LIQUID NITROGEN SPRAY CRYOTHERAPY FOR ERADICATION OF DYSPLASTIC BARRETT'S ESOPHAGUS: RESULTS FROM A MULTICENTER PROSPECTIVE REGISTRY.

BACKGROUND AND AIMS: Liquid nitrogen spray cryotherapy (SCT) is an alternative to radiofrequency ablation (RFA) for eradication of dysplastic Barrett's esophagus (BE). We aimed to assess the safety, efficacy, and durability of SCT in a multicenter U.S. registry. METHODS: This is a multicenter prospective registry of adults with BE treated with truFreeze Spray Cryotherapy (4 community and 11 academic sites, 2013-2022). Complete eradication of intestinal metaplasia (CEIM) and dysplasia (CED) were assessed in BE with dysplasia or intramucosal adenocarcinoma (IMC). Kaplan-Meier analysis of CEIM and CED was performed. Hazard ratios for CEIM stratified by baseline risk factors were calculated. RESULTS: Among 138 subjects, with LGD (24%), HGD (49%) and IMC (27%), 34% received prior RFA therapy. Subjects received a median of 2 SCT sessions. Adverse events were uncommon, with 5.5% reporting strictures and 0.7% a perforation. Rates of CEIM and CED, respectively, were 66% and 84% after two years, and 67% and 92% after three years. In RFA-naive patients, CEIM was 77% and CED was 96% at 3 years. Increasing BE length (adjusted hazard ratio [95% CI]:0.90 [0.83-0.96] per cm) and prior treatment with RFA (0.39 [0.22-0.69]) were associated with a lower rate of CEIM. Recurrence occurred in 8.8% (n=6) at a mean follow-up of 2.5 years after CEIM. CONCLUSION: In this largest reported prospective cohort, liquid nitrogen SCT was safe and effective for treatment of dysplastic and neoplastic BE. Response was lower in those with prior failed RFA; in that cohort approximately 50% attained CEIM at 3 years.

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.).

Training for communication in forensic science.

Scientists are increasingly becoming better prepared to communicate science in a variety of different settings, yet significantly less attention has been paid to communicating science in the courtroom, a setting which carries major societal impact. This article explores key issues surrounding science communication in the courtroom. We outline a conceptual system for communication training that includes ideas about fostering greater collaboration across different stakeholder groups, and training expert witnesses to communicate scientific evidence in ways that are accessible and accurate. Critical to this concept is supporting communication that upholds the integrity of the science, while also maintaining expectations for interactions in the courtroom.

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.

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.

Preoperative Risk Assessment and Management in Adults Receiving Maintenance Dialysis and Those With Earlier Stages of CKD.

With an increasingly aging population and improved mortality in individuals with end-stage kidney disease, more surgeries are being performed on patients with all stages of chronic kidney disease (CKD). This high-risk population carries unique risk factors that have been associated with increased adverse perioperative outcomes, including acute kidney injury, cardiovascular events, and mortality. In this article, we review the literature describing absolute risks associated with common surgeries performed in patients with CKD and patients receiving maintenance dialysis. We also review perioperative optimization with special risk assessment including evaluation of cardiovascular and bleeding risk evaluation, hypertension management, and timing of dialysis. Predictive model scores are reviewed as a method to stratify risk for acute kidney injury, major adverse cardiac events, or other serious complications with elective surgeries. A multidisciplinary approach with individualized counseling is necessary to counsel the patient with advanced CKD or patients treated with maintenance dialysis considering elective surgery.

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.

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.

Management of the Dialysis Patient with Sickle Cell Disease.

While patients with sickle cell disease currently constitute a very small minority of the US dialysis population (0.1%), there is anticipated growth of this group as the life expectancy of those with sickle cell disease (SCD) increases. SCD patients suffer a high burden of morbidity, which is enhanced by the presence of end-stage renal disease (ESRD). In this review, we discuss the pathophysiology of SCD and the basic tenets of its management with focus on the dialysis patient with SCD. Anemia in dialysis patients with SCD is a unique challenge. The hemoglobin target in SCD dialysis patients with ESRD should not exceed 10 g/dl. SCD patients, and particularly those on dialysis, are likely to be poorly responsive to erythropoietin-stimulating agent (ESA) therapy and might be at increased risk for vaso-occlusive crisis (VOC) with ESA. Iron chelation and hydroyxurea therapy require special considerations and modifications in dialysis patients with SCD. There are theoretical advantages to both hemodialysis (HD) and peritoneal dialysis (PD) in SCD patients. With HD, there is a secure vascular access available for both standard and exchange blood transfusion in patients who need them. With PD, the absence of an acute rise in hematocrit with ultrafiltration (UF) might offer lower risk of VOC. During VOC, reduction in UF goals should be considered but administration of intravenous fluids should be reserved only for clear cases of volume depletion. Finally, renal transplantation appears to confer a survival advantage to dialysis in SCD patients and should be pursued when possible.

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.

Poor 'real-life' negative predictive value of cross-sectional imaging in obstructive jaundice.

BACKGROUND: Cross-sectional imaging remains the first-line test for obstructive jaundice despite high miss rates for pancreatobiliary tumours. Improvements in resolution and slice thickness of spiral computed tomography/magnetic resonance imaging/magnetic resonance cholangiopancreatography promised to increase accuracy. OBJECTIVE: To assess whether the post-test probability of neoplasm is truly altered by the presence or absence of a mass on computed tomography/magnetic resonance imaging in obstructive jaundice. METHODS: The institutional endoscopic ultrasound (EUS) database was retrospectively reviewed to stratify patients presenting to EUS over a two-year period for obstructive jaundice (suspicious for malignancy) according to their pre-EUS imaging results. The primary analysis involved the calculation of the positive predictive value and negative predictive value (NPV) of imaging with 95% binomial CIs. Test performance of EUS/fine-needle aspiration (FNA) was also calculated. Final diagnosis was determined by positive cytology/histology; negative EUS was supplemented by clinical follow-up. RESULTS: The positive predictive value (n = 51) and NPV (n = 53) of pre-EUS imaging was 98% (95% CI 90% to 100%) and 9% (95% CI 3% to 21%), respectively (accuracy 53%), with post-test suspicion of malignancy similar between imaging-positive and -negative groups. EUS demonstrated a mass in 96% of imaging-positive cases versus 85% in imaging-negative cases (exact P = 0.09). Malignant or suspicious FNA cytology was obtained with EUS in 92% of the imaging-positive group, and 62% of the imaging-negative group (75% of subgroup with FNA) (P < 0.001). CONCLUSION: Lack of a definite mass on pre-EUS imaging had low NPV, and was clearly not sufficiently accurate or reassuring in this clinical setting. In suspicious obstructive jaundice, EUS with FNA has a high diagnostic yield regardless of the findings of pre-EUS cross-sectional imaging and, as such, EUS may be a more reasonable first-line test in this high-suspicion setting.

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.