RESUMO
INTRODUCTION: Treatment of advanced pancreatic adenocarcinoma remains suboptimal. Therapeutic agents with a novel mechanism of action are desperately needed; one such novel agent is CPI-613 targets. We here analyze the outcomes of 20 metastatic pancreatic cancer patients treated with CPI-613 and FOLFIRINOX in our institution and evaluate their outcomes to borderline-resectable patients treated with curative surgery. METHODS: A post hoc analysis was performed of the phase I CPI-613 trial data (NCT03504423) comparing survival outcomes to borderline-resectable cases treated with curative resection at the same institution. Survival was measured by overall survival (OS) for all study cases and disease-free survival (DFS) for resected cases with progression-free survival for CPI-613 cases. RESULTS: There were 20 patients in the CPI-613 cohort and 60 patients in the surgical cohort. Median follow-up times were 441 and 517 days for CPI-613 and resected cases, respectively. There was no difference in survival times between CPI-613 and resected cases with a mean OS of 1.8 versus 1.9 year (p = 0.779) and mean PFS/DFS of 1.4 versus 1.7 years (p = 0.512). There was also no difference in 3-year survival rates for OS (hazard ratio [HR] = 1.063, 95% confidence interval [CI] 0.302-3.744, p = 0.925) or DFS/PFS (HR = 1.462, 95% CI 0.285-7.505, p = 0.648). CONCLUSION: The first study to evaluate the survival between metastatic patients treated with CPI-613 versus borderline-resectable cases undergoing curative resection. Analysis revealed no significant differences in survival outcomes between the cohorts. Study results are suggestive that there may be potential utility with the addition of CPI-613 to potentially resectable pancreatic adenocarcinoma, although additional research with more comparable study groups are required.
Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Terapia Neoadjuvante/métodos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias PancreáticasRESUMO
INTRODUCTION: There is a paucity in the literature in regard to the incidence, risk factors, and outcomes for post-operative cholangitis following hepatic resection. METHODS: Retrospective review of the ACS NSQIP main and targeted hepatectomy registries for 2012-2016. RESULTS: A total of 11,243 cases met the selection criteria. The incidence of post-operative cholangitis was 0.64% (151 cases). Multivariate analysis identified several risk factors associated with the development of post-operative cholangitis, stratified out by pre-operative and operative factors. The most significant risk factors were biliary anastomosis and pre-operative biliary stenting with odds ratios (OR) of 32.39 (95% CI 22.91-45.79, P value < 0.0001) and 18.32 (95% CI 10.51-31.94, P value < 0.0001) respectively. Cholangitis was significantly associated with post-operative bile leaks, liver failure, renal failure, organ space infections, sepsis/septic shock, need for reoperation, longer length of stay, increased readmission rates, and death. CONCLUSION: Largest analysis of post-operative cholangitis following hepatic resection. While a rare occurrence, it is associated with significantly increased risk for severe morbidity and mortality. The most significant risk factors were biliary anastomosis and stenting.
Assuntos
Doenças Biliares , Colangite , Humanos , Fígado/cirurgia , Colangite/epidemiologia , Colangite/etiologia , Colangite/cirurgia , Fatores de Risco , Hepatectomia/efeitos adversos , Doenças Biliares/cirurgia , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
INTRODUCTION: Pancreaticoduodenectomy performed with underlying hepatic disease has been reported to have increased adverse events postoperatively. This study aimed to further evaluate that association. METHODS: Retrospective review of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) main and targeted pancreatectomy registries for 2014-2016. High-risk liver patients were defined by MELD scores, received neoadjuvant chemotherapy, and had hepatosteatosis; two separate subgroups of MELD ≥9 and ≥ 11. High-risk liver patients were then compared to control cases via propensity score matching. RESULTS: There were 156 and 132 cases that met the high-risk liver criteria for the MELD cutoffs of ≥9 and ≥ 11 respectively. Propensity score matching left 2527 cases for final adjusted analysis. On both univariate and multivariate analysis high-risk liver patients were not associated with increased adverse events following Whipple resection. Lack of association with increased adverse events held for both the ≥9 and ≥ 11 MELD score cohorts. CONCLUSION: High-risk liver patients defined by MELD scores, neoadjuvant chemotherapy utilization, and hepatosteatosis were not associated with any increased incidence of adverse events following pancreaticoduodenectomy. Patients with underlying high-risk liver disease in this study did not appear to pose as a contraindication for oncologic resection of pancreatic adenocarcinoma.
