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BACKGROUND: Histotripsy is a novel, ultrasound-based ablative technique that was recently approved by the Food and Drug Administration for hepatic targets. It has several promising additional theoretical applications that need to be further investigated. Its basis as a nonthermal cavitational technology presents a unique advantage over existing thermal ablation techniques in maximizing local effects while minimizing adjacent tissue destruction. This review discusses the technical basis and current preclinical and clinical data surrounding histotripsy. METHODS: This was a comprehensive review of the literature surrounding histotripsy and the clinical landscape of existing ablative techniques using the PubMed database. A technical summary of histotripsy's physics and cellular effect was described. Moreover, data from recent clinical trials, including Hope4Liver, and future implications regarding its application in various benign and malignant conditions were discussed. RESULTS: Preclinical data demonstrated the efficacy of histotripsy ablation in various organ systems with minimal tissue destruction when examined at the histologic level. The first prospective clinical trial involving histotripsy in hepatocellular carcinoma and liver metastases, Hope4Liver, demonstrated a primary efficacy of 95.5% with minimal complications (6.8%). This efficacy was replicated in similar trials involving the treatment of benign prostatic hypertrophy. DISCUSSION: In addition to the noninvasive ability to ablate lesions in the liver, histotripsy offers additional therapeutic potential. Early data suggest a potential complementary therapeutic effect when combining histotripsy with existing immunologic therapies because of the technology's theoretical ability to sensitize tumors to adaptive immunity. As with most novel therapies, the effect of histotripsy on the oncologic therapeutic landscape remains uncertain.
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Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/terapia , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Animales , PredicciónRESUMEN
BACKGROUND: Computed tomography imaging routinely detects incidental findings; most research focuses on malignant findings. However, benign diseases such as hiatal hernia also require identification and follow-up. Natural language algorithms can help identify these non-malignant findings. METHODS: Imaging of adult trauma patients from 2010 to 2020 who underwent CT chest/abdomen/pelvis was evaluated using an open-source natural language processor to query for hiatal hernias. Patients who underwent subsequent imaging, endoscopy, fluoroscopy, or operation were retrospectively reviewed. RESULTS: 1087(10.6%) of 10 299 patients had incidental hiatal hernias: 812 small (74.7%) and 275 moderate/large (25.3%). 224 (20.7%) had subsequent imaging or endoscopic evaluation. Compared to those with small hernias, patients with moderate/large hernias were older (66.3 ± 19.4 vs 79.6 ± 12.6 years, P < .001) and predominantly female (403[49.6%] vs 199[72.4%], P < .001). Moderate/large hernias were not more likely to grow (small vs moderate/large: 13[7.6%] vs 8[15.1%], P = .102). Patients with moderate/large hernias were more likely to have an intervention or referral (small vs moderate/large: 6[3.5%] vs 7[13.2%], P = .008). No patients underwent elective or emergent hernia repair. Three patients had surgical referral; however, only one was seen by a surgeon. One patient death was associated with a large hiatal hernia. CONCLUSIONS: We demonstrate a novel utilization of natural language processing to identify patients with incidental hiatal hernia in a large population, and found a 10.6% incidence with only 1.2%. (13/1087) of these receiving a referral for follow-up. While most incidental hiatal hernias are small, moderate/large and symptomatic hernias have high risk of loss-to-follow-up and need referral pipelines to improve patient outcomes.
