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1.
Fed Pract ; 38(6): 270-275, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34733074

RESUMO

Introduction: Colonoscopies and fecal immunochemical tests (FITs) are the preferred modalities for colorectal cancer (CRC) screening. In addition to proper patient selection, appropriate fecal immunochemical testing requires that negative tests be repeated annually, positive tests lead to a diagnostic colonoscopy, and FIT not be performed within 5 years of a colonoscopy with adequate bowel preparation. We sought to study the frequency of inappropriate FITs at the Veterans Affairs Pittsburgh Health Care System in Pennsylvania. Methods: A retrospective quality assurance study was undertaken of veterans undergoing FIT in a 3-year period (2015-2017). We calculated the rate of a negative initial FIT in 2015/2016 followed by a second FIT in 2016/2017 in a random selection of veterans (3% SE, 95% CI). Demographics were compared in an equal random number of veterans that did and did not have a follow-up FIT (5% SE, 95% CI of all negative FIT). We also calculated the rate of completing colonoscopy following a positive FIT in a random selection of veterans (3% SE, 95% CI). Finally, we investigated use of FIT following a colonoscopy for all veterans in the study period. Results: A total of 6,766 FITs were performed; 4,391 unique veterans had at least 1 negative FIT, and 709 unique veterans had a positive FIT. Of 1,742 veterans with at least 1 negative FIT, 870 were eligible for repeat testing during the study period, and only 543 (62.4%) underwent at least 2 FITs. There was no significant demographic difference in veterans that had only 1 or at least 2 FITs. Of 410 veterans with a positive FIT, 113 (27.5%) did not undergo a subsequent colonoscopy within 1 year due to patient refusal, or failure to schedule or keep a colonoscopy appointment. Of 832 veterans who had both a FIT and colonoscopy in the interval, 108 veterans underwent colonoscopy with a subsequent FIT (1.6% of total FITs performed). Of these, 95 (88%) were judged to be inappropriate. Thirteen instances of FIT following colonoscopy were appropriate based on patient preference to undergo fecal immunochemical testing for CRC screening modality after undergoing colonoscopy with an inadequate bowel preparation. Conclusions: Veterans underwent inappropriate testing due to failure to undergo serial FIT after a negative result (37.6%), failure to complete colonoscopy following a positive FIT (27.5%), and undergoing inappropriate FIT following a recent colonoscopy (88%). Efforts are still required to improve both patient and provider education and adherence to appropriate fecal immunochemical testing and CRC screening guidelines.

2.
Gut ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849943

RESUMO

OBJECTIVE: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown. DESIGN: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS). RESULTS: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%). CONCLUSIONS: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.

