Delta radiomics analysis of Magnetic Resonance guided radiotherapy imaging data can enable treatment response prediction in pancreatic cancer.

BACKGROUND: Magnetic Resonance Image guided Stereotactic body radiotherapy (MRgRT) is an emerging technology that is increasingly used in treatment of visceral cancers, such as pancreatic adenocarcinoma (PDAC). Given the variable response rates and short progression times of PDAC, there is an unmet clinical need for a method to assess early RT response that may allow better prescription personalization. We hypothesize that quantitative image feature analysis (radiomics) of the longitudinal MR scans acquired before and during MRgRT may be used to extract information related to early treatment response. METHODS: Histogram and texture radiomic features (n = 73) were extracted from the Gross Tumor Volume (GTV) in 0.35T MRgRT scans of 26 locally advanced and borderline resectable PDAC patients treated with 50 Gy RT in 5 fractions. Feature ratios between first (F1) and last (F5) fraction scan were correlated with progression free survival (PFS). Feature stability was assessed through region of interest (ROI) perturbation. RESULTS: Linear normalization of image intensity to median kidney value showed improved reproducibility of feature quantification. Histogram skewness change during treatment showed significant association with PFS (p = 0.005, HR = 2.75), offering a potential predictive biomarker of RT response. Stability analyses revealed a wide distribution of feature sensitivities to ROI delineation and was able to identify features that were robust to variability in contouring. CONCLUSIONS: This study presents a proof-of-concept for the use of quantitative image analysis in MRgRT for treatment response prediction and providing an analysis pipeline that can be utilized in future MRgRT radiomic studies.

Intensity-modulated radiotherapy at high-volume centers improves survival in patients with esophageal adenocarcinoma receiving trimodality therapy.

The standard of care trimodality therapy for resectable locally advanced esophageal adenocarcinoma is complex and necessitates multidisciplinary care and expertise. In this work, it is hypothesized that facility clinical volume and utilization of intensity-modulated radiotherapy (IMRT) may influence outcomes. The National Cancer Data Base was queried for patients with cT1-4-N0-3 M0 esophageal adenocarcinoma undergoing trimodality therapy from 2004 to 2013 (n = 2445). All patients received chemoradiation followed by esophagectomy at a Commission on Cancer facility. The facility volume was categorized into tertiles: high-volume centers (HVCs) in the highest 25th percentile of cases per year, intermediate-volume centers (IVCs) with the next highest 25th percentile of cases, and low- and very low-volume centers (LVCs) in the lowest 50th percentile. Overall survival (OS) was estimated using Kaplan-Meier methods and Cox proportional hazard regression. Propensity score matching to balance patient characteristics between volume centers was performed. Subgroup analysis was done comparing IMRT versus 3D conformal radiotherapy. The median follow-up was 26 months. Treatment at an HVC (hazard ratio 0.63, 95% CI 0.49-0.81, P < 0.001) was found to be independently associated with improved overall survival in multivariable analysis. Three-year OS was 58.4%, 46.2%, and 47.5% for HVCs, IVCs, and LVCs, respectively (P < 0.001). Patients at HVCs were more likely to receive IMRT over 3D chemoradiation (CRT; OR 3.45, 95% CI 2.4-5.0, P < 0.001). Patients treated using IMRT at HVCs had improved OS compared to those treated at IVCs or LVCs (HR 0.68, 95% CI 0.52-0.90, P < 0.01), while patients treated with 3D CRT at HVCs had no survival advantage over those at IVCs or LVCs (P = 0.28). Patients with locally advanced esophageal adenocarcinoma treated with IMRT and at HVCs appear to have improved survival.

Dose escalated neoadjuvant chemoradiotherapy with dose-painting intensity-modulated radiation therapy and improved pathologic complete response in locally advanced esophageal cancer.

