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PURPOSE: To evaluate associations of ghrelin, glucagon-like peptide 1 (GLP-1), and peptide YY 3-36 (PYY3-36) with weight change after bariatric arterial embolization (BAE). MATERIALS AND METHODS: Subgroup analysis of data collected during the BEAT Obesity Trial involving 7 participants with BMI > 40 who were embolized with 300- to 500-µm Embosphere Microspheres. Three participants were characterized as "responders" (top tertile of weight loss at each visit) and 4 as "non-responders" (bottom tertile of weight loss at each visit). Mean ± standard deviation participant age was 44 ± 11 years, and 6 of 7 participants were women. Participants were evaluated at baseline, 2 weeks, and 1, 3, 6, and 12 months after BAE. After fasting, participants consumed a mixed meal test at each visit; blood samples were collected at 0, 15, 30, 60, 120, 180, and 240 min. Study outcome measures were changes in weight from baseline and plasma serum hormone levels. RESULTS: Percentage change in ghrelin decreased significantly in non-responders at 60 and 120 min at 1 and 12 months (estimated difference between 60 vs. 0 min at 1 month: 69% [95% CI - 126%, - 13%]; estimated difference between 120 vs. 0 min at 12 months: - 131% (95% CI - 239%, - 23%]). Responders had significantly lower ghrelin and greater weight loss than non-responders at 6 and 12 months. GLP-1 and PYY3-36 levels did not differ between groups. CONCLUSION: Participants with consistent weight loss throughout follow-up had lower ghrelin than non-responders, supporting decreased ghrelin as a mechanism underlying BAE-induced weight loss. LEVEL OF EVIDENCE I: High-quality randomized trial or prospective study; testing of previously developed diagnostic criteria on consecutive patients; sensible costs and alternatives; values obtained from many studies with multiway sensitivity analyses; systematic review of Level I RCTs and Level I studies.
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Bariatria , Ghrelina , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Estudios Prospectivos , Obesidad , Pérdida de Peso , Péptido 1 Similar al GlucagónRESUMEN
The unprecedented impact of the Sars-CoV-2 pandemic (COVID-19) has strained the healthcare system worldwide. The impact is even more profound on diseases requiring timely complex multidisciplinary care such as pancreatic cancer. Multidisciplinary care teams have been affected significantly in multiple ways as healthcare teams collectively acclimate to significant space limitations and shortages of personnel and supplies. As a result, many patients are now receiving suboptimal remote imaging for diagnosis, staging, and surgical planning for pancreatic cancer. In addition, the lack of face-to-face interactions between the physician and patient and between multidisciplinary teams has challenged patient safety, research investigations, and house staff education. In this study, we discuss how the COVID-19 pandemic has transformed our high-volume pancreatic multidisciplinary clinic, the unique challenges faced, as well as the potential benefits that have arisen out of this situation. We also reflect on its implications for the future during and beyond the pandemic as we anticipate a hybrid model that includes a component of virtual multidisciplinary clinics as a means to provide accessible world-class healthcare for patients who require complex oncologic management.
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COVID-19 , Neoplasias Pancreáticas , Atención a la Salud , Humanos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/terapia , Pandemias , SARS-CoV-2RESUMEN
The incidence of colorectal cancer (CRC) is increasing in patients under the age of 50. The purpose of this study was to assess the cost-utility of available screening modalities starting at 40â¯years in the general population compared to standard screening at 50â¯years old. A decision tree modeling average-risk of CRC in the United States population was constructed for the cost per quality-adjusted life year (QALY) of the five most common and effective CRC screening modalities in average-risk 40-year olds versus deferring screening until 50â¯years old (standard of care) under a limited societal perspective. All parameters were derived from existing literature. We evaluated the incremental cost-utility ratio of each comparator at a willingness-to-pay threshold of $50,000/QALY and included multivariable probabilistic sensitivity analysis. All screening modalities assessed were more cost-effective with increased QALYs than current standard care (no screening until 50). The most favorable intervention by net monetary benefit was flexible sigmoidoscopy ($3284 per person). Flexible sigmoidoscopy, FOBT, and FIT all dominated the current standard of care. Colonoscopy and FIT-DNA were both cost-effective (respectively, $4777 and $11,532 per QALY). The cost-effective favorability of flexible sigmoidoscopy diminished relative to colonoscopy with increasing willingness-to-pay. Regardless of screening modality, CRC screening at 40â¯years old is cost-effective with increased QALYs compared to current screening initiation at 50â¯years old, with flexible sigmoidoscopy most preferred. Consideration should be given for a general recommendation to start screening at age 40 for average risk individuals.
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Importance: Performing elective upper and lower endoscopic procedures on the same day is a patient-centered and less costly approach than a 2-stage approach performed on different days, when clinically appropriate. Whether this practice pattern varies based on practice setting has not been studied. Objectives: To estimate the rate of different-day upper and lower endoscopic procedures in 3 types of outpatient settings and investigate the factors associated with the performance of these procedures on different days. Design, Setting, and Participants: A retrospective analysis was conducted of Medicare claims between January 1, 2011, and June 30, 2018, for Medicare beneficiaries who underwent a pair of upper and lower endoscopic procedures performed within 90 days of each other at hospital outpatient departments (HOPDs), freestanding ambulatory surgery centers (ASCs), and physician offices. Main Outcomes and Measures: Undergoing an upper and a lower endoscopic procedure on different days, adjusted for patient characteristics (age, sex, race/ethnicity, residence location and region, comorbidity, and procedure indication) and physician characteristics (sex, years in practice, procedure volume, and primary specialty). Adjusted odds ratios (aORs) and 95% CIs were calculated. Results: A total of 4â¯028â¯587 procedure pairs were identified, of which 52.5% were performed in HOPDs, 43.3% in ASCs, and 4.2% in physician offices. The rate of different-day procedures was 13.6% in HOPDs, 22.2% in ASCs, and 47.7% in physician offices. For the 7564 physicians who practiced at both HOPDs and ASCs, their different-day procedure rate changed from 14.1% at HOPDs to 19.4% at ASCs. For the 993 physicians who practiced at both HOPDs and physician offices, their different-day procedure rate changed from 15.8% at HOPDs to 37.4% at physician offices. Patients were more likely to undergo different-day procedures at physician offices and ASCs compared with HOPDs, even after adjusting for patient and physician characteristics (physician office vs HOPD: aOR, 2.02; 95% CI, 1.85-2.20; ASC vs HOPD: aOR, 1.27; 95% CI, 1.23-1.32). Older age (85-94 years vs 65-74 years: aOR, 1.10; 95% CI, 1.08-1.11; 95 years or older vs 65-74 years: aOR, 1.14; 95% CI, 1.03-1.26), black and Hispanic race/ethnicity (black: aOR, 1.15; 95% CI, 1.12-1.17; Hispanic: aOR, 1.12; 95% CI, 1.10-1.14), and residing in the Northeast region (adjusted OR, 1.32; 95% CI, 1.28-1.36) were risk factors for undergoing different-day procedures. Micropolitan location (aOR, 0.94; 95% CI, 0.92-0.96) and rural location (aOR, 0.91; 95% CI, 0.89-0.93), more comorbidities (≥5: aOR, 0.75; 95% CI, 0.74-0.76), physician's fewer years in practice (aOR, 0.84; 95% CI, 0.81-0.87), physician's higher procedure volume (aOR, 0.65; 95% CI, 0.62-0.68), and physician's specialty of general surgery (aOR, 0.86; 95% CI, 0.80-0.91) were protective factors. Conclusions and Relevance: Physician offices and ASCs had much higher different-day procedure rates compared with HOPDs. This disparity may represent an opportunity for quality improvement and financial savings for common endoscopic procedures.
