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GOALS: To describe the long-term outcomes of patients after EUS-guided gallbladder drainage (EUS-GBD), including those who underwent standardized stent exchanges for permanent plastic stents. BACKGROUND: EUS-GBD has become one of the first-line alternatives for gallbladder decompression, with outcomes and safety profiles comparable to that of percutaneous gallbladder drainage. However, the long-term outcomes of EUS-GBD are not well-described. We report our single-center experience of a large cohort who underwent EUS-GBD. STUDY: Patients who underwent EUS-GBD from August 2014 to December 2022 were included in the study. Patient demographics, comorbidities, and procedure details were recorded. Patients were followed until complete stent removal, end of study period, or death. Short and long-term outcomes include technical and clinical success, stent patency, recurrent cholecystitis, cholecystectomy, and death. RESULTS: During the study period, 128 patients were included. One hundred and one patients had benign indications for EUS-GBD, including cholecystitis and choledocholithiasis. Of those with malignant indications, 23 of 27 had distal malignant biliary obstruction. Technical and clinical successes were 95.3% and 95.1%, respectively. Stents were exchanged for 2 permanent double pigtail plastic stents in 43.0%. The mean stent patency was 421 days (488 d among those still alive) without any recurrent cholecystitis. CONCLUSION: EUS-GBD demonstrates prolonged stent patency and minimal long-term adverse events, particularly among patients who underwent stent exchanges for permanent plastic stents. EUS-GBD is also promising for patients presenting with choledocholithiasis and biliary colic who are not surgical candidates.
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Drenaje , Endosonografía , Stents , Humanos , Drenaje/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Endosonografía/métodos , Resultado del Tratamiento , Estudios Retrospectivos , Vesícula Biliar/cirugía , Vesícula Biliar/diagnóstico por imagen , Adulto , Anciano de 80 o más Años , Ultrasonografía Intervencional/métodos , Colecistitis/cirugíaRESUMEN
Video 1A 51-year-old woman underwent orthotopic liver transplant with duct-to-duct anastomosis for primary biliary cholangitis 8 months prior to presentation. Two months postoperatively, she presented with clinical biliary pancreatitis. An MRCP performed on admission demonstrates dilated donor biliary tree and a severe stricture at the anastomosis. An index ERCP shows an indwelling surgical biliary "stent" exiting the duodenal papillae and anastomotic stricture. The surgical stent was removed, a sphincterotomy was performed, and there was an inability to traverse the anastomotic stricture. A representative cholangiogram shown here demonstrates the presence of a severe stricture completely obstructing the biliary tree. ERCP was done the next day, placing a 10-mm × 8-cm fully covered metal stent throughout the anastomosis. Three months later, the stent was removed because there was recurrent stricture at the site of anastomosis. Four months after stent removal, the patient again presented with clinical and laboratory obstructive biliary disease. A follow-up MRCP showed a severe anastomotic biliary stricture with an upstream stone. Several attempts were made to pass ERCP antegrade through the stenosis. However, they were unsuccessful. The rate-limiting step for successful recanalization was guidewire passage across the stricture. In this case, there was complete obliteration of the lumen by fibrosis. Efforts to pass 0.025-inch and 0.035-inch angled hydrophilic guidewires were unsuccessful. Recurrent stricturing was believed to be because of ischemia or inadequate recanalization. Our approach was to attempt antegrade recanalization and biliary decompression through an EUS-guided hepatogastrostomy. However, antegrade recanalization was unsuccessful and led to retrograde cholangioscopy using a single-use endoscope (SpyScope DS-2; Boston Scientific, Marlborough, Mass, USA) 4 weeks later. This video shows the cholangioscopic recanalization process. There was no passage of contrast antegrade or