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BACKGROUND: Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that preclude receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease-oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan. METHODS: We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010 and 2022. We compared overall survival (OS) between patients diagnosed from 2010 to 2018, which will be referred to as the historical control era and patients diagnosed from 2019 to 2022, which will be called the aggressive supportive care era. RESULTS: Fifty-four patients were included in our analysis; 31 patients were treated in the historical control time frame, and 23 patients were treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p < 0.01). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p < 0.01). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median OS for historical control patients was 5.4 months as compared with 10.4 months for patients treated during aggressive supportive care era (p = 0.04). CONCLUSIONS: Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared with historic controls. Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance.
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Adenocarcinoma , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Neoplasias Gástricas/tratamento farmacológico , Ascite/etiologia , Ascite/terapia , Prognóstico , Neoplasias Peritoneais/patologia , Adenocarcinoma/terapia , Adenocarcinoma/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: Insulinomas are rare pancreatic neuroendocrine tumors for which the main curative treatment is surgical resection. Enucleation is preferred over pancreatoduodenectomy to minimize morbidity and function loss.1 Robotic-assisted surgery offers improved versatility and less blood loss than laparoscopic surgery for pancreatic enucleation.2-4 Our video describes the technique for robotic enucleation of pancreatic head insulinomas in close proximity to the pancreatic duct. PATIENTS AND METHODS: The video describes the presentation, diagnostic imaging, and technical aspects of the surgical approach in two patients with pancreatic head insulinomas that underwent robotic enucleation. RESULTS: Case one was a 76-year-old woman who experienced syncope for 2 months. Case two was a 61-year-old man, previously treated for renal cancer, who had documented hypoglycemic symptoms. Computed tomography (CT) scan and magnetic resonance imaging (MRI) identified a 1.5 cm and 1.2 cm pancreatic head mass, respectively. Both patients presented with low glucose levels, and elevated C-peptide and proinsulin. In both cases, endoscopic retrograde cholangiopancreatography (ERCP) and pancreatic duct stent placement were performed the same day of surgery for intraoperative identification and preservation of the duct. Robotic enucleation of the masses was performed, and an ultrasound was used to identify the masses and relation with main pancreatic duct. Pathology revealed a well-differentiated neuroendocrine tumor in both cases. The patient's postoperative course was uneventful, and they were discharged on day 5. Successful resolution of hypoglycemic events occurred in both patients. CONCLUSION: Robotic enucleation is a safe and feasible option for treating pancreatic head tumors in challenging locations. Intraoperative ultrasound is an essential tool for the successful robotic enucleation of pancreatic head tumors.
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Neoplasias de Cabeça e Pescoço , Insulinoma , Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Masculino , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Insulinoma/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Ductos Pancreáticos/patologia , Laparoscopia/métodos , Neoplasias de Cabeça e Pescoço/cirurgia , HipoglicemiantesRESUMO
BACKGROUND: Neoadjuvant therapy (NAT) emerged as the standard of care for patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgery; however, surgery is morbid, and tools to predict resection margin status (RMS) and prognosis in the preoperative setting are needed. Radiomic models, specifically delta radiomic features (DRFs), may provide insight into treatment dynamics to improve preoperative predictions. METHODS: We retrospectively collected clinical, pathological, and surgical data (patients with resectable, borderline, locally advanced, and metastatic disease), and pre/post-NAT contrast-enhanced computed tomography (CT) scans from PDAC patients at the University of Texas Southwestern Medical Center (UTSW; discovery) and Humanitas Hospital (validation cohort). Gross tumor volume was contoured from CT scans, and 257 radiomics features were extracted. DRFs were calculated by direct subtraction of pre/post-NAT radiomic features. Cox proportional models and binary prediction models, including/excluding clinical variables, were constructed to predict overall survival (OS), disease-free survival (DFS), and RMS. RESULTS: The discovery and validation cohorts comprised 58 and 31 patients, respectively. Both cohorts had similar clinical