Morbidity following salvage esophagectomy for squamous cell carcinoma: the MD Anderson experience.

The survival advantage associated with the addition of surgical therapy in esophageal squamous cell carcinoma (ESCC) patients who demonstrate a complete clinical response to chemoradiotherapy is unclear, and many institutions have adopted an organ-preserving strategy of selective surgery in this population. We sought to characterize our institutional experience of salvage esophagectomy (for failure of definitive bimodality therapy) and planned esophagectomy (as a component of trimodality therapy) by retrospectively analyzing patients with ESCC of the thoracic esophagus and GEJ who underwent esophagectomy following chemoradiotherapy between 2004 and 2016. Of 76 patients who met inclusion criteria, 46.1% (35) underwent salvage esophagectomy. Major postoperative complications (major cardiovascular and pulmonary events, anastomotic leak [grade ≥ 2], and 90-day mortality) were frequent and occurred in 52.6% of the cohort (planned resection: 36.6% [15/41]; salvage esophagectomy: 71.4% [25/35]). Observed rates of 30- and 90-day mortality for the entire cohort were 7.9% (planned: 7.3% [3/41]; salvage: 8.6% [3/35]) and 13.2% (planned: 9.8% [4/41]; salvage: 17.1% [6/35]), respectively. In summary, esophagectomy following chemoradiotherapy for ESCC at our institution has been associated with frequent postoperative morbidity and considerable rates of mortality in both planned and salvage settings. Although a selective approach to surgery may permit organ preservation in many patients with ESCC, these results highlight that salvage esophagectomy for failure of definitive-intent treatment of ESCC may also constitute a difficult clinical undertaking in some cases.

Association between clinical complete response and pathological complete response after preoperative chemoradiation in patients with gastroesophageal cancer: analysis in a large cohort.

BACKGROUND: Chemoradiation followed by surgery is the preferred treatment of localized gastroesophageal cancer (GEC). Surgery causes considerable life-altering consequences and achievement of clinical complete response (clinCR; defined as postchemoradiation [but presurgery] endoscopic biopsy negative for cancer and positron emission tomographic (PET) scan showing physiologic uptake) is an enticement to avoid/delay surgery. We examined the association between clinCR and pathologic complete response (pathCR). PATIENTS AND METHODS: Two hundred eighty-four patients with GEC underwent chemoradiation and esophagectomy. The chi-square test, Fisher exact test, t-test, Kaplan-Meier method, and log-rank test were used. RESULTS: Of 284 patients, 218 (77%) achieved clinCR. However, only 67 (31%) of the 218 achieved pathCR. The sensitivity of clinCR for pathCR was 97.1% (67/69), but the specificity was low (29.8%; 64/215). Of the 66 patients who had less than a clinCR, only 2 (3%) had a pathCR. Thus, the rate of pathCR was significantly different in patients with clinCR than in those with less than a clinCR (P < 0.001). CONCLUSIONS: clinCR is not highly associated with pathCR; the specificity of clinCR for pathCR is too low to be used for clinical decision making on delaying/avoiding surgery. Surgery-eligible GEC patients should be encouraged to undergo surgery following chemoradiation despite achieving a clinCR.

Results of the baseline positron emission tomography can customize therapy of localized esophageal adenocarcinoma patients who achieve a clinical complete response after chemoradiation.

BACKGROUND: Patients with localized esophageal adenocarcinoma (EAC) who achieve a clinical complete response (clinCR) after preoperative chemoradiation (trimodality therapy; TMT) or definitive chemoradiation (bimodality therapy; BMT) live longer than those who achieve a

A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer.

BACKGROUND: The contribution of induction chemotherapy (IC) before preoperative chemoradiation for esophageal cancer (EC) is not known. We hypothesized that IC would increase the rate of pathologic complete response (pathCR). METHODS: Trimodality-eligibile patients were randomized to receive no IC (Arm A) or IC (oxaliplatin/FU; Arm B) before oxaliplatin/FU/radiation. Surgery was attempted ∼5-6 weeks after chemoradiation. The pathCR rate, post-surgery 30-day mortality, overall survival (OS), and toxic effects were assessed. Bayesian methods and Fisher's exact test were used. RESULTS: One hundred twenty-six patients were randomized dynamically to balance the two arms for histology, baseline stage, gender, race, and age. Fifty-five patients in Arm A and 54 in Arm B underwent surgery. The median actuarial OS for all patients (54 deaths) was 45.62 months [95% confidence interval (CI), 27.63-NA], with median OS 45.62 months (95% CI 25.56-NA) in Arm A and 43.68 months (95% CI 27.63-NA) in Arm B (P = 0.69). The pathCR rate in Arm A was 13% (7 of 55) and 26% (14 of 54) in Arm B (two-sided Fisher's exact test, P = 0.094). Safety was similar in both arms. CONCLUSIONS: These data suggest that IC produces non-significant increase in the pathCR rate and does not prolong OS. Further development of IC before chemoradiation may not be beneficial. Clinical trial no.: NCT 00525915 (www.clinicaltrials.gov).

