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1.
BMJ Open Qual ; 13(2)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589054

RESUMO

INTRODUCTION: Effective communication in the operating room (OR) is crucial. Addressing a colleague by their name is respectful, humanising, entrusting and associated with improved clinical outcomes. We aimed to enhance team communication in the perioperative environment by offering personalised surgical caps labelled with name and provider role to all OR team members at a large academic medical centre. MATERIALS AND METHODS: This was a quasi-experimental, uncontrolled, before-and-after quality improvement study. A survey regarding perceptions of team communication, knowledge of names and roles, communication barriers, and culture was administered before and after cap delivery. Survey results were measured on a 5-point Likert Scale; descriptive statistics and mean scores were compared. All cause National Surgical Quality Improvement Project (NSQIP) morbidity and mortality outcomes for surgical specialties were examined. RESULTS: 1420 caps were delivered across the institution. Mean survey scores increased for knowing the names and roles of providers around the OR, feeling that people know my name and feeling comfortable communicating without barriers across disciplines. The mean score for team communication around the OR is excellent was unchanged. The highest score both before and after was knowing the name of an interdisciplinary team member is important for patient care. A total of 383 and 212 providers participated in the study before and after cap delivery, respectively. Participants agreed or strongly agreed that labelled surgical caps made it easier to talk to colleagues (64.9%) while improving communication (66.0%), team culture (60.5%) and patient care (56.8%). No significant differences were noted in NSQIP outcomes. CONCLUSIONS: Personalised labelled surgical caps are a simple, inexpensive tool that demonstrates promise in improving perioperative team communication. Creating highly reliable surgical teams with optimal communication channels requires a multifaceted approach with engaged leadership, empowered front-line providers and an institutional commitment to continuous process improvement.


Assuntos
Beluga , Salas Cirúrgicas , Humanos , Animais , Comunicação , Centros Médicos Acadêmicos , Complicações Pós-Operatórias
2.
Surg Endosc ; 38(1): 348-355, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37783778

RESUMO

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis which can resemble gallbladder adenocarcinoma (GAC) on preoperative imaging and present technical challenges in the performance of cholecystectomy. We examined our experience with each pathology to identify distinguishing characteristics that may guide patient counseling and surgical management. METHODS: A retrospective review of all pathologically confirmed cases of XGC and GAC following cholecystectomy between 2015 and 2021 at a single institution was performed. Clinical, biochemical, radiographic, and intraoperative features were compared. RESULTS: There were 37 cases of XGC and 20 cases of GAC. Patients with GAC were older (mean 70.3 years vs 58.0, p = 0.01) and exclusively female (100% vs 45.9%, p < 0.0001). There were no significant differences in accompanying symptoms between groups (nausea/vomiting, fevers, or jaundice). The mean maximum white blood cell count was elevated for XGC compared to GAC (16.4 vs 8.6 respectively, p = 0.044); however, there were no differences in the remainder of the biochemical profile, including bilirubin, liver transaminases, CEA, and CA 19-9. The presence of an intraluminal mass (61.1% vs 9.1%, p = 0.0001) and lymphadenopathy (18.8%. vs 0.0%, p = 0.045) were associated with malignancy, whereas gallbladder wall thickening as reported on imaging (87.9% vs 38.9%, p = 0.0008) and gallstones (76.5% vs. 50.0%, p = 0.053) were more often present with XGC. Cases of XGC more often had significant adhesions/inflammation (83.8% vs 55.0%, p = 0.03). CONCLUSION: Clinical features that may favor benign chronic cholecystitis over gallbladder adenocarcinoma include younger age, male gender, current or prior leukocytosis, and the absence of an intraluminal mass or lymphadenopathy. Laparoscopic cholecystectomy is a safe surgical option for equivocal presentations. Intraoperative frozen section or intentional staging of more extensive procedures based upon final histopathology are valuable surgical strategies.