characteristics, apart from differences in NAT (FOLFIRINOX vs. gemcitabine/nab-paclitaxel; p < 0.05) and type of surgery resections (pancreatoduodenectomy, distal or total pancreatectomy; p < 0.05). The model that combined clinical variables (pre-NAT carbohydrate antigen (CA) 19-9, the change in CA19-9 after NAT (∆CA19-9), and resectability status) and DRFs outperformed the clinical feature-based models and other radiomics feature-based models in predicting OS (UTSW: 0.73; Humanitas: 0.66), DFS (UTSW: 0.75; Humanitas: 0.64), and RMS (UTSW 0.73; Humanitas: 0.69). CONCLUSIONS: Our externally validated, predictive/prognostic delta-radiomics models, which incorporate clinical variables, show promise in predicting the risk of predicting RMS in NAT-treated PDAC patients and their OS or DFS.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante , Estudos Retrospectivos , Margens de Excisão , Radiômica , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgiaRESUMO
BACKGROUND: Performance of complex cancer surgeries at high-volume (HV) centers has been shown to reduce operative mortality. However, the case volume threshold that should be used to define HV centers is unknown. In this study, we determined thresholds to define HV pancreaticoduodenectomy, esophagectomy, and major lung resection centers based on clinical parameters. Then, we assessed the association of hospital volume with oncologic outcomes and overall survival. METHODS: We identified adult NCDB patients undergoing pancreaticoduodenectomy, esophagectomy, and major lung resections between 2004 and 2015. Multivariable models with restricted cubic splines were built to predict 5-year overall survival for each surgery group according to average yearly case volume, adjusting for demographic and clinicopathologic factors. The change point procedure was then used to identify volume cut-points for each surgery type. RESULTS: We identified the following thresholds to define HV status: 25 cases/year for pancreaticoduodenectomy; 18 cases/year for esophagectomy; and 54 cases/year for major lung resections. For all surgery types, treatment at a HV center was associated with an increased likelihood of R0 resection and adequate lymph node evaluation. HV centers had significantly decreased 30- and 90-day, postoperative mortality after adjusting for age, sex, race, comorbidities, histology, and stage. An overall survival benefit also was observed for patients undergoing resections at HV centers. CONCLUSIONS: Using novel methodology, our study identified volume thresholds for HV pancreaticoduodenectomy, esophagectomy, and major lung resection centers that were associated with improved oncologic outcomes and overall survival. These definitions of HV centers should be considered when evaluating regionalization of complex cancer care.
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Esofagectomia , Pancreaticoduodenectomia , Adulto , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Pulmão , Mortalidade Hospitalar , Hospitais com Alto Volume de AtendimentosRESUMO
OBJECTIVE: To identify novel prognostic and predictive biomarkers for gastric and gastroesophageal junction (G+GEJ) adenocarcinoma. BACKGROUND: There are few biomarkers to guide treatment for G+GEJ. The systemic inflammatory response of G+GEJ patients is associated with survival. In this study, we evaluated the relationship of circulating serum cytokine levels with overall survival (OS) and pathologic tumor regression grade (TRG) in G+GEJ patients. PATIENTS AND METHODS: We queried the UT Southwestern gastric cancer biobank to identify consecutive patients diagnosed with G+GEJ from 2016 to 2022; these patients had pretreatment serum collected at diagnosis. For patients who received neoadjuvant therapy, an additional serum sample was collected immediately before surgical resection. An unbiased screen of 17 cytokines was measured in a discovery cohort. A multivariable Cox proportional hazards model was used to assess the association of cytokine concentration with OS. Findings were validated in additional patients. In patients who received neoadjuvant therapy, we assessed whether the change in interleukin 6 (IL-6) after therapy was associated with TRG. RESULTS: Sixty-seven patients were included in the discovery cohort, and IL-6 was the only pretreatment cytokine associated with OS; this was validated in 134 other patients (hazard ratio: 1.012 per 1 pg/mL increase, 95% CI: 1.006-1.019, P = 0.0002). Patients in the top tercile of IL-6 level had worse median OS (10.6 months) compared with patients in the intermediate (17.4 months) and bottom tercile (35.8 months, P < 0.0001). Among patients who underwent neoadjuvant therapy (n = 50), an unchanged or decrease in IL-6 level from pretreatment to posttreatment, had a sensitivity and specificity of 80% for predicting complete or near-complete pathologic tumor regression (TRG 0-1). CONCLUSIONS: Pretreatment serum level of IL-6 is a promising prognostic biomarker for G+GEJ patients. Comparing pre and post-neoadjuvant IL-6 levels may predict pathologic response to neoadjuvant therapy.
