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1.
Am J Hosp Palliat Care ; : 10499091231218257, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37991926

RESUMEN

INTRODUCTION: Symptom burden management is a major goal of pancreatic cancer care given that most patients are diagnosed late. Early palliative care is recommended in addition to concurrent active treatment; however, disparities exist. We sought to determine the factors associated with inpatient palliative treatment among pancreatic cancer patients and compare treatment outcomes in terms of mortality, discharge disposition and resource utilization. METHODS: We conducted a retrospective study of 22,053 pancreatic cancers using the National Inpatient Sample (NIS) database (January - December 2020). Patient and hospital characteristics, mortality, discharge disposition, length of stay (LOS), hospital costs and charges were compared between pancreatic cancer patients based on palliative treatment. Multivariate regression was used to evaluate patient and hospital characteristics and outcomes associated with palliative treatment. RESULTS: A total number of 3839 (17.4%) patients received palliative care. Patients who received palliative care were more likely to be older, Medicaid insured, and nonobese. Patients were less likely to receive palliative care if they are males, Medicare insured, had a lower Charlson comorbidity score, or treated in Urban nonteaching hospitals. Patients who received palliative care displayed higher odds of in-hospital mortality and prolonged LOS. The adjusted additional mean hospital cost and charges in patients who received palliative care were lower by $1459, and $4222 respectively. CONCLUSIONS: Inpatient palliative treatment in pancreatic cancer patients is associated with an older age, a higher comorbidity burden, non-obesity, insurance status and urban teaching hospitals. Our study suggests that inpatient palliative treatment decreased hospital resource utilization without prolonging survival.

2.
Endosc Int Open ; 10(10): E1399-E1405, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36262518

RESUMEN

Background and study aims Adenoma recurrence is one of the key limitations of endoscopic mucosal resection (EMR), which occurs in 15 % to 30 % of cases during first surveillance colonoscopy. The main hypothesis behind adenoma recurrence is leftover micro-adenomas at the margins of post-EMR defects. In this systematic review and meta-analysis, we evaluated the efficacy of snare tip soft coagulation (STSC) at the margins of mucosal defects to reduce adenoma recurrence and bleeding complications. Methods Electronic databases such as PubMed and the Cochrane library were used for systematic literature search. Studies with polyps only resected by piecemeal EMR and active treatment: with STSC, comparator: non-STSC were included. A random effects model was used to calculate the summary of risk ratio and 95 % confidence intervals. The main outcome of the study was to compare the effect of STSC versus non-STSC with respect to adenoma recurrence at first surveillance colonoscopy after thermal ablation of post-EMR defects. Results Five studies were included in the systematic review and meta-analysis. The total number patients who completed first surveillance colonoscopy (SC1) in the STSC group was 534 and in the non-STSC group was 514. The pooled adenoma recurrence rate was 6 % (37 of 534 cases) in the STSC arm and 22 % (115 of 514 cases) in the non-STSC arm, (odds ratio [OR] 0.26, 95 % confidence interval [CI], 0.16-0.41, P  = 0.001). The pooled delayed post-EMR bleeding rate 19 % (67 of 343) in the STSC arm and 22 % (78 of 341) in the non-STSC arm (OR 0.82, 95 %CI, 0.57-1.18). Conclusions Thermal ablation of post-EMR defects significantly reduces adenoma recurrence at first surveillance colonoscopy.

5.
Pancreas ; 50(7): 1007-1013, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-34629449

RESUMEN

OBJECTIVES: Pancreatic acinar cell carcinoma (ACC) is a rare pancreatic cancer. The advancement of treatment is hampered because of the limited knowledge of its molecular mechanism. METHODS: Whole-exome sequencing was performed on DNA extracted from 11 pure ACC surgical samples. Potential germline variants were removed on the basis of polymorphic databases, alternative allele frequency, coverage depth, and Catalogue of Somatic Mutations in Cancer (COSMIC) annotations after variant calling procedure. Mutation profiles and signatures were assessed through the Mutational Patterns package. RESULTS: A median of 34 somatic mutations were detected (range, 19-60). Three novel recurrent small deletions were identified. Common pancreatic ductal adenocarcinoma mutations or neuroendocrine tumor mutants were not found. FAT atypical cadherin 4, mucin 5B, titin, and zinc finger homeobox 3 were consistently mutated across 4 independent ACC studies. A high contribution of COSMIC mutational signature 1 was seen in ACC, indicating deamination of 5-methylcytosine. The majority of the patients had COSMIC signatures 6, 15, or 20, relating to defective DNA mismatch repair. Six patients showed COSMIC mutational signature 10 because of the altered activity of DNA polymerase epsilon. CONCLUSIONS: Distinct mutational signatures pathways were found in ACC and targeting them may improve clinical outcome.