Assuntos
Adenocarcinoma , Colecistite , Neoplasias da Vesícula Biliar , Linfadenopatia , Xantomatose , Humanos , Masculino , Feminino , Vesícula Biliar/cirurgia , Colecistite/diagnóstico , Colecistite/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/cirurgia , Xantomatose/diagnóstico , Xantomatose/cirurgia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Linfadenopatia/patologia
3.
J Surg Educ ; 80(12): 1755-1761, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37978011

RESUMO

INTRODUCTION: Originally designed as a forum to discuss adverse patient events, Surgery Morbidity & Mortality Conference (M&M) has evolved into an integral tool within surgical education where trainees at all levels are taught to critically examine decision-making. Others have expanded the scope of subsets of M&M conferences to include additional factors that influence patient outcomes, such as social determinants of health, implicit bias and structural policies that contribute to health disparities. In this study, we implemented a disparities-based discussion into our surgical department's weekly M&M conference and examined the effect(s) on participants' understanding and perceptions of key disparities in access to surgical care. METHODS: An anonymous electronic survey was sent to attendees of the Department of Surgery's M&M conference including faculty, residents and medical students prior to implementation of the intervention. The survey queried perceptions of the presence and impact of disparities in access to surgical care and how these are addressed at the study institution. The standard presenter slide template was updated to include a "Disparities Factors" section within the "Reasons for Complication" slide. After over 1 year, a postintervention survey was sent to conference attendees that included the same questions as the initial survey, as well as new questions related to the intervention. Descriptive statistics were performed on survey results, and comparisons were made for paired pre-post items. RESULTS: Eighty conference attendees completed the pre-intervention survey, and 70 completed the postintervention survey (22 [27.5%]; 22 [31.4%] attendings, 24 [30.0%]; 21 [30.0%] residents, 34 [42.5%]; 27 [38.6%] medical students respectively). Socioeconomics and language were most commonly identified both pre- and postintervention as the most important factors contributing to disparities in care experienced by patients at the study institution. Respondents agreed disparities in access significantly impact surgical care, and there was an increase in the number of respondents who reported feeling that disparities are being addressed postintervention. A total of 69% (n = 48) of respondents thought that integrating discussion of disparities in access to surgical care into M&M improved their understanding of the role these disparities play, 66% (n = 46) felt that their own thinking or practice changed regarding patient disparities, 84% (n = 59) reported integrating these discussions of disparities into M&M has been helpful overall. CONCLUSION: The inclusion of a disparities discussion in weekly M&M conference has led to positive change at the study institution, fostering a more comprehensive and socially conscious dialogue within the Department of Surgery. Survey respondents agreed that disparities exist in access to surgical care, and that the intervention improved their perceptions of how the study institution addresses disparities. Respondents felt that the integration of a disparities discussion was overall helpful, improved their knowledge of disparities in access to surgical care, and impacted their plans to address disparities in their own practices.


Assuntos
Internato e Residência , Estudantes de Medicina , Humanos , Inquéritos e Questionários , Morbidade
4.
J Pers Med ; 13(5)2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37241027

RESUMO

Accurately identifying metastatic disease is critical to directing the appropriate treatment in pancreatic cancer. Mucin 5AC is overexpressed in pancreatic cancer but absent in normal pancreas tissue. The present proof-of-concept study demonstrates the efficacy of an anti-mucin 5AC antibody conjugated to an IR800 dye (MUC5AC-IR800) to preferentially label a liver metastasis of pancreatic cancer (Panc Met) in a unique patient-derived orthotopic xenograft (PDOX) model. In orthotopic models, the mean tumor to background ratio was 1.787 (SD ± 0.336), and immunohistochemistry confirmed the expression of MUC5AC within tumor cells. MUC5AC-IR800 provides distinct visualization of pancreatic cancer liver metastasis in a PDOX mouse model, demonstrating its potential utility in staging laparoscopy and fluorescence-guided surgery.