3.
Ther Adv Gastrointest Endosc ; 14: 26317745211001750, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33855293

RESUMO

Introduction: The safety and efficacy of colonic band ligation and auto-amputation (1) as adjunct to endoscopic mucosal resection of large laterally spreading tumors and (2) for polyps not amenable to routine polypectomy due to polyp burden or difficult location remain unknown. Methods: An institutional review board-approved retrospective single-institution study was undertaken of patients undergoing colonic band ligation and auto-amputation from 2014 to date. Patients with indications of 'endoscopic mucosal resection for laterally spreading tumors' and 'polyp not amenable to snare polypectomy' were included in the study. Data were collected on patient demographics, colonoscopy details (laterally spreading tumors/polyp characteristics, therapies applied, complications), pathology results, and follow-up (polyp eradication based on endoscopic appearance and biopsy results). Results: Patients undergoing endoscopic mucosal resection for laterally spreading tumors: Thirty-two patients (31 males, aged 68 ±â€„9.17 years) underwent endoscopic mucosal resection-band ligation and auto-amputation of 34 laterally spreading tumors (40 ±â€„10.9 mm). A median of 2 ±â€„1.09 bands were placed. Follow-up colonoscopy and biopsy results confirmed complete eradication in 21 laterally spreading tumors (70%). Nine (30%) laterally spreading tumors required additional endoscopic therapy to achieve complete eradication. Four (13%) patients underwent surgery for cancer, and two of them had resection specimens negative for cancer or residual adenoma. One patient suffered post-polypectomy syndrome. Patients undergoing band ligation and auto-amputation for polyps not amenable to snare polypectomy: Seven patients underwent band ligation and auto-amputation due to serrated polyposis syndrome (one patient) and innumerable polyps, or polyps in difficult locations (extension into diverticula: two patients; terminal ileum: two patients; appendiceal orifice: one patient; anal canal: one patient). The patient with serrated polyposis syndrome achieved dramatic decrease in polyp burden, but not eradication. Follow-up in five of the six remaining patients documented polyp eradication. The patient with serrated polyposis syndrome suffered from rectal pain and tenesmus following placement of 18 bands. Conclusions: Band ligation and auto-amputation in the colon may be a safe and effective adjunct to current endoscopic mucosal resection and polypectomy methods and warrants further study. Plain Language Summary: Colonoscopy with rubber band placement to aid in complete removal of large polyps and polyps in technically challenging locationsColonoscopy is a commonly performed procedure for the early detection of colon and rectal cancer, and prevention through polyp removal.During colonoscopy, sometimes situations are encountered making polyp removal difficult. These can include the presence of larger polyps or the location of a polyp in an area that makes removal technically challenging or high risk.A particularly challenging situation arises when after extensive effort there is still polyp tissue remaining that cannot be removed using routine techniques. We are interested in exploring a technique which involves the placement of a rubber band after sucking a small area of the colon lining into a cap loaded onto the tip of the colonoscope. With time the rubber band strangulates the tissue and falls off along with captured tissue and passes out of the colon naturally.To assess the effectives of this technique we studied patients that have undergone this procedure at our GI unit. We identified 32 patients with 34 large polyps between 4cm to 6cm that we placed rubber bands on polyp tissue after we were unable to completely remove the polyp. On their follow up colonoscopy, complete polyp removal was successful in 21 polyps. We were also able to achieve complete polyp removal in 9 of the remaining large polyps after additional treatment. Four patients underwent surgery because cancer was found in analysis of polyp tissue.In 5 of 6 patients with polyps in difficult locations (e.g. partly within the lumen of the appendix), placement of a rubber band led to complete removal of polyp tissue.Two patients in our study population had mild adverse events that were managed with simple measures.We believe our results show promise for our described technique and this technique should be tested in larger studies.

5.
Ann Surg Oncol ; 28(5): 2438-2446, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33523364

RESUMO

AIMS: National studies have demonstrated disparities in the treatment and survival of pancreatic cancer patients based on socioeconomic status (SES). This study aimed to identify specific differences in perioperative management and outcomes based on patient SES and to study the role of a multidisciplinary clinic (MDC) in mitigating any variations. METHODS: The study analyzed patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma in a large hospital system. The patients were categorized into groups of high and low SES and whether they were managed by the authors' pancreatic cancer MDC or not. The study compared differences in disease characteristics, receipt of multimodality therapy, perioperative outcomes, and recurrence-free and overall survival. RESULTS: Of the 162 low-SES patients and 119 high-SES patients, 54% were managed in the MDC. Outside the MDC, low-SES patients were less likely to receive neoadjuvant chemotherapy and had less minimally invasive surgery, a longer OR time, less enhanced recovery participation, and more major complications (p < 0.05). No SES disparities were observed among the MDC patients. Despite similar tumor characteristics, the low-SES patients had inferior median overall survival (21 vs 32 months; p = 0.005), but the MDC appeared to eliminate this disparity. Low SES correlated with inferior survival for the non-MDC patients (17 vs 32 months; p < 0.001), but not for the MDC patients (24 vs 25 months; p = 0.33). These findings persisted in the multivariable analysis. CONCLUSION: A pancreatic cancer MDC standardizes treatment decisions, eliminates disparities in surgical outcomes, and improves survival for low-SES patients.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/cirurgia , Disparidades em Assistência à Saúde , Humanos , Recidiva Local de Neoplasia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Classe Social
6.
Surg Endosc ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33543349