Assuntos
Adenocarcinoma , Hepatopatias , Neoplasias Pancreáticas , Humanos , Pancreaticoduodenectomia/efeitos adversos , Pancreatectomia/efeitos adversos , Adenocarcinoma/complicações , Neoplasias Pancreáticas/etiologia , Hepatopatias/complicações , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
INTRODUCTION: Hepatobiliary malignancies present with advanced disease precluding upfront resection. Liver-directed therapy (LDT), particularly Y-90 radioembolization and transarterial chemoembolization (TACE), has become increasingly utilized to facilitate attempt at oncologic resection. However, the safety profile of preoperative LDT is limited. METHODS: Retrospective review of the ACS NSQIP main and targeted hepatectomy registries for 2014-2016. Primary objective was evaluation of outcomes between preoperative LDT cases and those that received upfront resection. RESULTS: A total of 8923 cases met selection criteria. 192 cases (2.15%) received either Y-90 or TACE prior to hepatectomy. Multivariate analysis for all study patients revealed preoperative LDT significantly increased the risk of perioperative transfusion (OR 2.19, 95% CI 1.445-3.328, P < 0.0001), sepsis (OR 2.21, 95% CI 1.104-4.411, P = 0.022), and liver failure (OR 2.72, 95% CI 1.562-4.747, P < 0.0001). Subgroup analysis found for primary hepatobiliary malignancies LDT only increased the risk for liver failure. While for secondary hepatic tumors LDT significantly increased perioperative transfusion, sepsis, cardiac failure, renal failure, liver failure, and mortality. The complication profile also significantly increased with advanced T stage. Conversely, on propensity score matching preoperative LDT did not significantly increase perioperative complications. CONCLUSION: Preoperative LDT has the potential to convert inoperable hepatic tumors into resectable disease but there is a general increased risk for significant postoperative complications, most notable liver failure. However, on controlled analysis preoperative LDT does not increase perioperative complications and should not be considered a contraindication to resection.
Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Gastrointestinais , Falência Hepática , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/cirurgia , Radioisótopos de Ítrio , Hepatectomia/efeitos adversos , Neoplasias Gastrointestinais/cirurgia , Estudos Retrospectivos , Falência Hepática/etiologia , Resultado do TratamentoRESUMO
OBJECTIVE: To determine whether trauma patients managed by an admitting or consulting service with a high proportion of physicians exhibiting patterns of unprofessional behaviors are at greater risk of complications or death. SUMMARY BACKGROUND DATA: Trauma care requires high-functioning interdisciplinary teams where professionalism, particularly modeling respect and communicating effectively, is essential. METHODS: This retrospective cohort study used data from 9 level I trauma centers that participated in a national trauma registry linked with data from a national database of unsolicited patient complaints. The cohort included trauma patients admitted January 1, 2012 through December 31, 2017. The exposure of interest was care by 1 or more high-risk services, defined as teams with a greater proportion of physicians with high numbers of patient complaints. The study outcome was death or complications within 30âdays. RESULTS: Among the 71,046 patients in the cohort, 9553 (13.4%) experienced the primary outcome of complications or death, including 1875 of 16,107 patients (11.6%) with 0 high-risk services, 3788 of 28,085 patients (13.5%) with 1 high-risk service, and 3890 of 26,854 patients (14.5%) with 2+ highrisk services (P < 0.001). In logistic regression models adjusting for relevant patient, injury, and site characteristics, patients who received care from 1 or more high-risk services were at 24.1% (95% confidence interval 17.2% to 31.3%; P < 0.001) greater risk of experiencing the primary study outcome. CONCLUSIONS: Trauma patients who received care from at least 1 service with a high proportion of physicians modeling unprofessional behavior were at an increased risk of death or complications.