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Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Interleucina-6 , Junção Esofagogástrica/patologia , Terapia Neoadjuvante , BiomarcadoresRESUMO
INTRODUCTION: Curative intent for localized pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) requires surgery, but despite improved perioperative outcomes, surgery remains underutilized. This study analyzed the Texas Cancer Registry (TCR) to identify resectable PDAC patients who underwent curative-intent surgery in Texas between 2004 and 2018. We then evaluated demographic and clinical factors associated with failure to operate and survival (OS). METHODS: We identified patients with localized PDAC or regional lymph node spread between 2004 and 2018 in the TCR. Resection rates were determined and multivariable regression and cox proportional hazards were used to identify factors associated with failure to OS. RESULTS: Of 4274 patients, 22% underwent resection, 57% were not offered surgery, 6% had comorbidities precluding surgery, and 3% refused. Resection rates decreased from 31% in 2004 to 22% in 2018. Increasing age was associated with failure to operate (odds ratio [OR] 2.55; 95% confidence interval [CI] 1.80-3.61; p < 0.0001) while treatment at a Commission on Cancer (CoC) center correlated with reduced failure to operate (OR 0.63; 95% CI 0.50-0.78; p < 0.0001). Resection correlated with survival (HR 0.34; 95% CI 0.31-0.38; p < 0.0001) as did treatment at a National Cancer Institute (NCI)-designated center (hazard ratio 0.79; 95% CI 0.70-0.89; p < 0.0001). CONCLUSIONS: Surgery is underutilized for the treatment of resectable PDAC in Texas with decreasing utilization, annually. Evaluation at CoC was associated with improved resection rates and NCI was associated with increased survival. Expanding access to multidisciplinary care including trained hepato-pancreatico-biliary surgeons may improve outcomes for PDAC patients.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Pancreatectomia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Receptores de Antígenos de Linfócitos T , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) requires complex multidisciplinary care. European evidence suggests potential benefit from regionalization, however, data characterizing the ideal setting in the United States are sparse. Our study compares the significance of four hospital designations on guideline-concordant care (GCC) and overall survival (OS). PATIENTS AND METHODS: The Texas Cancer Registry was queried for 17,071 patients with PDAC treated between 2004 and 2015. Clinical data were correlated with hospital designations: NCI designated (NCI), high volume (HV), safety net (SNH), and American College of Surgeons Commission on Cancer accredited (ACS). Univariable (UVA) and multivariable (MVA) logistic regression were used to assess associations with GCC [on the basis of National Comprehensive Cancer Network (NCCN) recommendations]. Cox regression analysis assessed survival. RESULTS: Only 43% of patients received GCC. NCI had the largest associated risk reduction (HR 0.61, CI 0.58-0.65), followed by HV (HR 0.87, CI 0.83-0.90) and ACS (HR 0.91, CI 0.87-0.95). GCC was associated with a survival benefit in the full (HR 0.75, CI 0.69-0.81) and resected cohort (HR 0.74, CI 0.68-0.80). NCI (OR 1.52, CI 1.37-1.70), HV (OR 1.14, CI 1.05-1.23), and SNH (OR 0.78, CI 0.68-0.91) all correlated with receipt of GCC. For resected patients, ACS (OR 0.63, CI 0.50-0.79) and SNH (OR 0.50, CI 0.33-0.75) correlate with GCC. CONCLUSIONS: A total of 43% of patients received GCC. Treatment at NCI and HV correlated with improved GCC and survival. Including GCC as a metric in accreditation standards could impact survival for patients with PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Estados Unidos/epidemiologia , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/terapia , Texas/epidemiologia , Hospitais , Neoplasias PancreáticasRESUMO
PURPOSE: We sought to identify biomarkers that predict overall survival (OS) and response to immune checkpoint inhibitors (ICI) for patients with gastric cancer. EXPERIMENTAL DESIGN: This was a retrospective study of multiple independent cohorts of patients with gastric cancer. The association between tumor ACTA2 expression and OS and ICI response were determined in patients whose tumors were analyzed with bulk mRNA sequencing. Single-cell RNA sequencing (scRNA-seq) and digital spatial profiling data were used to compare tumors from patients with gastric cancer who did and did not respond to ICI. RESULTS: Increasing tumor ACTA2 expression was independently associated with worse OS in a 567-patient discovery cohort [HR, 1.28 per unit increase; 95% confidence interval (CI), 1.02-1.62]. This finding was validated in three independent cohorts (n = 974; HR, 1.52 per unit increase; 95% CI, 1.34-1.73). Of the 108 patients treated with ICI, 56% of patients with low ACTA2 expression responded to ICI versus 25% of patients with high ACTA2 expression (P = 0.004). In an analysis of a publicly available scRNA-seq dataset of 5 microsatellite instability-high patients treated with ICI, the patient who responded to ICI had lower tumor stromal ACTA2 expression than the 4 nonresponders. Digital spatial profiling of tumor samples from 4 ICI responders and 5 ICI nonresponders revealed that responders may have lower ACTA2 expression in α-SMA-positive cancer-associated fibroblasts (CAF) than nonresponders (median: 5.00 vs. 5.50). CONCLUSIONS: ACTA2 expression is associated with survival and ICI response in patients with gastric cancer. ACTA2 expression in CAFs, but not in other cellular compartments, appears to be associated with ICI response.