5.
J Surg Educ ; 79(4): 839-844, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35414475

RESUMO

Value-based, outcome-oriented care supported with innovative technology is the future of surgery. We established a novel fellowship in Perioperative Administration, Quality, and Informatics. The aim is to equip future surgeon scholars with the requisite knowledge base and skillset to serve as institutional leaders capable of transforming surgical healthcare delivery. The model was designed as a project-based, "operations-focused" education with supplemental didactics and mentored by surgical leaders and institutional executives. We describe our initial experience, successes, and challenges such that a similar model may be replicated elsewhere.


Assuntos
Bolsas de Estudo , Liderança , Currículo , Informática
6.
Hepatobiliary Surg Nutr ; 10(3): 315-324, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34159159

RESUMO

BACKGROUND: Selection of the optimal treatment modality for primary liver cancers remains complex, balancing patient condition, liver function, and extent of disease. In individuals with preserved liver function, liver resection remains the primary approach for treatment with curative intent but may be associated with significant mortality. The purpose of this study was to establish a simple scoring system based on Model for End-stage Liver Disease (MELD) and extent of resection to guide risk assessment for liver resections. METHODS: The 2005-2015 NSQIP database was queried for patients undergoing liver resection for primary liver malignancy. We first developed a model that incorporated the extent of resection (1 point for major hepatectomy) and a MELD-Na score category of low (MELD-Na =6, 1 point), medium (MELD-Na =7-10, 2 points) or high (MELD-Na >10, 3 points) with a score range of 1-4, called the Hepatic Resection Risk Score (HeRS). We tested the predictive value of this model on the dataset using logistic regression. We next developed an optimal multivariable model using backwards sequential selection of variables under logistic regression. We performed K-fold cross validation on both models. Receiver operating characteristics were plotted and the optimal sensitivity and specificity for each model were calculated to obtain positive and negative predictive values. RESULTS: A total of 4,510 patients were included. HeRS was associated with increased odds of 30-day mortality [HeRS =2: OR =3.23 (1.16-8.99), P=0.025; HeRS =3: OR =6.54 (2.39-17.90), P<0.001; HeRS =4: OR =13.69 (4.90-38.22), P<0.001]. The AUC for this model was 0.66. The AUC for the optimal multivariable model was higher at 0.76. Under K-fold cross validation, the positive predictive value (PPV) and negative predictive value (NPV) of these two models were similar at PPV =6.4% and NPV =97.7% for the HeRS only model and PPV =8.4% and NPV =98.1% for the optimal multivariable model. CONCLUSIONS: The HeRS offers a simple heuristic for estimating 30-day mortality after resection of primary liver malignancy. More complicated models offer better performance but at the expense of being more difficult to integrate into clinical practice.

7.
Int J Cancer ; 148(3): 702-712, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32700810

RESUMO

Biliary tract cancers have dismal prognoses even when cytotoxic chemotherapy is administered. There is an unmet need to develop precision treatment approaches using comprehensive genomic profiling. A total of 121 patients with biliary tract cancers were analyzed for circulating-tumor DNA (ctDNA) and/or tissue-based tumor DNA (tissue-DNA) using clinical-grade next-generation sequencing: 71 patients (59%) had ctDNA; 90 (74%), tissue-DNA; and 40 (33%), both. Efficacy of targeted therapeutic approaches was assessed based upon ctDNA and tissue-DNA. At least one characterized alteration was detected in 76% of patients (54/71) for ctDNA [median, 2 (range, 0-9)] and 100% (90/90) for tissue-DNA [median, 4 (range, 1-9)]. Most common alterations occurred in TP53 (38%), KRAS (28%), and PIK3CA (14%) for ctDNA vs TP53 (44%), CDKN2A/B (33%) and KRAS (29%) for tissue-DNA. In 40 patients who had both ctDNA and tissue-DNA sequencing, overall concordance was higher between ctDNA and metastatic site tissue-DNA than between ctDNA and primary tumor DNA (78% vs 65% for TP53, 100% vs 74% for KRAS and 100% vs 87% for PIK3CA [But not statistical significance]). Among 80 patients who received systemic treatment, the molecularly matched therapeutic regimens based on genomic profiling showed a significantly longer progression-free survival (hazard ratio [95%confidence interval], 0.60 [0.37-0.99]. P = .047 [multivariate]) and higher disease control rate (61% vs 35%, P = .04) than unmatched regimens. Evaluation of ctDNA and tissue-DNA is feasible in biliary tract cancers.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , DNA Tumoral Circulante/genética , DNA de Neoplasias/genética , Análise de Sequência de DNA/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Estudos de Viabilidade , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Medicina de Precisão , Proteínas Proto-Oncogênicas p21(ras)/genética , Análise de Sobrevida , Resultado do Tratamento , Proteína Supressora de Tumor p53/genética
8.
Ann Surg ; 272(5): 715-722, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32833764