Assuntos
Profissionalismo , Ferimentos e Lesões , Estudos de Coortes , Hospitalização , Humanos , Estudos Retrospectivos , Centros de Traumatologia , Ferimentos e Lesões/terapiaRESUMO
INTRODUCTION: Metastatic progression occurs along the locoregional vasculature, and a common anatomic variant is an aberrant right hepatic artery (aRHA). This study evaluated the effect of an aRHA following pancreaticoduodenectomy, with a focus on hepatic metastases. METHODS: This was a single-institution retrospective review of non-metastatic pancreatic cancer cases between 2012 and 2020. aRHA cases were compared with patients with conventional anatomy. The primary outcome was hepatic recurrence rates, while secondary analysis survival outcomes were measured by overall survival (OS) and disease-free survival (DFS). Subgroup analysis was stratified by tumor resectability and utilization of systemic therapy. RESULTS: Overall, 207 cases were reviewed, with 17.4% having aRHA anatomy. On multivariate analysis, aRHA increased hepatic recurrence for all-comers (odds ratio [OR] 4.76, 95% confidence interval [CI] 2.18-10.38; p < 0.001). aRHA was significant for resectable tumors (OR 2.58, 95% CI 1.89-6.66; p = 0.045) and borderline resectable tumors (OR 28.88, 95% CI 5.52-151.18; p < 0.0001) in regard to hepatic recurrence on univariate analysis. Increased hepatic recurrence correlated with decreased 3-year OS and DFS rates of 30.6% versus 50.3% (OR 0.44, 95% CI 0.20-0.94; p = 0.032) and 13.6% versus 36.9% (OR 0.27, 95% CI 0.08-0.97; p = 0.035). Systemic therapy limited the effects of aRHA. CONCLUSION: aRHA was associated with inferior survival outcomes due to the significantly increased risk of hepatic metastatic disease with aberrant anatomy. This study provides important prognostic information for a commonly encountered anatomic variant.
Assuntos
Neoplasias Hepáticas , Neoplasias Pancreáticas , Artéria Hepática/patologia , Artéria Hepática/cirurgia , Humanos , Neoplasias Hepáticas/patologia , Pancreatectomia , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , PrognósticoRESUMO
OBJECTIVE: To identify the survival benefit of different adjuvant approaches and factors influencing their efficacy after upfront resection of pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: The optimal adjuvant approach for PDAC remains controversial. METHODS: Patients from the National Cancer Database who underwent upfront PDAC resection from 2010 to 2014 were analyzed to determine clinical outcomes of different adjuvant treatment approaches, stratified according to pathologic characteristics. Factors associated with overall survival were identified with multivariable logistic regression and Cox proportional hazards were used to compare overall survival of different treatment approaches in the whole cohort, and propensity score matched groups. RESULTS: We included 16,709 patients who underwent upfront resection of PDAC. On multivariable analysis, tumor size, grade, positive margin, nodal involvement, lymphovascular invasion (LVI), stage, lymph node ratio, not receiving chemotherapy, and/or radiation were predictors for worse survival. In the presence of at least 1 high-risk pathologic feature (nodal or margin involvement or LVI) chemotherapy with subsequent radiation provided the most significant survival benefit (median survivals: 24.8 vs 21.0 mo for adjuvant chemotherapy; HR = 0.81; 95% CI: 0.77-0.86; P < 0.001 in propensity score matching). The addition of radiation to adjuvant chemotherapy did not significantly improve overall survival in those with no high-risk pathologic features (median survivals: 54.6 vs 42.7 mo for adjuvant chemotherapy; HR=0.90; 95% CI: 0.75-1.08; P = 0.25 in propensity score matching). CONCLUSIONS: In the presence of any high-risk pathologic features (nodal or margin involvement or LVI), adjuvant chemotherapy followed by radiation provides a better survival advantage over chemotherapy alone after upfront resection of PDAC.
Assuntos
Adenocarcinoma/radioterapia , Neoplasias Pancreáticas/radioterapia , Radioterapia Adjuvante , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Recent reports indicate improved survival in patients undergoing surgical treatment for colorectal liver metastases (CRLM) with hepatic arterial infusion (HAI) pump chemotherapy compared to surgery alone. METHODS: Patients who underwent resection and/or ablation of CRLM between 1996 and 2016 were included from a single-institution prospectively maintained database. Proportional hazards regression analysis was performed to determine predictors of overall survival (OS) and 3:1 propensity score analysis (PSA). RESULTS: Of 349 patients included, 36 had HAI pumps placed (HAI group) and 313 did not (no-HAI group). There was no difference in primary tumor grade (p = 0.24), ECOG status (p = 0.44), tumor number (p = 0.1), tumor size (p = 0.56), margin status (p = 0.76) between the two groups. Median overall survival was 44.7months vs 37.1months for the HAI versus no-HAI group (p = 0.01). Cox proportional hazards regression analysis demonstrated positive margin status (HR:2.47,p < 0.0001), HAI therapy (HR:0.56,p = 0.02), preoperative chemotherapy (HR:0.69,p = 0.02) and tumor diameter (HR:1.07,p = 0.005) as predictors of OS. In 3:1 PSA, 32 HAI subjects were matched with 87 non-HAI subjects balancing all covariates. Median OS was 42.4 months versus 35.6 months for the HAI versus no-HAI group (p = 0.03). CONCLUSION: Surgical treatment of CRLM combined with HAI chemotherapy is associated with improved OS compared to surgery alone. Further study of this treatment approach is indicated.