We compared pathologic complete response (pCR) rate, toxicity, and postoperative complications between patients treated preoperatively with 50.4 Gy versus dose escalation with dose-painting intensity-modulated radiation therapy (dp-IMRT) to 56 Gy in locally advanced esophageal cancer. We evaluated esophageal cancer patients treated between 2006 and 2014 with preoperative IMRT chemoradiation to a dose of 50.4 Gy versus 56 Gy. The endpoints were pCR and toxicity. We identified 113 patients (50.4 Gy: n = 40; 56 Gy: n = 73). There were no significant differences in tumor or patient characteristics. Patients treated with 56 Gy demonstrated a higher pCR rate (56.2% vs. 30.0%) and lower pathologic nonresponse rate (4.1% vs. 20.0%) compared to patients treated to 50.4 Gy (P = 0.008). This remained significant on multivariate analysis (OR 3.375 95%CI 1.3-8.8, P = 0.013). Patients treated to 56 Gy also had an improved 3-year locoregional control rate compared to those treated to 50.4 Gy (93.8% vs. 78.5%; P = 0.022). The estimated 3-year freedom from failure was also superior in the 56 Gy arm (73.7% vs. 52.2%; P = 0.051), approaching significance. There were no differences in treatment related grade ≥3 toxicities, hospital admissions, feeding tube, esophageal stent placement, or dilation. There was, however, a statistically significant increase in postoperative atrial fibrillation in patients treated with 56 Gy (30.1% vs. 12.5%; P = 0.036). There was no difference in postoperative 30 or 60 day mortality. Dose escalation to 56 Gy with dp-IMRT is safe and results in significantly higher complete pathologic response rates in esophageal cancer without an increase in treatment-related toxicity. Prospective trials using dp-IMRT are needed to address the role of dose escalation on pCR rate and survival in esophageal cancer.

Computer-assisted analysis of abrasive transepithelial brush biopsies increases the effectiveness of esophageal screening: a multicenter prospective clinical trial by the EndoCDx Collaborative Group.

BACKGROUND: The sensitivity of screening for Barrett's esophagus (BE) and esophageal dysplasia (ED) is hampered by the limited amount of tissue that can be sampled by forceps biopsy (FB). AIM: The aim of this study was to evaluate computer assisted analysis of an abrasive, transepithelial brush biopsy as an adjunct to FB to increase detection of BE and ED. METHODS: This was a multicenter prospective trial of patients being screened for BE and ED. Each patient had two brush biopsies (BB) and then random four-quadrant FB every 1-2 cm of the esophagus. All BB were examined with computer assistance by pathologists at CDx Laboratories (Suffern, NY), and all FB were examined by the investigators' local pathologists. RESULTS: Of 1,266 patients enrolled, 363 were diagnosed with BE by FB alone and 146 additional cases of BE were identified by adding BB. The addition of BB to FB increased the overall detection of BE by 39.8% (95% CI 32-48%). This added detection of BE in 11.5% of all patients tested with the BB (146/1266) resulted in a number of patients needed to test (NNT) to obtain each additional positive finding of Barrett's esophagus of 8.7. Among a subset of 848 patients with gastroesophageal reflux disease and no prior history of BE, the addition of BB to FB identified an additional 105 patients with BE increasing the overall detection of BE by 70.5% (95% CI 54-90%). Dysplasia was diagnosed in 16 patients by FB alone, with an additional 14 cases detected by adding BB. The addition of BB to FB thus increased the detection of ED by 87.5%. CONCLUSION: These results suggest that adjunctive computer-assisted analysis of an abrasive brush biopsy has the potential to substantially improve the detection of Barrett's esophagus and dysplasia in screening populations.

Outcomes of acute esophageal food impaction: success of the push technique.

BACKGROUND: Acute esophageal food impaction (AEFI) is the most common form of esophageal impaction in adults. The current recommendation for management is extraction by using an overtube to protect the airway, which facilitates multiple passages of the endoscope and protects the esophageal mucosa. Typically, AEFI in our patients is treated with the push technique, a method found to be highly successful and without complications. METHODS: All patients with a diagnosis of AEFI from 1993 to 1998 were identified by computer search of ICD-9 diagnosis code 935.1 (foreign body of the esophagus). Patients were excluded if they were less than 18 years of age, had an acute esophageal foreign body other than food, or if the medical record was incomplete. RESULTS: The analysis included 189 patients: 114 men and 75 women. Of these, 77 (41%) had a Schatzki's ring, 61 (32%) had an esophageal stricture, and 4 (2%) had esophageal cancer. In 47 patients (25%) no obvious structural cause for AEFI was noted at endoscopy. In addition, 67 patients had breaks in the esophageal mucosa. The push technique resolved the food impaction in 184 of 189 (97%) of the patients. In no subgroup was there an instance of perforation, aspiration, or bleeding. Forty-five patients underwent dilation at the time of food disimpaction without complication. CONCLUSIONS: The push technique is both safe and effective in the treatment of AEFI. Dilation at the initial presentation of a patient with AEFI likewise appears to be safe. The push technique is recommended as the initial therapy of choice for AEFI. Dilation at the time of esophageal food disimpaction can be considered if there are no obvious contraindications.