retrograde. During the cholangioscopy, there was no visible lumen. The area of suspected anastomosis based on the pearly white appearance of scar tissue was approached using mini-forceps (SpyBite; Boston Scientific) and a bite-on-bite approach to re-establish a lumen for stent placement. We used the pearly scar tissue as a guide to ensure the correct site for recanalization. We felt comfortable doing this because a hepatogastrostomy and sphincterotomy were thought to be protective against any bile leak if tunneling had dissected out of the duct. Moreover, contrast injection was used periodically to monitor progression into the duct. Eventually, the forceps were advanced into the proximal biliary tree under cholangioscopic direction, re-establishing a lumen. Bile is seen flowing through the identified lumen. While a rendezvous approach with antegrade transillumination and a percutaneous SpyScope DS-2 might be safer for recanalization of complete obstruction, the process would require multiple admissions and procedures for percutaneous access and fistula maturation. This might increase morbidity for this patient with no difference in outcome. We propose that cholangioscopic recanalization along with protection from bile leakage would be a reasonable approach in this case and similar cases with altered anatomy, hepatogastrostomy in place, or unavailability for follow-up or multiple procedures. This is an intraoperative radiographic representation. On the left, the cholangiogram is seen in place and the mini-forceps are passing through it into the proximal biliary tree. On the right, passage of the guidewire with balloon dilation of the stricture is shown. The stone previously seen on MRCP passed spontaneously. A follow-up cholangiogram showed luminal patency. A 10-mm × 10-cm fully covered metal stent (Viabil; W.L. Gore, Flagstaff, Ariz, USA) was placed across anastomosis.
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The management of walled-off necrosis has evolved substantially over the past 23 years since its first description. In this article, we review its history and the evidence supporting modern treatment, which is still subject to heterogeneity across centers and among endoscopists. This allows for creativity and customization of what can be an endoscopic marathon. Our typical practice is discussed with image and video guides aimed at improving procedure success.
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Endoscopía , Humanos , Necrosis/cirugíaRESUMEN
BACKGROUND: Following liver transplant (LT) with duct-to-duct anastomosis, biliary strictures and leaks are typically managed with endoscopic retrograde cholangiopancreatography (ERCP) and stenting. While multiple side-by-side plastic stents are typically used for management of anastomotic strictures, fully covered self-expandable metal stents (FCSEMS) can be used to decrease the number of ERCPs with longer periods of stent patency. The risk of migration can limit their use. FCSEMS with antimigration fins to manage benign biliary complications following LT may provide stricture resolution with limited adverse events (AEs). METHODS: Single center retrospective study of LT patients who required FCSEMS from 1/2014 to 4/2022. Primary outcomes included stricture resolution and recurrence. Secondary outcomes were stent migration, occlusion, removability, and number of ERCPs. RESULTS: Forty-three patients (mean age 55.5 years) with anastomotic strictures (N.=37), bile leaks (N.=4) or both (N.=2) were included. The median time from LT to FCSEMS placement was 125 days. Within one year of LT, 31 patients required intervention; early intervention at less than 30 and 90 days was needed in 7 and 19 patients, respectively. The median length of follow up was 816.5 days. Stricture resolution was seen in 35 patients (81%) after a median stent dwell time of 130.5 days; recurrence occurred in 8 patients. There were three instances of partial stent migration that did not require reintervention or interfere with removability. The mean number of ERCPs required was 2.5. CONCLUSIONS: The use of a FCSEMS with antimigration features yields effective stricture resolution with longer stent dwell times and fewer ERCPs.