Endoscopic ultrasound-guided radiation therapy in pancreatic cancer.

During the last two decades, endoscopic ultrasound has revolutionized the diagnosis and treatment of gastrointestinal (GI) malignancies. The role of EUS has expanded well beyond its role as a diagnostic modality, and has emerged as a highly sophisticated interventional modality. More recently, EUS has paved its way into radiation oncology by either facilitating highly targeted image guided radiotherapy (IGRT) by insertion of fiducial markers in tumors or by direct instillation of radioactive seeds (brachytherapy). Although the experience regarding these techniques is in a preliminary stage, if developed further, this can potentially provide a highly accurate and minimally invasive approach for implantation of fiducial and radioactive seeds. This review will discuss potential role of EUS in implantation therapy, current literature and also speculate on future prospects for these EUS-guided interventions in pancreatic cancer.

Feasibility study of EUS-NOTES as a novel approach for peroral cholecysto-gastrostomy.

BACKGROUND: EUS-guided cholecysto-gastrostomy might be a useful minimally invasive procedure used for salvage drainage in advanced pancreaticobiliary cancers, but also for drainage of the gallbladder in acute cholecystitis in patients deemed unfit for laparoscopic surgery. OBJECTIVE: Direct EUS-guided cholecysto-gastrostomy with placement of a double flanged expandable metal stents. DESIGN/SETTING: This was an animal pilot/feasibility study. INTERVENTIONS: The feasibility of EUS-guided cholecysto-gastrostomy through a transgastric approach was tested in five pigs. Specially designed EUS-guided devices for initial access in the gallbladder and a double flanged expandable metal stent were used in this study. RESULT: The results showed the feasibility of EUS-guided cholecysto-gastrostomy based on prototype devices for access in the gallbladder and transgastric stent placement. LIMITATIONS: Survival feasibility study with prototype devices in a small number of animals. CONCLUSIONS: EUS guided cholecysto-gastrostomy in a porcine model is feasible but technically demanding due to anatomical limitations of the pig and/or complexity of the procedure and the preliminary stage of development of the accessory devices. ABBREVIATIONS: NOTES - Natural Orifice Translumenal Endoscopic Surgery; EUS - Endoscopic Ultrasound; EUSFNA - Endoscopic Ultrasound Fine Needle Aspiration.

Clinical parameters model for predicting pathologic complete response following preoperative chemoradiation in patients with esophageal cancer.

BACKGROUND: Approximately 25% of patients with esophageal cancer (EC) who undergo preoperative chemoradiation, achieve a pathologic complete response (pathCR). We hypothesized that a model based on clinical parameters could predict pathCR with a high (≥60%) probability. PATIENTS AND METHODS: We analyzed 322 patients with EC who underwent preoperative chemoradiation. All the patients had baseline and postchemoradiation positron emission tomography (PET) and pre- and postchemoradiation endoscopic biopsy. Logistic regression models were used for analysis, and cross-validation via the bootstrap method was carried out to test the model. RESULTS: The 70 (21.7%) patients who achieved a pathCR lived longer (median overall survival [OS], 79.76 months) than the 252 patients who did not achieve a pathCR (median OS, 39.73 months; OS, P = 0.004; disease-free survival, P = 0.003). In a logistic regression analysis, the following parameters contributed to the prediction model: postchemoradiation PET, postchemoradiation biopsy, sex, histologic tumor grade, and baseline (EUS)T stage. The area under the receiver-operating characteristic curve was 0.72 (95% confidence interval [CI] 0.662-0.787); after the bootstrap validation with 200 repetitions, the bias-corrected AU-ROC was 0.70 (95% CI 0.643-0.728). CONCLUSION: Our data suggest that the logistic regression model can predict pathCR with a high probability. This clinical model could complement others (biomarkers) to predict pathCR.