Asunto(s)
Carcinoma de Células Acinares/genética , Secuenciación del Exoma/métodos , Mutación , Neoplasias Pancreáticas/genética , Anciano , Carcinoma de Células Acinares/patología , Reparación de la Incompatibilidad de ADN/genética , Replicación del ADN/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Transducción de Señal/genética
6.
Pancreatology ; 21(8): 1428-1433, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34518096

RESUMEN

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is a procoagulant state, and markers of coagulopathy are associated with AP severity. We aimed to explore the association of systemic anticoagulation therapy before AP onset with the inpatient outcomes of patients with acute pancreatitis. METHODS: This case-control, retrospective study used data from the Nationwide Inpatient Sample (Jan 2014-Dec 2016). We used medical coding data to identify patients with a principal diagnosis of AP who were receiving systemic anticoagulation therapy. Patients with anticoagulation were matched to those without it on the propensity for having anticoagulation. The propensity for having anticoagulation was estimated using a logistic regression model, matching for age, gender, race, median household income for patients' zip code, Charlson comorbidity score, region of hospital, location of hospital (urban/rural), teaching status of hospital, if admission day was on a weekend, pancreatic cancer class, obesity, tobacco usage. Secondary outcomes were inpatient outcomes and hospital expenditures. RESULTS: A total of 190,474 patients admitted for acute pancreatitis were identified, out of which 7827 patients were on anticoagulation. After propensity matching, 5776 matched pairs were successfully identified. Patients with AP on anticoagulation tended to have lower risk for ICU admission, acute kidney injury, organ failure or inpatient mortality. However, the group with anticoagulation had longer hospital length of stay and higher hospital costs. CONCLUSIONS: Anticoagulation therapy may have a pivotal role in the pathogenesis and progression of AP. These data suggest a potential therapeutic role for anticoagulants in AP. Further studies are needed to better understand these observations.


Asunto(s)
Pancreatitis , Enfermedad Aguda , Anticoagulantes/uso terapéutico , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Morbilidad , Pancreatitis/tratamiento farmacológico , Pancreatitis/epidemiología , Estudios Retrospectivos
7.
Dig Liver Dis ; 53(10): 1294-1300, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33972190

RESUMEN

BACKGROUND: Idiopathic recurrent acute pancreatitis (IRAP) describes frequent episodes of pancreatitis without an etiology found using current testing. We compared the natural history of IRAP with recurrent acute pancreatitis with genetic mutations. METHODS: Retrospective cohort of patients with recurrent acute pancreatitis (≥2 episodes) and negative conventional testing. All patients had ≥1 episode after cholecystectomy and completed genetic testing. Primary outcomes were chronic pancreatitis incidence, pancreatic cancer, and mortality. Secondary outcomes included opioid and ERCP utilization. RESULTS: 128 patients met criteria for presumed IRAP. 35 patients met criteria for true IRAP. 12 patients had recurrent acute pancreatitis with gene mutations. Chronic pancreatitis developed in 27 (77.1%) IRAP patients over a median of 6 years. Chronic pancreatitis incidence was similar in IRAP and CFTR mutation carriers; but developed later in SPINK1 carriers. No patients developed pancreatic cancer or died from pancreatic-related causes. Patients were frequently treated with oral opioids and ERCP, without significant differences within or between groups. CONCLUSION: IRAP and pancreatitis in mutation carriers is associated with chronic pancreatitis. Important differences in natural history were observed, but no association was found with cancer or pancreas-related mortality. Efforts to understand the genetic contributions to IRAP, minimize opioids and unnecessary ERCPs are encouraged.