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BACKGROUND AND AIMS: Palliation of malignant gastric outlet obstruction (mGOO) allows resumption of peroral intake. Although surgical gastrojejunostomy (SGJ) provides durable relief, it may be associated with a higher morbidity, interfere with chemotherapy, and require an optimum nutritional status. EUS-guided gastroenterostomy (EUS-GE) has emerged as a minimally invasive alternative. We aimed to conduct the largest comparative series to date between EUS-GE and SGJ for mGOO. METHODS: This multicenter retrospective study included consecutive patients undergoing SGJ or EUS-GE at 6 centers. Primary outcomes included time to resumption of oral intake, length of stay (LOS), and mortality. Secondary outcomes included technical and clinical success, reintervention rates, adverse events (AEs), and resumption of chemotherapy. RESULTS: A total of 310 patients were included (EUS-GE, n = 187; SGJ, n = 123). EUS-GE exhibited significantly lower time to resumption of oral intake (1.40 vs 4.06 days, P < .001), at lower albumin levels (2.95 vs 3.33 g/dL, P < .001), and a shorter LOS (5.31 vs 8.54 days, P < .001) compared with SGJ; there was no difference in mortality (48.1% vs 50.4%, P = .78). Technical (97.9% and 100%) and clinical (94.1% vs 94.3%) success was similar in the EUS-GE and SGJ groups, respectively. EUS-GE had lower rates of AEs (13.4% vs 33.3%, P < .001) but higher reintervention rates (15.5% vs 1.63%, P < .001). EUS-GE patients exhibited significantly lower interval time to resumption of chemotherapy (16.6 vs 37.8 days, P < .001). Outcomes between the EUS-GE and laparoscopic (n = 46) surgical approach showed that EUS-GE had shorter interval time to initiation/resumption of oral intake (3.49 vs 1.46 days, P < .001), decreased LOS (9 vs 5.31 days, P < .001), and a lower rate of AEs (11.9% vs 17.9%, P = .003). CONCLUSIONS: This is the largest study to date showing that EUS-GE can be performed among nutritionally deficient patients without affecting the technical and clinical success compared with SGJ. EUS-GE is associated with fewer AEs while allowing earlier resumption of diet and chemotherapy.
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Derivación Gástrica , Obstrucción de la Salida Gástrica , Humanos , Estudios Retrospectivos , Endosonografía , Stents , Gastroenterostomía , Obstrucción de la Salida Gástrica/etiología , Obstrucción de la Salida Gástrica/cirugíaRESUMEN
BACKGROUND AND AIMS: Interventions for malignant small-bowel obstruction (SBO) may be limited by extent of peritoneal disease, rendering surgical or traditional endoscopic methods (ie, luminal stenting or decompressive gastrostomy) unfeasible. We demonstrated the novel use of EUS-guided lumen-apposing metal stent placement for enterocolonic bypass in patients with malignant SBO who were deemed high risk for surgery. METHODS: Across 3 tertiary U.S. centers, a retrospective series of consecutive patients underwent attempted EUS-guided enterocolostomy (EUS-EC) for palliation of acute SBO because of malignant causes. Technique and devices used were described, and patient demographics and outcome data were collected. RESULTS: Ten patients were included, of whom 9 (90.0%) were men, with a mean age of 64.5 ± 14.0 years and who were 1.5 ± 2.1 years postdiagnosis. Technical success was achieved in 8 of 10 patients (80.0%) and clinical success in 7 of 10 (70.0%), with a single major adverse event (10.0%) of aspiration. Median time until resumption of oral intake was 1.0 day (range, 0-8) after the procedure, with an interval to discharge home of 6.5 days and survival of 57.0 days. CONCLUSIONS: EUS-EC is a new alternative for palliation of acute SBO because of advanced malignant disease when conservative measures fail and other surgical or endoscopic options are not possible. Additional larger studies with longer duration of follow-up are needed to further define efficacy and safety of this approach.