RESUMO

OBJECTIVE: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe. SUMMARY/BACKGROUND: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients. METHODS: Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers. RESULTS: Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries. CONCLUSIONS: Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.


Assuntos
Neoplasias Colorretais/patologia , Tomada de Decisões , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Consenso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
J Gastrointest Surg ; 24(5): 1165-1172, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31468331

RESUMO

BACKGROUND: A significant proportion of patients with rectal cancer will present with synchronous metastasis at the time of diagnosis. Overall survival (OS) for these patients are highly variable and previous attempts to build predictive models often have low predictive power, with concordance indexes (c-index) less than 0.70. METHODS: Using the National Cancer Database (2010-2014), we identified patients with synchronous metastatic rectal cancer. The data was split into a training dataset (diagnosis years 2010-2012), which was used to build the machine learning model, and a testing dataset (diagnosis years 2013-2014), which was used to externally validate the model. A nomogram predicting 3-year OS was created using Cox proportional hazard regression with lasso penalization. Predictors were selected based on clinical significance and availability in NCDB. Performance of the machine learning model was assessed by c-index. RESULTS: A total of 4098 and 3107 patients were used to construct and validate the nomogram, respectively. Internally validated c-indexes at 1, 2, and 3 years were 0.816 (95% CI 0.813-0.818), 0.789 (95% CI 0.786-0.790), and 0.778 (95% CI 0.775-0.780), respectively. External validated c-indexes at 1, 2, and 3 years were 0.811, 0.779, and 0.778, respectively. CONCLUSIONS: There is wide variability in the OS for patients with metastatic rectal cancer, making accurate predictions difficult. However, using machine learning techniques, more accurate models can be built. This will aid patients and clinicians in setting expectations and making clinical decisions in this group of challenging patients.


Assuntos
Nomogramas , Neoplasias Retais , Humanos , Aprendizado de Máquina , Prognóstico , Programa de SEER
11.
Am J Surg ; 220(2): 408-414, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31864521

RESUMO

BACKGROUND: The role of laterality for patients with synchronous metastatic colon cancer (SMCC) is not well-defined. METHODS: Using the National Cancer Database (2010-2015), we compared patients with metastatic right- (RCC) versus left-sided colon cancer (LCC). We performed Kaplan-Meier analysis to compare overall survival (OS) for each metastatic site and utilized adjusted Cox proportional hazard analysis to identify predictors of OS. RESULTS: Patients with RCCs were more likely to be older, female, and have more comorbidities. LCCs were more likely to metastasize to liver and lung, whereas RCCs were more likely to metastasize to peritoneum and brain. There was equal likelihood to metastasize to bone. OS was significantly longer for LCCs for all metastatic sites. After controlling for multiple variables, RCC (HR 1.426, p < 0.001) remained an independent predictor of worse OS compared to LCC. CONCLUSIONS: Laterality of the primary tumor plays an important role in outcomes for patients with SMCC.


