number, NCT00282672.)

Durability of radiofrequency ablation in Barrett's esophagus with dysplasia.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barrett's esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE. METHODS: We performed a randomized trial of 127 subjects with dysplastic BE; after cross-over subjects were included, 119 received RFA. Subjects were followed for a mean time of 3.05 years; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years. Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years, durability of response, disease progression, and adverse events. RESULTS: After 2 years, 101 of 106 patients had complete eradication of all dysplasia (95%) and 99 of 106 had eradication of intestinal metaplasia (93%). After 2 years, among subjects with initial low-grade dysplasia, all dysplasia was eradicated in 51 of 52 (98%) and intestinal metaplasia was eradicated in 51 of 52 (98%); among subjects with initial high-grade dysplasia, all dysplasia was eradicated in 50 of 54 (93%) and intestinal metaplasia was eradicated in 48 of 54 (89%). After 3 years, dysplasia was eradicated in 55 of 56 of subjects (98%) and intestinal metaplasia was eradicated in 51 of 56 (91%). Kaplan-Meier analysis showed that dysplasia remained eradicated in >85% of patients and intestinal metaplasia in >75%, without maintenance RFA. Serious adverse events occurred in 4 of 119 subjects (3.4%); the rate of stricture was 7.6%. The rate of esophageal adenocarcinoma was 1 per 181 patient-years (0.55%/patient-years); there was no cancer-related morbidity or mortality. The annual rate of any neoplastic progression was 1 per 73 patient-years (1.37%/patient-years). CONCLUSIONS: In subjects with dysplastic BE, RFA therapy has an acceptable safety profile, is durable, and is associated with a low rate of disease progression, for up to 3 years.

A resource-efficient tool for training novices in wireless capsule endoscopy.

Nurses often function as capsule endoscopy "pre-readers" to save physicians' time and potentially increase diagnostic yield. Training pre-readers is time consuming, not standardized, and may not be feasible during regular business hours. A way to evaluate the progress and accuracy of pre-readers is needed to ensure competency. The aim of this study was to introduce a feedback and progress assessment tool for training novice capsule endoscopy pre-readers. We created a 1-page form with listings of potential findings for each segment of the examination. Findings could be circled or written in. The trainee reviewed capsule studies and filled out the form on each of 220 patients. The physician reviewers subsequently critiqued the data forms, providing feedback regarding missed lesions, overcalls, and overall agreement. Our trainee achieved consistent agreement with the physician reviewers, after reading 80 studies. In conclusion, a simple, 1-page standardized data sheet can be used to facilitate training of novice capsule pre-readers without significant time commitment from the supervising physician. Future studies may validate this resource-efficient instrument as a training and assessment tool for nurses, physicians, and other practitioners learning capsule endoscopy.

Endosonographic features predictive of malignancy in mediastinal lymph nodes in patients with lung cancer.

BACKGROUND: EUS is useful in determining mediastinal lymph node (LN) metastases in patients undergoing staging for lung cancer. However, FNA of LNs is often performed only if suspicious features are present. The utility of individual LN features in predicting malignant cytology remains unclear. OBJECTIVE: To evaluate the utility of EUS-determined LN features for predicting malignant cytology. DESIGN: Prospective observational study. SETTING: Two U.S. tertiary-care centers. PATIENTS: This study involved 425 patients with primary lung cancer who underwent EUS. INTERVENTION: All mediastinal LNs were described according to size, shape, echogenicity, and margin characteristics. FNA was performed on LNs with any features suggestive of malignancy. EUS-guided FNA cytology was classified as benign or abnormal (suspicious/malignant). The utility of LN features in predicting malignant cytology was determined and further analyzed by logistic regression, and a predictive model was established. MAIN OUTCOME MEASUREMENTS: Accuracy of individual LN features for predicting malignancy. RESULTS: EUS detected 836 LNs in 425 patients, and FNA was obtained in 698 patients. On multivariable analysis, only round shape, a short axis of >8.3 mm, and sharp margins were predictive of malignant cytology. According to the predictive model, the calculated probability of having malignancy is less than 4% (95% confidence interval [CI], 0.022-0.064) when none of the LN features are present and 63% (95% CI, 51%-72.2%) when all features were seen. LIMITATIONS: No surgical histology as the criterion standard. CONCLUSION: Among patients with lung cancer, EUS features of round shape, sharp margins, and short axis of >8.3 mm are significant predictors of malignancy. The probability of malignancy is low when none of the features are present.