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Endosonografía , Neoplasias , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , Endosonografía/métodos , Estudios Retrospectivos , Stents/efectos adversos , Drenaje/métodos , Ultrasonografía Intervencional/métodosRESUMEN
Low socioeconomic status (SES) is associated with greater morbidity and increased healthcare resource utilization (HRU) in IBD. We examined whether a financial assistance program (FAP) to improve healthcare access affected outcomes and HRU in a cohort of indigent IBD patients requiring biologics. IBD patients (>18 years) receiving care at a 'safety-net' hospital who initiated biologics as outpatients between 1 January 2010 and 1 January 2019 were included. Patients were divided by FAP status. Patients without FAP had Medicare, Medicaid, or commercial insurance. Primary outcomes were steroid-free clinical remission at 6 and 12 months. Secondary outcomes were surgery, hospitalization, and ED utilization. Multivariate logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI). Decision tree analysis (DTA) was also performed. We included 204 patients with 258 new biologic prescriptions. FAP patients had less complex Crohn's disease (50.7% vs. 70%, p = 0.033) than non-FAP patients. FAP records indicated fewer prior surgeries (19.6% vs. 38.4% p = 0.003). There were no statistically significant differences in remission rates, disease duration, or days between prescription and receipt of biologics. In multivariable logistic regression, adjusting for baseline demographics and disease severity variables, FAP patients were less likely to undergo surgery (OR: 0.28, 95% CI [0.08−0.91], p = 0.034). DTA suggests that imaging utilization may shed light on surgical differences. We found FAP enrollment was associated with fewer surgeries in a cohort of indigent IBD patients requiring biologics. Further studies are needed to identify interventions to address healthcare disparities in IBD.
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PURPOSE: Postconsolidation immunotherapy including dinutuximab, granulocyte-macrophage colony-stimulating factor, and interleukin-2 improved outcomes for patients with high-risk neuroblastoma enrolled on the randomized portion of Children's Oncology Group study ANBL0032. After random assignment ended, all patients were assigned to immunotherapy. Survival and toxicities were assessed. PATIENTS AND METHODS: Patients with a pre-autologous stem cell transplant (ASCT) response (excluding bone marrow) of partial response or better were eligible. Demographics, stage, tumor biology, pre-ASCT response, and adverse events were summarized using descriptive statistics. Event-free survival (EFS) and overall survival (OS) from time of enrollment (up to day +200 from last ASCT) were evaluated. RESULTS: From 2009 to 2015, 1,183 patients were treated. Five-year EFS and OS for the entire cohort were 61.1 ± 1.9% and 71.9 ± 1.7%, respectively. For patients ≥ 18 months old at diagnosis with International Neuroblastoma Staging System stage 4 disease (n = 662) 5-year EFS and OS were 57.0 ± 2.4% and 70.9 ± 2.2%, respectively. EFS was superior for patients with complete response/very good partial response pre-ASCT compared with those with PR (5-year EFS: 64.2 ± 2.2% v 55.4 ± 3.2%, P = .0133); however, OS was not significantly different. Allergic reactions, capillary leak, fever, and hypotension were more frequent during interleukin-2-containing cycles than granulocyte-macrophage colony-stimulating factor-containing cycles (P < .0001). EFS was superior in patients with higher peak dinutuximab levels during cycle 1 (P = .034) and those with a high affinity FCGR3A genotype (P = .0418). Human antichimeric antibody status did not correlate with survival. CONCLUSION: Analysis of a cohort assigned to immunotherapy after cessation of random assignment on ANBL0032 confirmed previously described survival and toxicity outcomes. EFS was highest among patients with end-induction complete response/very good partial response. Among patients with available data, higher dinutuximab levels and FCGR3A genotype were associated with superior EFS. These may be predictive biomarkers for dinutuximab therapy.