RESUMO

INTRODUCTION: Treatment of pancreaticobiliary pathology following Roux-en-Y gastric bypass (RYGB) poses significant technical challenges. Laparoscopic-assisted endoscopic retrograde cholangiopancreatography (LA-ERCP) can overcome those anatomical hurdles, allowing access to the papilla. Our aims were to analyze our 12-year institutional outcomes and determine the learning curve for LA-ERCP. METHODS: A retrospective review of cases between 2007 and 2019 at a high-volume pancreatobiliary unit was performed. Logistic regression was used to identify predictors of specific outcomes. To identify the learning curve, CUSUM analyses and innovative methods for standardizing the surgeon's timelines were performed. RESULTS: 131 patients underwent LA-ERCP (median age 60, 81% females) by 17 surgeons and 10 gastroenterologists. Cannulation of the papilla was achieved in all cases. Indications were choledocholithiasis (78%), Sphincter of Oddi dysfunction/Papillary stenosis (18%), management of bile leak (2%) and stenting/biopsy of malignant strictures (2%). Median total, surgical and ERCP times were 180, 128 and 48 min, respectively, and 47% underwent concomitant cholecystectomy. Surgical site infection developed in 9.2% and post-ERCP pancreatitis in 3.8%. Logistic regression revealed multiple abdominal operations and magnitude of BMI decrease (between RYGB and LA-ERCP) to be predictive of conversion to open approach. CUSUM analysis of operative time demonstrated a learning curve at case 27 for the surgical team and case 9 for the gastroenterology team. On binary cut analysis, 3-5 cases per surgeon were needed to optimize operative metrics. CONCLUSION: LA-ERCP is associated with high success rates and low adverse events. We identify outcome benchmarks and a learning curve for new adopters of this increasingly performed procedure.

8.
Gastrointest Endosc ; 94(1): 160-168.e3, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33497642

RESUMO

BACKGROUND AND AIMS: During the severe acute respiratory syndrome coronavirus 2 pandemic, N95 filtering facepiece respirator (FFR) use was required while performing aerosol-generating procedures. We studied the physiologic effects of N95 FFR use in a cohort of gastroenterologists performing simulated colonoscopies. METHODS: Data collection and comparisons included (1) symptoms and change in vital signs in 12 gastroenterologists performing simulated colonoscopy for 60 minutes while wearing a surgical mask (SM) and faceshield (FS); N95 FFR, SM, and FS; and powered air-purifying respirator (PAPR) and (2) respiratory belt plethysmography and continuous electrocardiographic frequency-based heart rate (HR) variability indices including very low frequency power (measures intracardiac sympathetic tone) and low frequency to high frequency ratios (intracardiac sympathetic to vagal ratio) in 11 gastroenterologists performing simulated colonoscopy while wearing an SM (15 minutes), N95 FFR and SM (60 minutes), and SM (15 minutes) in rapid sequence. RESULTS: Ten of 12 gastroenterologists (83%) reported symptoms with N95 FFR use, most commonly breathing difficulty, frustration, fatigue, and headache. Nine of these gastroenterologists (75%) had associated significant HR elevation. Respiratory peak to trough measurement showed a significant increase (F(2) = 7.543, P = .004) during the N95 FFR stage, which resolved after removal of the N95 FFR. Although not statistically different, all gastroenterologists showed a decrease in sympathetic to vagal ratios and an increase in intracardiac sympathetic effects in the N95 FFR stage. PAPR use was better tolerated but was associated with headache and elevated HR in 4 gastroenterologists (33%). CONCLUSIONS: N95 FFR use by gastroenterologists is associated with development of acute physiologic changes and symptoms.


Assuntos
COVID-19 , Gastroenterologistas , Respiradores N95 , Exposição Ocupacional , Colonoscopia , Eletrocardiografia , Frequência Cardíaca , Humanos , Exposição Ocupacional/prevenção & controle
9.
Artigo em Inglês | MEDLINE | ID: mdl-33278573

RESUMO

BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, P < .001) and AJCC 8th edition T-stage (r = 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P = .007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.