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Hernia Hiatal , Hallazgos Incidentales , Tomografía Computarizada por Rayos X , Humanos , Hernia Hiatal/diagnóstico por imagen , Hernia Hiatal/complicaciones , Femenino , Masculino , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Anciano de 80 o más Años , Herniorrafia/métodos , Procesamiento de Lenguaje NaturalRESUMEN
BACKGROUND: Pediatric renal trauma is rare and lacks sufficient population-specific data to generate evidence-based management guidelines. A non-operative approach is preferred and has been shown to be safe. However, bleeding risk assessment and management of collecting system injury is not well understood. We introduce the Multi-institutional Pediatric Acute Renal Trauma Study (Mi-PARTS), a retrospective cohort study designed to address these questions. This manuscript describes the demographics and contemporary management of pediatric renal trauma at Level I trauma centers in the United States. METHODS: Retrospective data were collected at 13 participating Level I trauma centers on pediatric patients presenting with renal trauma between 2010-2019. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Descriptive statistics were used to report on demographics, acute management and outcomes. RESULTS: In total 1216 cases were included in this study. 67.2% were male, and 93.8% had a blunt injury mechanism. 29.3% had isolated renal injuries. 65.6% were high-grade (AAST Grade III-V) injuries. The mean Injury Severity Score (ISS) was 20.5. Most patients were managed non-operatively (86.4%) 3.9% had an open surgical intervention, including 2.7% having nephrectomy. Angioembolization was performed in 0.9%. Collecting system intervention was performed in 7.9%. Overall mortality was 3.3% and was only observed in polytrauma. The rate of avoidable transfer was 28.2%. CONCLUSION: The management and outcomes of pediatric renal trauma lacks data to inform evidence-based guidelines. Non-operative management of bleeding following renal injury is a well-established practice. Intervention for renal trauma is rare. Our findings reinforce differences from the adult population, and highlights opportunities for further investigation. With data made available through Mi-PARTS we aim to answer pediatric specific questions, including a pediatric-specific bleeding risk nomogram, and better understanding indications for interventions for collecting system injuries. LEVEL OF EVIDENCE: IV, Epidemiological (prognostic/epidemiological, therapeutic/care management, diagnostic test/criteria, economic/value-based evaluations, and Systematic Review and Meta-Analysis).
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PURPOSE: Treatment of invasive rectal adenocarcinoma is stratified into upfront surgery versus neoadjuvant chemoradiotherapy, in part, based on tumor distance from the anal verge (AV). This study examines the correlation between tumor distance measurements (endoscopic and MRI) and relationship to the anterior peritoneal reflection (aPR) on MRI. METHODS: A single-center retrospective study was performed at a tertiary center accredited by the National Accreditation Program for Rectal Cancer (NAPRC). 162 patients with invasive rectal cancer were seen between October of 2018 and April of 2022. Sensitivity and specificity were determined for MRI and endoscopic measurements in their ability to predict tumor location relative to the aPR. RESULTS: One hundred nineteen patients had tumors endoscopically and radiographically measured from the AV. Pelvic MRI characterized tumors as above (intraperitoneal) or at/straddles/below the aPR (extraperitoneal). True positives were defined as extraperitoneal tumors [Formula: see text] 10 cm. True negatives were defined as intraperitoneal tumors > 10 cm. Endoscopy was 81.9% sensitive and 64.3% specific in predicting tumor location with respect to the aPR. MRI was 86.7% sensitive and 92.9% specific. Utilizing a 12 cm cutoff, sensitivity of both modalities increased (94.3%, 91.4%) but specificity decreased (50%, 64.3%). CONCLUSION: For locally invasive rectal cancers, tumor position relative to the aPR is an important factor in determining the role of neoadjuvant therapy. These results suggest endoscopic tumor measurements do not accurately predict tumor location relative to the aPR, and may lead to incorrect treatment stratification recommendation. When the aPR is not identified, MRI-reported tumor distance may be a better predictor of this relationship.
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Neoplasias del Recto , Humanos , Estudios Retrospectivos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Recto/patología , Canal Anal/patología , Terapia Neoadyuvante , Endoscopía Gastrointestinal , Resultado del TratamientoRESUMEN
BACKGROUND: Colostomy reversal is a common procedure. Patients often have baseline comorbidities associated with postoperative morbidity. We utilized a modified frailty index (mFI-5) to predict postoperative complications. METHODS: Patients who underwent elective, open Hartmann's reversal were queried from the National Surgical Quality Improvement Program (NSQIP) database. Patients were stratified to low, medium, or high frailty groups. Statistical analysis was performed using chi-squared, ANOVA, and logistic regression. RESULTS: There were 9272 patients with Hartmann's reversal. 48.78%, 30.31%, and 12.89% had low, moderate, or high frailty, respectively. High frailty was associated with cardiac arrest, myocardial infarction, reintubation, prolonged intubation, early reoperation, and mortality. After multivariate analysis, high frailty was associated with prolonged intubation (OR 3.147, P = .001), reintubation (OR 2.548, P = .002), and reoperation (OR 1.67, P < .001). CONCLUSIONS: Frailty was associated with greater risk of postoperative complications in patients undergoing Hartmann's reversal. Frailty may be a useful adjunct to stratify for patients who are at risk for postoperative complications.