Assuntos
Neoplasias do Colo/patologia , Idoso , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos
13.
J Surg Res ; 236: 110-118, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30694743

RESUMO

BACKGROUND: Surgical supplies occupy a large portion of health care expenditures but is often under the surgeon's control. We sought to assess whether an automated, surgeon-directed, cost feedback system can decrease supply expenditures for five common general surgery procedures. MATERIALS AND METHODS: An automated "surgical receipt" detailing intraoperative supply costs was generated and emailed to surgeons after each case. We compared the median cost per case for 18 mo before and after implementation of the surgical receipt. We controlled for price fluctuations by applying common per-unit prices in both periods. We also compared the incision time, case length booking accuracy, length of stay, and postoperative occurrences. RESULTS: Median costs decreased significantly for open inguinal hernia ($433.45 to $385.49, P < 0.001), laparoscopic cholecystectomy ($886.77 to $816.13, P = 0.002), and thyroidectomy ($861.21 to $825.90, P = 0.034). Median costs were unchanged for laparoscopic appendectomy and increased significantly for lumpectomy ($325.67 to $420.53, P < 0.001). There was an increase in incision-to-closure minutes for open inguinal hernia (71 to 75 min, P < 0.001) and laparoscopic cholecystectomy (75 to 96 min, P < 0.001), but a decrease in thyroidectomy (79 to 73 min, P < 0.001). There was an increase in booking accuracy for laparoscopic appendectomy (38.6% to 55.0%, P = 0.001) and thyroidectomy (32.5% to 48.1%, P = 0.001). There were no differences in postoperative occurrence rates and length of stay duration. CONCLUSIONS: An automated surgeon-directed surgical receipt may be a useful tool to decrease supply costs for certain procedures. However, curtailing surgical supply costs with surgeon-directed cost feedback alone is challenging and a multimodal approach may be necessary.


Assuntos
Equipamentos e Provisões Hospitalares/economia , Custos Hospitalares/organização & administração , Salas Cirúrgicas/economia , Cirurgiões/organização & administração , Procedimentos Cirúrgicos Operatórios/economia , Redução de Custos/economia , Redução de Custos/estatística & dados numéricos , Análise Custo-Benefício , Correio Eletrônico , Equipamentos e Provisões Hospitalares/estatística & dados numéricos , Estudos de Viabilidade , Retroalimentação , Humanos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Salas Cirúrgicas/organização & administração , Duração da Cirurgia , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Cirurgiões/economia , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos
14.
Ann Surg Oncol ; 25(7): 1852-1859, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29600347

RESUMO

BACKGROUND: A scholar's h-index is defined as the number of h papers published, each of which has been cited at least h times. We hypothesized that the h-index strongly correlates with the academic rank of surgical oncologists. METHODS: We utilized the National Cancer Institute (NCI) website to identify NCI-designated Comprehensive Cancer Centers (CCC) and Doximity to identify the 50 highest-ranked general surgery residency programs with surgical oncology divisions. Demographic data of respective academic surgical oncologists were collected from departmental websites and Grantome. Bibliometric data were obtained from Web of Science. RESULTS: We identified 544 surgical oncologists from 64 programs. Increased h-index was associated with academic rank (p < 0.001), male gender (p < 0.001), number of National Institutes of Health (NIH) grants (p < 0.001), and affiliation with an NCI CCC (p = 0.018) but not number of additional degrees (p = 0.661) or Doximity ranking (p = 0.102). H-index was a stronger predictor of academic rank (r = 0.648) than total publications (r = 0.585) or citations (r = 0.450). CONCLUSIONS: This is the first report to assess the h-index within academic surgical oncology. H-index is a bibliometric predictor of academic rank that correlates with NIH grant funding and NCI CCC affiliation. We also highlight a previously unexpected and unappreciated gender disparity in the academic productivity of US surgical oncologists. When academic rank was accounted for, female surgical oncologists had lower h-indices compared with their male colleagues. Evaluation of the etiologies of this gender disparity is needed to address barriers to academic productivity faced by female surgical oncologists as they progress through their careers.