Patients with high body mass index tend to have lower stage of esophageal carcinoma at diagnosis.

High body mass index (H-BMI; ≥25 kg/m(2) ) is common in US adults. In a small cohort of esophageal cancer (EC) patients treated with surgery, H-BMI and diagnosis of early stage EC appeared associated. We evaluated a much larger cohort of EC patients. From a prospectively maintained database, we analyzed 925 EC patients who had surgery with or without adjunctive therapy. Various statistical methods were used. Among 925 patients, 69% had H-BMI, and 31% had normal body mass index (<25 kg/m(2) ; N-BMI). H-BMI was associated with men (P<0.001), Caucasians (P=0.064; trend), lower esophageal localization (P<0.001), adenocarcinoma histology (P<0.001), low baseline cT-stage (P=0.003), low baseline overall clinical stage (P=0.003), coronary artery disease (P=0.036), and diabetes (P<0.001). N-BMI was associated with weight loss (P<0.001), alcohol abuse (P=0.056; trend), ever/current smoking (P=0.014), and baseline cN+ (P=0.018). H-BMI patients with cT1 tumors (n=110) had significantly higher rates of gastresophageal reflux disease symptoms (P<0.001), gastresophageal reflux disease history (P<0.001), and Barrett's esophagus history (P<0.001) compared with H-BMI patients with cT2 tumors (n=114). Median survival of N-BMI patients was 36.66 months compared with 53.20 months for H-BMI patients (P=0.005). In multivariate analysis, older age (P<0.001), squamous histology (P=0.002), smoking (P=0.040), weight loss (P=0.002), high baseline stage (P<0.001), high number of ypN+ (P=0.005), high surgical stage (P<0.001), and American Society of Anesthesia scores, three out of four (P<0.001) were independent prognosticators for poor overall survival. We were able to perform propensity-based analysis of surgical complications between H-BMI and N-BMI patients. A comparison of fully matched 376 patients (188 with H-BMI and 188 with N-BMI) found no significant differences in the rate of complications between the two groups. This larger data set confirms that a fraction of H-BMI patients with antecedent history is diagnosed with early baseline EC. Upon validation of our data in an independent cohort, refinements in surveillance of symptomatic H-BMI patients are warranted and could be implemented. Our data also suggest that H-BMI patients do not experience higher rate of surgical complications compared with N-BMI patients.

The year of improved tissue acquisition, randomized trials, and endoscopic ultrasound-guided therapy.

Presentations at this year's Digestive Disease Week (DWW; 7-10 May, 2011; Chicago, Illinois, USA) reflected a very active year for endoscopic ultrasound (EUS). There were numerous abstracts on EUS-guided fine-needle aspiration (FNA) and core biopsy to improve tissue acquisition, improve diagnostic accuracy, and indeed go beyond routine cytology and tissue diagnosis. EUS-guided therapy including drainage, anastomoses, injection of therapeutic agents, and ablation were other common themes with a lot of new information presented, much of which was obtained from randomized trials. This review discusses in detail some of the abstracts that followed a common theme. Additional interesting abstracts on this topic are listed at the end of the review.

Novel endoscopic application of a new flexible-fiber CO2 laser for esophageal mucosal ablation in a porcine model.

BACKGROUND AND STUDY AIMS: The CO (2) laser is a surgical tool that is widely used because of its predictable penetration depth and minimal collateral damage due to efficient absorption of CO (2) laser energy by tissue water. Until recently, endoscopic use was limited by lack of an efficient, flexible delivery system. The aim of the current study was to evaluate the performance, efficacy, and safety of a novel, photonic band-gap CO (2) laser configured for esophageal mucosal ablation. MATERIALS AND METHODS: This was an endoscopic experimental study in a porcine survival model. Initial evaluation was done on ex vivo tissue followed by endoscopic studies at 7-, 10-, 15-, and 20-W power and at 0-, 1-, 2-, 5-, and 10-mm distances, using continuous and pulsed currents, to determine optimal performance settings. In an IACUC-approved protocol, six pigs underwent circumferential ablation of the distal 6 cm of the esophagus at 10W continuous current. The animals were monitored for 2 or 4 weeks to evaluate delayed effects. Prior to euthanasia, the proximal esophagus was ablated to evaluate the homogeneity of ablation and depth of injury immediately after single and repeat ablation. RESULTS: The animals resumed normal diets within 24 hours and experienced no dysphagia or weight loss. Pathology at 2 and 4 weeks revealed complete re-epithelialization with minimal histologic injury. A single application of the laser produced complete transepithelial ablation of a mean of 83.3 % of the surface area (range 55 % - 100 %); depth of injury was to the muscularis mucosa in five pigs and to the superficial submucosa in one pig. With ablation, sloughing, and re-ablation, a mean of 95 % transepithelial ablation was achieved (range 80 % -100 %) with similar depth of injury. CONCLUSIONS: Using a novel, flexible CO (2) laser, homogeneous ablation was achieved with predictable penetration and minimal deep tissue injury. These results warrant further evaluation of the laser in Barrett's esophagus, as it may overcome the limitations of current technologies including perforation, stricture, and inhomogeneity.