Salvage cryotherapy in patients undergoing endoscopic eradication therapy for complicated Barrett's esophagus.

Background and study aims Some patients with dysplastic Barrett's esophagus (BE) experience suboptimal response to radiofrequency ablation (RFA), endoscopic mucosal resection (EMR), or the combination. Cryotherapy has been used as salvage therapy in these patients, but outcomes data are limited. We aimed to assess clinical outcomes among a large cohort of patients with dysplastic BE whose condition had failed to respond to RFA and/or EMR. Patients and methods This was a retrospective cohort study of consecutive cases of dysplastic BE or intramucosal carcinoma (IMC) treated with salvage cryotherapy at a tertiary-care academic medical center. The primary goal of cryotherapy treatment was eradication of all neoplasia. The secondary goal was eradication of all intestinal metaplasia. The proportion of patients undergoing salvage cryotherapy who achieved complete eradication of dysplasia (CE-D) and metaplasia (CE-IM), as well as the time to CE-D and CE-IM were calculated. Results Over a 12-year period, 46 patients received salvage cryotherapy. All patients underwent RFA prior to cryotherapy, either at our center or prior to referral, and 50 % of patients underwent EMR. A majority of patients (54 %) had high-grade dysplasia (HGD) at referral, while 33 % had low-grade dysplasia (LGD), and 13 % had IMC. Overall, 38 patients (83 %) reached CE-D and 21 (46 %) reached CE-IM. Median time to CE-D was 18 months, median number of total interventions (RFA, cryotherapy, and EMR) was five, and median number of cryotherapy sessions was two. Conclusion Salvage cryotherapy appears safe and effective for treating BE that is refractory to RFA and/or EMR.

Endoscopic ultrasound: a meta-analysis of test performance in suspected biliary obstruction.

BACKGROUND & AIMS: Endoscopic ultrasound (EUS) achieves high-resolution images of the bile duct and pancreas, while avoiding the risks of ERCP (endoscopic retrograde cholangiopancreatography). It appears comparable to MRCP (magnetic resonance cholangiopancreatography), although its use is less widely disseminated. We aimed to summarize EUS test performance in suspected biliary disease with meta-analysis. METHODS: MEDLINE search (January 1987-September 2006), selected reference lists, external experts, and manual search of abstracts were used. Studies permitting (re)construction of 2 x 2 tables for EUS versus a gold standard were used. Random-effects models were used to estimate pooled sensitivity and specificity after adjusting for a number of potential confounders. Summary receiver operating characteristic analysis, with the sensitivity corresponding to the point on the receiver operating characteristic curve where sensitivity equals specificity (Q*) and area under the curve, was performed. The effects of sample size, quality, disease prevalence and spectrum, pancreatitis, echoendoscope type, and EUS era on diagnostic performance were assessed. Performance regarding presence of obstruction, choledocholithiasis, and malignancy was analyzed. RESULTS: Thirty-six eligible, non-overlapping studies met inclusion criteria (3532 subjects). EUS had a high overall pooled sensitivity (88%; 95% confidence interval, 85%-91%) and specificity (90%; 87%-93%) for biliary obstruction (area under the curve = 0.97; Q* = 0.92). EUS had higher sensitivity (89%; 87%-91%) and specificity (94%; 91%-96%) for choledocholithiasis than for malignancy (sensitivity, 78%; 69%-85%; specificity, 84%; 78%-91%). Smaller studies and ones mainly studying patients with suspected strictures were associated with lower test performance. CONCLUSIONS: There is excellent overall accuracy for EUS in diagnosing choledocholithiasis, with less impressive results for malignancy (when fine-needle aspiration is not used).