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Fragilidad , Mejoramiento de la Calidad , Humanos , Fragilidad/complicaciones , Anastomosis Quirúrgica/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Complicaciones Posoperatorias/etiologíaRESUMEN
BACKGROUND: Mixed medullary-papillary thyroid carcinoma (MMPTC) and mixed medullary-follicular thyroid carcinoma (MMFTC) are rare variants with little known regarding behavior and prognosis. METHODS: Using the National Cancer Database (NCDB), demographics, clinicopathologic features, treatment, and overall survival (OS) from patients with MMPTC and MMFTC were compared to more prevalent subtypes. RESULTS: There were 296,101 patients: 421 MMPTC (0.14%), 133 MMFTC (0.04%), 263,140 PTC (88.87%), 24,208 FTC (8.18%) and 8,199 MTC (2.77%). Compared to PTC, MMPTC and MMFTC patients were older (p < 0.001) with a higher Charlson-Deyo comorbidity index (p < 0.001). Mixed tumors exhibited lower rates of nodal disease but more distant metastases compared to PTC (p < 0.001). MMPTC demonstrated lower estimated 10-year OS than PTC and FTC (76.04%vs 89.04% and 81.95%,p < 0.001), yet higher than MTC (70.29%,p < 0.001). MMFTC had a worse OS compared to all groups (63.32%,p < 0.001). CONCLUSION: Patients with MMFTC had significantly worse OS compared to DTC, portending a worse prognosis.
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Adenocarcinoma Folicular , Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Adenocarcinoma Folicular/patología , Carcinoma Papilar/patología , Neoplasias de la Tiroides/patología , PronósticoRESUMEN
BACKGROUND: Epigenetic dysregulation is an integral step in the progression of pancreatic neuroendocrine tumors. We hypothesized that tumor suppressor repression by DNA methyltransferase 1 in pancreatic neuroendocrine tumors could be targeted with epigenetic treatment. METHODS: Resected pancreatic neuroendocrine tumors from 32 patients were stained for DNA methyltransferase 1 and scored. Human (BON1) and murine (STC) pancreatic neuroendocrine tumor cells were treated with DNA methyltransferase 1 inhibitor 5-azacytidine and chemotherapeutic agents 5-fluorouracil and temozolomide. Cell proliferation assay and tumor suppressor gene analysis were performed with qRT-PCR and Clarion S microarray. Tumor measurements were compared in a murine treatment model. RESULTS: High DNA methyltransferase scores were associated with high Ki-67 (6.7% vs 70.6% P < .01), mitotic rate (0.0% vs 31.3%), and grade (20.0% vs 80.4%, P < .01). Treatment with 5-azacytidine and chemotherapy resulted in a reduction of cell proliferation compared to chemotherapy alone in BON1 (77.3% vs 53.1%, P < .001) and STC (73.4% vs 34.2%, P < .001). Treatment with 5-azacytidine and chemotherapy resulted in upregulation of tumor suppressors CDKN1A (7.6 rel. fold, P < .001), BRCA2 (4.3 rel. fold, P < .001), and CDH1 (6.0 rel. fold, P = .026) in BON1 and CDKN1a (14.5 rel. fold, P < .001) and CDH (17.5 rel. fold, P < .001) in STC. In microarray, 5-azacytidine drove global genetic changes in combination treatment. In vivo tumors treated with chemotherapy measured 88.6 ± 19.54 mm3 vs 52.89 ± 10.51 mm3 in those treated with combination therapy (P = .009). CONCLUSION: Epigenetic dysregulation with DNA methyltransferase 1 is associated with pancreatic neuroendocrine tumors and is a potential targetable strategy. 5-azacytidine and chemotherapy in combination can reduce cell proliferation, upregulate silenced tumor suppressor genes, and decrease in vivo tumors in pancreatic neuroendocrine tumors.