An animal model for studying endoscopic ultrasound changes of early chronic pancreatitis with histologic correlation: a pilot study.

BACKGROUND AND STUDY AIMS: Due to the difficulty in obtaining pancreatic tissue for histology in humans, we developed an animal model for studying endoscopic ultrasound (EUS) changes of early chronic pancreatitis. This report on the animal model describes the serial changes of early chronic pancreatitis by EUS and correlates results with histology. MATERIALS AND METHODS: Four 60 - 80-lb dogs were used in the study. Pancreatic EUS was performed to provide baseline images prior to any procedure. At laparotomy, a guide wire was passed into the pancreatic duct, and a 5-Fr pancreatic stent was introduced over the wire into the pancreatic duct. Animals were divided into two survival groups - 2 weeks and 4 weeks. In each group, EUS examination was performed under anesthesia to image the pancreas and then followed by euthanasia. Sequential pancreatic sections were taken from the head, body, and tail of the pancreas. EUS findings were correlated with histologic results with respect to degree of fibrosis, inflammation, and edema. RESULTS: At baseline EUS, the pancreas appeared homogeneous with only a few echogenic septations and echogenic margins of the main pancreatic duct. At 2 and 4 weeks poststenting, EUS images showed the following changes: lobularity, hyper and hypoechoic foci, increased echogenic septations, visible pancreatic duct side branches, and irregular margins of the main pancreatic duct. CONCLUSIONS: The dog model for chronic pancreatitis appears to be a promising method for studying sequential changes of chronic pancreatitis by EUS and correlating results with histology.

Therapy-induced expression of NF-kappaB portends poor prognosis in patients with localized esophageal cancer undergoing preoperative chemoradiation.

Activated nuclear factor-kappa B (NF-kappaB) in the pretreatment cancer tissue of patients with localized esophageal adenocarcinoma (LEA) undergoing preoperative chemoradiation is associated with poor prognosis. It is known that constitutively activated NF-kappaB prior to any therapy portends poor prognosis, and it is also known that activated NF-kappaB in the treated specimen is associated with poor prognosis. However, the prognosis of patients who have treatment-induced activation of NF-kappaB (meaning their cancers activate NF-kappaB during or after therapy) is not been reported. We hypothesized that the treatment-induced activation of NF-kappaB would impart poor prognosis similar to that imparted by constitutively activated NF-kappaB cancer. Patients with LEA who had undergone preoperative chemoradiation plus surgery and had pre- and post-therapy cancer tissue available were selected. Pre- and post-therapy cancer tissues were stained by immunohistochemistry for nuclear staining of NF-kappaB. The overall survival (OS) and disease-free survival were assessed and compared for patients who had intrinsic constitutively activated NF-kappaB cancer with those who had induced activation of NF-kappaB only post-therapy. A total of 41 patients with LEA were investigated. Twenty-five patients had NF-kappaB positive cancer at baseline, and 16 had NF-kappaB negative cancer at baseline but became positive post-therapy. There was no difference in the location, histology grade, clinical stage, or the curative resection (RO) resection rate in the two populations. OS (P = 0.71), disease-free survival (P = 0.86), and median survivals (Converters: 24 months [95% confidence intervals: 7.78 to 40.22]vs. Nonconverters: 34.13 months [95% confidence intervals: 3.54 to 64.27]) were not different between the two groups. Our data suggest that activation of NF-kappaB in response to stress/injury of therapy leads to poor OS. These results need to be confirmed in a larger number of patients. It may be that only pre-therapy evaluation of NF-kappaB is insufficient to assess prognosis of patients with LEA. Additional implications include that when effective anti-NF-kappaB therapies become available, they may have to be considered in patients whose cancers do not have constitutively activated NF-kappaB or cancer may have to be monitored during therapy with biomarker assessments.