Accurate discrimination of Barrett's esophagus and esophageal adenocarcinoma using a quantitative three-tiered algorithm and multimarker real-time reverse transcription-PCR.

Esophageal adenocarcinoma (EA) is increasing faster than any other cancer in the U.S. In this report, we first show that EA can be distinguished from normal esophagus (NE) and esophageal squamous cell carcinoma by plotting expression values for EpCam, TFF1, and SBEM in three-dimensional Euclidean space. For monitoring progression of Barrett's esophagus (BE) to EA, we developed a highly sensitive assay for limited quantities of tissue whereby 50 ng of RNA are first converted to cDNA using 16 gene-specific primers. Using a set of training tissues, we developed a novel quantitative three-tiered algorithm that allows for accurate (overall accuracy = 61/63, 97%) discrimination of BE versus EA tissues using only three genes. The gene used in the first tier of the algorithm is TSPAN: samples not diagnosed as BE or EA by TSPAN in the first tier are then subjected to a second-tier analysis using ECGF1, followed by a third-tier analysis using SPARC. Addition of TFF1 and SBEM to the first tier (i.e., a five-gene marker panel) increases the overall accuracy of the assay to 98% (62/63) and results in mean molecular diagnostic scores (+/- SD) that are significantly different between EA and BE samples (3.19 +/- 1.07 versus -2.74 +/- 1.73, respectively). Our results suggest that relatively few genes can be used to monitor progression of BE to EA.

Accurate molecular detection of non-small cell lung cancer metastases in mediastinal lymph nodes sampled by endoscopic ultrasound-guided needle aspiration.

OBJECTIVES: The recurrence of disease after the complete resection of early stage non-small cell lung cancer (NSCLC) indicates that undetected metastases were present at the time of surgery. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is a highly sensitive technique for detecting rare gene transcripts that may indicate the presence of cancer cells, and endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a minimally invasive technique for the nonoperative sampling of mediastinal lymph nodes. The aim of this study was to determine whether these two techniques could enhance the preoperative detection of occult metastases. METHODS: Patients with NSCLC were evaluated with chest CT and positron emission tomography scans. Those patients without evidence of metastases (87 patients) underwent EUS-guided FNA. Lymph nodes from levels 2, 4, 5, 7, 8, and 9 were sampled and evaluated by standard cytopathology and real-time RT-PCR. Normal control FNA specimens were obtained from patients without cancer who were undergoing EUS for benign disease (17 control specimens). For each sample, messenger RNA was extracted and real-time RT-PCR was used to quantitate the expression of six lung cancer-associated genes (ie, CEA, CK19, KS1/4, lunx, muc1, and PDEF) relative to the expression of an internal control gene (beta(2)-microglobulin). RESULTS: Clinical thresholds of marker positivity were set at 100% specificity, as determined by the receiver operating characteristic curve analysis. Of the cytology-positive lymph nodes (27 lymph nodes), the expression of the KS1/4 gene was above its respective clinical threshold in 25 of 27 samples (93%), making this the most sensitive marker for the detection of metastatic NSCLC. At least one of the six lung cancer-associated genes was overexpressed in 18 of 61 cytology-negative patients (30%), of which KS1/4 was overexpressed in 15 of 61 patients (25%). CONCLUSIONS: Based on the high accuracy of EUS-guided FNA/RT-PCR, we predict that some of the patients in the cytology-negative/marker-positive category will have high NSCLC recurrence rates. Among the genes used in our marker panel, KS1/4 appears particularly useful for the detection of overt or occult metastatic disease.

Endoscopic ultrasound for thoracic malignancy: a review.

Accurate cancer staging is critical in providing the most appropriate therapy for patients with lung cancer. The decision to attempt a curative surgery or avoid an unnecessary surgery is dependent on accurate staging. In the case of non-small-cell lung cancer (NSCLC), the most important parameters for optimal treatment and prognosis are the presence of cancer spread to the lymph nodes within the mediastinum and to distant organs. Endoscopic ultrasound (EUS) has become an important tool for the assessment of mediastinal lymph nodes and in some cases, distant organ metastases, because of its minimally invasive access to these sites through a transesophageal, transgastric, or transduodenal approach. The capability of performing fine needle aspiration (FNA) has greatly improved the accuracy and acceptability of EUS for lung cancer staging. This review will outline the basic principals of EUS-guided lung cancer staging and EUS-FNA techniques and outline the indications and contraindications to EUS staging of thoracic malignancy.