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Factor Estimulante de Colonias de Granulocitos y Macrófagos , Interleucina-2 , Niño , Humanos , Lactante , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos adversos , Interleucina-2/efectos adversos , Proyectos de InvestigaciónAsunto(s)
Gastrostomía , Stents Metálicos Autoexpandibles , Humanos , Stents , Resultado del TratamientoRESUMEN
BACKGROUND: Data describing the effect of obesity on antitumor necrosis factor (anti-TNF) treatment response are inconsistent. Visceral adipose tissue (VAT) is a superior marker of adiposity to body mass index. However, its effect on treatment response is unclear. We aimed to evaluate the effect of VAT on anti-TNF treatment response. METHODS: Inflammatory bowel disease (IBD) patients starting anti-TNF agents between January 1, 2009, and July 31, 2019, were included. 3-dimensional measurements of VAT volume and visceral fat index (visceral:subcutaneous adipose tissue ratio; VFI) were obtained from computed tomography (CT) scans. Subjects were categorized by predefined volume cutoffs (<1500cm3, 1500-2999cm3, ≥3000cm3) and VFI (<0.33, 0.33-0.66, ≥0.67). Primary outcomes included a composite treatment response end point at 6 and 12 months. Secondary outcomes were surgery at 6 and 12 months. Multivariable logistic regression was used to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI). RESULTS: The final cohort included 176 patients. No significant differences in treatment response at 6 months was observed. At 12 months, compared with volume <1500cm3, patients with volume 1500-2999cm3 had higher odds of response (aOR, 3.52; 95% CI, 1.16-10.71; P = .023), whereas volume ≥3000cm3 did not. Compared with VFI<0.33, VFIâ ≥0.67 had higher odds of surgery at 6 (aOR, 48.22; 95% CI, 4.73-491.57; P = .023) and 12 months (aOR, 20.94; 95% CI, 3.14-139.67; P = .004). Post hoc analysis suggested VAT may affect drug pharmacokinetics. CONCLUSIONS: We found VAT volume is associated with anti-TNF treatment response in a nondose dependent manner, and VFI may inform risk of surgery after anti-TNF initiation. If confirmed by prospective studies, VAT volumetrics are potentially useful biomarkers to inform IBD treatment decisions.
Visceral adipose tissue volume is associated with anti-TNF treatment response in a nondose response manner. Additionally, high visceral fat index is associated with significantly increased risk of early surgery after anti-TNF initiation.
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Enfermedades Inflamatorias del Intestino , Grasa Intraabdominal , Índice de Masa Corporal , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/cirugía , Grasa Intraabdominal/diagnóstico por imagen , Necrosis , Estudios Prospectivos , Factores de Riesgo , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
Granulocyte colony-stimulating factor (G-CSF) used after hematopoietic stem cell transplantation (HSCT) can enhance neutrophil recovery in patients rendered neutropenic by the preparative regimen. G-CSF is contraindicated in patients with sickle cell disease (SCD), because life-threatening complications can ensue in the presence of sickle vasculopathy. The safety profile of G-CSF after HSCT for SCD has not been described, however. We report clinical outcomes in the first 100 days post-HSCT in 62 patients supported with G-CSF until neutrophil recovery on a clinical trial of reduced- intensity conditioning HSCT for SCD. The patients received G-CSF for a median of 9 days (range, 5 to 33 days) post-transplantation from the best available stem cell source. Preparation for transplantation included a target hemoglobin S level of ≤45%. Neutrophil engraftment (absolute neutrophil count >0.5 × 103/mL) was achieved at a median of 13 days (range, 10 to 34 days), and platelet engraftment (>50 × 103/mL) was achieved at a median of 19 days (range, 12 to 71 days). The median duration of inpatient hospitalization following stem cell infusion (day 0) was 21.5 days (range, 11 to 33 days). No patient developed SCD-related complications following G-CSF use. The most common organ toxicities encountered between G-CSF initiation (on day +7) and day +100 were anorexia (n = 14), hypertension (n = 11), and electrolyte imbalance requiring correction (n = 9). Central nervous system-related events were noted in 5 patients, all of whom had preexisting cerebral vasculopathy/moyamoya disease, attributed to reversible posterior leukoencephalopathy syndrome in the presence of calcineurin inhibitor therapy and hypertension. We conclude that G-CSF does not adversely impact SCD HSCT recipients and can be safely used post-transplantation to enhance neutrophil recovery.