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Endoscopía Gastrointestinal/economía , Gastroenterología/normas , Servicio Ambulatorio en Hospital/economía , Consultorios Médicos/economía , Centros Quirúrgicos/economía , Anciano , Anciano de 80 o más Años , Endoscopía Gastrointestinal/estadística & datos numéricos , Femenino , Gastroenterología/economía , Gastroenterología/estadística & datos numéricos , Humanos , Masculino , Servicio Ambulatorio en Hospital/estadística & datos numéricos , Consultorios Médicos/estadística & datos numéricos , Centros Quirúrgicos/estadística & datos numéricosRESUMEN
Background Bariatric embolization is a new endovascular procedure to treat patients with obesity. However, the safety and efficacy of bariatric embolization are unknown. Purpose To evaluate the safety and efficacy of bariatric embolization in severely obese adults at up to 12 months after the procedure. Materials and Methods For this prospective study (NCT0216512 on ClinicalTrials.gov ), 20 participants (16 women) aged 27-68 years (mean ± standard deviation, 44 years ± 11) with mean body mass index of 45 ± 4.1 were enrolled at two institutions from June 2014 to February 2018. Transarterial embolization of the gastric fundus was performed using 300- to 500-µm embolic microspheres. Primary end points were 30-day adverse events and weight loss at up to 12 months. Secondary end points at up to 12 months included technical feasibility, health-related quality of life (Short Form-36 Health Survey ([SF-36]), impact of weight on quality of life (IWQOL-Lite), and hunger or appetite using a visual assessment scale. Analysis of outcomes was performed by using one-sample t tests and other exploratory statistics. Results Bariatric embolization was performed successfully for all participants with no major adverse events. Eight participants had a total of 11 minor adverse events. Mean excess weight loss was 8.2% (95% confidence interval [CI]: 6.3%, 10%; P < .001) at 1 month, 11.5% (95% CI: 8.7%, 14%; P < .001) at 3 months, 12.8% (95% CI: 8.3%, 17%; P < .001) at 6 months, and 11.5% (95% CI: 6.8%, 16%; P < .001) at 12 months. From baseline to 12 months, mean SF-36 scores increased (mental component summary, from 46 ± 11 to 50 ± 10, P = .44; physical component summary, from 46 ± 8.0 to 50 ± 9.3, P = .15) and mean IWQOL-Lite scores increased from 57 ± 18 to 77 ± 18 (P < .001). Hunger or appetite decreased for 4 weeks after embolization and increased thereafter, without reaching pre-embolization levels. Conclusion Bariatric embolization is well tolerated in severely obese adults, inducing appetite suppression and weight loss for up to 12 months. Published under a CC BY-NC-ND 4.0 license. Online supplemental material is available for this article.
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Cirugía Bariátrica , Embolización Terapéutica , Obesidad/cirugía , Adulto , Anciano , Cirugía Bariátrica/efectos adversos , Cirugía Bariátrica/métodos , Cirugía Bariátrica/estadística & datos numéricos , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Embolización Terapéutica/estadística & datos numéricos , Endoscopía Gastrointestinal , Femenino , Fundus Gástrico/irrigación sanguínea , Fundus Gástrico/diagnóstico por imagen , Fundus Gástrico/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Pérdida de Peso/fisiologíaRESUMEN
PURPOSE: Barrett's esophagus is the only known precursor of esophageal adenocarcinoma (EAC). Although endoscopy and biopsy are standard methods for Barrett's esophagus diagnosis, their high cost and risk limit their use as a screening modality. Here, we sought to develop a Barrett's esophagus detection method based on methylation status in cytology samples captured by EsophaCap using a streamlined sensitive technique, methylation on beads (MOB). EXPERIMENTAL DESIGN: We conducted a prospective cohort study on 80 patients (52 in the training set; 28 in the test set). We used MOB to extract and bisulfite-convert DNA, followed by quantitative methylation-specific PCR to assess methylation levels of 8 previously selected candidate markers. Lasso regression was applied to establish a prediction model in the training set, which was then tested on the independent test set. RESULTS: In the training set, five of eight candidate methylation biomarkers (p16, HPP1, NELL1, TAC1, and AKAP12) were significantly higher in Barrett's esophagus patients than in controls. We built a four-biomarker-plus-age lasso regression model for Barrett's esophagus diagnosis. The AUC was 0.894, with sensitivity 94.4% [95% confidence interval (CI), 71%-99%] and specificity 62.2% (95% CI, 44.6%-77.3%) in the training set. This model also performed with high accuracy for Barrett's esophagus diagnosis in an independent test set: AUC = 0.929 (P < 0.001; 95% CI, 0.810%-1%), with sensitivity=78.6% (95% CI, 48.8%-94.3%) and specificity = 92.8% (95% CI, 64.1%-99.6%). CONCLUSIONS: EsophaCap, in combination with an epigenetic biomarker panel and the MOB method, is a promising, well-tolerated, low-cost esophageal sampling strategy for Barrett's esophagus diagnosis. This approach merits further prospective studies in larger populations.
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Esófago de Barrett/diagnóstico , Esófago de Barrett/etiología , Biomarcadores , Citodiagnóstico , Metilación de ADN , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Citodiagnóstico/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Stereotactic body radiation therapy (SBRT) represents a promising treatment option for patients with localized pancreatic ductal adenocarcinoma (PDAC) who cannot tolerate surgical therapy. We retrospectively reviewed the records of patients with localized PDAC treated with SBRT at our institution between 2010 and 2016 to identify patients deemed medically inoperable due to poor performance status, advanced age, and/or comorbid conditions. Overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS) were estimated using Kaplan-Meier curves. Twenty-nine patients were included. Median age was 74 (IQR 68-79). Thirteen patients (45%) had an Eastern Cooperative Oncology Group performance status of 2. Six patients (19%) had chronic obstructive pulmonary disease, 9 (31%) had cardiovascular disease, and 17 (58%) had diabetes mellitus. SBRT was delivered over 5 fractions to a median dose of 28 Gy (IQR, 25-33). Twenty-two patients (76%) received induction chemotherapy prior to SBRT, and 9 (31%) received maintenance chemotherapy after SBRT. Median OS was 13 months from diagnosis. Median OS and PFS were 8 and 6 months from SBRT, respectively. Six and 12-month LPFS rates were 91% and 78%, respectively. Patients receiving induction chemotherapy had superior survival from diagnosis than those who did not (14 vs. 7 months, p = 0.01). Three patients (10%) experienced acute grade ≥3 toxicity, and 1 patient (4%) experienced grade ≥3 late toxicity. Symptom relief was achieved at three-month follow-up in 8 of 11 patients (73%) experiencing abdominal pain. These results suggest SBRT may be safe and effective for patients who cannot tolerate surgery.
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PURPOSE: We report a very unique case of an esophageal metastasis from a pancreatic ductal adenocarcinoma (PDAC) primary. METHODS: After obtaining consent from the patient, all relevant records of the case were obtained and retrospectively reviewed. RESULTS: At presentation, the patient was diagnosed with synchronous pancreatic and esophageal cancer. He received six months of neoadjuvant therapy including FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and stereotactic body radiation therapy (SBRT) to the pancreatic tumor followed by a combined pancreaticoduodenectomy and Ivor Lewis esophagectomy. Review of the final esophageal specimen revealed normal overlying squamous mucosa with an underlying focus of metastatic PDAC. The patient remains alive with no evidence of disease 17 months from surgery and 25 months from diagnosis. CONCLUSIONS: Differentiating an esophageal metastasis from a PDAC primary versus a synchronous esophageal carcinoma is very difficult despite state-of-the-art diagnostic techniques performed at a high-volume tertiary cancer center. Extensive evaluation and continued follow-up of PDAC patients presenting with a synchronous esophageal lesion in a multidisciplinary setting may help ensure efficient and accurate management. In our case, neoadjuvant FOLFIRINOX and SBRT to the primary PDAC tumor followed by surgery has been an effective approach for this patient.
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Purpose To conduct a pilot prospective clinical trial to evaluate the feasibility, safety, and short-term efficacy of bariatric embolization, a recently developed endovascular procedure for the treatment of obesity, in patients with severe obesity. Materials and Methods This is an institutional review board- and U.S. Food and Drug Administration-approved prospective physician-initiated investigational device exemption study. This phase of the study ran from June 2, 2014, to August 4, 2015. Five severely obese patients (four women, one man) who were 31-49 years of age and who had a mean body mass index of 43.8 kg/m2 ± 2.9 with no clinically important comorbidities were enrolled in this study. Transarterial embolization of the gastric fundus with fluoroscopic guidance was performed with 300-500-µm Embosphere microspheres. The primary end point was 30-day adverse events (AEs). The secondary end points included short-term weight loss, serum obesity-related hormone levels, hunger and satiety assessments, and quality of life (QOL) surveys, reported up to 3 months. Simple statistics of central tendencies and variability were calculated. No hypothesis testing was performed. Results The left gastric artery, with or without the gastroepiploic artery, was embolized in five patients, with a technical success rate of 100%. There were no major AEs. There were two minor AEs-subclinical pancreatitis and a mucosal ulcer that had healed by the time of 3-month endoscopy. A hospital stay of less than 48 hours for routine supportive care was provided for three patients. Mean excess weight loss of 5.9% ± 2.4 and 9.0% ± 4.1 was noted at 1 month and at 3 months, respectively. Mean change in serum ghrelin was 8.7% ± 34.7 and -17.5% ± 29 at 1 month and 3 months, respectively. Mean changes in serum glucagon-like peptide 1 and peptide YY were 106.6% ± 208.5 and 17.8% ± 54.8 at 1 month. There was a trend toward improvement in QOL parameters. Hunger/appetite scores decreased in the first 2 weeks after the procedure and then rose without reaching preprocedure levels. Conclusion Bariatric embolization is feasible and appears to be well tolerated in severely obese patients. In this small patient cohort, it appears to induce appetite suppression and may induce weight loss. Further expansion of this study will provide more insight into the long-term safety and efficacy of bariatric embolization. © RSNA, 2017 Online supplemental material is available for this article.
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Embolización Terapéutica/métodos , Hemostáticos/uso terapéutico , Obesidad Mórbida/diagnóstico por imagen , Obesidad Mórbida/terapia , Radiografía Intervencional/métodos , Estómago/irrigación sanguínea , Adulto , Embolización Terapéutica/efectos adversos , Femenino , Hemostáticos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Since 1985, the American Society for Gastrointestinal Endoscopy (ASGE) has awarded grants for endoscopic-related research. The goals of this study were to examine trends in ASGE grant funding and to assess productivity of previous recipients of the ASGE grant awards. METHODS: This was a retrospective cohort analysis of all research grants awarded by the ASGE through 2009. Measures of academic productivity and self-assessment of the ASGE awards' impact on the recipients' careers were defined by using publicly available resources (eg, National Library of Medicine-PubMed) and administration of an electronic survey to award recipients. RESULTS: The ASGE awarded 304 grants totaling $12.5 million to 214 unique awardees. Funding increased 7.5-fold between 1985 and 1989 (mean $102,000/year) and between 2005 and 2009 (mean $771,000/year). The majority of awardees were men (83%), were at or below the level of assistant professor (82%), with a median of 3 years of postfellowship experience at the time of the award, and derived from a broad spectrum of institutions as measured by National Institutes of Health funding rank (median 26, interquartile range [IQR] 12-64). Nineteen percent had a master's degree in a research-related field. Awardees' median publications per year increased from 3.5 (IQR 1.2-9.0) before funding to 5.7 (IQR 1.8-9.5) since funding; P = .04, and median h-index scores increased from 3 (IQR 1-8) to 17 (IQR 8-26); P < .001. Multivariate analysis found that the presence of a second advanced degree (eg, masters or doctorate) was independently predictive of high productivity (odds ratio [OR] 2.92; 95% confidence interval [CI], 1.09-7.81). Among 212 unique grant recipients, 82 (40%) completed the online survey. Of the respondents, median peer-reviewed publications per year increased from 3.4 (IQR 1.9-5.5) to 4.5 (IQR 2.0-9.5); P = .17. Ninety-one percent reported that the ASGE grant had a positive or very positive impact on their careers, and 85% of respondents are currently practicing in an academic environment. Most of the grants resulted in at least 1 peer-reviewed publication (67% per Internet-based search and 81% per survey). CONCLUSIONS: The ASGE research program has grown considerably since 1985, with the majority of grants resulting in at least 1 grant-related publication. Overall academic productivity increased after the award, and the majority of awardees report a positive or very positive impact of the award on their careers. Medical professional societies are an important sponsor of clinical research.
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Investigación Biomédica , Gastroenterología , Apoyo a la Investigación como Asunto , Estudios de Cohortes , Eficiencia , Endoscopía Gastrointestinal , Femenino , Humanos , Masculino , National Institutes of Health (U.S.) , Edición , Investigadores , Estudios Retrospectivos , Sociedades Médicas , Estados UnidosRESUMEN
BACKGROUND AND STUDY AIMS: A new on-demand enteroscopy (ODE) device has been designed to allow deep enteroscopy using a standard adult colonoscope with the aid of a novel through-the-scope balloon. The aims of the current study were to establish the feasibility, efficacy, and safety of ODE in performing anterograde and retrograde enteroscopy. PATIENTS AND METHODS: A retrospective, single-center study of 28 consecutive deep ODE procedures (11 anterograde and 17 retrograde) was performed. Diagnostic yield, therapeutic yield, technical success, procedure time, depth of maximal insertion (DMI), time to DMI, and adverse events were recorded. RESULTS: The mean diagnostic and therapeutic yields were 45â% and 36â% for anterograde enteroscopy and 59â% and 47â% for retrograde enteroscopy, respectively. Technical success was achieved in 100â%. For anterograde enteroscopy, the mean total procedure time was 24 minutes, with a mean DMI of 1.2âm. For retrograde enteroscopy, the mean total procedure time was 31 minutes, with a mean DMI of 1.1âm. No adverse events were recorded. CONCLUSION: Deep enteroscopy using a novel through-the-scope balloon and standard endoscope appeared to be feasible and safe, with rapid procedures times.
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Colonoscopios , Endoscopía Gastrointestinal/métodos , Intestino Delgado , Anciano , Anciano de 80 o más Años , Endoscopía Gastrointestinal/efectos adversos , Endoscopía Gastrointestinal/instrumentación , Diseño de Equipo , Seguridad de Equipos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios RetrospectivosRESUMEN
PURPOSE OF REVIEW: Standard endoscopic polypectomy is a powerful technique to remove most polyps found in the gastrointestinal tract. However, a small percentage of polyps can be classified as difficult, based on size, location, and/or configuration. Traditionally, these difficult polyps were referred for surgical segmental colectomy. Recently, with advancements in endoscopic techniques and accessories, a majority of these difficult polyps are now able to be completely resected using entirely endoscopic techniques. RECENT FINDINGS: Endoscopic techniques and accessories have been evolving during recent years, including increased dissemination of techniques of endoscopic submucosal dissection to the western hemisphere. In addition to refinement of endoscopic techniques, there has been increased interest in developing improved endoscopic accessories, including novel submucosal injectate with auto-dissecting properties, to improve safety and efficiency of endoscopic resection of difficult polyps. SUMMARY: This article will review currently available techniques and strategies for successful endoscopic resection for difficult polyps.
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Colonoscopía/métodos , Pólipos Intestinales/cirugía , Colectomía/métodos , Pólipos del Colon/cirugía , Colonoscopía/efectos adversos , Disección/métodos , Humanos , Laparoscopía/métodosRESUMEN
Thermally activated, untethered microgrippers can reach narrow conduits in the body and be used to excise tissue for diagnostic analyses. As depicted in the figure, the feasibility of an in vivo biopsy of the porcine bile duct using untethered microgrippers is demonstrated.
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Conductos Biliares/patología , Robótica/instrumentación , Animales , Conductos Biliares/metabolismo , Biopsia , Mucina 4/genética , Mucina 4/metabolismo , PorcinosRESUMEN
Esophageal cancer ranks sixth in cancer death. To explore its genetic origins, we conducted exomic sequencing on 11 esophageal adenocarcinomas (EAC) and 12 esophageal squamous cell carcinomas (ESCC) from the United States. Interestingly, inactivating mutations of NOTCH1 were identified in 21% of ESCCs but not in EACs. There was a substantial disparity in the spectrum of mutations, with more indels in ESCCs, A:T>C:G transversions in EACs, and C:G>G:C transversions in ESCCs (P < 0.0001). Notably, NOTCH1 mutations were more frequent in North American ESCCs (11 of 53 cases) than in ESCCs from China (1 of 48 cases). A parallel analysis found that most mutations in EACs were already present in matched Barrett esophagus. These discoveries highlight key genetic differences between EACs and ESCCs and between American and Chinese ESCCs, and suggest that NOTCH1 is a tumor suppressor gene in the esophagus. Finally, we provide a genetic basis for the evolution of EACs from Barrett esophagus.
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Adenocarcinoma/genética , Esófago de Barrett/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Exoma , Neoplasias de Cabeza y Cuello/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Esófago de Barrett/metabolismo , Esófago de Barrett/patología , Secuencia de Bases , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , China , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Geografía , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , Mutación , América del Norte , Receptor Notch1/genética , Receptor Notch2/genética , Receptor Notch3 , Receptores Notch/genética , Análisis de Secuencia de ADN , Carcinoma de Células Escamosas de Cabeza y Cuello , Proteína p53 Supresora de Tumor/genéticaRESUMEN
INTRODUCTION: Lasers 2-microm in wavelength offer efficient tissue cutting with limited thermal damage in biological tissue. OBJECTIVE: To evaluate the dissection capabilities of a 2-microm continuous-wave laser for NOTES procedures. METHODS AND PROCEDURES: We conducted 18 acute animal experiments. Group 1 (three animals): transcolonic access to the peritoneal cavity (15-W transcolonic laser puncture, balloon dilation over the laser probe). Group 2 (six animals): transcolonic access with needle-knife puncture and balloon dilation. Group 3 (three animals): transgastric access to the peritoneal cavity (similar technique as group 1) followed by laser-assisted dissection of the kidney. In one animal of group 3, a therapeutic target (hematoma) was created by percutaneous puncture of the kidney. Group 4 (six animals): transgastric access (similar to the technique of group 2). RESULTS: Translumenal access to the peritoneal cavity was achieved in 2-3 min in group 1 (significantly shorter than with the needle-knife-assisted technique, 4-5 min, p=0.02) and in 7-10 min in group 3 (compared to 6-17 min in group 4, p=0.88). In group 3, laser dissection of the parietal peritoneum and of perinephric connective tissue allowed access to the retroperitoneum with complete removal of a blood collection in the animal with puncture trauma. Laser dissection demonstrated good maneuverability, clean and rapid cutting, and excellent hemostasis. Peritoneoscopy and necropsy showed no damage of targeted tissue and surrounding organs. CONCLUSIONS: The 2-microm continuous-wave laser system showed promising capabilities for highly precise and safe dissection during NOTES procedures.
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Disección/instrumentación , Laparoscopios , Laparoscopía , Rayos Láser , Cavidad Peritoneal/cirugía , Tulio , Animales , Cateterismo , Colon/cirugía , Modelos Animales de Enfermedad , Disección/efectos adversos , Diseño de Equipo , Femenino , Hematoma/cirugía , Técnicas Hemostáticas/instrumentación , Riñón/cirugía , Laparoscopía/efectos adversos , Neumoperitoneo Artificial , Estómago/cirugía , Sus scrofaRESUMEN
BACKGROUND: Closure of the transgastric access to the peritoneal cavity is a critical step in natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: To perform a direct comparison of the histological healing post clips and threaded tags (T-tags) closure after transgastric NOTES procedures. DESIGN AND INTERVENTION: Twelve survival porcine experiments. After standardized endoscopic gastric wall puncture, balloon-dilation, and transgastric peritoneoscopy, closure of the gastric wall was performed with either clips or T-tags. Necropsy at 14 days was performed for histological evaluation of 2-mm interval transversal cross sections of the gastrotomy site. MAIN OUTCOME MEASUREMENTS: Histological healing of the gastric wall opening. RESULTS: Endoscopic closure of the gastrotomy was successfully achieved in all 12 animals, followed by an uneventful 2-week clinical follow-up. Transmural healing was seen in 3 (75%) animals after clip closure compared with only 1 (12.5%) in the group with T-tag closure (P = .06). Gastric wall muscular bridging was observed in 4 (100%) animals with clip closure compared with only 1 (12.5%) in the group with T-tag closure (P = .01). LIMITATIONS: Animal model with short-term follow-up. CONCLUSIONS: Endoscopic clip closure results in a layer-to-layer transmural healing of the gastric wall. In contrast, T-tag gastric wall plication impairs gastric layer bridging. These findings might guide the future design of new endoscopic devices and techniques for gastrotomy closure after NOTES procedures.
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Endoscopía Gastrointestinal , Gastrostomía/métodos , Laparoscopía/métodos , Estómago/cirugía , Técnicas de Sutura/instrumentación , Suturas , Cicatrización de Heridas/fisiología , Animales , Modelos Animales de Enfermedad , Estudios de Seguimiento , Estómago/patología , PorcinosRESUMEN
INTRODUCTION: The utility of the greater omentum has not been assessed in transluminal access closure after natural orifice transluminal endoscopic surgery (NOTES) procedures. OBJECTIVE: Our purpose was to evaluate the feasibility, efficacy, and safety of omentoplasty for gastrotomy closure. METHODS AND PROCEDURES: Survival experiments in 9 female 40-kg pigs were randomly assigned to 3 groups: group A, endoscopic full-thickness resection (EFTR) for transgastric access and peritoneoscopy without closure; group B, ETFR and peritoneoscopy with omentoplasty (flap of omentum is pulled into the stomach and attached to the gastric mucosa with clips but no clips are used for gastrotomy closure itself); group C, balloon dilation for opening and peritoneoscopy followed by omentoplasty for closure. The animals were observed for 2 weeks and then underwent endoscopy and necropsy with histologic evaluation. RESULTS: Transgastric opening and peritoneoscopy were achieved in all pigs. In groups B and C, a flap of omentum was easily placed to seal the gastrotomy and then attached to the gastric mucosa with 2 to 5 clips (median 4) in 7 to 20 minutes (median 15 minutes). In group A, peritonitis developed in all animals. In both groups B and C, all animals survived 15 days with no peritonitis and minimal adhesions outside the gastrotomy site. In addition, all achieved complete healing (transmural, n = 4; mucosal ulceration, n = 2) of the gastrotomy site. One animal in group B had an 18-mm abscess in the omental flap. LIMITATIONS: Animal model, small sample size, lack of appropriate controls for group C. CONCLUSIONS: Omentoplasty of the gastrotomy site is a technically feasible method to seal balloon-created transgastric access to the peritoneal cavity after NOTES procedures.
Asunto(s)
Endoscopía Gastrointestinal/métodos , Epiplón/trasplante , Procedimientos de Cirugía Plástica/métodos , Estómago/cirugía , Colgajos Quirúrgicos , Técnicas de Sutura/instrumentación , Animales , Modelos Animales de Enfermedad , Femenino , Porcinos , Cicatrización de HeridasRESUMEN
BACKGROUND: Leak-resistant closure of transluminal access is a major challenge facing natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: To evaluate a hydrogen (H(2))-based leak test for assessment of transluminal-access closure integrity after NOTES procedures. SETTING: Nine acute porcine experiments. DESIGN AND INTERVENTION: After gastric-wall puncture and balloon dilation, peritoneoscopy was performed, followed by transmural closure of the gastric opening. The animals were randomly assigned to complete or incomplete closure groups. The H(2) leak test was performed by using 1000 mL of 4% H(2) gas mixture and the Hydrogen Leak Detector H2000+. The animals were then euthanized for a methylene blue (MB) test of gastric closure integrity. MAIN OUTCOME MEASUREMENT: Intraperitoneal H(2) concentration after gastric insufflation with H(2). RESULTS: The H(2) leak test was quick and easy. Intraperitoneal H(2) concentrations in parts per million in both groups were similar at baseline (mean +/- SD, 0.18 +/- 0.29 parts per million [ppm] vs 0.22 +/- 0.35 ppm, P = .97) and after balloon dilation (414.8 +/- 198.5 ppm vs 601.3 +/- 116.1 ppm, P > .99). Postclosure intraperitoneal H(2) concentrations dropped to 0.01 +/- 0.77 ppm in the complete-closure group, similar (P = .81) to matched-pairs preopening levels and significantly lower than in the incomplete-closure group (162.0 +/- 83.0 ppm, P < .02). On necropsy, the MB test was negative in all 5 animals of the complete-closure group and positive in all 4 animals of the incomplete-closure group. A cutoff of 25 ppm in intraperitoneal H(2) concentration after closure gave 100% sensitivity, specificity, and positive and negative predictive values for MB leakage. LIMITATIONS: Nonsurvival animal experiments. CONCLUSIONS: The H(2) leak test is highly accurate for detection of leakage after NOTES procedures and could become a substitute for currently used MB leak tests.
Asunto(s)
Endoscopía Gastrointestinal/métodos , Hidrógeno/análisis , Animales , Porcinos , Grabación en VideoRESUMEN
BACKGROUND: Portal vein (PV) pressure measurements can provide valuable information for the management of patients with liver disease and portal hypertension. OBJECTIVE: To evaluate the feasibility and the safety of EUS-guided PV catheterization and pressure measurements in a porcine model. SETTING: Acute and survival experiments on five 50-kg pigs. DESIGN AND INTERVENTIONS: Intrahepatic PV was punctured under EUS guidance by using a 19-gauge FNA needle. A 0.035-inch guidewire was advanced through the needle into the PV. The needle was withdrawn. A 5.5F ERCP catheter was advanced over the guidewire into the PV and then connected to a pressure monitor. Continuous PV measurements were obtained for an hour. Afterward, the catheter was removed, and the animals were observed for 30 minutes. Three animals were then immediately euthanized for a necropsy. The other two animals were observed for two weeks and then were euthanized. MAIN OUTCOME MEASUREMENTS: The ability to perform EUS-guided PV catheterization and pressure measurement without complications. RESULTS: PV catheterization, angiography, and pressure measurements were performed without any problems or complications. There were no changes in vital signs and hemodynamic parameters during PV catheterizations, angiography, pressure measurements, and catheter removal. Survival experiments did not demonstrate any change in animal condition, behavior, or eating habits after the procedure. A necropsy in all animals revealed no active bleeding, and no damage to the liver, other intra-abdominal organs, or blood vessels. LIMITATIONS: No validation of measured PV pressure was made. CONCLUSIONS: EUS-guided PV catheterization is feasible, safe, and can be used for portal angiography and pressure measurements.