An analysis of multiple staging management strategies for carcinoma of the esophagus: computed tomography, endoscopic ultrasound, positron emission tomography, and thoracoscopy/laparoscopy.

BACKGROUND: This study compares the health care costs and effectiveness of multiple staging options for patients with esophageal cancer. Techniques studied included computed tomographic (CT) scan, endoscopic ultrasound with fine-needle aspiration biopsy (EUS-FNA), positron emission tomography (PET), thoracoscopy/laparoscopy, and combinations of these. METHODS: A decision-analysis model was constructed to compare different staging strategies. Costs were derived from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases and from other Medicare reimbursement rates. Life expectancies were obtained from the 1973-1996 SEER database and adjusted for quality of life. Cost and effectiveness measures were discounted at 0% and 3% per year. Sensitivity and specificity measures were obtained from the published literature and a parallel prospective clinical trial, and all key variables were subjected to sensitivity analyses. RESULTS: Under baseline assumptions, CT + EUS-FNA was the most inexpensive strategy and offered more quality-adjusted life-years, on average, than all other strategies with the exception of PET + EUS-FNA. The latter was slightly more effective but also more expensive. The marginal cost-effectiveness ratio for PET + EUS-FNA was $60,544 per quality-adjusted life-year. These findings were robust and changed very little in all of the sensitivity analyses. CONCLUSIONS: The combination of PET + EUS-FNA should be the recommended staging procedure for patients with esophageal cancer, unless resources are scarce or PET is unavailable. In these instances, CT + EUS-FNA can be considered the preferred strategy.

Endoscopic ultrasound in lung cancer patients with a normal mediastinum on computed tomography.

BACKGROUND: Computed tomography (CT) is the most common method of staging lung cancer. We have previously shown endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) to be highly accurate in staging patients with nonsmall cell lung cancer (NSCLC) who have enlarged mediastinal lymph nodes on CT scan. In this study we report the accuracy and yield of EUS-FNA in staging patients without enlarged mediastinal lymph nodes by CT. METHODS: Patients with NSCLC and CT scan showing no enlarged mediastinal lymph nodes (> 1 cm for all nodes except > 1.2 cm for subcarinal) in the mediastinum underwent EUS. Fine needle aspiration was performed on at least one lymph node, if present, in the upper mediastinum, aortopulmonary window, subcarinal, and periesophagus regions. Each specimen was evaluated with on-site cytopathology and confirmed with complete cytopathologic examination. RESULTS: Sixty-nine patients without enlarged mediastinal lymph nodes were evaluated. Endoscopic ultrasound detected malignant mediastinal lymph nodes in 14 of 69 patients as well as other advanced (American Joint Committee on Cancer [AJCC] stage III/IV) in 3 others (1 left adrenal, and 2 with mediastinal invasion of tumor) for a total of 17 of 69 (25%, 95% confidence interval: 16% to 34%) patients. Eleven additional patients were found to have advanced disease by bronchoscopy (2), mediastinoscopy (2), and thoracotomy with mediastinal lymph node dissection (7). The sensitivity of EUS for advanced mediastinal disease was 61% (49% to 75%), and the specificity was 98% (95% to 100%). CONCLUSIONS: Endoscopic ultrasound guided fine needle aspiration can detect advanced mediastinal disease and avoid unnecessary surgical exploration in almost one of four patients who have no evidence of mediastinal disease on CT scan. In addition to previously reported results in patients with enlarged lymph nodes on CT, these data suggest that all potentially operable patients with nonmetastatic NSCLC may benefit from EUS staging.

Phase 2 trial of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer.

PURPOSE: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). METHODS AND MATERIALS: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; "downstaged" patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. RESULTS: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. CONCLUSIONS: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved.