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BACKGROUND: Healthcare policies have focused on centralizing care to high-volume centers in an effort to optimize patient outcomes; however, little is known about patients' and caregivers' considerations and selection process when selecting hospitals for care. We aim to explore how patients and caregivers select hospitals for complex cancer care and to develop a taxonomy for their selection considerations. METHODS: This was a qualitative study in which data were gathered from in-depth interviews conducted from March to November 2019 among patients with hepatopancreatobiliary cancers who were scheduled to undergo a pancreatectomy (n = 20) at a metropolitan, urban regional, or suburban medical center and their caregivers (n = 10). RESULTS: The interviews revealed six broad domains that characterized hospital selection considerations: hospital factors, team characteristics, travel distance to hospital, referral or recommendation, continuity of care, and insurance considerations. The identified domains were similar between participants seen at the metropolitan center and urban/suburban medical centers, with the following exceptions: participants receiving care specifically at the metropolitan center noted operative volume and access to specific services such as clinical trials in their hospital selection; participants receiving care at urban/suburban centers noted health insurance considerations and having access to existing medical records in their hospital selection. CONCLUSIONS: This study delineates the many considerations of patients and caregivers when selecting hospitals for complex cancer care. These identified domains should be incorporated into the development and implementation of centralization policies to help increase patient access to high-quality cancer care that is consistent with their priorities and needs.
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Cuidadores , Neoplasias , Hospitais , Humanos , Seguro Saúde , Neoplasias/terapia , Pesquisa Qualitativa , Qualidade da Assistência à SaúdeRESUMO
BACKGROUND: Our previous case series suggested that a 1-week, low-calorie and low-fat diet was associated with decreased intraoperative blood loss in patients undergoing liver surgery. OBJECTIVE: The current study evaluates the effect of this diet in a randomized controlled trial. METHODS: We randomly assigned 60 patients with a body mass index ≥25âkg/m(2) to no special diet or an 800-kcal, 20 g fat, and 70 g protein diet for 1 week before liver resection. Surgeons were blinded to diet assignment. Hepatic glycogen stores were evaluated using periodic acid Schiff (PAS) stains. RESULTS: Ninety four percent of the patients complied with the diet. The diet group consumed fewer daily total calories (807 vs 1968 kcal, P < 0.001) and fat (21 vs 86 g, P < 0.001) than the no diet group. Intraoperative blood loss was less in the diet group: mean blood loss 452 vs 863 mL (P = 0.021). There was a trend towards decreased transfusion in the diet group (138 vs 322 mL, P = 0.06). The surgeon judged the liver to be easier to manipulate in the diet group: 1.86 versus 2.90, P = 0.004. Complication rate (20% vs 17%), length of stay (median 5 vs 4 days) and mortality did not differ between groups. There was no difference in hepatic steatosis between groups. There was less glycogen in hepatocytes in the diet group (PAS stain score 1.61 vs 2.46, P < 0.0001). CONCLUSIONS: A short-course, low-fat, and low-calorie diet significantly decreases bleeding and makes the liver easier to manipulate in hepatic surgery.
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Dieta/métodos , Hepatectomia/efeitos adversos , Hemorragia Pós-Operatória/prevenção & controle , Cuidados Pré-Operatórios/métodos , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Treatments that generate T cell-mediated immunity to a patient's unique neoantigens are the current holy grail of cancer immunotherapy. In particular, treatments that do not require cumbersome and individualized ex vivo processing or manufacturing processes are especially sought after. Here we report that AGI-134, a glycolipid-like small molecule, can be used for coating tumor cells with the xenoantigen Galα1-3Galß1-4GlcNAc (α-Gal) in situ leading to opsonization with pre-existing natural anti-α-Gal antibodies (in short anti-Gal), which triggers immune cascades resulting in T cell mediated anti-tumor immunity. METHODS: Various immunological effects of coating tumor cells with α-Gal via AGI-134 in vitro were measured by flow cytometry: (1) opsonization with anti-Gal and complement, (2) antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells, and (3) phagocytosis and antigen cross-presentation by antigen presenting cells (APCs). A viability kit was used to test AGI-134 mediated complement dependent cytotoxicity (CDC) in cancer cells. The anti-tumoral activity of AGI-134 alone or in combination with an anti-programmed death-1 (anti-PD-1) antibody was tested in melanoma models in anti-Gal expressing galactosyltransferase knockout (α1,3GT-/-) mice. CDC and phagocytosis data were analyzed by one-way ANOVA, ADCC results by paired t-test, distal tumor growth by Mantel-Cox test, C5a data by Mann-Whitney test, and single tumor regression by repeated measures analysis. RESULTS: In vitro, α-Gal labelling of tumor cells via AGI-134 incorporation into the cell membrane leads to anti-Gal binding and complement activation. Through the effects of complement and ADCC, tumor cells are lysed and tumor antigen uptake by APCs increased. Antigen associated with lysed cells is cross-presented by CD8α+ dendritic cells leading to activation of antigen-specific CD8+ T cells. In B16-F10 or JB/RH melanoma models in α1,3GT-/- mice, intratumoral AGI-134 administration leads to primary tumor regression and has a robust abscopal effect, i.e., it protects from the development of distal, uninjected lesions. Combinations of AGI-134 and anti-PD-1 antibody shows a synergistic benefit in protection from secondary tumor growth. CONCLUSIONS: We have identified AGI-134 as an immunotherapeutic drug candidate, which could be an excellent combination partner for anti-PD-1 therapy, by facilitating tumor antigen processing and increasing the repertoire of tumor-specific T cells prior to anti-PD-1 treatment.
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BACKGROUND AND OBJECTIVES: Lymphatic mapping (LM) and blue dye injections are essential to identification of sentinel lymph nodes (SLN) for melanoma. LM is performed the day before (DB) or the same day (SD) of surgery, but the optimal timing is unknown. Similarly, methylene blue (MB), used during SLN biopsy (SLNB), is administered diluted (dMB) or undiluted (uMB), but the relative efficacies are unknown. METHODS: Patients who underwent SLNB for melanoma from 2009 to 2013 at our institution were evaluated. Outcomes included operative correlation with LM, SLN identification, and postoperative complications. RESULTS: One hundred seventy-one patients underwent SLNB. Sixty-seven (39%) had DB LM. Sixty-seven (39%) received uMB. Operative findings correlated with both LM groups, though the DB patients had lower background count (P = 0.018) and lower highest SLN radioactive signal count (P = 0.046). More uMB patients had blue SLNs (90% vs. 68%, P = 0.001). There was no difference in the total number of SLNs or complication rates in the LM and MB groups. CONCLUSIONS: This is the first study to compare the use of DB LM with SD LM and the efficacy of uMB versus dMB. DB LM and uMB offer advantageous alternatives for patients and their surgeons without loss of accuracy or increased morbidity. J. Surg. Oncol. 2016;114:947-950. © 2016 Wiley Periodicals, Inc.
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Corantes , Linfocintigrafia , Melanoma/patologia , Azul de Metileno , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgiaRESUMO
BACKGROUND: Long-term incidence of endocrine and exocrine insufficiency after pancreatectomy is poorly described. We analyze the long-term risks of pancreatic insufficiency after pancreatectomy. METHODS: Subjects who underwent pancreatectomy from 2002 to 2012 were identified from a prospective database (n = 227). Subjects who underwent total pancreatectomy or pancreatitis surgery were excluded. New post-operative endocrine and exocrine insufficiency was defined as the need for new pharmacologic intervention within 1000 days from resection. RESULTS: 28 (16%) of 178 subjects without pre-existing endocrine insufficiency developed post-operative endocrine insufficiency: 7 (25%) did so within 30 days, 8 (29%) between 30 and 90 days, and 13 (46%) after 90 days. 94 (43%) of 214 subjects without pre-operative exocrine insufficiency developed exocrine insufficiency: 20 (21%) did so within 30 days, 29 (31%) between 30 and 90 days, and 45 (48%) after 90 days. Adjuvant radiation was associated with new endocrine insufficiency. On multivariate regression, pancreaticoduodenectomy and chemotherapy were associated with a greater risk of exocrine insufficiency. CONCLUSION: Reporting 30-day functional outcomes for pancreatic resection is insufficient, as nearly 45% of subjects who develop disease do so after 90 days. Reporting of at least 90-day outcomes may more reliably assess risk for post-operative endocrine and exocrine insufficiency.
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Insuficiência Pancreática Exócrina/etiologia , Ilhotas Pancreáticas/cirurgia , Pâncreas Exócrino/cirurgia , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/efeitos adversos , Bases de Dados Factuais , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/tratamento farmacológico , Insuficiência Pancreática Exócrina/fisiopatologia , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/patologia , Ilhotas Pancreáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pâncreas Exócrino/efeitos dos fármacos , Pâncreas Exócrino/patologia , Pâncreas Exócrino/fisiopatologia , Neoplasias Pancreáticas/patologia , Radioterapia Adjuvante/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Peritoneal dissemination of cancer is a terminal condition with limited therapeutic options. Because the peritoneal cavity is a single enclosed space, regional treatment approaches for isolated peritoneal cancrinomatosis are appealing. There is a potential role for gene therapy in the management of peritoneal cancrinomatosis. MATERIALS AND METHODS: An adenoviral construct of the human p14ARF gene (a tumor suppressor) and a 22 amino acid sequence of the ARF gene product, which has cell membrane penetrating properties, were assayed for proapoptotic properties in a human colorectal cancer cell line (Clone A) cells in vitro. Peritoneal carcinomatosis derived from Clone A cells was also established in nude mice and then treated with intraperitoneal administration of an adenoviral construct of the human p14ARF gene. RESULTS: Treatment of ARF-negative Clone A cells with Ad-hARF in vitro reestablished ARF function. However, the cell penetrating ARF-related peptide did not restore ARF function in Clone A cells. Treatment of Clone A peritoneal xenografts with a single intraperitoneal dose of Ad-hARF (9 × 10(6) viral particles) suppressed the progression of peritoneal disease. Weekly (six times) administration of the Ad-hARF at a lower dose (3 × 10(6) viral particles) also suppressed tumor progression. CONCLUSIONS: Treatment of peritoneal carcinomatosis by intraperitoneal administration of adenoviral constructs of inactivated tumor suppressor genes may be a feasible clinical approach, and ARF may represent a suitable molecular target for tumors where the ARF gene is inactivated.
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Antineoplásicos/uso terapêutico , Neoplasias Colorretais/patologia , Genes p16 , Terapia Genética/métodos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Proteína Supressora de Tumor p14ARF/uso terapêutico , Adenoviridae , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Vetores Genéticos , Humanos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neoplasias Peritoneais/genética , Distribuição Aleatória , Resultado do Tratamento , Proteína Supressora de Tumor p14ARF/genética , Proteína Supressora de Tumor p14ARF/farmacologiaRESUMO
BACKGROUND: A novel data warehouse based on automated retrieval from an institutional health care information system (HIS) was made available to be compared with a traditional prospectively maintained surgical database. METHODS: A newly established institutional data warehouse at a single-institution academic medical center autopopulated by HIS was queried for International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes for pancreatic neoplasm. Patients with ICD-9-CM diagnosis codes for pancreatic neoplasm were captured. A parallel query was performed using a prospective database populated by manual entry. Duplicated patients and those unique to either data set were identified. All patients were manually reviewed to determine the accuracy of diagnosis. RESULTS: A total of 1107 patients were identified from the HIS-linked data set with pancreatic neoplasm from 1999-2009. Of these, 254 (22.9%) patients were also captured by the surgical database, whereas 853 (77.1%) patients were only in the HIS-linked data set. Manual review of the HIS-only group demonstrated that 45.0% of patients were without identifiable pancreatic pathology, suggesting erroneous capture, whereas 36.3% of patients were consistent with pancreatic neoplasm and 18.7% with other pancreatic pathology. Of the 394 patients identified by the surgical database, 254 (64.5%) patients were captured by HIS, whereas 140 (35.5%) patients were not. Manual review of patients only captured by the surgical database demonstrated 85.9% with pancreatic neoplasm and 14.1% with other pancreatic pathology. Finally, review of the 254 patient overlap demonstrated that 80.3% of patients had pancreatic neoplasm and 19.7% had other pancreatic pathology. CONCLUSIONS: These results suggest that cautious interpretation of administrative data rely only on ICD-9-CM diagnosis codes and clinical correlation through previously validated mechanisms.
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Pesquisa Biomédica/métodos , Bases de Dados Factuais/normas , Registros Eletrônicos de Saúde/normas , Sistemas de Informação Hospitalar/normas , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Centros Médicos Acadêmicos , Idoso , Feminino , Humanos , Classificação Internacional de Doenças , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
BACKGROUND/OBJECTIVES: Heated intraperitoneal chemotherapy (HIPEC) kills cancer cells via thermal injury and improved chemotherapeutic cytotoxicity. We hypothesize that higher HIPEC flow rates improve peritoneal heating and HIPEC efficacy. METHODS: (1) A HIPEC-model (30.8 L cooler with attached extracorporeal pump) was filled with 37°C water containing a suspended 1 L saline bag (SB) wrapped in a cooling sleeve, creating a constant heat sink. (2) HIPECs were performed in a swine model. Inflow, outflow, and peritoneal temperatures were monitored as flow rates varied. (3) Flow rates and temperatures during 20 HIPECs were reviewed. RESULTS: Higher flow rates decreased time required to increase water bath (WB) and SB temperature to 43°C. With a constant heat sink, the minimum flow rate required to reach 43°C in the WB was 1.75 L/min. Higher flow rates lead to greater temperature gradients between the WB and SB. In the swine model, the minimum flow rate required to reach 43°C outflow was 2.5-3.0 L/min. Higher flows led to more rapid heating of the peritoneum and greater peritoneal/outflow temperature gradients. Increased flow during clinical HIPEC suggested improved peritoneal heating with lower average visceral temperatures. CONCLUSIONS: There is a minimum flow rate required to reach goal temperature during HIPEC. Flow rate is an important variable in achieving and maintaining goal temperatures during HIPEC.
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Antineoplásicos/administração & dosagem , Hipertermia Induzida/métodos , Neoplasias Peritoneais/terapia , Animais , Terapia Combinada , Humanos , Injeções Intraperitoneais , SuínosRESUMO
BACKGROUND: Because of the malignant potential, resection has been recommended for some intraductal papillary mucinous neoplasms (IPMN). We hypothesize that a large cancer database could be used to evaluate national resection rates and survival for malignant IPMN. MATERIALS AND METHODS: Using the Surveillance Epidemiology and End Results (SEER) database, 1988-2003, cases of malignant IPMN were identified using histology codes. Age-adjusted incidence rates were calculated; Cochran-Armitage tests evaluated trends over time. Predictors of resection were evaluated using χ(2) and logistic regression. Kaplan-Meier curves and Cox models were constructed to evaluate survival. RESULTS: Of 1834 patients, 209 (11.4%) underwent resection. Annual age-adjusted incidence decreased over the study time-course (P<0.05), while annual proportion of patients presenting with localized lesions and the proportion being resected increased (P<0.05). Predictors of resection on multivariate analysis included localized stage [versus distant, adjusted odds ratio (OR) 31; 95% confidence interval (CI) 17-56], and more recent diagnosis [referent 1988-1991; 2000-2003, OR 3.0 (95%CI 1.7-5.3)]. Median survival for resected patients was 16 mo versus 3 mo without resection (P<0.0001). After adjusting for age, gender, stage, year, and tumor location, surgical resection remained a significant predictor of survival [hazard ratio 0.44 (95% CI 0.36-0.54), P<0.0001]. CONCLUSIONS: In this population-based cohort, detection of malignant IPMNs is decreasing, with an increasing proportion of patients diagnosed at local stages and undergoing resection. Increased awareness of IPMN may be contributing to earlier detection, which might include benign/premalignant lesions, and greater utilization of resection for appropriate candidates; thus, we may be improving survival for this most treatable form of pancreatic cancer.
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Adenocarcinoma Mucinoso/epidemiologia , Carcinoma Papilar/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/cirurgia , Idoso , Carcinoma Papilar/mortalidade , Carcinoma Papilar/cirurgia , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER , Estados Unidos/epidemiologiaRESUMO
As the world embarks on mass vaccination for COVID-19, we are beginning to encounter unintended dilemmas in imaging oncology patients; particularly with regards to FDG PET/CT. In some cases, vaccine-related lymphadenopathy and FDG uptake on PET/CT can mimic cancer and lead to confounding imaging results. These cases where findings overlap with cancer pose a significant dilemma for diagnostic purposes, follow-up, and management leading to possible treatment delays, unnecessary repeat imaging and sampling, and patient anxiety. These cases can largely be avoided by optimal coordination between vaccination and planned imaging as well as preemptive selection of vaccine administration site. This coordination hinges on patient, oncologist, and radiologists' awareness of this issue and collaboration. Through close communication and patient education, we believe this will eliminate significant challenges for our oncology patients as we strive to end this pandemic.
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Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Linfadenopatia/diagnóstico , Neoplasias/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Vacinação/efeitos adversos , COVID-19/virologia , Diagnóstico Diferencial , Progressão da Doença , Fluordesoxiglucose F18/metabolismo , Humanos , Linfadenopatia/induzido quimicamente , Linfadenopatia/diagnóstico por imagem , Neoplasias/induzido quimicamente , Neoplasias/diagnóstico por imagem , Compostos Radiofarmacêuticos/metabolismo , SARS-CoV-2/isolamento & purificaçãoRESUMO
BACKGROUND: Pancreatectomy for cancer continues to have substantial perioperative risk, and the factors affecting mortality are ill defined. An integer-based risk score based on national data might help clarify the risk of in-hospital mortality in patients undergoing pancreatic resection. METHODS: Records with the diagnosis of pancreatic cancer were queried from the Nationwide Inpatient Sample for 1998-2006. Procedures were categorized as proximal, distal, or nonspecified pancreatectomies on the basis of ICD-9 codes. Logistic regression and bootstrap methods were used to create an integer risk score for estimating the risk of in-hospital mortality using patient demographics, comorbidities (Charlson comorbidity score), procedure, and hospital type. A random sample of 80% of the cohort was used to create the risk score with a 20% internal validation set. RESULTS: A total of 5715 patient discharges were identified. Composite in-hospital mortality was 5.8%. Predictors used for the final model were age group, Charlson score, sex, type of pancreatectomy, and hospital volume status (low-, medium-, or high-volume center). Integer values were assigned to these characteristics and then used for calculating an additive score. Three clinically useful score groups were defined to stratify the risk of in-hospital mortality (mortality was 2.0, 6.2, and 13.9%, respectively; P < 0.0001), with a 6.95-fold difference between the low- and high-risk groups. There was sufficient discrimination of both the derivation set and the validation set, with c statistics of 0.71 and 0.72, respectively. CONCLUSIONS: An integer-based risk score can be used to accurately predict in-hospital mortality after pancreatectomy and may be useful for preoperative risk stratification and patient counseling.
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Mortalidade Hospitalar/tendências , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Comorbidade , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Adrenalectomy remains the definitive therapy for most adrenal neoplasms. Introduced in the 1990s, laparoscopic adrenalectomy is reported to have lower associated morbidity and mortality. This study aimed to evaluate national adrenalectomy trends, including major postoperative complications and perioperative mortality. METHODS: The Nationwide Inpatient Sample was queried to identify all adrenalectomies performed during 1998-2006. Univariate and multivariate logistic regression were performed, with adjustments for patient age, sex, comorbidities, indication, year of surgery, laparoscopy, hospital teaching status, and hospital volume. Annual incidence, major in-hospital postoperative complications, and in-hospital mortality were evaluated. RESULTS: Using weighted national estimate, 40,363 patients with a mean age of 54 years were identified. Men made up 40% of these patients, and 77% of the patients were white. The majority of adrenalectomies (83%) were performed for benign disease. The annual volume of adrenalectomies increased from 3,241 in 1998 to 5,323 in 2006 (p < 0.0001, trend analysis). The overall in-hospital mortality was 1.1%, with no significant change. Advanced age (< 45 years as the referent; ≥ 65 years: adjusted odds ratio [AOR], 4.10; 95%; confidence Interval [CI], 1.66-10.10) and patient comorbidities (Charlson score 0 as the referent; Charlson score ≥ 2: AOR, 4.33; 96% CI, 2.34-8.02) were independent predictors of in-hospital mortality. Indication, year, hospital teaching status, and hospital volume did not independently affect perioperative mortality. Major postoperative in-hospital complications occurred in 7.2% of the cohort, with a significant increasing trend (1998-2000 [5.9%] vs 2004-2006 [8.1%]; p < 0.0001, trend analysis). Patient comorbidities (Charlson score 0 as the referent; Charlson score ≥ 2: AOR, 4.77; 95% CI, 3.71-6.14), recent year of surgery (1998-2000 as the referent; 2004-2006: AOR, 1.40; 95% CI, 1.09-1.78), and benign disease (malignant disease as the referent; benign disease: AOR, 1.98; 95% CI, 1.55-2.53) were predictive of major postoperative complications at multivariable analyses, whereas laparoscopy was protective (no laparoscopy as the referent; laparoscopy: AOR, 0.62; 95% CI, 0.47-0.82). CONCLUSION: Adrenalectomy is increasingly performed nationwide for both benign and malignant indications. In this study, whereas perioperative mortality remained low, major postoperative complications increased significantly.
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Adrenalectomia/estatística & dados numéricos , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/efeitos adversos , Adrenalectomia/mortalidade , Adrenalectomia/tendências , Feminino , Mortalidade Hospitalar , Humanos , Laparoscopia/estatística & dados numéricos , Laparoscopia/tendências , Masculino , Pessoa de Meia-Idade , Estados UnidosRESUMO
BACKGROUND: Recent studies have shown adjuvant therapy improves outcomes from pancreatic cancer (PC). This study investigates receipt and timing of PC treatments, and association with outcomes. METHODS: The analysis cohort consisted of patients with newly-diagnosed PC at a single institution over 5 years. Primary Endpoints were (i) receipt of recommended therapy, and (ii) overall survival (OS). RESULTS: Among 102 patients, 52 underwent resection. Out of 36 localized resected and 16 locally advanced resected (LAR) patients, 26 and 13, respectively, received adjuvant therapy. Six of the latter group received neoadjuvant therapy. Median OS for resected patients was 15.7 months (range 0.6-51.4), compared with 7.7 for unresected patients (range 0.4-32.0) (P < 0.001), and 14.0 months for patients with resection alone (range 0.6-24.4) vs. 16.1 for patients who also received adjuvant therapy (range 3.2-51.4) (P= 0.027). Out of 46 patients undergoing up-front resection, 33 had R0 surgical margins. For the six LAR patients undergoing neoadjuvant therapy, all margins were R0. CONCLUSION: After resection, a substantial proportion of patients do not receive adjuvant therapy, and have worse survival. In this study, neoadjuvant treatment increased both the proportion of patients receiving all components of recommended therapy and the R0 resection rate.
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Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Terapia Neoadjuvante , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Cetuximab , Quimioterapia Adjuvante , Estudos de Coortes , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia , Complicações Pós-Operatórias , Radioterapia Adjuvante , GencitabinaRESUMO
OBJECTIVES: To develop a population-based risk score for stratifying patients by risk of in-hospital mortality following procedural intervention for hepatic neoplasm. BACKGROUND: There has been growing support for the value of surgical management of hepatic neoplastic disease, both primary and metastatic. Advances in surgical and ablative technologies have contributed to a decrease in the mortality associated with these procedures. However, multiple patient-, disease- and treatment-related factors can contribute to perioperative morbidity and mortality. METHODS: Using the Nationwide Inpatient Sample from 1998 to 2005, a retrospective cohort of patient-discharges for hepatic procedures with a concurrent diagnosis of hepatic primary or metastatic neoplasm to the liver was assembled. Procedures were categorized as lobectomy, wedge resection, or enucleation/ablation. Logistic regression and bootstrap methods were used to create an integer score for estimating the risk of in-hospital mortality using patient demographics, comorbidities, procedure type, tumor type, and hospital characteristics. A randomly selected sample of 80% of the cohort was used to create the risk score. Testing was conducted in the remaining 20% validation-set. RESULTS: In total, 12,969 patient-discharges were identified. Overall in-hospital mortality was 3.45%. Predictive characteristics incorporated into the model included: age, sex, Charlson comorbidity score, procedure type, hospital type, and type of neoplasm. Integer values were assigned to these, and used to calculate an additive score. Five clinically relevant groups were assembled to stratify risk, with a 36-fold gradient in mortality. Rates in the groups were as follows: 0.9%, 2.5%, 6.8%, 17.6%, and 35.9%. In the derivation set, as well as in the validation set, the simple score discriminated well, with c-statistics of 0.76 and 0.70, respectively. CONCLUSIONS: An integer-based risk score can be used to predict in-hospital mortality after hepatic procedure for neoplasm, and may be useful for preoperative risk stratification and patient counseling.
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Hepatectomia/métodos , Neoplasias Hepáticas/mortalidade , Medição de Risco/métodos , Idoso , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologiaRESUMO
Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in the United States. Sp1 is a sequence-specific DNA binding protein that is important in the transcription of a number of regulatory genes involved in cancer cell growth, differentiation, and metastasis. In this study, we investigated Sp1 expression in pancreatic ductal adenocarcinoma and its association with clinical outcome. We studied 42 patients with primary pancreatic adenocarcinoma. The expression of Sp1 in pancreatic adenocarcinoma was evaluated by immunohistochemical staining. All 42 patients had clinical follow-up information and were evaluated for survival. Sp1 protein was aberrantly overexpressed in a subset of primary pancreatic adenocarcinoma. These tumors all developed metastasis, whereas none of the primary tumors without lymph node metastasis showed Sp1 overexpression. Statistically, Sp1 overexpression was associated with higher stage, higher grade, and lymph node metastasis (P < 0.001, P = 0.036, and P < 0.0001, respectively). Additionally, patients of this subset had a much shorter overall survival than patients without Sp1 overexpression, as evidenced by Kaplan-Meier plots and the log-rank test (P = 0.002). The 5-year overall survival rate was 19% in patients with Sp1 overexpression, compared with 55% in patients without Sp1 overexpression. The median survival was only 13 months for patients with Sp1 overexpression, compared with 65 months for patients without Sp1 overexpression. In conclusion, Sp1 is a new biomarker that identifies a subset of pancreatic ductal adenocarcinoma with aggressive clinical behavior. It can be used at initial diagnosis of pancreatic adenocarcinoma to identify patients with an increased probability of cancer metastasis and much shortened overall survival.
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Biomarcadores Tumorais/biossíntese , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/metabolismo , Fator de Transcrição Sp1/biossíntese , Idoso , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Massachusetts/epidemiologia , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida/tendênciasRESUMO
HYPOTHESIS: That factors affecting outcomes of surgical resection in the treatment of gastric cancer can be identified using a large US database. DESIGN: Retrospective observational study. SETTING: The Nationwide Inpatient Sample from January 1, 1998, through December 31, 2003. PATIENTS: We included 13 354 patient discharges (approximately 66 096 nationally by weighted analysis) who underwent gastric resection for neoplasm. MAIN OUTCOME MEASURE: In-hospital mortality. Univariate analyses were performed by means of chi(2) tests. A multivariate logistic regression was performed to determine which variables were independently predictive of in-hospital mortality. RESULTS: During the study period, 50 738 patients (approximately 250 420 nationally) were discharged with the diagnosis of gastric neoplasm. Of those, 13 354 (26.3%) underwent gastric resection during their hospitalization. In-hospital mortality for patients undergoing surgery was 6.0%, without significant change from 1998 through 2003. Factors predictive of significantly increased in-hospital mortality included low annual hospital surgical volume (lowest [
Assuntos
Gastrectomia/tendências , Avaliação de Resultados em Cuidados de Saúde , Neoplasias Gástricas/cirurgia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Intervalos de Confiança , Feminino , Gastrectomia/métodos , Gastrectomia/mortalidade , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição por Sexo , Neoplasias Gástricas/mortalidade , Estados Unidos/epidemiologiaRESUMO
This session focused on issues related to implementation of randomized clinical trials in palliative care studies. Topics discussed included what kinds of clinical sites and patient populations were suitable, what types of clinical investigators (clinical specialty) should be involved in or lead the studies, what multisite mechanisms could be used to conduct the trials, and what funding issues were related to these studies. A trial of operative versus nonoperative management for small bowel obstruction caused by recurrent intra-abdominal cancer was considered. The feasibility of such a trial was examined in terms of whether there was "equipoise" for a majority of likely investigators in the field around the trial question, what other issues might impact accrual to the trial, and how many patients would be required to answer which of these two treatment arms was better. This last question is related to selection of a primary endpoint for the trial and was a modestly contentious issue for the trial design group. Both sensible compromises in endpoint selection and the education of the community of investigators for a particular randomized trial in palliative care are crucial steps for successful implementation. A major conclusion of this session is that implementation considerations are intimately related to the architecture of a specific trial and should be addressed practically and early in the design phase of any randomized trial addressing a palliative care question. In this respect, randomized trials in palliative care are no different than in other fields.
Assuntos
Estudos Multicêntricos como Assunto/métodos , Cuidados Paliativos/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , HumanosRESUMO
KOC (K homology domain containing protein overexpressed in cancer) is a novel oncofetal RNA-binding protein highly expressed in pancreatic carcinomas. Recently, Corixa Corporation developed a monoclonal antibody specific for KOC that can be used with standard immunohistochemical techniques. The purposes of this study were 1) to assess KOC mRNA expression in pancreatic carcinoma, 2) to determine the pattern of KOC immunoexpression among benign, borderline, and malignant pancreatic epithelial lesions, and 3) to evaluate the utility of the KOC antibody in distinguishing between these entities. mRNA was isolated from fresh pancreatic tissues (19 carcinomas, 2 normal pancreas, 1 chronic pancreatitis) and amplified using standard RT-PCR techniques. Fifteen of 19 (79%) carcinomas overexpressed KOC mRNA relative to non-neoplastic tissue samples and expression increased progressively with tumor stage: the mean copy number of KOC mRNA transcripts was 1.5, 11.1, 31, and 28 for stage I, II, III, and IV carcinomas, respectively, compared with 0.9 and 1 for normal pancreatic tissue and chronic pancreatitis, respectively. Immunostains using the KOC antibody were performed on 50 surgical resection specimens (38 invasive adenocarcinomas, 3 intraductal papillary-mucinous neoplasms, 2 mucinous cystic neoplasms, 7 chronic pancreatitis). KOC staining was present in 37 of 38 (97%) carcinomas: the staining reaction was moderate or strong in 36 of 38 (94%) and present in >50% of the tumor cells in 35 of 38 (92%) cases. Severe dysplasia of the ductal epithelium, present in 19 foci of intraductal papillary mucinous carcinoma, mucinous cystadenocarcinoma, and grade 3 pancreatic intraepithelial neoplasia (PanIN3) showed strong or moderate staining in 15 (79%) cases, whereas foci of mild and moderate dysplasia (intraductal papillary-mucinous neoplasms and mucinous cystic neoplasms with adenoma and/or moderate dysplasia, PanIN1, and PanIN2) were uniformly negative for this marker in 25 and 22 cases, respectively. In the normal pancreas, weak background staining of acini was present in 12 of 50 (24%) cases but was easily distinguishable from the type of staining identified in neoplastic epithelium, and benign ducts and ductules were negative in all cases. Four of 38 (11%) foci of chronic pancreatitis, present in the 7 resections performed for chronic pancreatitis as well as 31 foci of peritumoral chronic pancreatitis, showed weak staining in <10% of the ductules. We conclude that KOC is a sensitive and specific marker for carcinomas and high-grade dysplastic lesions of the pancreatic ductal epithelium. Therefore, immunostains directed against KOC may be of diagnostic utility in the evaluation of pancreatic lesions, particularly when biopsy material is limited.