10.
Ann Surg ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33201115

RESUMO

OBJECTIVE: To evaluate the significance of UDD in IPMNs. BACKGROUND: The uncinate process of the pancreas has an independent ductal drainage system. International consensus guidelines of IPMNs still consider it as a branch-duct, even though it is the main drainage system for the uncinate process. METHODS: A retrospective review of all surgically treated IPMNs at our institution after 2008 was performed. Preoperative radiological studies were reviewed by an abdominal radiologist who was blinded to the pathological results. In addition to the Fukuoka criteria, presence of UDD was recorded. Using multivariate analysis, the pathological significance of UDD in predicting advanced neoplasia [high grade dysplasia or invasive carcinoma (HGD/IC)] was determined. RESULTS: Two hundred sixty patients were identified (mean age at diagnosis was 68 years and 49% were females): 122 (47%) had HGD/IC. UDD was noted in 59 (23%), of which 36 (61%) had HGD/IC (P < 0.003). On multivariate analysis, UDD was an independent predictor of HGD/IC (odds ratio = 2.99, P < 0.04). Subgroup analysis on patients with IPMNs confined to the dorsal portion of the gland (n = 161), also demonstrated UDD to be a significant predictor of HGD/IC in those remote lesions (odds ratio: 4.41, P = 0.039). CONCLUSIONS: This is the largest study to evaluate the significance of UDD in IPMNs and shows it to be a high-risk feature. This association persisted for remote IPMNs limited to the dorsal pancreas, suggesting UDD may be associated with an aggressive phenotype even in remote IPMN lesions.

11.
Fed Pract ; 37(5): 224-228, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32454576

RESUMO

Introduction: The Veterans Choice Program (VCP) was designed to provide a pathway for veterans to access health care in the community if wait times at the US Department of Veterans Affairs (VA) were > 30 days. However, the performance of this program, in terms of timeliness, quality assurance, and overall utilization by veterans for colonoscopy is not well studied. Methods: We reviewed records of veterans at VA Pittsburgh Healthcare System (VAPHS) who underwent VCP colonoscopy from June 2015 through March 2017. We compared the number of days from the scheduling encounter to the first available colonoscopy at VAPHS to the actual colonoscopy through the VCP. Additionally, we examined the availability of procedure and pathology results, documentation of quality metrics, and if clear follow-up recommendations were present in community care records. We then separately examined VCP utilization in a representative sample (5% margin of error, 95% CI) of all colonoscopy referrals through the VCP. Results: During the study period 3,855 veterans were eligible for colonoscopy via the VCP, and 190 colonoscopies were performed through VCP. Records were absent for 29 exams (15.3%). There was no statistically significant difference for the number of days from a veteran's initially scheduled first-available colonoscopy at VAPHS when compared with the actual VCP colonoscopy (median 2 days earlier, P = .62). Pathology results were absent in 14 of 118 (11.9%) patient records, and follow-up recommendations were absent in 29 of 161 (18%) cases. Documentation of colonoscopy quality metrics were deficient in 27% to 70% of procedure reports. In a utilization sample of 350 veterans, only 26 (7.4%) veterans referred for colonoscopy had documented VCP colonoscopies, and 231 (66%) had a VAPHS colonoscopy. The median actual wait time for colonoscopy was 61 days for VAPHS and 66 days through VCP (P = .15). Conclusions: Colonoscopies referred through the VCP were not performed sooner in aggregate compared with the first available colonoscopy at VAPHS, although there was wide variability in wait times. We recommend additional mechanisms be put into place when outsourcing to community care: Ensure seamless and require prompt transfer of records back to the VA, require reporting of quality metrics standard at the VA for community care colonoscopies, and establish clinically meaningful wait-time thresholds for referral into the community, rather than static ones.

12.
Gut ; 69(1): 52-61, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30971436

RESUMO

OBJECTIVE: Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. DESIGN: We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. RESULTS: The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. CONCLUSIONS: The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Doenças Biliares/diagnóstico , Doenças Biliares/genética , Doenças Biliares/patologia , Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Constrição Patológica/diagnóstico , Constrição Patológica/genética , Diagnóstico Diferencial , Feminino , Humanos , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/genética , Cirrose Hepática Biliar/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Manejo de Espécimes/métodos , Adulto Jovem
13.
Gastrointest Endosc ; 90(5): 859-860, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31635719

Assuntos
Endoscopia
14.
Gastrointest Endosc ; 89(4): 818-824, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30391253