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Fibroblastos Associados a Câncer , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Instabilidade de Microssatélites , ActinasRESUMO
BACKGROUND: Multimodal analgesia techniques, including regional analgesia, have been shown to provide effective analgesia and minimize opioid consumption after liver resection surgery. While thoracic epidural analgesia (TEA) is considered the gold standard, its role in the current era of enhanced recovery after surgery (ERAS) has been questioned. Erector spinae plane blocks (ESPBs) have the potential to provide effective postoperative analgesia without the risks associated with epidural analgesia. The primary aim of this quality improvement project was to evaluate the analgesic efficacy of ultrasound-guided ESPB in comparison with TEA in patients undergoing open liver resection. METHODS: Fifty patients who underwent open liver resection and received TEA (n=25) or ESPB (n=25) as part of an ERAS pathway were retrospectively identified. The primary outcome measure was cumulative postoperative opioid consumption at 24 hours. Secondary outcomes included opioid consumption, pain scores, the incidence of nausea and vomiting requiring antiemetics, lower extremity muscle weakness, and occurrence of hypotension requiring treatment on arrival to the post-anesthesia care unit and at 2, 6, 12, 24 hours, and daily through postoperative day 7. Results: Opioid requirements were significantly lower in the TEA group compared to the ESPB group. Postoperative pain scores at rest and with deep inspiration were significantly lower in the TEA group through postoperative day 5. There were no differences in other outcome measures. CONCLUSIONS: These findings suggest that compared with ESPB, TEA provides superior pain relief after open liver resection.
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BACKGROUND: Veteran populations have five times the incidence of hepatocellular carcinoma (HCC) compared with the general population. The incidence of HCC has increased in the Veteran's Affairs Health System (VAHS), primarily due to the increased prevalence of cirrhosis. This study aimed to characterize differences in treatment patterns and overall survival rates across the five VAHS geographic regions. METHODS: Using the VA Corporate Data Warehouse, the authors built a comprehensive national dataset of Veteran patients with HCC diagnosed between 2001 and 2015 to compare patients across VAHS regions. A multivariable Cox proportional hazards model was used to identify factors associated with 5-year all-cause mortality. Kaplan-Meier curves were used to visualize the patient survival function, and the log-rank test was applied to test statistical significance. RESULTS: This retrospective study analyzed 13,434 patients. The West region had the highest rate of overall treatment receipt (63.6%), and the Southwest had the lowest rate (52.9%). After adjustment for demographic, clinicopathologic, treatment, and hospital factors, treatment in a non-West region continued to be significantly associated with a 10% to 13% increased risk of 5-year mortality (Midwest: hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.03-1.17; Northeast: HR, 1.10; 95% CI, 1.03-1.17; Southeast: HR, 1.13; 95% CI, 1.06-1.21; Southwest: HR, 1.11; 95% CI, 1.03-1.19) (p < 0.01). CONCLUSIONS: Treatment patterns and overall survival rates of HCC patients differ significantly across VAHS geographic regions. Targeted interventions to increase the rate of treatment in the non-West regions are needed to improve survival of HCC Veterans and provide uniformly high-quality care across VAHS facilities.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Veteranos , Humanos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/diagnóstico , Estudos Retrospectivos , Cirrose Hepática , Modelos de Riscos ProporcionaisRESUMO