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Anemia de Células Falciformes , Factor Estimulante de Colonias de Granulocitos , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Trasplante de Células Madre Hematopoyéticas , Humanos , Hipertensión/epidemiología , Trasplante HomólogoRESUMEN
PURPOSE: Previously our randomized phase III trial demonstrated that immunotherapy including dinutuximab, a chimeric anti-GD2 mAb, GM-CSF, and IL2 improved survival for children with high-risk neuroblastoma that had responded to induction and consolidation therapy. These results served as the basis for FDA approval of dinutuximab. We now present long-term follow-up results and evaluation of predictive biomarkers. PATIENTS AND METHODS: Patients recieved six cycles of isotretinoin with or without five cycles of immunotherapy which consists of dinutuximab with GM-CSF alternating with IL2. Accrual was discontinued early due to meeting the protocol-defined stopping rule for efficacy, as assessed by 2-year event-free survival (EFS). Plasma levels of dinutuximab, soluble IL2 receptor (sIL2R), and human anti-chimeric antibody (HACA) were assessed by ELISA. Fcγ receptor 2A and 3A genotypes were determined by PCR and direct sequencing. RESULTS: For 226 eligible randomized patients, 5-year EFS was 56.6 ± 4.7% for patients randomized to immunotherapy (n = 114) versus 46.1 ± 5.1% for those randomized to isotretinoin only (n = 112; P = 0.042). Five-year overall survival (OS) was 73.2 ± 4.2% versus 56.6 ± 5.1% for immunotherapy and isotretinoin only patients, respectively (P = 0.045). Thirteen of 122 patients receiving dinutuximab developed HACA. Plasma levels of dinutuximab, HACA, and sIL2R did not correlate with EFS/OS, or clinically significant toxicity. Fcγ receptor 2A and 3A genotypes did not correlate with EFS/OS. CONCLUSIONS: Immunotherapy with dinutuximab improved outcome for patients with high-risk neuroblastoma. Early stoppage for efficacy resulted in a smaller sample size than originally planned, yet clinically significant long-term differences in survival were observed.
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Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Interleucina-2/administración & dosificación , Neuroblastoma/tratamiento farmacológico , Adolescente , Anticuerpos Monoclonales/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Preescolar , Estudios de Seguimiento , Humanos , Lactante , Interleucina-2/efectos adversos , Isotretinoína/administración & dosificación , Isotretinoína/efectos adversos , Masculino , Neuroblastoma/mortalidad , Supervivencia sin Progresión , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversosRESUMEN
Purpose: A phase 3 randomized study (COG ANBL0032) demonstrated significantly improved outcome by adding immunotherapy with ch14.18 antibody to isotretinoin as post-consolidation therapy for high-risk neuroblastoma (NB). This study, ANBL0931, was designed to collect FDA-required safety/toxicity data to support FDA registration of ch14.18. Experimental design: Newly diagnosed high-risk NB patients who achieved at least a partial response to induction therapy and received myeloablative consolidation with stem cell rescue were enrolled to receive six courses of isotretinoin with five concomitant cycles of ch14.18 combined with GM-CSF or IL2. Ch14.18 infusion time was 10-20 h per dose. Blood was collected for cytokine analysis and its association with toxicities and outcome. Results: Of 105 patients enrolled, five patients developed protocol-defined unacceptable toxicities. The most common grade ≥ 3 non-hematologic toxicities of immunotherapy for cycles 1-5, respectively, were neuropathic pain (41, 28, 22, 31, 24%), hypotension (10, 17, 4, 14, 8%), allergic reactions (ARs) (3, 10, 5, 7, 2%), capillary leak syndrome (1, 4, 0, 2, 0%), and fever (21, 59, 6, 32, 5%). The 3-year event-free survival and overall survival were 67.6 ± 4.8% and 79.1 ± 4.2%, respectively. AR during course 1 was associated with elevated serum levels of IL-1Ra and IFNγ, while severe hypotension during this course was associated with low IL5 and nitrate. Higher pretreatment CXCL9 level was associated with poorer event-free survival (EFS). Conclusion: This study has confirmed the significant, but manageable treatment-related toxicities of this immunotherapy and identified possible cytokine biomarkers associated with select toxicities and outcome. EFS and OS appear similar to that previously reported on ANBL0032.