RESUMO

BACKGROUND AND AIMS: Nonuniversal use of facial protection during endoscopy may place endoscopists at risk of exposure to blood and body fluids; however, the frequency of exposure is unknown. METHODS: A prospective 6-month study of 4 gastroenterologists using a face shield during endoscopy was undertaken. The face shield was swabbed in a standardized fashion before and at the end of the session. Controls included pre- and post-swabs of face shields placed on the (1) endoscopy suite wall, (2) remote patient intake bay wall, and (3) after deliberate contamination with a colonoscope immediately after colonoscopy. The swabs were cultured for 48 hours, and growth was reported as no growth or by number of colony-forming units (CFUs). The groups were compared for +CFU rate and CFU number. RESULTS: A total of 1100 procedures were performed in 239 endoscopy sessions. The +CFU rate in the pre-endoscopy groups (2%-4.8%, not significant) was significantly lower than the postendoscopist face shield (45.8%, P < .001) and endoscopy suite wall groups (21.4%, P < .001), respectively. Using a cut-off of >15 CFUs as an indicator of definite exposure, the occurrence rate was 5.6 per 100 half days of endoscopy to the endoscopist's face and 3.4 per 100 half days of endoscopy 6 feet away. CONCLUSIONS: This is the first study to quantify the rate of unrecognized exposure to the endoscopist's face to potentially infectious biologic samples during endoscopy (5.6/100 days of endoscopy). This exposure may result in transmission of infectious diseases. As such, we recommend the use of universal facial protection during GI endoscopy.


Assuntos
Bactérias/isolamento & purificação , Endoscopia do Sistema Digestório , Gastroenterologistas , Máscaras/microbiologia , Exposição Ocupacional/estatística & dados numéricos , Atitude do Pessoal de Saúde , Colonoscopia , Contagem de Colônia Microbiana , Técnicas de Cultura , Endossonografia , Humanos , Incidência , Estudos Prospectivos
15.
Int J Biol Macromol ; 120(Pt B): 1525-1532, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30227209

RESUMO

A lentinan (LEN) functionalized multi-walled carbon nanotubes (MWCNTs) drug delivery system, using tamoxifen (TAM) as a model anticancer agent, was developed by a simple non-covalent approach. This developed system (MWCNTs-TAM-LEN) possessed good stability, water dispersibility and extraordinary photothermal properties. It was demonstrated by the in vitro experiments that MWCNTs-TAM-LEN had enhanced cellular uptake, antitumor activity and cell apoptosis on Mcf-7 cells in comparison with TAM and MWCNTs-TAM. The cell inhibition rate and apoptosis rate of Mcf-7 cells treated by MWCNTs-TAM-LEN with near-infrared (NIR) were 67.1% and 66.5% higher than that of equivalent concentration of TAM with NIR irradiation treatment, respectively. The enhanced antitumor efficacy of MWCNTs-TAM-LEN was realized via the synergistic function of chemotherapy and photothermal ablation under NIR laser irradiation.


Assuntos
Técnicas de Ablação , Portadores de Fármacos/química , Lentinano/química , Nanotubos de Carbono/química , Tamoxifeno/química , Tamoxifeno/farmacologia , Transporte Biológico , Terapia Combinada , Humanos , Células MCF-7 , Modelos Moleculares , Conformação Molecular , Tamoxifeno/metabolismo , Tamoxifeno/uso terapêutico
16.
Therap Adv Gastroenterol ; 11: 1756284818785574, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30034531

RESUMO

Background: Endoscopic management of pelvic abscesses not amenable to percutaneous drainage has been described. The technique employs endoscopic ultrasound (EUS)-guided placement of stents or drains, which may require multiple procedures, is cumbersome and uncomfortable for the patient. We describe the successful management of these abscesses in a single step involving EUS-guided lavage and instillation of antibiotics. Methods: Six consecutive patients with seven symptomatic pelvic abscesses not amenable to percutaneous drainage were referred for EUS-guided drainage. The abscesses were aspirated with a 19-gauge needle under EUS guidance and serially lavaged with an equal aspirate to instillation volume of sterile saline until cleared of pus. The residual cavity was then instilled with gentamicin 40 mg/ml. Patients were followed clinically and radiographically with repeat computed tomography or magnetic resonance imaging. Results: All patients had rapid resolution of symptoms. The abscesses disappeared completely in four patients. One patient with recurrent diverticulitis and abscess had marked decrease in abscess size and inflammation to permit planned sigmoid resection. One patient with Crohn's disease had clinical improvement and marked decrease in abscess size, permitting outpatient management of Crohn's disease. Conclusions: EUS-guided lavage and instillation of antibiotics is a simple, one-step approach in the management of pelvic abscesses and may obviate the need for prolonged drain management and repeat procedures in select cases.