Endoscopic transpapillary drainage of pancreatic abscess: technique and results.

BACKGROUND: Pancreatic abscess is one of the serious complications of acute pancreatitis. Traditionally, pancreatic abscess has been treated by operative drainage. Based on experience with endoscopic transpapillary drainage of pseudocysts, a similar technique was used in patients with pancreatic abscess. METHOD: Patients were evaluated by endoscopic retrograde cholangiopancreatography. In those with pancreatic abscess communicating with the main pancreatic duct, pancreatic sphincterotomy, saline irrigation of the abscess cavity, and catheter dilation followed by 10F pancreatic stent placement were done. Instillation of gentamicin and nasopancreatic catheter drainage were used in difficult cases. RESULTS: Of 22 patients with pancreatic abscess, 11 underwent endoscopic transpapillary drainage with technical success in 10 patients (90%); 8 patients (74%) had resolution of pancreatic abscess, clinically and radiographically. Intracavitary instillation of gentamicin and nasopancreatic catheter drainage were used in 2 patients. Two patients in whom endoscopic transpapillary drainage failed underwent operative drainage with a favorable outcome, and the one patient in whom endoscopic treatment was technically unsuccessful underwent successful percutaneous drainage. One patient had mild pancreatitis. CONCLUSION: Endoscopic transpapillary drainage is an effective nonoperative therapy for selected cases of pancreatic abscess and is associated with minimal morbidity and no mortality.

Characteristics of best gastroenterology practices.

OBJECTIVE: As health care costs continue to rise, competition among providers is increasing. Although this competition is currently based on price, quality of care will become an increasingly important issue. One popular method to assess quality is by comparing physicians' performance with that of a representative group of physicians, in a process called benchmarking. The purpose of this study was to survey private practice gastroenterologists to identify the practice characteristics, so-called "best practices," associated with high-quality health care delivery to provide data for use as benchmarks. METHODS: Three hundred randomly selected gastroenterology practices were surveyed regarding practice demographics, administration, financial management, and use of outcomes techniques by mail questionnaire. Analogous questionnaires were completed by representatives of the gastroenterology practices comprising the Gastroenterology Practice Management Group, LLC (GMPG). RESULTS: One hundred and eighty-two (61%) of the 300 eligible practices responded to the questionnaire. Increasing differences between survey and benchmark GPMG practices were observed as the complexity of quality measures increased. Among structure measures, the groups were similar. By contrast, significant differences were observed between survey and benchmark groups with regards to outcomes measures such as the use of practice guidelines, continuous quality improvement, and outcomes assessment. CONCLUSIONS: These results provide a snapshot of gastroenterology practices across the country and can be used as a benchmark for quality assessment purposes to compare with one's practice, suggesting areas for change or improvement. It seems clear that the defining characteristic of best gastroenterology practices is the demonstration of quality patient care. It also appears that many practices' efforts in this regard could be increased.

Biliary pancreatitis: a review. Emphasizing appropriate endoscopic intervention.

Gallstones are a common cause of acute pancreatitis. This article reviews acute biliary pancreatitis and includes natural history, noting the serious nature of some cases; pathogenesis, identifying transient obstruction as the primary pathogenetic event; diagnosis, including biochemical parameters and imaging; assessment of severity, underlining the importance of early prognostic signs, organ failure, and local complications; and management. Management is reviewed in detail, giving a historical perspective to the role of surgery, highlighting the role of endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy and paying particular attention to the four prospective randomized clinical trials in suggesting which patients are most likely to benefit from early endoscopic evaluation and therapy. Also discussed are additional clinical situations related to biliary pancreatitis in which endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy play a role. Finally, a suggested endoscopic approach to acute biliary pancreatitis is presented along with an algorithm incorporating severity stratification, principles of endoscopic intervention, and concepts of sterile and infected pancreatic necrosis.

Endoscopic intervention for biliary leaks after laparoscopic cholecystectomy: a multicenter review.