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[This corrects the article DOI: 10.3389/fimmu.2018.01355.].
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GOALS: To examine the role that autoantibodies (auto-abs) play in chronic hepatitis C virus (HCV) regarding demographics, presence of extrahepatic manifestations and long-term outcomes in a large US cohort. BACKGROUND: Auto-abs have been reported to be prevalent in patients with chronic HCV infection, but data on the natural history of these patients are limited. STUDY: The study included 1556 consecutive patients with HCV without concurrent HIV and/or HBV who had testing for antinuclear antibody (ANA), antimitochondrial antibody (AMA), antismooth muscle antibody (ASMA) and/or antiliver kidney microsomal antibody (LKM). Primary outcomes included development of cirrhosis, hepatic decompensations, hepatocellular carcinoma (HCC), mortality and/or sustained virological response (SVR) to antiviral therapy. RESULTS: A total of 388 patients tested positive for any auto-ab (ANA 21.8%, ASMA 13.3%, AMA 2.2% and LKM 1.2%). Patients who tested positive versus negative were more likely to be women (29.3% vs 20.9%, p<0.001) and less likely to achieve SVR with most treated patients receiving interferon-based therapies (37.2% vs 47.1%, p=0.031). There was no difference between groups for baseline laboratory data, disease state or rate of extrahepatic manifestations (42.8% vs 45.0%, p=0.44). Kaplan-Meier analysis revealed no statistically significant difference between groups for the 10-year development of cirrhosis, hepatic decompensations, HCC nor survival. Furthermore, auto-ab positivity was only found to be a predictor for a lower rate of SVR on multivariate analysis (adjusted OR=1.61, 95 % CI 1.00 to 2.58, p=0.048). CONCLUSIONS: In our cohort, auto-ab positivity was common, especially in women, and predicted a lower rate of SVR but otherwise had no impact on the natural history of chronic HCV or presence of extrahepatic manifestations.
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Purpose: In 2010, a Children's Oncology Group (COG) phase III randomized trial for patients with high-risk neuroblastoma (ANBL0032) demonstrated improved event-free survival (EFS) and overall survival (OS) following treatment with an immunotherapy regimen of dinutuximab, GM-CSF, IL2, and isotretinoin compared with treatment with isotretinoin alone. Dinutuximab, a chimeric anti-GD2 monoclonal antibody, acts in part via natural killer (NK) cells. Killer immunoglobulin-like receptors (KIR) on NK cells and their interactions with KIR-ligands can influence NK cell function. We investigated whether KIR/KIR-ligand genotypes were associated with EFS or OS in this trial.Experimental Design: We genotyped patients from COG study ANBL0032 and evaluated the effect of KIR/KIR-ligand genotypes on clinical outcomes. Cox regression models and log-rank tests were used to evaluate associations of EFS and OS with KIR/KIR-ligand genotypes.Results: In this trial, patients with the "all KIR-ligands present" genotype as well as patients with inhibitory KIR2DL2 with its ligand (HLA-C1) together with inhibitory KIR3DL1 with its ligand (HLA-Bw4) were associated with improved outcome if they received immunotherapy. In contrast, for patients with the complementary KIR/KIR-ligand genotypes, clinical outcome was not significantly different for patients who received immunotherapy versus those receiving isotretinoin alone.Conclusions: These data show that administration of immunotherapy is associated with improved outcome for neuroblastoma patients with certain KIR/KIR-ligand genotypes, although this was not seen for patients with other KIR/KIR-ligand genotypes. Further investigation of KIR/KIR-ligand genotypes may clarify their role in cancer immunotherapy and may enable KIR/KIR-ligand genotyping to be used prospectively for identifying patients likely to benefit from certain cancer immunotherapy regimens. Clin Cancer Res; 24(1); 189-96. ©2017 AACRSee related commentary by Cheung and Hsu, p. 3.