17.
Gut ; 67(12): 2131-2141, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-28970292

RESUMO

OBJECTIVE: DNA-based testing of pancreatic cyst fluid (PCF) is a useful adjunct to the evaluation of pancreatic cysts (PCs). Mutations in KRAS/GNAS are highly specific for intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), while TP53/PIK3CA/PTEN alterations are associated with advanced neoplasia. A prospective study was performed to evaluate preoperative PCF DNA testing. DESIGN: Over 43-months, 626 PCF specimens from 595 patients were obtained by endoscopic ultrasound (EUS)-fine needle aspiration and assessed by targeted next-generation sequencing (NGS). Molecular results were correlated with EUS findings, ancillary studies and follow-up. A separate cohort of 159 PCF specimens was also evaluated for KRAS/GNAS mutations by Sanger sequencing. RESULTS: KRAS/GNAS mutations were identified in 308 (49%) PCs, while alterations in TP53/PIK3CA/PTEN were present in 35 (6%) cases. Based on 102 (17%) patients with surgical follow-up, KRAS/GNAS mutations were detected in 56 (100%) IPMNs and 3 (30%) MCNs, and associated with 89% sensitivity and 100% specificity for a mucinous PC. In comparison, KRAS/GNAS mutations by Sanger sequencing had a 65% sensitivity and 100% specificity. By NGS, the combination of KRAS/GNAS mutations and alterations in TP53/PIK3CA/PTEN had an 89% sensitivity and 100% specificity for advanced neoplasia. Ductal dilatation, a mural nodule and malignant cytopathology had lower sensitivities (42%, 32% and 32%, respectively) and specificities (74%, 94% and 98%, respectively). CONCLUSIONS: In contrast to Sanger sequencing, preoperative NGS of PCF for KRAS/GNAS mutations is highly sensitive for IPMNs and specific for mucinous PCs. In addition, the combination of TP53/PIK3CA/PTEN alterations is a useful preoperative marker for advanced neoplasia.


Assuntos
Biomarcadores Tumorais/genética , Líquido Cístico/química , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Cisto Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/cirurgia , Cromograninas/genética , DNA de Neoplasias/genética , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Seguimentos , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Neoplasias Císticas, Mucinosas e Serosas/diagnóstico , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Císticas, Mucinosas e Serosas/cirurgia , Cisto Pancreático/genética , Cisto Pancreático/patologia , Cisto Pancreático/cirurgia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Cuidados Pré-Operatórios , Estudos Prospectivos , Proteínas Proto-Oncogênicas p21(ras)/genética , Sensibilidade e Especificidade , Adulto Jovem
18.
Endosc Int Open ; 4(10): E1023-E1027, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27747273

RESUMO

Background and aims: Adenoma detection rate (ADR) and cecal withdrawal time (CWT) have been identified as measures of colonoscopy quality. This study evaluates the impact of monitoring these measures on provider performance. Methods: Six blinded gastroenterologists practicing at a Veterans Affairs Medical Center were prospectively monitored over 9 months. Data for screening, adenoma surveillance, and fecal occult blood test positive (FOBT +) indicated colonoscopies were obtained, including exam preparation quality, cecal intubation rate, CWT, ADR, adenomas per colonoscopy (APC), and adverse events. Metrics were continuously monitored after a period of informed CWT monitoring and informed CWT + ADR monitoring. The primary outcome was impact on ADR and APC. Results: A total of 1671 colonoscopies were performed during the study period with 540 before informed monitoring, 528 during informed CWT monitoring, and 603 during informed CWT + ADR monitoring. No statistically significant impact on ADR was noted across each study phase. Multivariate regression revealed a trend towards fewer adenomas removed during the CWT monitoring phase (OR = 0.79; 95 %CI 0.62 - 1.02, P = 0.065) and a trend towards more adenomas removed during the CWT + ADR monitoring phase when compared to baseline (OR = 1.26; 95 %CI 0.99 - 1.61, P = 0.062). Indication for examination and provider were significant predictors for higher APC. Provider-specific data demonstrated a direct relationship between high ADR performers and increased CWT. Conclusions: Monitoring quality metrics did not significantly alter colonoscopy performance across a small heterogeneous group of providers. Non-significant trends towards higher APC were noted with CWT + ADR monitoring. Providers with a longer CWT had a higher ADR. Further studies are needed to determine the impact of monitoring on colonoscopy performance.

