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1.
J Int Soc Prev Community Dent ; 12(4): 468-473, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312585

RESUMO

This case report describes the treatment outcome and further retreatment of an immature permanent maxillary right central incisor with necrotic pulp and chronic apical abscess using regenerative endodontic therapy (RET). The patient had a history of traumatic injury. The initial periapical radiographic and cone-beam computed tomographic (CBCT) examinations revealed tooth #8 had incomplete root formation, thin dentinal walls, and pulp necrosis associated with a large apical periodontitis lesion. RET was conducted in two visits and included a disinfection protocol with 5.25% NaOCl irrigation and medication with a double antibiotic paste (metronidazole and ciprofloxacin). At the second visit, a blood clot was induced, and the cervical third was sealed with a mineral trioxide aggregate plug and the coronal portion with light-cure composite. The tooth was asymptomatic at the 12-, 24-, and 36-month follow-ups, and radiographs showed continued root development with healed periradicular tissues. However, the 4-year radiographic follow-up revealed a recurrent apical periodontitis lesion. A second attempt of RET was conducted in one visit using 1% NaOCl irrigation and stimulation of a blood clot. A double seal with silicate-based cement and composite was placed. At the 24-month follow-up, the tooth remained asymptomatic, and both radiographic and CBCT examinations showed apical closure and complete repair of the periradicular tissues. When a tooth develops recurrent apical periodontitis, a second attempt of RET is a feasible option to control infection, helping to promote tooth retention associated with healthy periradicular conditions.

2.
J Clin Exp Dent ; 14(6): e506-e509, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35765354

RESUMO

This case report describes the procedure and outcome of regenerative endodontic treatment (RET) in a tooth with incomplete root apex and posttreatment apical periodontitis. A 44-year-old patient was referred to the endodontist because of a periapical lesion on tooth #21 and a recent episode of acute periapical abscess. On clinical and radiographic examination, this tooth presented with tenderness to percussion and palpation, periapical radiolucent lesion, external apical resorption, and incomplete apex formation. After coronal access, the filling material was removed, and the canal was gently prepared with hand files, using 1% NaOCl as the main irrigant followed by final irrigation with 17% EDTA, activated with XP-endo Finisher (FKG Dentaire, La Chaux-de-Fonds, Switzerland). The root canal was filled with a double antibiotic paste with ciprofloxacin and metronidazole (1:1). After three weeks, RET was performed by stimulating bleeding into the canal, and when a clot was formed, a bioceramic (EndoSequence BC Sealer, Brasseler USA, Savannah, GA) plug was placed on it, followed by coronal restoration. The tooth remained asymptomatic since RET was concluded. Clinical and radiographic follow-ups showed complete repair of the apical periodontitis lesion and the absence of symptoms after eight months. This satisfactory outcome was confirmed after 34 months. Key words:Bioceramic material; ciprofloxacin; metronidazole; persistent apical periodontitis; regenerative endodontic treatment.

3.
J Endod ; 47(7): 1166-1176, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33864883

RESUMO

This article shows the follow-up of several cases of maxillary sinusitis of dental (usually endodontic) origin, with different manifestations, diagnostic challenges, and outcomes.Cases from 14 patients from 3 countries and treated by 7 different endodontists are presented, all of them with inflammatory sinus changes represented by mucositis, osteoperiostitis, and/or partial/full obstruction. All cases showed dental and/or sinus signs/symptoms that resolved after dental management. In 13 cases, the sinus condition had an endodontic origin, 4 of them concurrently with periodontal involvement. In 1 case, sinusitis was caused by trauma to the face. All cases but 1 had a satisfactory response of the periradicular tissues and maxillary sinus to treatment that consisted of root canal therapy, root amputation, extraction, or trauma management.The successful management of most cases reported in this article emphasizes the importance of endodontics as a specialty engaged in saving teeth and promoting health not only in the oral cavity but also in other areas that may be affected by infections of endodontic origin, including the maxillary sinus.