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Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Animales , Ratones , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Azacitidina/uso terapéutico , Epigénesis Genética , Metiltransferasas/genética , Metiltransferasas/uso terapéutico , ADN/uso terapéuticoRESUMEN
BACKGROUND: In unresectable dermatofibrosarcoma protuberans (DFSP), no clear guideline exists regarding the use of tyrosine kinase inhibitors (TKI) versus radiotherapy. This study reviews current literature regarding TKI and radiotherapy in unresectable DFSP. METHODS: Following PROSPERO registration (CRD42021232508), a systematic literature search was performed including all studies reporting clinical results of TKI and/or radiotherapy in the treatment of unresectable DFSP. A narrative synthesis was used to compare patient characteristics, outcomes, and adverse effects. RESULTS: Of 1345 screened studies, 14 were included for review. Patient age ranged 18-77 years and 55% were male. Radiotherapy patients exhibited lower grade disease than TKI patients. Overall clinical benefit following TKI ranged from 70% to 96%. Radiotherapy patients exhibited control or resolution on last follow-up in 90% of cases. Radiotherapy adverse effects were mild, while TKI adverse effects were more severe and managed with dose reduction. CONCLUSION: TKI may be employed in unresectable DFSP of all histology types whereas radiation alone may be limited to low-grade and classic-type DFSP. TKI may cause more severe adverse effects compared to radiation alone.
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Dermatofibrosarcoma , Neoplasias Cutáneas , Humanos , Masculino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Femenino , Mesilato de Imatinib/uso terapéutico , Dermatofibrosarcoma/tratamiento farmacológico , Dermatofibrosarcoma/radioterapia , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/radioterapiaRESUMEN
BACKGROUND: Anastomotic strictures represent a major source of morbidity in colorectal surgery with an incidence reported up to 30%. Despite this, the mechanism by which strictures develop remains unclear. This study aims to determine the incidence of colorectal anastomotic strictures and associated risk factors among a series of diverted patients. MATERIALS AND METHODS: A retrospective chart review was conducted of 142 patients over a 7-year period at a single institution after colorectal resection with anastomosis and diverting ileostomy creation re-examined with postoperative endoscopy. One patient was removed due to anastomotic tumor recurrence. Patient and technical factors were examined for significance using chi-square analysis. Logistic regression was used to perform multivariate analysis to estimate odds ratio (OR) and 95% confidence intervals (CI). RESULTS: Among 141 patients, 14.1% (20 patients) developed strictures detected on endoscopy. Strictures were observed in a greater percentage of women than men (21.2% vs 8%, P = .025). 30.6% of patients who underwent resections for diverticulitis developed strictures while those with neoplastic lesions and other indications had stricture rates of 6.8% and 17.6%, respectively (P = .002). Anastomoses performed during a colostomy reversal were associated with a higher stricture rate (OR 4.23, 95% CI 1.37-13.40, P = .012). Anastomoses performed with a 28/29 mm EEA circular stapler demonstrated a significantly higher stricture rate versus a 31/33 mm stapler (OR 7.21, 95% CI 1.23-155.58, P = .045). DISCUSSION: Our data reveal that female sex, history of diverticulitis, anastomoses performed in the setting of colostomy reversal, and smaller stapler size are associated with a higher rate of anastomotic stricture.