Assuntos
Centros Médicos Acadêmicos/tendências , Pesquisa Biomédica/estatística & dados numéricos , Eficiência , Oncologistas/estatística & dados numéricos , Publicações/estatística & dados numéricos , Apoio à Pesquisa como Assunto/estatística & dados numéricos , Oncologia Cirúrgica , Feminino , Humanos , Masculino , National Cancer Institute (U.S.) , National Institutes of Health (U.S.) , Fatores Sexuais , Estados Unidos
15.
Oncotarget ; 9(99): 37333-37342, 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30647873

RESUMO

Pancreatic cancer is a highly lethal disease in part due to incomplete tumor resection. Targeting by tumor-specific antibodies conjugated with a fluorescent label can result in selective labeling of cancer in vivo for surgical navigation. In the present study, we describe a patient-derived orthotopic xenograft model of pancreatic cancer that recapitulated the disease on a gross and microscopic level, along with physiologic clinical manifestations. We additionally show that the use of an anti-CEA antibody conjugated to the near-infrared (NIR) fluorescent dye, IRDye800CW, can selectively highlight the pancreatic cancer and its metastases in this model with a tumor-to-background ratio of 3.5 (SEM 0.9). The present results demonstrate the clinical potential of this labeling technique for fluorescence-guided surgery of pancreatic cancer.

16.
Oncotarget ; 8(29): 47490-47496, 2017 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-28537897

RESUMO

A pancreatic ductal adenocarcinoma (PDAC), obtained from a patient, was grown orthotopically in the pancreatic tail of nude mice to establish a patient-derived orthotopic (PDOX) model. Seven weeks after implantation, PDOX nude mice were divided into the following groups: untreated control (n = 7); gemcitabine (100 mg/kg, i.p., once a week for 2 weeks, n = 7); cobimetinib (5 mg/kg, p.o., 14 consecutive days, n = 7); trametinib (0.3 mg/kg, p.o., 14 consecutive days, n = 7); trabectedin (0.15 mg/kg, i.v., once a week for 2 weeks, n = 7); temozolomide (25 mg/kg, p.o., 14 consecutive days, n = 7); carfilzomib (2 mg/kg, i.v., twice a week for 2 weeks, n = 7); bortezomib (1 mg/kg, i.v., twice a week for 2 weeks, n = 7); MK-1775 (20 mg/kg, p.o., 14 consecutive days, n = 7); BEZ-235 (45 mg/kg, p.o., 14 consecutive days, n = 7); vorinostat (50 mg/kg, i.p., 14 consecutive days, n = 7). Only the MEK inhibitors, cobimetinib and trametinib, regressed tumor growth, and they were more significantly effective than other therapies (p < 0.0001, respectively), thereby demonstrating the precision of the PDOX models of PDAC and its potential for individualizing pancreatic-cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Azetidinas/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Piridonas/farmacologia , Pirimidinonas/farmacologia , Animais , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Camundongos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
17.
Oncotarget ; 8(12): 19065-19073, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-27683127

RESUMO

Liver metastasis is the main cause of colon cancer-related death and is a recalcitrant disease. We report here the efficacy and safety of intra-portal-vein (iPV) targeting of Salmonella typhimurium A1-R on colon cancer liver metastasis in a nude-mouse orthotopic model. Nude mice with HT29 human colon cancer cells, expressing red fluorescent protein (RFP) (HT29-RFP), growing in the liver were administered S. typhimurium A1-R by either iPV (1×104 colony forming units (CFU)/100 µl) or, for comparison, intra-venous injection (iv; 5×107 CFU/100 µl). Similar amounts of bacteria were delivered to the liver with the two doses, indicating that iPV delivery is 5×103 times more efficient than iv delivery. Treatment efficacy was evaluated by tumor fluorescent area (mm2) and total fluorescence intensity. Tumor fluorescent area and fluorescence intensity highly correlated (p<0.0001). iPV treatment was more effective compared to both untreated control and iv treatment (p<0.01 and p<0.05, respectively with iPV treatment with S. typhimurium arresting metastatic growth). There were no significant differences in body weight between all groups. The results of this study suggest that S. typhimurium A1-R administered iPV has potential for peri-operative adjuvant treatment of colon cancer liver metastasis.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias do Colo/patologia , Neoplasias Hepáticas/secundário , Salmonelose Animal , Salmonella typhimurium , Animais , Células HT29 , Humanos , Injeções Intravenosas , Camundongos , Camundongos Nus , Veia Porta , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Surg Oncol ; 114(8): 951-958, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27696448