EUS for portal hypertension: a comprehensive and critical appraisal of clinical and experimental indications.

Endoscopic ultrasonography (EUS) has significantly improved our understanding of the complex vascular structural changes that occur in portal hypertension and their clinical and prognostic significance. EUS in combination with color Doppler technique enables us to study the hemodynamic changes in the portal venous system noninvasively, and to determine objectively the effect of different pharmacological agents on portal hypertension. EUS has also found some role in the treatment and follow up of esophageal and gastric varices. It may play a clinical role in the diagnosis of gastric, duodenal, and rectal varices. Recently reported EUS-based devices that measure variceal wall tension and intravariceal pressure noninvasively could have an impact on the identification of patients at high risk of variceal bleeding with the aim of initiating prophylactic treatment, and in the assessment of patients' responses to drug therapy of portal hypertension. EUS is occasionally very helpful in the clinical management of portal hypertension. It is an interesting and important research tool for many experimental indications that are not routinely applied in clinical practice at this time.

Anaplastic Thyroid Carcinoma with Gastric Metastasis.

INTRODUCTION: Carcinomas of the thyroid gland represent 3% of all malignancies, with 1.3 to 9.8% corresponding to anaplastic thyroid carcinomas (ATC). Metastases are present in 50% of patients when ATC is diagnosed. Gastrointestinal metastases are a rare finding in patients with thyroid carcinoma. CASE REPORT: A 68-year old gentleman with a history of papillary thyroid carcinoma (PTC) underwent surgery and radiopharmaceutical therapy. Restaging studies nine months later suggested wall thickening localizing to the distal stomach. Endoscopy results showed a large, infiltrative, subepithelial, and ulcerated gastric mass and biopsies revealed anaplastic thyroid carcinoma Conclusion. Incidental thickening or other findings in the stomach in a patient with ATC without gastrointestinal symptoms should be further investigated with endoscopy and biopsies to rule out gastric metastases from anaplastic thyroid carcinoma.

A Diagnostic Challenge: Pancreatic Cancer or Autoimmune Pancreatitis?

We report a rare case of seronegative autoimmune pancreatitis (AIP) that presented as a pancreatic focal lesion and was considered to be pancreatic cancer based on the clinical presentation and imaging findings. The endoscopic ultrasound-guided biopsies of the pancreatic mass revealed no malignant cells and the pancreatic swelling had become diffuse on repeat imaging. AIP was suspected and a trial of steroids was considered as a diagnostic and therapeutic method. The patient responded dramatically to corticosteroid treatment with resolution of symptoms and normal imagining and laboratory parameters. This case highlights the challenge in the diagnostic approach of a pancreatic mass.

Analysis of air contrast barium enema, computed tomographic colonography, and colonoscopy: prospective comparison.

BACKGROUND: The usefulness of currently available colon imaging tests, including air contrast barium enema (ACBE), computed tomographic colonography (CTC), and colonoscopy, to detect colon polyps and cancers is uncertain. We aimed to assess the sensitivity of these three imaging tests. METHODS: Patients with faecal occult blood, haematochezia, iron-deficiency anaemia, or a family history of colon cancer underwent three separate colon-imaging studies--ACBE, followed 7-14 days later by CTC and colonoscopy on the same day. The primary outcome was detection of colonic polyps and cancers. Outcomes were assessed by building an aggregate view of the colon, taking into account results of all three tests. FINDINGS: 614 patients completed all three imaging tests. When analysed on a per-patient basis, for lesions 10 mm or larger in size (n=63), the sensitivity of ACBE was 48% (95% CI 35-61), CTC 59% (46-71, p=0.1083 for CTC vs ACBE), and colonoscopy 98% (91-100, p<0.0001 for colonoscopy vs CTC). For lesions 6-9 mm in size (n=116), sensitivity was 35% for ACBE (27-45), 51% for CTC (41-60, p=0.0080 for CTC vs ACBE), and 99% for colonoscopy (95-100, p<0.0001 for colonoscopy vs CTC). For lesions of 10 mm or larger in size, the specificity was greater for colonoscopy (0.996) than for either ACBE (0.90) or CTC (0.96) and declined for ACBE and CTC when smaller lesions were considered. INTERPRETATION: Colonoscopy was more sensitive than other tests, as currently undertaken, for detection of colonic polyps and cancers. These data have important implications for diagnostic use of colon imaging tests.