PURPOSE: The oligometastatic state is observed in patients across many malignancies, with increased recognition regarding improved outcomes after local therapies. However, there is limited data specifically regarding pancreatic ductal adenocarcinoma. We hypothesized that an oligometastatic pancreatic ductal adenocarcinoma (OPanc) phenotype would benefit from stereotactic ablative radiation therapy (SABR) to all active metastatic sites. Here, we report our institutional experience of SABR-treated OPanc to evaluate the feasibility of the approach. METHODS AND MATERIALS: A retrospective review of patients with synchronous or metachronous OPanc (1 to 5 metastases) who received SABR to all active metastatic sites was performed. We identified a comparable group of patients with similar metastatic burden, range of CA19-9 levels, and no progression for at least 5 months who did not receive SABR. We compared overall survival as the primary outcome, and polyprogression-free survival and time off chemotherapy as the secondary exploratory assessments. A third group presenting with stage IV pancreatic ductal adenocarcinoma and more than 5 distant lesions (polymetastatic) was identified to help define expected outcomes after polyprogression. RESULTS: Our study included 20 patients with OPanc receiving SABR and 21 who did not. SABR was delivered to 38 metastatic tumors. Out of the 20 SABR-treated OPanc patients, 17 (85%) had 6 or more months of time off chemotherapy, compared with 7 patients (33.3%) among the chemotherapy-treated group. Median polyprogression-free survival was 40 and 14 months (hazard ratio = 0.2; 95% confidence interval, 0.07-0.54; P = .0009), and overall survival was 42 and 18 months (hazard ratio = 0.21; 95% confidence interval, 0.08-0.53; P = .0003), for SABR- and chemotherapy-treated cohorts, respectively. CONCLUSIONS: Management of OPanc with SABR as local regional therapy could improve outcomes in a selected population and warrants prospective evaluation.
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Adenocarcinoma , Neoplasias Pancreáticas , Radiocirurgia , Antígeno CA-19-9 , Humanos , Neoplasias Pancreáticas/radioterapia , Radiocirurgia/métodos , Neoplasias PancreáticasRESUMO
Objective: Distant metastases from papillary thyroid carcinoma (PTC) are relatively rare and may be associated with a poor prognosis. The adrenal gland is a highly unusual site of metastasis in the natural course of PTC. Herein, we describe a case of an incidentally detected metastatic solid variant of PTC in the adrenal gland of an asymptomatic patient as the initial presentation. Case Report: A 67-year-old male patient was evaluated for a 4.7-cm adrenal incidentaloma discovered during a workup for nephrolithiasis. Biochemical evaluation revealed a nonfunctioning adrenal mass. The patient underwent adrenalectomy, which revealed metastatic PTC. A subsequent thyroid ultrasound revealed an isthmic nodule. Fine needle aspiration of the nodule was cytologically suspicious for a follicular neoplasm, and gene expression analysis revealed an HRAS c.182A>G sequence variation. The patient subsequently underwent total thyroidectomy, which revealed a 1.2-cm solid variant of PTC in the thyroid isthmus. Postoperatively, the patient underwent radioactive iodine ablation. Discussion: Our case illustrates an exceedingly rare and challenging situation-a metastatic solid variant of PTC in the adrenal gland of a patient with no prior history of PTC. When confronted with a PTC in the adrenal gland in the absence of a previously identified primary tumor, our experience suggests that the next step in management should be total thyroidectomy followed by radioactive iodine ablation. Conclusion: A solid variant of PTC is a rare cause of an incidentally detected adrenal lesion. Multidisciplinary care team coordination is essential for accurate diagnosis and treatment plan formulation.