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Neoplasias Colorrectales , Diverticulitis , Masculino , Humanos , Femenino , Constricción Patológica/etiología , Constricción Patológica/epidemiología , Ileostomía/efectos adversos , Estudios Retrospectivos , Anastomosis Quirúrgica/efectos adversos , Factores de Riesgo , Diverticulitis/complicaciones , Fuga Anastomótica/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
OBJECTIVES: During the coronavirus-19 pandemic, experts recommended delaying routine cancer screening and modifying treatment strategies. We sought to understand the sequalae of these recommendations. MATERIALS AND METHODS: We performed a retrospective single-center analysis of screening, diagnosis, and treatment of lung, colorectal, and breast cancer. Data was collected from our institutional cancer registry. Prepandemic (2016-2019) was compared with pandemic (2020) data. RESULTS: Three thousand three sixty one screening chest computed tomography scans (CTs), 35,917 colonoscopies, and 48,093 screening mammograms were performed. There was no difference in CTs [81.0 (SEM10.0) vs. 65.6 (SEM3.29), P =0.067] or mammograms [1017.0 (SEM171.8) vs. 809.4 (SEM56.41), P =0.177] in 2020 versus prepandemic. There were fewer colonoscopies in 2020 [651.4 (SEM103.5) vs. 758.91 (SEM11.79), P =0.043]. There was a decrease in cancer diagnoses per month in 2020 of lung [22.70 (SEM1.469) vs. 28.75 (SEM0.8216), P =0.003] and breast [38.56 (SEM6.133) vs. 51.82 (SEM1.257), P =0.001], but not colorectal [13.11 (SEM1.467) vs. 15.88 (SEM0.585), P =0.074] cancer. There was no change in stage at presentation for lung ( P =0.717), breast ( P =0.115), or colorectal cancer ( P =0.180). Lung had a shorter time-to-treatment in 2020 [38.92 days (SEM 2.48) vs. 66 (SEM1.46), P =0.002]. CONCLUSIONS: In 2020, there was no difference in screening studies for lung and breast cancer but there was a decrease in new diagnoses. Although there were fewer colonoscopies performed in 2020, there was no change in new colorectal cancer diagnoses. Despite changes in guidelines during the pandemic, the time-to-treatment for lung cancer was shorter and was unchanged for colorectal and breast cancer. These findings highlight the importance of continuing care for a vulnerable patient population despite a pandemic.
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Neoplasias de la Mama , COVID-19 , Neoplasias Colorrectales , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , COVID-19/epidemiología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/terapia , Detección Precoz del Cáncer , Femenino , Humanos , Pulmón , Pandemias/prevención & control , Estudios RetrospectivosRESUMEN
BACKGROUND: The field of cardiothoracic surgery has been striving to increase its gender and racial diversity. We sought to examine changes in gender and racial diversity in cardiothoracic fellowships and integrated residencies in the past decade. METHODS: Accreditation Council for Graduate Medical Education data were obtained from 2011 to 2019. Linear trends were assessed for year-by-year data. Average percentages of women and underrepresented minorities were then calculated in 3-year intervals. Intervals were compared with Student's t test and χ2 tests. RESULTS: There was no statistically significant increase in percent female trainees in cardiothoracic fellowships (18.5% to 22.1%, P = .10) or integrated residencies (22.8% to 27.8%, P = .17), despite a significant increase in percent female applicants to fellowship (18.2% to 35.3%, P < .01) and integrated residency (8.9% to 33.0%, P < .01). Cardiothoracic fellowships had no increase in underrepresented minority trainees (8.3% to 9.4%, P = .48). Underrepresented minority trainees in integrated residencies increased from 2.7% to 6.9% (P = .03). Although there was no significant increase in underrepresented minority applicants to fellowships (10.2% to 11.3%, P = .66), the percent of underrepresented minority applicants to integrated residencies increased from 13.1% to 19.3% (P < .01). CONCLUSIONS: Cardiothoracic surgery training programs are attracting more female applicants, but that has not yet resulted in a higher percentage of female trainees. Although percentages of underrepresented minorities increased among integrated residency applicants and trainees, they remain low compared with other specialties. These data reflect positive changes but also highlight that much remains to be done to increase diversity in cardiothoracic surgery training.