Asunto(s)
Progresión de la Enfermedad , Pancreatitis Crónica/genética , Adulto , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Femenino , Humanos , Masculino , Mutación , Pancreatitis Crónica/diagnóstico , Recurrencia , Estudios Retrospectivos , Tripsina/genética , Inhibidor de Tripsina Pancreática de Kazal/genética
8.
ACG Case Rep J ; 8(2): e00539, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33654702

RESUMEN

Insulinomas are rare, with an annual incidence of 1-4 people per mission. Insulinomas are the most common functioning endocrine neoplams of the pancreas. Endoscopic ultrasound has both diagnostic and therapeutic yield in undifferentiated pancreatic tumors. We present a case of a recurrent insulinoma, refractory to surgical and medical management diagnosed with endoscopic ultrasound. Our case uniquely conveys a successful, alternative approach to addressing symptomatic insulinomas refractory to surgical or medical management through computed tomography-guided percutaneous ethanol-lipiodol injection.

9.
Cancer Invest ; 39(3): 229-234, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33571039

RESUMEN

Pancreatic cancer will become the second leading cause of cancer-related death in the United States by 2030. Survival improves when it is identified at an early-stage and resected. Increasing public attention and cross-section imaging may shift detection to earlier stages. We found a small total increase in the proportion of stage-I cancer relative to all stages and a significant increase compared to distant disease in the Surveillance, Epidemiology, and End Results (SEER) database. Despite this, our ability to screen and identify early-stage disease is still lacking. Additional research and population-based interventions are necessary to improve early detection.


Asunto(s)
Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Programa de VERF , Estados Unidos/epidemiología
10.
Pancreatology ; 21(2): 428-433, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33485792

RESUMEN

BACKGROUND: The prevalence of pancreatic ductal adenocarcinoma (PDAC) is on the rise, driven by factors such as aging and an increasing prevalence of obesity and diabetes mellitus. To improve the poor survival rate of PDAC, early detection is vital. Recently, pancreatic steatosis has gained novel interest as a risk factor for PDAC. This study aimed to investigate if pancreatic steatosis on computed tomography (CT) is an early imaging feature in patients with pre-diagnostic PDAC. METHODS: A retrospective case-control study was performed. Patients diagnosed with PDAC (2010-2016) were reviewed for abdominal non-contrast CT-imaging 1 month-3 years prior to their diagnosis. Cases were matched 1:4 with controls based on age, gender and imaging date. Unenhanced CT-images were evaluated for pancreatic steatosis (pancreas-to-spleen ratio in Hounsfield Units <0.70) by a blinded radiologist and results were compared between cases and controls. RESULTS: In total, 32 cases and 117 controls were included in the study with a comparable BMI (29.6 and 29.2 respectively, p = 0.723). Pancreatic steatosis was present in 71.9% of cases compared to 45.3% of controls (Odds ratio (OR) 3.09(1.32-7.24), p = 0.009). Adjusted for BMI and diabetes mellitus, pancreatic steatosis on CT remained a significant independent risk factor for PDAC (Adjusted OR 2.70(1.14-6.58), p = 0.037). CONCLUSION: Pancreatic steatosis measured on CT is independently associated with PDAC up to three years before the clinical diagnosis in overweight patients. If these data are confirmed, this novel imaging feature may be used to identify high-risk individuals and to stratify the risk of PDAC in individuals that already undergo PDAC screening.


Asunto(s)
Carcinoma Ductal Pancreático/diagnóstico , Sobrepeso , Enfermedades Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Carcinoma Ductal Pancreático/patología , Estudios de Casos y Controles , Femenino , Humanos , Metabolismo de los Lípidos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
11.
Pancreas ; 50(1): 54-63, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33370023

RESUMEN

OBJECTIVE: Solid organ transplant (SOT) recipients have moderately increased risk of pancreatic adenocarcinoma (PAC). We evaluated the incidence and survival of PAC in 2 cohorts and aimed to identify potential risk factors. METHODS: This study performed a retrospective cohort analysis. Cohort A was extracted from the United Network of Organ Sharing data set and cohort B from SOT recipients evaluated at 3 Mayo Clinic transplant centers. The primary outcome was age-adjusted annual incidence of PAC. Descriptive statistics, hazard ratios, and survival rates were compared. RESULTS: Cohort A and cohort B included 617,042 and 29,472 SOT recipients, respectively. In cohort A, the annual incidence rate was 12.78 per 100,000 in kidney-pancreas, 13.34 in liver, and 21.87 in heart-lung transplant recipients. Receiving heart-lung transplant, 50 years or older, and history of cancer (in either recipient or donor) were independent factors associated with PAC. Fifty-two patients developed PAC in cohort B. Despite earlier diagnosis (21.15% with stage I-II), survival rates were similar to those reported for sporadic (non-SOT) patients. CONCLUSIONS: We report demographic and clinical risk factors for PAC after SOT, many of which were present before transplant and are common to sporadic pancreatic cancer. Despite the diagnosis at earlier stages, PAC in SOT portends a very poor survival.


Asunto(s)
Adenocarcinoma/epidemiología , Trasplante de Órganos/efectos adversos , Neoplasias Pancreáticas/epidemiología , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Adulto , Anciano , Supervivientes de Cáncer , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Obtención de Tejidos y Órganos , Resultado del Tratamiento , Estados Unidos/epidemiología
12.
Endoscopy ; 53(4): 376-382, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32767288

RESUMEN

BACKGROUND: National guidelines recommend genomic profiling of tumor tissue to guide precision therapy. We compared the specimen adequacy for genomic profiling and yield of DNA between endoscopic ultrasound (EUS)-guided fine-needle biopsy (FNB) and EUS-guided fine-needle aspiration (FNA). METHODS: In our tandem, randomized controlled trial, consecutive patients undergoing EUS for evaluation of pancreatic masses underwent both conventional EUS-FNA with a 25-gauge needle and paired EUS-FNB (19 or 22-gauge needle), with the order randomized (EUS-FNA first followed by EUS-FNB, or vice versa). A minimum of one pass with each needle was obtained for histology. Second and third passes were performed to collect DNA. Specimens were evaluated by a cytopathologist blinded to the needle type. Specimen adequacy for genomic profiling was calculated based on FoundationOne clinical diagnostic (CDx) adequacy requirements. We compared the adequacy for genomic profiling DNA (quantity) and histology yields with both needles. RESULTS: Analysis included 50 patients (25 men; mean age 68 [standard deviation (SD) 13] years), with a mean lesion size of 38 (SD 17) mm; 37 lesions (74 %) were pancreatic ductal adenocarcinoma (PDAC). The mean DNA concentrations in PDAC by FNB and FNA needles were 5.930 (SD 0.881) µg/mL vs. 3.365 (SD 0.788) µg/mL, respectively (P = 0.01). The median standardized histology score per pass with EUS-FNB was 5 (sufficient for histology) and for EUS-FNA was 2 (enough for cytology). Specimen adequacy for genomic profiling and yield of DNA was significantly higher with FNB than with FNA needles. CONCLUSIONS: In this study, adequacy for genomic profiling, DNA, and histology yield were considerably superior using an EUS-FNB needle compared with an EUS-FNA needle.


Asunto(s)
Agujas , Neoplasias Pancreáticas , Anciano , Estudios Cruzados , ADN , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Genómica , Humanos , Masculino , Neoplasias Pancreáticas/genética
13.
Endoscopy ; 53(11): 1132-1140, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33197941

RESUMEN

BACKGROUND: Pancreatic cystic lesions (PCLs) are increasingly found on cross-sectional imaging, with the majority having a low risk for malignancy. The added value of fine-needle aspiration (FNA) in risk stratification remains unclear. We evaluated the impact of three FNA needles on diagnostic accuracy, clinical management, and the ability to accrue fluid for tumor markers. METHODS: A multicenter prospective trial randomized 250 patients with PCLs ≥ 13 mm 2:1:1 to 19G Flex, 19G, and 22G needles with crossover for repeated FNA procedures. Diagnostic accuracy was established at 2-year follow-up, with the final diagnosis from surgical histopathology or consensus diagnosis by experts based sequentially on clinical presentation, imaging, and aspirate analysis in blinded review. RESULTS: Enrolled patients (36 % symptomatic) had PCLs in the head (44 %), body (28 %), and tail (26 %). Percentage of cyst volume aspirated was 78 % (72 % - 84 %) for 19G Flex, 74 % (64 % - 84 %) for 22G, and 73 % (63 % - 83 %) for 19G (P = 0.84). Successful FNA was significantly higher for 19G Flex (89 % [82 % - 94 %]) and 22G (82 % [70 % - 90 %]) compared with 19G (75 % [63 % - 85 %]) (P = 0.02). Repeated FNA was required more frequently in head/uncinate lesions than in body and tail (P < 0.01). Diagnostic accuracy of the cyst aspirate was 84 % (73 % - 91 %) against histopathology at 2-year follow-up (n = 79), and 77 % (70 % - 83 %) against consensus diagnosis among nonsurgical cases (n = 171). Related serious adverse events occurred in 1.2 % (0.2 % - 3.5 %) of patients. CONCLUSIONS: Our study results demonstrate a statistically significant difference among the three needles in the overall success rate for aspiration, but not in the percentage of cyst volume aspirated. Flexible needles may be particularly valuable in sampling cystic PCLs in the pancreatic head/uncinate process.


Asunto(s)
Quiste Pancreático , Neoplasias Pancreáticas , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Estudios de Seguimiento , Humanos , Agujas , Quiste Pancreático/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Estudios Prospectivos
14.
Obes Surg ; 30(6): 2325-2330, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32056075

RESUMEN

INTRODUCTION: Bariatric surgery (BSx) leads to weight loss and causes alterations in gastrointestinal and pancreatic peptides. This raises questions on acute pancreatitis (AP) occurrence and outcomes in this cohort of patients. We aim to assess mortality, morbidity, and resource utilization of AP in patients with BSx. METHODS: Observational retrospective cohort study (2012-2016) with propensity score match. Patients with a principal diagnostic ICD9-10CM code for AP were included. Stratification for the coexistence of history of BSx was performed. The primary outcome was mortality. Secondary outcomes were morbidity, resource utilization, length of hospital stay (LOS), total hospital charges, and costs. RESULTS: Out of 920,615 AP patients, 15,345 had undergone BSx. After propensity matching, 8220 patients with BSx had AP. The mortality for AP was 0.42 (p < 0.01) and for biliary AP 0.29 (< 0.04) in the history of BSx group compared to patients without BSx history. Acute kidney insufficiency (AKI), shock, ICU, multiorgan failure, ERCP, costs, charges, and LOS were all lower for patients with AP who had history of BSx. Patients with biliary AP showed even lower odds of AKI, ICU, multiorgan failure, costs, charges, and LOS, but higher odds of cholecystectomy. CONCLUSION: Patients with AP with history of BSx have lower mortality, morbidity, and resource utilization. This may be due to post-surgical alterations in pancreatic and gastrointestinal functions including hormonal and anatomical changes. Interestingly, patients with biliary AP and BSx had even lower odds of mortality and morbidity than patients with non-biliary AP, suggesting an added benefit with milder disease course.


Asunto(s)
Cirugía Bariátrica , Obesidad Mórbida , Pancreatitis , Enfermedad Aguda , Humanos , Obesidad Mórbida/cirugía , Pancreatitis/etiología , Estudios Retrospectivos
15.
Clin Gastroenterol Hepatol ; 18(3): 676-683.e3, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31323382

RESUMEN

BACKGROUND & AIMS: Precursors of pancreatic cancer arise in the ductal epithelium; markers exfoliated into pancreatic juice might be used to detect high-grade dysplasia (HGD) and cancer. Specific methylated DNA sequences in pancreatic tissue have been associated with adenocarcinoma. We analyzed these methylated DNA markers (MDMs) in pancreatic juice samples from patients with pancreatic ductal adenocarcinomas (PDACs) or intraductal papillary mucinous neoplasms (IPMNs) with HGD (cases), and assessed their ability to discriminate these patients from individuals without dysplasia or with IPMNs with low-grade dysplasia (controls). METHODS: We obtained pancreatic juice samples from 38 patients (35 with biopsy-proven PDAC or pancreatic cystic lesions with invasive cancer and 3 with HGD) and 73 controls (32 with normal pancreas and 41 with benign disease), collected endoscopically from the duodenum after secretin administration from February 2015 through November 2016 at 3 medical centers. Samples were analyzed for the presence of 14 MDMs (in the genes NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4), by quantitative allele-specific real-time target and signal amplification. We performed area under the receiver operating characteristic curve analyses to determine the ability of each marker, and panels of markers, to distinguish patients with HGD and cancer from controls. MDMs were combined to form a panel for detection using recursive partition trees. RESULTS: We identified a group of 3 MDMs (at C13orf18, FER1L4, and BMP3) in pancreatic juice that distinguished cases from controls with an area under the receiver operating characteristic value of 0.90 (95% CI, 0.83-0.97). Using a specificity cut-off value of 86%, this group of MDMs distinguished patients with any stage of pancreatic cancer from controls with 83% sensitivity (95% CI, 66%-93%) and identified patients with stage I or II PDAC or IPMN with HGD with 80% sensitivity (95% CI, 56%-95%). CONCLUSIONS: We identified a group of 3 MDMs in pancreatic juice that identify patients with pancreatic cancer with an area under the receiver operating characteristic value of 0.90, including patients with early stage disease or advanced precancer. These DNA methylation patterns might be included in algorithms for early detection of pancreatic cancer, especially in high-risk cohorts. Further optimization and clinical studies are needed.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/diagnóstico , ADN , Detección Precoz del Cáncer , Humanos , Jugo Pancreático , Neoplasias Pancreáticas/diagnóstico
16.
Am J Gastroenterol ; 114(9): 1539-1549, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31306149

RESUMEN

OBJECTIVES: Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cyst fluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND). METHODS: From an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs. RESULTS: Of 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs (TBX15, BMP3) achieved sensitivity and specificity above 90%. Discrimination was significantly better by this CF-MDM panel than by mutant KRAS or carcinoembryonic antigen, with areas under the receiver operating characteristic curve of 0.93 (95% confidence interval: 0.86-0.99), 0.71 (0.57-0.85), and 0.72 (0.60-0.84), respectively. Cutoffs for the MDM panel applied to an independent CF validation set (31 cases, 56 controls) yielded similarly high discrimination, areas under the receiver operating characteristic curve = 0.86 (95% confidence interval: 0.77-0.94, P = 0.2). DISCUSSION: Novel MDMs discovered and validated in tissue accurately identify PCLs harboring HGD/PC. A panel of 2 MDMs assayed in CF yielded results with potential to enhance current risk prediction algorithms. Prospective studies are indicated to optimize and further evaluate CF-MDMs for clinical use.


Asunto(s)
Carcinoma Ductal Pancreático/genética , Cistadenoma Seroso/genética , Metilación de ADN/genética , Quiste Pancreático/genética , Neoplasias Intraductales Pancreáticas/genética , Neoplasias Pancreáticas/genética , Lesiones Precancerosas/genética , Anciano , Proteína Morfogenética Ósea 3/genética , Antígeno Carcinoembrionario/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patología , Líquido Quístico/metabolismo , Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Quiste Pancreático/diagnóstico , Quiste Pancreático/patología , Neoplasias Intraductales Pancreáticas/diagnóstico , Neoplasias Intraductales Pancreáticas/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Reacción en Cadena de la Polimerasa , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Proteínas de Dominio T Box/genética
17.
Dig Dis Sci ; 64(11): 3300-3306, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31098871

RESUMEN

BACKGROUND: Up to 20% of patients can have recurrence of adenomatous tissue at first surveillance study after colon endoscopic mucosal resection of large polyps. AIMS: To determine whether an educational intervention discussing thermal ablation of lateral margins of the mucosectomy site of post-endoscopic mucosal resection defect with snare tip soft coagulation (STSC) would decrease adenoma recurrence. METHODS: We performed a single-center quality improvement project from November 1, 2016, to November 30, 2017. Gastroenterologists underwent an educational intervention demonstrating the treatment of peripheral margins of mucosectomy site with STSC after standard mucosectomy technique. These cases (intervention group) were compared with consecutive procedures performed prior to commencement of the quality improvement study (pre-intervention group). Patients with large colorectal lesions (≥ 20 mm) were included. RESULTS: Of the 120 patients here included, overall demographics of the groups were similar and the most common histology was sessile serrated adenoma (study group 45% vs 32% control group). Adenoma recurrence on intervention group and pre-intervention group was 12% versus 30%; p = 0.01. On univariate analysis, biopsy prior to mucosectomy, intraprocedural bleeding, and application of STSC on mucosectomy defect were the strongest predictors of adenoma recurrence. Adenoma recurrence in the intervention group was significantly lower than in the pre-intervention group in both univariate (odds ratio, 0.3 [95% CI, 0.11-0.80]) and multivariate analyses (odds ratio, 0.2 [95% CI, 0.12-0.92]). CONCLUSIONS: The implementation of STSC of post-endoscopic mucosal resection peripheral defects is clinically feasible and significantly decreased adenoma recurrence.


Asunto(s)
Pólipos del Colon/diagnóstico , Pólipos del Colon/cirugía , Colonoscopía/métodos , Resección Endoscópica de la Mucosa/métodos , Profilaxis Posexposición/métodos , Adenoma/diagnóstico , Adenoma/cirugía , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Colon/patología , Colon/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/cirugía , Estudios Prospectivos
18.
Gut ; 68(9): 1633-1641, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30635409

RESUMEN

OBJECTIVE: It is unclear whether endoscopic assessment of scars after colorectal endoscopic mucosal resection (EMR) has to include biopsies, even if endoscopy is negative. Vice versa, endoscopic diagnosis of recurrent adenoma may not require biopsy before endoscopic reinterventions. We prospectively analysed various endoscopic modalities in the diagnosis of recurrence following EMR. DESIGN: We conducted a prospective study of patients undergoing colonoscopy after EMR of large (≥20 mm) colorectal neoplasia. Endoscopists predicted recurrence and confidence level with four imaging modes: high-definition white light (WL) and narrow-band imaging (NBI) with and without near focus (NF). Separately, 26 experienced endoscopists assessed offline images. RESULTS: Two hundred and thirty patients with 255 EMR scars were included. The prevalence of recurrent adenoma was 24%. Diagnostic values were high for all modes (negative predictive value (NPV) ≥97%, positive predictive value (PPV) ≥81%, sensitivity ≥90%, specificity ≥93% and accuracy ≥93%). In high-confidence cases, NBI with NF had NPV of 100% (95% CI 98% to 100%) and sensitivity of 100% (95% CI 93% to 100%). Use of clips at initial EMR increased diagnostic inaccuracy (adjusted OR=1.68(95% CI 1.01 to 2.75)). In offline assessment, specificity was high for all imaging modes (mean: ≥93% (range: 55%-100%)), while sensitivity was significantly higher for NBI-NF (82%(72%-93%)%)) compared with WL (69%(38%-86%); p<0.001), WL-NF (68%(55%-83%); p<0.001) and NBI (71%(59%-90%); p<0.001). CONCLUSION: Our study demonstrates very high sensitivity and accuracy for all four imaging modalities, especially NBI with NF, for diagnosis of recurrent neoplasia after EMR. Our data strongly suggest that in cases of high confidence negative optical diagnosis based on NBI-NF, no biopsy is needed to confirm absence of recurrence during colorectal EMR follow-up. A high confidence positive optical diagnosis can lead to immediate resection of any suspicious area. In all cases of low confidence, biopsy is still required. TRIAL REGISTRATION NUMBER: NCT02668198.


Asunto(s)
Cicatriz/patología , Neoplasias Colorrectales/cirugía , Resección Endoscópica de la Mucosa , Recurrencia Local de Neoplasia/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Imagen de Banda Estrecha/métodos , Recurrencia Local de Neoplasia/patología , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Procedimientos Innecesarios
19.
Surgery ; 164(5): 1035-1048, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30029989

RESUMEN

BACKGROUND: The optimal nutritional therapy in the field of pancreatic surgery is still debated. METHODS: An international panel of recognized pancreatic surgeons and pancreatologists decided that the topic of nutritional support was of importance in pancreatic surgery. Thus, they reviewed the best contemporary literature and worked to develop a position paper to provide evidence supporting the integration of appropriate nutritional support into the overall management of patients undergoing pancreatic resection. Strength of recommendation and quality of evidence were based on the approach of the grading of recommendations assessment, development and evaluation Working Group. RESULTS: The measurement of nutritional status should be part of routine preoperative assessment because malnutrition is a recognized risk factor for surgery-related complications. In addition to patient's weight loss and body mass index, measurement of sarcopenia and sarcopenic obesity should be considered in the preoperative evaluation because they are strong predictors of poor short-term and long-term outcomes. The available data do not show any definitive nutritional advantages for one specific type of gastrointestinal reconstruction technique after pancreatoduodenectomy over the others. Postoperative early resumption of oral intake is safe and should be encouraged within enhanced recovery protocols, but in the case of severe postoperative complications or poor tolerance of oral food after the operation, supplementary artificial nutrition should be started at once. At present, there is not enough evidence to show the benefit of avoiding oral intake in clinically stable patients who are complicated by a clinically irrelevant postoperative pancreatic fistula (a so-called biochemical leak), while special caution should be given to feeding patients with clinically relevant postoperative pancreatic fistula orally. When an artificial nutritional support is needed, enteral nutrition is preferred whenever possible over parenteral nutrition. After the operation, regardless of the type of pancreatic resection or technique of reconstruction, patients should be monitored carefully to assess for the presence of endocrine and exocrine pancreatic insufficiency. Although fecal elastase-1 is the most readily available clinical test for detection of pancreatic exocrine insufficiency, its sensitivity and specificity are low. Pancreatic enzyme replacement therapy should be initiated routinely after pancreatoduodenectomy and in patients with locally advanced disease and continued for at least 6 months after surgery, because untreated pancreatic exocrine insufficiency may result in severe nutritional derangement. CONCLUSION: The importance of this position paper is the consensus reached on the topic. Concentrating on nutritional support and therapy is of utmost value in pancreatic surgery for both short- and long-term outcomes.


Asunto(s)
Insuficiencia Pancreática Exocrina/terapia , Desnutrición/terapia , Apoyo Nutricional/métodos , Pancreaticoduodenectomía/efectos adversos , Complicaciones Posoperatorias/terapia , Consenso , Terapia de Reemplazo Enzimático/métodos , Medicina Basada en la Evidencia/métodos , Medicina Basada en la Evidencia/normas , Insuficiencia Pancreática Exocrina/diagnóstico , Insuficiencia Pancreática Exocrina/etiología , Insuficiencia Pancreática Exocrina/metabolismo , Heces/química , Humanos , Desnutrición/diagnóstico , Desnutrición/etiología , Desnutrición/metabolismo , Estado Nutricional , Apoyo Nutricional/normas , Elastasa Pancreática/análisis , Fístula Pancreática/diagnóstico , Fístula Pancreática/etiología , Fístula Pancreática/metabolismo , Fístula Pancreática/terapia , Atención Perioperativa/métodos , Atención Perioperativa/normas , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/metabolismo , Factores de Tiempo , Resultado del Tratamiento
20.
Surg Endosc ; 32(6): 2859-2869, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29392469

RESUMEN

BACKGROUND: Sporadic nonampullary duodenal neoplasms (SNADN) can have malignant potential for which endoscopic and surgical resections are offered. We report combined gastroenterologic and surgical experience for treatment of SNADN, including endoscopic mucosal resection (EMR) and pancreas-preserving partial duodenectomy (PPPD). METHODS: We retrospectively reviewed 121 consecutive patients, who underwent 30 PPPDs and 91 EMRs for mucosal and submucosal SNADN. Decision to undergo EMR or surgical resection was based on expert endoscopist and surgeon discretion including multidisciplinary tumor board review. Main outcomes were recurrence rate of neoplasia and adverse events requiring hospital admission or prolonged care. EMRs were performed with submucosal lifting followed by snare resection. PPPD included total duodenectomy, supra-ampullary PPPD for neoplasms proximal to the ampulla, and infra-ampullary PPPD for lesions distal to the ampulla. Follow-up data were available for 65% of EMR and 73% of surgical patients. RESULTS: Surgically resected neoplasia was larger with more advanced neoplasia and submucosal lesions. En bloc resection was achieved in all surgical resections and in 53% of EMRs. Post-EMR, mucosal and submucosal neoplasia recurred in 32 and 0%, respectively, including five neoplasms (26%) after an initial negative esophagogastroduodenoscopy. All recurrences were treated endoscopically. Complications occurred in 14 endoscopically and eight surgically treated patients, none requiring surgical intervention. CONCLUSIONS: Post-EMR patients had higher recurrence of mucosal neoplasia, whereas submucosal neoplasms, mainly carcinoid, did not recur. Polyp size and positive resection margin were not associated with neoplasia recurrence. Patients with SNADN could benefit from a multidisciplinary approach to stratify the optimal treatment based on local expertise.


Asunto(s)
Neoplasias Duodenales/cirugía , Resección Endoscópica de la Mucosa , Endoscopía del Sistema Digestivo , Adenoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Carcinoma/cirugía , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Tempo Operativo , Tratamientos Conservadores del Órgano , Complicaciones Posoperatorias , Estudios Retrospectivos , Adulto Joven
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