19.
Gut ; 65(1): 100-11, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25500204

RESUMO

BACKGROUND AND AIMS: Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. METHODS: We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1ß and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. RESULTS: NCs had higher fatty acids, IL-8 and IL-1ß versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. CONCLUSIONS: UFAs, IL-1ß and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.


Assuntos
Necrose Gordurosa/metabolismo , Ácidos Graxos Insaturados/metabolismo , Pancreatite Necrosante Aguda/patologia , Células Acinares/metabolismo , Células Acinares/patologia , Adulto , Idoso , Animais , Biomarcadores/metabolismo , Citocinas/administração & dosagem , Citocinas/metabolismo , Citocinas/farmacologia , Necrose Gordurosa/etiologia , Feminino , Humanos , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Lipólise , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Pâncreas/efeitos dos fármacos , Pseudocisto Pancreático/metabolismo , Pancreatite Necrosante Aguda/metabolismo , Ratos , Ratos Wistar , Índice de Gravidade de Doença
20.
Gastrointest Endosc ; 83(6): 1107-1117.e2, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26709110

RESUMO

BACKGROUND AND AIMS: The American Gastroenterological Association (AGA) recently reported evidence-based guidelines for the management of asymptomatic neoplastic pancreatic cysts. These guidelines advocate a higher threshold for surgical resection than prior guidelines and imaging surveillance for a considerable number of patients with pancreatic cysts. The aims of this study were to assess the accuracy of the AGA guidelines in detecting advanced neoplasia and present an alternative approach to pancreatic cysts. METHODS: The study population consisted of 225 patients who underwent EUS-guided FNA for pancreatic cysts between January 2014 and May 2015. For each patient, clinical findings, EUS features, cytopathology results, carcinoembryonic antigen analysis, and molecular testing of pancreatic cyst fluid were reviewed. Molecular testing included the assessment of hotspot mutations and deletions for KRAS, GNAS, VHL, TP53, PIK3CA, and PTEN. RESULTS: Diagnostic pathology results were available for 41 patients (18%), with 13 (6%) harboring advanced neoplasia. Among these cases, the AGA guidelines identified advanced neoplasia with 62% sensitivity, 79% specificity, 57% positive predictive value, and 82% negative predictive value. Moreover, the AGA guidelines missed 45% of intraductal papillary mucinous neoplasms with adenocarcinoma or high-grade dysplasia. For cases without confirmatory pathology, 27 of 184 patients (15%) with serous cystadenomas (SCAs) based on EUS findings and/or VHL alterations would continue magnetic resonance imaging (MRI) surveillance. In comparison, a novel algorithmic pathway using molecular testing of pancreatic cyst fluid detected advanced neoplasias with 100% sensitivity, 90% specificity, 79% positive predictive value, and 100% negative predictive value. CONCLUSIONS: The AGA guidelines were inaccurate in detecting pancreatic cysts with advanced neoplasia. Furthermore, because the AGA guidelines manage all neoplastic cysts similarly, patients with SCAs will continue to undergo unnecessary MRI surveillance. The results of an alternative approach with integrative molecular testing are encouraging but require further validation.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Císticas, Mucinosas e Serosas/diagnóstico , Cisto Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Guias de Prática Clínica como Assunto , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário/sangue , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Cromograninas/genética , Classe I de Fosfatidilinositol 3-Quinases , Líquido Cístico , Cistadenoma Seroso/sangue , Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/genética , Cistadenoma Seroso/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Endossonografia , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Neoplasias Císticas, Mucinosas e Serosas/sangue , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Císticas, Mucinosas e Serosas/patologia , PTEN Fosfo-Hidrolase/genética , Cisto Pancreático/sangue , Cisto Pancreático/genética , Cisto Pancreático/patologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Sensibilidade e Especificidade , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Adulto Jovem
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