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BACKGROUND: Lenvatinib is a multitargeted tyrosine kinase inhibitor that is being tested in combination with immune checkpoint inhibitors to treat advanced gastric cancer; however, little data exists regarding the efficacy of lenvatinib monotherapy. Patient-derived xenografts (PDX) are established by engrafting human tumors into immunodeficient mice. The generation of PDXs may be hampered by growth of lymphomas. In this study, we compared the use of mice with different degrees of immunodeficiency to establish PDXs from a diverse cohort of Western gastric cancer patients. We then tested the efficacy of lenvatinib in this system. METHODS: PDXs were established by implanting gastric cancer tissue into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) or Foxn1nu (nude) mice. Tumors from multiple passages from each PDX line were compared histologically and transcriptomically. PDX-bearing mice were randomized to receive the drug delivery vehicle or lenvatinib. After 21 days, the percent tumor volume change (%Δvtumor) was calculated. RESULTS: 23 PDX models were established from Black, non-Hispanic White, Hispanic, and Asian gastric cancer patients. The engraftment rate was 17% (23/139). Tumors implanted into NSG (16%; 18/115) and nude (21%; 5/24) mice had a similar engraftment rate. The rate of lymphoma formation in nude mice (0%; 0/24) was lower than in NSG mice (20%; 23/115; p < 0.05). PDXs derived using both strains maintained histologic and gene expression profiles across passages. Lenvatinib treatment (mean %Δvtumor: -33%) significantly reduced tumor growth as compared to vehicle treatment (mean %Δvtumor: 190%; p < 0.0001). CONCLUSIONS: Nude mice are a superior platform than NSG mice for generating PDXs from gastric cancer patients. Lenvatinib showed promising antitumor activity in PDXs established from a diverse Western patient population and warrants further investigation in gastric cancer.
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Neoplasias Gástricas , Animais , Humanos , Camundongos , Xenoenxertos , Camundongos Endogâmicos NOD , Camundongos Nus , Compostos de Fenilureia , Quinolinas , Neoplasias Gástricas/tratamento farmacológico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Genomic profiling can provide prognostic and predictive information to guide clinical care. Biomarkers that reliably predict patient response to chemotherapy and immune checkpoint inhibition in gastric cancer are lacking. In this retrospective analysis, we use our machine learning algorithm NTriPath to identify a gastric-cancer specific 32-gene signature. Using unsupervised clustering on expression levels of these 32 genes in tumors from 567 patients, we identify four molecular subtypes that are prognostic for survival. We then built a support vector machine with linear kernel to generate a risk score that is prognostic for five-year overall survival and validate the risk score using three independent datasets. We also find that the molecular subtypes predict response to adjuvant 5-fluorouracil and platinum therapy after gastrectomy and to immune checkpoint inhibitors in patients with metastatic or recurrent disease. In sum, we show that the 32-gene signature is a promising prognostic and predictive biomarker to guide the clinical care of gastric cancer patients and should be validated using large patient cohorts in a prospective manner.
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Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Gastrectomia , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , TranscriptomaRESUMO
BACKGROUND: The U.S. foreign-born population is rapidly increasing, and cancer incidence/mortality rates have been shown to differ by nativity status. Our study aimed to characterize differences in gastric cancer presentation and survival among Hispanic patients in Texas by nativity status. METHODS: We conducted a retrospective review of the Texas Cancer Registry to identify Hispanic patients diagnosed with gastric adenocarcinoma between 2004 and 2017. Existing indices applied to 2010 census tract-level data were utilized to measure neighborhood socioeconomic status (nSES) and Hispanic enclaves. Nativity status was imputed for patients with missing data. Multivariable Cox proportional hazard models were fit for overall survival adjusted for age, insurance status, diagnosis year, tumor location, stage, grade, reporting source, nativity status, nSES, and Hispanic enclave. RESULTS: Our study cohort consisted of 6186 patients and 39% were foreign-born. A greater proportion of foreign-born patients were diagnosed at < 45 years old (16% vs. 11%, p < 0.0001) and had metastatic disease at presentation (47% vs. 34%, p < 0.0001). Foreign-born patients were more often uninsured, in the lowest nSES quintile, and the highest (most ethnically distinct) quintile for Hispanic enclave. Stage-specific overall survival was significantly higher among foreign-born patients. In our multivariate model, foreign-born Hispanic patients had improved survival versus US-born (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.82-0.99). CONCLUSIONS: The clinical presentation of gastric cancer differs significantly between foreign-born and U.S.-born Hispanic patients. Foreign-born Hispanic patients have improved survival after adjusting for socioeconomic, neighborhood, and clinical factors. Further studies are needed to identify specific causal mechanisms driving the observed survival difference by nativity status.