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica , Fluoruracila/uso terapêutico , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
BACKGROUND: Care of pancreatic cancer patients has become increasingly complex, which has led to delays in the initiation of therapy. Nurse navigators have been added to care teams, in part, to ameliorate this delay. This study investigated the difference in time from first oncology visit to first treatment date in patients with any pancreatic malignancy before and after the addition of an Oncology Navigator. METHODS: A single-institution database of patients with any pancreatic neoplasm evaluated by a provider in radiation, medical, or surgical oncology between 1 October 2015 and 30 September 2017 was analyzed. After 1 October 2016, an Oncology Navigator met patients at their initial visit and coordinated care throughout treatment. The cohort was divided into two groups: patients evaluated prior to the implementation of an Oncology Navigator and patients evaluated after implementation. Patient demographics and time from first visit to first intervention were compared. RESULTS: Overall, 147 patients with a new diagnosis of pancreatic neoplasm were evaluated; 57 patients were seen prior to the start of the Oncology Navigator program and 79 were evaluated after the navigation program was implemented. On univariate analysis, time from first contact by any provider to intervention was 46 days prior to oncology navigation and 26 days after implementation of oncology navigation (p = 0.005). While controlling for other covariates, employment of the Oncology Navigator decreased the time from first contact by any provider to intervention by almost 16 days (p = 0.009). CONCLUSIONS: Implementing an oncology navigation program significantly decreased time to treatment in patients with pancreatic malignancy.
Assuntos
Adenocarcinoma/terapia , Tumores Neuroendócrinos/terapia , Neoplasias Intraductais Pancreáticas/terapia , Neoplasias Pancreáticas/terapia , Navegação de Pacientes/métodos , Tempo para o Tratamento , Adenocarcinoma/psicologia , Idoso , Feminino , Seguimentos , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Tumores Neuroendócrinos/psicologia , Neoplasias Intraductais Pancreáticas/psicologia , Neoplasias Pancreáticas/psicologia , Navegação de Pacientes/estatística & dados numéricos , Poder Psicológico , Prognóstico , Estudos RetrospectivosAssuntos
Anestesia por Condução/métodos , Neoplasias Colorretais/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Importance: Unsolicited patient observations are associated with risk of medical malpractice claims. Because lawsuits may be triggered by an unexpected adverse outcome superimposed on a strained patient-physician relationship, a question remains as to whether behaviors that generate patient dissatisfaction might also contribute to the genesis of adverse outcomes themselves. Objective: To examine whether patients of surgeons with a history of higher numbers of unsolicited patient observations are at greater risk for postoperative complications than patients whose surgeons generate fewer such unsolicited patient observations. Design, Setting, and Participants: This retrospective cohort study used data from 7 academic medical centers participating in the National Surgical Quality Improvement Program and the Vanderbilt Patient Advocacy Reporting System from January 1, 2011, to December 31, 2013. Patients older than 18 years included in the National Surgical Quality Improvement Program who underwent inpatient or outpatient operations at 1 of the participating sites during the study period were included. Patients were excluded if the attending surgeon had less than 24 months of data in the Vanderbilt Patient Advocacy Reporting System preceding the date of the operation. Data analysis was conducted from June 1, 2015, to October 20, 2016. Exposures: Unsolicited patient observations for the patient's surgeon in the 24 months preceding the date of the operation. Main Outcomes and Measures: Postoperative surgical or medical complications as defined by the National Surgical Quality Improvement Program within 30 days of the operation of interest. Results: Among the 32â¯125 patients in the cohort (13â¯230 men, 18â¯895 women; mean [SD] age, 55.8 [15.8] years), 3501 (10.9%) experienced a complication, including 1754 (5.5%) surgical and 2422 (7.5%) medical complications. Prior unsolicited patient observations for a surgeon were significantly associated with the risk of a patient having any complication (odds ratio, 1.0063; 95% CI, 1.0004-1.0123; P = .03), any surgical complication (odds ratio, 1.0104; 95% CI, 1.0022-1.0186; P = .01), any medical complication (odds ratio, 1.0079; 95% CI, 1.0009-1.0148; P = .03), and being readmitted (odds ratio, 1.0088, 95% CI, 1.0024-1.0151; P = .007). The adjusted rate of complications was 13.9% higher for patients whose surgeon was in the highest quartile of unsolicited patient observations compared with patients whose surgeon was in the lowest quartile. Conclusions and Relevance: Patients whose surgeons have large numbers of unsolicited patient observations in the 24 months prior to the patient's operation are at increased risk of surgical and medical complications. Efforts to promote patient safety and address risk of malpractice claims should continue to focus on surgeons' ability to communicate respectfully and effectively with patients and other medical professionals.
Assuntos
Barreiras de Comunicação , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Garantia da Qualidade dos Cuidados de Saúde , Risco , Cirurgiões/estatística & dados numéricos , Estudos de Coortes , Comunicação , Estudos Transversais , Humanos , Comunicação Interdisciplinar , Colaboração Intersetorial , Imperícia/estatística & dados numéricos , Educação de Pacientes como Assunto , Segurança do Paciente , Satisfação do Paciente , Relações Médico-Paciente , Melhoria de Qualidade/estatística & dados numéricos , Estudos Retrospectivos , Estatística como Assunto , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricosRESUMO
BACKGROUND: Pancreatic cancer is a disease of older adults, who may present with limited physiologic reserve. The authors hypothesized that a frailty index can predict postoperative outcomes after pancreaticoduodenectomy (PD). METHODS: All patients who underwent PD were identified in the 2005-2012 NSQIP Participant Use File. Patients undergoing emergency procedures, those with an American Society of Anesthesiologists (ASA) classification of five, and those with a diagnosis of preoperative sepsis were excluded from the study. A modified frailty index (mFI) was defined by 11 variables within the National Surgical Quality Improvement Program (NSQIP) previously used for the Canadian Study of Health and Aging-Frailty Index. An mFI score of 0.27 or higher was defined as a high mFI. Uni- and multivariate analyses were performed to evaluate postoperative outcomes. RESULTS: This study enrolled 9986 patients (age 65 ± 12 years, 48.8% female) who underwent PD. Of these patients, 6.4% (n = 637) had a high mFI (>0.27). Increasing mFI was associated with higher prevalence of postoperative morbidity (p < 0.001) and 30-days mortality (p < 0.001). In the univariate analysis, high mFI was associated with increased morbidity (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.43-1.97; p < 0.001) and 30-days mortality (OR 2.45; 95% CI 1.74-3.45; p < 0.001). After adjustment for age, sex, ASA classification, albumin level, and body mass index (BMI), high mFI remained an independent preoperative predictor of postoperative morbidity (OR 1.544; 95% CI 1.289-1.850; p < 0.0001) and 30-days mortality (OR 1.536; 95% CI 1.049-2.248; p = 0.027). CONCLUSIONS: High mFI is associated with postoperative morbidity and mortality after PD and can aid in preoperative risk stratification.
Assuntos
Fragilidade/patologia , Neoplasias Pancreáticas/mortalidade , Pancreaticoduodenectomia/mortalidade , Complicações Pós-Operatórias , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Melhoria de Qualidade , Medição de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Surgical site infections (SSIs) remain a major source of morbidity and cost after resection of intra-abdominal malignancies. Negative-pressure wound therapy (NPWT) has been reported to significantly reduce SSIs when applied to the closed laparotomy incision. This article reports the results of a randomized clinical trial examining the effect of NPWT on SSI rates in surgical oncology patients with increased risk for infectious complications. STUDY DESIGN: From 2012 to 2016, two hundred and sixty-five patients who underwent open resection of intra-abdominal neoplasms were stratified into 3 groups: gastrointestinal (n = 57), pancreas (n = 73), or peritoneal surface (n = 135) malignancy. They were randomized to receive NPWT or standard surgical dressing (SSD) applied to the incision from postoperative days 1 through 4. Primary outcomes of combined incisional (superficial and deep) SSI rates were assessed up to 30 days after surgery. RESULTS: There were no significant differences in superficial SSIs (12.8% vs 12.9%; p > 0.99) or deep SSI (3.0% vs 3.0%; p > 0.99) rates between the SSD and NPWT groups, respectively. When stratified by type of surgery, there were still no differences in combined incisional SSI rates for gastrointestinal (25% vs 24%; p > 0.99), pancreas (22% vs 22%; p > 0.99), and peritoneal surface malignancy (9% vs 9%; p > 0.99) patients. When performing univariate and multivariate logistic regression analysis of demographic and operative factors for the development of combined incisional SSI, the only independent predictors were preoperative albumin (p = 0.0031) and type of operation (p = 0.018). CONCLUSIONS: Use of NPWT did not significantly reduce incisional SSI rates in patients having open resection of gastrointestinal, pancreatic, or peritoneal surface malignancies. Based on these results, at this time NPWT cannot be recommended as a therapeutic intervention to decrease infectious complications in these patient populations.
Assuntos
Neoplasias do Sistema Digestório/cirurgia , Laparotomia , Tratamento de Ferimentos com Pressão Negativa , Infecção da Ferida Cirúrgica/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Resultado do Tratamento , Adulto JovemRESUMO
Perioperative chemotherapy has been shown to improve disease-free survival compared with surgery alone for resectable colorectal liver metastases (CLM). We examined our experience with systemic chemotherapy in this clinical setting. A prospectively collected liver surgery database identified 210 patients treated for resectable CLM from 1996 to 2010. Results were correlated to four treatment groups: posthepatectomy adjuvant only, prehepatectomy preoperative only, perioperative (preoperative and adjuvant), and surgery only. Seventy-nine (37.6%) patients received posthepatectomy adjuvant only treatment, 33 (15.7%) received prehepatectomy preoperative only treatment, 46 (21.9%) received perioperative (preoperative and adjuvant) treatment, whereas 52 (24.8%) received surgery alone. Preoperative and adjuvant systemic chemotherapy regimens were as follows: 23 (29.1%) and 18 (14.4%) received a 5-fluorouracil monotherapy regimen, 19 (24.1%) and 31 (24.8%) received an irinotecan-based regimen, and 28 (35.4%) and 37 (29.6%) received an oxaliplatin-based regimen. Nine (11.4%) and 12 (9.6%) received some other unknown combination. Treatment groups showed no difference in gender, mean tumor size, number of tumors, margin status, or postoperative complications with the only difference being a higher incidence of metachronous tumors in the preoperative only and perioperative groups (P = 0.01). Median follow-up and overall survival were 25 and 41 months, respectively. The adjuvant, preoperative, perioperative, and surgery only groups had a median survival time of 48, 35, 39, and 29 months, respectively (log-rank P = 0.04). Independent predictors of overall survival on multivariate analysis included treatment algorithm used and postoperative complication status. Adjuvant only systemic therapy was associated with an improved survival in resectable CLM. Prospective randomized trials are needed to confirm these findings.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Hepatectomia , Neoplasias Hepáticas/cirurgia , Idoso , Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
BACKGROUND: Surgical resection is the treatment of choice for colorectal hepatic metastases (HM). In contrast, metastatic disease to the peritoneum is treated with systemic therapy. We examined our experience with cytoreductive surgery (CS) and intraperitoneal hyperthermic chemotherapy (IPHC) for peritoneal surface disease (PSD) compared with liver resection for HM. METHODS: A review of prospective databases of colorectal cancer patients undergoing surgery for metastatic disease to the peritoneum or liver (1992-2005) was carried out. RESULTS: One hundred and twenty-one patients underwent CS + IPHC and 101 patients underwent hepatic resection with median follow-up of 86 and 56 months, respectively. Fifty-five (45%) patients in the IPHC group had complete resection of all gross tumor. Ninety-five (94%) of the HM patients had negative surgical margins. Comparison of the R0/R1 PSD and margin-negative HM group demonstrated significant differences in age, performance status, and preoperative chemotherapy. The 1-, 3-, and 5-year overall survival for the R0/R1 PSD patients was 91, 48, and 26%; while it was 87, 59, and 34% for the HM patients (P = 0.32). Perioperative morbidity was 42% versus 34% (P = 0.38) and mortality was 5.5% versus 4.2% (P = 0.71) between the PSD and HM patients, respectively. CONCLUSION: R0/R1 resection during CS + IPHC compared with margin-negative hepatic resection demonstrated no significant difference in overall survival and for select patients should be considered a viable treatment option. Further studies to improve the resectability of PSD patients and define the role of neoadjuvant and adjuvant drug strategies are needed.