RESUMO

BACKGROUND AND OBJECTIVES: Delineation of adequate tumor margins is critical in oncologic surgery, particularly in resection of metastatic lesions. Surgeons are limited in visualization with bright-light surgery, but fluorescence-guided surgery (FGS) has been efficacious in helping the surgeon achieve negative margins. METHODS: The present study uses FGS in a mouse model that has undergone surgical orthotopic implantation (SOI) of colorectal liver metastasis tagged with green fluorescent protein (GFP). An anti-CEA antibody conjugated to DyLight 650 was used to highlight the tumor. RESULTS: The fluorescent antibody clearly demarcated the lesion at deeper tissue depth compared to GFP. Fluorescence of the anti-CEA-DyLight650 showed maximal tumor-to-liver contrast at 72 hr. Fifteen mice underwent bright-light surgery (BLS) versus FGS with GFP versus FGS with anti-CEA-DyLight650. Mice that underwent FGS had a significantly smaller area of residual tumor (P < 0.001) and significantly longer overall survival (P < 0.001) and disease-free survival (P < 0.001). Within the two FGS groups, mice undergoing surgery with anti-CEA-DyLight650 improved survival compared to only GFP labeling. CONCLUSIONS: In the present report, we demonstrate that an anti-CEA antibody conjugated to a DyLight 650 nm dye clearly labeled colon cancer liver metastases, thereby enabling successful FGS. J. Surg. Oncol. 2016;114:951-958. © 2016 Wiley Periodicals, Inc.


Assuntos
Anticorpos Monoclonais , Antígeno Carcinoembrionário/imunologia , Corantes Fluorescentes , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Imagem Óptica/métodos , Animais , Neoplasias Colorretais/patologia , Técnica Direta de Fluorescência para Anticorpo , Células HT29 , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Camundongos , Camundongos Nus , Transplante de Neoplasias , Distribuição Aleatória , Resultado do Tratamento
19.
Mol Ther Nucleic Acids ; 5: e315, 2016 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-27115840

RESUMO

The ability to selectively target disease-related tissues with molecules is critical to the design of effective therapeutic and diagnostic reagents. Recognizing the differences between the in vivo environment and in vitro conditions, we employed an in vivo selection strategy to identify RNA aptamers (targeting motifs) that could localize to tumor in situ. One of the selected molecules is an aptamer that binds to the protein DHX9, an RNA helicase that is known to be upregulated in colorectal cancer. Upon systemic administration, the aptamer preferentially localized to the nucleus of cancer cells in vivo and thus has the potential to be used for targeted delivery.

20.
J Gastrointest Surg ; 20(1): 221-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26489742

RESUMO

BACKGROUND: At a recently concluded Americas Hepato-Pancreato-Biliary Association Annual Meeting, a Clinical Practice Guidelines Conference Series was convened with the topic focusing on Venous Thromboembolism (VTE) Prophylaxis in Liver Surgery. The symposium brought together hepatobiliary surgeons from three continents as well as medical experts in hematology and coagulation. METHODS: The content of the discussion included literature reviews, evaluation of multi-institutional VTE outcome data, and examination of practice patterns at multiple high-volume centers. RESULTS: Literature review demonstrated that, within gastrointestinal surgery, liver resection patients are at particularly high-risk for VTE. Recent evidence clearly indicates a direct relationship between the magnitude of hepatectomy and postoperative VTE rates, however, the PT/INR does not accurately reflect the coagulation status of the post-hepatectomy patient. Evaluation of available data and practice patterns regarding the utilization and timing of anticoagulant VTE prophylaxis led to recommendations regarding preoperative and postoperative thromboprophylaxis for liver surgery patients. CONCLUSIONS: This conference was effective in consolidating our knowledge of coagulation abnormalities after liver resection. Based on the expert review of the available data and practice patterns, a number of recommendations were developed.


Assuntos
Hepatectomia/efeitos adversos , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/uso terapêutico , Humanos , Fígado/cirurgia , Fatores de Risco
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