BACKGROUND: Endoscopic therapy of biliary tract leaks was uncommon before laparoscopic cholecystectomy. Studies have demonstrated the efficacy of endoscopic drainage by endoscopic sphincterotomy or stent placement. Various endoscopic therapeutic modalities and long-term follow-up of this problem were studied. METHODS: Members of the Midwest Pancreaticobiliary Group reviewed all patients referred for endoscopic therapy of biliary leaks after laparoscopic cholecystectomy from 1990 to 1994. Long-term follow-up was by direct patient contact. RESULTS: Fifty patients were referred for endoscopic therapy of biliary leaks. Abdominal pain was present in 94%. The mean time from laparoscopic cholecystectomy to referral was 6.9 days. Therapy consisted of sphincterotomy only in 6 patients, stent only in 13, and sphincterotomy with stent in 31. Biliary leaks were healed in 44 patients at a mean of 5.4 weeks. A second or third endoscopic procedure was necessary to achieve healing in five patients. Two stent-related complications were noted. Percutaneous or surgical drainage of biliary fluid collections was required in 16 patients. The mean hospital stay for treatment of the leak was 11.1 days after endoscopic therapy. On follow-up (mean 17.5 months), all patients were well except two with mild abdominal discomfort. CONCLUSIONS: Endoscopic sphincterotomy, stent placement, or sphincterotomy with stent are effective in healing biliary leaks after laparoscopic cholecystectomy. Despite prolonged treatment for the leak, patients did well on long-term follow-up.

Managed care. Evolution and distinguishing features.

Managed care as a system of health care delivery has grown tremendously in popularity in the United States during the past decade in response to demands by employers and government for cost containment, enhanced access, and improved quality. Managed care took root in the 1800s as prepaid health services provided by employers for immigrants coming to the United States to work. The forerunner of modern managed care, prepaid group practice, later was dwarfed by the unbridled development of FFS medicine under indemnity insurance in the post-World War II period and stunted by early reactions of organized medicine. The early health care reform years of the 1960s spawned HMO legislation in the 1970s, which prompted ever-escalating growth in HMO enrollment. Market-driven health reform has prompted the evolution of health care delivery to the modern-day version of managed care. In this system, health care is provided by a limited number of contracted providers at reduced rates of reimbursement. Patients are channeled to these contracted providers, and clinical decision making of these providers is influenced by the MCO through utilization management and quality assurance. Financial risk is shifted from payers and insurance companies to providers to influence further clinical decision making. All of these characteristics of managed care pressure providers toward higher levels of integration and foster greater reliance on management information systems. Gaining a perspective from the history of managed care, understanding managed care's distinguishing features, and dealing effectively with the pressures of these unique characteristics are important in successfully caring for patients, managing the risk structure, and succeeding professionally in this current environment for health care delivery.

Glossary of managed care terms.

The terminology of managed care and healthspeak are confusing and foreign-sounding to many physicians. The acronyms have been described as "thick alphabet soup." A glossary of these terms and acronyms is presented to aid the reader in understanding the articles in this issue.

Optimal timing for stent replacement in malignant biliary tract obstruction.

Endoscopic stent placement has become accepted palliative therapy for malignant biliary tract obstruction. Because stent occlusion remains a significant late complication, prophylactic replacement has been suggested, although the appropriate time interval remains unclear. Patients with malignant biliary strictures who received 10F or 11.5F stents were analyzed with respect to clinical response, occlusion rates at 3 and 6 months, and survival rates. Seventy stents were placed in 50 patients. Pancreatic carcinoma was the most common underlying malignancy. Overall, obstructive symptoms resolved in 94% of cases. Occlusion rates at 3 months (4.2%) and 6 months (10.8%) were not significantly different. Median overall survival averaged 22 weeks. Results were also stratified by underlying diagnosis, with the worst clinical response and survival being seen in the group of patients with metastatic cancer. Findings suggest that the time interval for stent replacement can be extended safely from 3 to 6 months, resulting in decreased patient discomfort and cost and obviating any replacement in that significant percentage of patients who expire before 6 months.

Gallstone pancreatitis: mechanisms and management.

We now have a better understanding of the pathogenesis of gallstone pancreatitis, although many questions and ambiguities remain. What we do know has led to improved tools for diagnosis and therapy.