Assuntos
Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/cirurgia , Neoplasias Peritoneais/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia do Câncer por Perfusão Regional , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Seguimentos , Hepatectomia , Humanos , Hipertermia Induzida , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Morbidade , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Telomerase activity is up-regulated in pancreatic cancer. Hence, measurement of telomerase activity in pancreatic needle-biopsy specimens could assist in establishing a positive diagnosis in specimens that are inadequate for cytology. OBJECTIVE: To determine the sensitivity and specificity of telomerase activity for neoplasia in a series of EUS-guided fine-needle aspirate (EUS-FNA) biopsies of pancreatic mass lesions. DESIGN: Prospective, consecutive, non-randomized cohort. SETTING: Academic hospital, tertiary referral center. PATIENTS: Seventy-one patients with a pancreatic mass diagnosed by cross-sectional imaging. INTERVENTIONS: EUS-FNA of 52 solid and 18 cystic pancreatic lesions. MAIN OUTCOME MEASUREMENTS: (1) Cytologic diagnosis; (2) tissue telomerase activity by semi-quantitative polymerase chain reaction; (3) patient demographics; (4) clinical outcomes. RESULTS: Cytology results were positive for adenocarcinoma in 40 patients with a solid pancreatic mass; of these, telomerase activity was detected in 31. There were no telomerase false-positive results. Telomerase results were positive in 6 of the 7 patients (86%) who had negative cytology results and who eventually were found to have biopsy-proven adenocarcinoma. The sensitivity and specificity of telomerase activity for detecting pancreatic adenocarcinoma in solid masses was 79% (95% CI, 64%-89%) and 100% (95% CI, 55%-100%). LIMITATIONS: Extremely high sensitivity and specificity of EUS-FNA cytology in solid lesions minimized the incremental benefit of telomerase. CONCLUSIONS: Telomerase activity can be measured readily in specimens obtained at EUS-FNA and accurately predicts malignancy. Used in combination with cytology, telomerase increased the sensitivity from 85% to 98% while maintaining the specificity at 100%. Lesions with negative cytology result and positive telomerase activity should be evaluated aggressively to exclude malignancy.
Assuntos
Adenocarcinoma/enzimologia , DNA de Neoplasias/genética , Endossonografia , Neoplasias Pancreáticas/enzimologia , Telomerase/metabolismo , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Biomarcadores Tumorais , Biópsia por Agulha Fina/métodos , Diagnóstico Diferencial , Seguimentos , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Reação em Cadeia da Polimerase , Estudos Prospectivos , Sensibilidade e Especificidade , Telomerase/genéticaRESUMO
PURPOSE: This phase II trial of induction irinotecan/gemcitabine followed by twice-weekly gemcitabine and upper abdominal radiation was initiated to determine the activity of this regimen in patients with unresectable pancreatic cancer. METHODS: Patients with locally advanced, nonmetastatic adenocarcinoma of the pancreas received 2 cycles of induction irinotecan (100 mg/m2 IV) and gemcitabine (1000 mg/2 IV) on days 1 and 8 of each 3-week cycle. Following the induction, patients without disease progression received gemcitabine administered twice weekly (40 mg/m2/day) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy over 5.5 weeks). RESULTS: From April 2000 to August 2003, 20 patients were entered into this study, 17 of whom were evaluable for treatment response. Characteristics included a median age of 67 years (range, 44-87 years) and 14 men (70%). Grades III and IV hematologic toxicity occurred in 25% and 5% of patients respectively and was primarily thrombocytopenia. No grade IV gastrointestinal toxicities or deaths due to therapy were observed. All therapy was completed in 8 patients, 7 patients were removed due to progression, 2 due to toxicity, 2 refused further treatment, and 1 was removed per the treating physician. The median time to progression and median survival was 5.1 months (95% CI, 3.2-6.7) and 8.8 months (95% CI, 6.4-10.1) respectively. Four patients (20%) were alive at 12 and 18 months. CONCLUSION: Induction irinotecan/gemcitabine followed by twice-weekly gemcitabine and upper abdominal radiation is feasible in patients with locally advanced pancreatic cancer. This regimen, however, has only modest activity and should not be explored further.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Diarreia/induzido quimicamente , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Fadiga/induzido quimicamente , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Radioterapia Adjuvante , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente , Vômito/induzido quimicamente , GencitabinaRESUMO
We report an unusual case of biliary cystadenocarcinoma with oncocytic differentiation. The patient was a 43-year-old woman who presented with right upper quadrant pain. Imaging revealed a 16 x 10 x 10-cm, heterogenous, right hepatic mass with extension into the right atrium. Surgical resection revealed a papillary neoplasm of malignant cells with atypical hyperchromatic nuclei and prominent nucleoli lining fibrovascular cores. Mesenchymal stroma was not present. The majority of the epithelial cells had abundant eosinophilic granular cytoplasm, consistent with oncocytic differentiation. There was extensive stromal and hepatic parenchymal invasion. Immunohistochemical staining revealed a "biliary pattern" of cytokeratin subset immunoreactivity, with positivity for cytokeratin 7 and an absence of staining with cytokeratin 20. The tumor was negative for mucin, carcinoembryonic antigen, alpha-fetoprotein, calretinin, CD31, and chromogranin. There was granular cytoplasmic staining with phosphotungstic acid hematoxylin, consistent with the presence of abundant mitochondria. Electron microscopy revealed abundant mitochondria within the neoplastic cells. This case is quite unusual because female patients only rarely lack the characteristic ovarian-like mesenchymal stroma of biliary cystadenomas/cystadenocarcinomas. Furthermore, to our knowledge, oncocytic differentiation in this neoplasm has been reported previously on only 2 occasions. The biologic behavior and prognostic significance, if any, of the lack of mesenchymal stroma in female patients or the presence of oncocytic differentiation remains to be further elucidated as more of these cases are described.
Assuntos
Neoplasias do Sistema Biliar/patologia , Cistadenocarcinoma/patologia , Células Oxífilas/patologia , Adulto , Neoplasias do Sistema Biliar/diagnóstico , Neoplasias do Sistema Biliar/ultraestrutura , Diferenciação Celular , Cistadenocarcinoma/diagnóstico , Cistadenocarcinoma/ultraestrutura , Feminino , Histocitoquímica , Humanos , Mitocôndrias/ultraestruturaRESUMO
Obtaining a one-centimeter negative margin is an important factor in preventing disease recurrence after surgery for hepatic tumors. Cryotherapy of the resected edge has been used to achieve optimal margin clearance in cases in which the alternative would be an extended high-risk liver resection. The effect of this technique on margin recurrence was examined. Between 1994 and 2001 a total of 56 patients underwent cryosurgery with or without resection for primary and metastatic hepatobiliary malignancies. A 5-cm cryotherapy lollipop probe was used to ablate surgical margins less than one centimeter in 13 of these patients. There were seven colorectal metastases, three hepatocellular carcinomas, and three gallbladder carcinomas. The median size of the colorectal and hepatocellular lesions was 3 cm (range 2-14 cm), and all gallbladder primaries were T2 tumors. All tumors except three were located centrally in the liver requiring cryoablation of margins at segments 4, 5, and 8. Most patients had one site frozen (n = 9) with a median target temperature of -190 degrees C and a median of two freeze-thaw cycles. Final pathological analysis of the resected specimens revealed nine close (<1 cm) and four positive margins. With a median follow-up of 16 months seven patients are alive with no evidence of disease and six have developed recurrences with three of them dying of their disease. Only one (8%) of the initial recurrences was at the cryoablated margin. Cryosurgery of the resection edge facilitates liver resection for malignant tumors when margins are close or positive. Because disease recurrence at the cryoablated margin is low this technique may allow more patients to undergo effective surgical treatment of their hepatobiliary cancers.
Assuntos
Neoplasias do Sistema Biliar/cirurgia , Criocirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/secundário , Neoplasias Colorretais/cirurgia , Feminino , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Excisão de Linfonodo , Masculino , Pessoa de Meia-IdadeRESUMO
Early clinical studies combining irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) have yielded encouraging results. Gemcitabine administered via a twice-weekly schedule results in an enhanced radiation-sensitizing effect. This multi-institution phase II trial of induction irinotecan/gemcitabine followed by twice-weekly gemcitabine and upper abdominal radiation has been initiated to determine the activity of this regimen in patients with unresectable pancreatic cancer. Patients received two cycles of induction irinotecan (100 mg/ m2 IV) and gemcitabine (1,000 mg/m2 IV) on days 1 and 8 of each 3-week cycle. Following the induction therapy, patients without disease progression received twice-weekly gemcitabine at 40 mg/m2 and radiation. Nine patients have been enrolled in the study to date. Median patient age was 71 years (range: 65-85 years). The major toxicity observed thus far was grade 3/4 neutropenia. Grade 3/4 nonhematologic toxicity was rarely observed and included dehydration (12%) and diarrhea (12%), which were likely related to the irinotecan. No treatment-related deaths have occurred. These preliminary data suggest that this regimen is well tolerated. Although the data are limited, tumor progression during the induction chemotherapy has not been observed thus far (radiographically or biochemically [CA-19-9]).