Assuntos
Seio Maxilar , Sinusite Maxilar , Apicectomia , Humanos , Seio Maxilar/diagnóstico por imagem , Sinusite Maxilar/diagnóstico por imagem , Sinusite Maxilar/etiologia , Tratamento do Canal Radicular/efeitos adversos , Resultado do Tratamento
4.
Clin Gastroenterol Hepatol ; 15(11): 1791-1799, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28579181

RESUMO

BACKGROUND & AIMS: Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. The authors investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC. METHODS: We performed a case-control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls) from January 1, 2004 through May 31, 2015. We collected detailed information on environmental exposures, ages of menarche and menopause, hysterectomies, and uses of birth control and MHT. We performed multivariable logistic and Cox regression analyses to determine the independent effects of factors associated with women on risk and clinical outcome in HCC. The primary outcomes were effect of MHT on HCC risk, the relationship between MHT with hepatitis virus infection on HCC development, and effect of MHT on age at HCC onset or survival after diagnosis of HCC. RESULTS: The estimated adjusted odds ratio (AOR) for HCC in women who ever used estrogen was 0.53 (95% confidence interval [CI], 0.32-0.88). This association was supported by the older age of HCC onset among estrogen users (mean, 64.5 ± 0.9 years) vs nonusers (mean 59.2 ± 1.1 years; P = .001) and the reduced risk of HCC among long-term users (more than 5 years) (AOR, 0.36; 95% CI, 0.20-0.63). Users of estrogen also had a reduced risk for hepatitis-associated HCC: AOR for users, 4.37 (95% CI, 1.67-11.44) vs AOR for nonusers, 17.60 (95% CI, 3.88-79.83). Estrogen use reduced risk of death from HCC (hazard ratio, 0.55; 95% CI, 0.40-0.77; P = .01). Median overall survival times were 33.5 months for estrogen users (95% CI, 25.7-41.3 months) and 24.1 months for nonusers (95% CI, 19.02-29.30 months; P = .008). CONCLUSION: In a case-control study of women with HCC vs female control subjects at a single center, we associated use of estrogen MHT with reduced risk of HCC and increased overall survival times of patients with HCC. Further studies are needed to determine the benefits of estrogen therapy for women and patients with HCC, and effects of tumor expression of estrogen receptor.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Terapia de Reposição de Estrogênios/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
5.
J Natl Compr Canc Netw ; 12(7): 969-74, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24994917

RESUMO

The NCCN Guidelines for Occult Primary tumors provide recommendations for the evaluation, workup, management, and follow-up of patients with occult primary tumors (cancers of unknown primary). These NCCN Guidelines Insights summarize major discussion points of the 2014 NCCN Occult Primary panel meeting. The panel discussed gene expression profiling (GEP) for the identification of the tissue of origin and concluded that, although GEP has a diagnostic benefit, a clinical benefit has not been demonstrated. The panel recommends against GEP as standard management, although 20% of the panel believes the diagnostic benefit of GEP warrants its routine use. In addition, the panel discussed testing for actionable mutations (eg, ALK) to help guide choice of therapy, but declined to add this recommendation.


Assuntos
Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/genética , Biópsia com Agulha de Grande Calibre , Perfilação da Expressão Gênica , Humanos , Mutação , Neoplasias Primárias Desconhecidas/terapia
6.
Int J Clin Oncol ; 18(2): 226-31, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22218909

RESUMO

BACKGROUND: Preclinical and clinical data suggest synergy for gemcitabine and oxaliplatin. These agents were tested in several known cancers that also comprise the common carcinoma of unknown primary (CUP) subtypes; namely, lung and pancreaticobiliary profiles. METHODS: The study enrolled 29 patients of whom 28 patients were eligible for treatment. Gemcitabine was given at 1,000 mg/m(2) as a fixed dose rate infusion and oxaliplatin was infused at 100 mg/m(2) every 2 weeks with restaging performed after 3 cycles at 6 weeks. RESULTS: The study reported one complete response (CR) (4%), 6 patients with a partial response (PR) (25%), and 13 with stable disease (SD) (54%); and 4 patients had progressive disease (PD) (17%) on restaging. Median overall survival (OS) and progression-free survival were 12.8 months (95% confidence interval [CI] 8.5-18.5) and 3.1 months (95% CI 1.7-6), respectively. The 1-year OS was 54%. The most common grade 3 toxicities were nausea (22%), vomiting (15%), and fatigue (11%). There were no grade 4 toxicities. This study was closed early as we moved from an empiric therapy platform to a more individualized approach. CONCLUSIONS: Gemcitabine and oxaliplatin is a well-tolerated regimen in CUP with similar outcomes to previously documented CUP studies. In selected good performance status patients this combination may serve as a first-line doublet chemotherapy option for CUP patients.


Assuntos
Desoxicitidina/análogos & derivados , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Compostos Organoplatínicos/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/patologia , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Gencitabina
7.
J Endod ; 38(3): 411-4, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22341086

RESUMO

INTRODUCTION: The revitalization of a previously necrotic pulp space has been shown to be possible and even considered predictable. However, exact criteria for success are still lacking, and, in fact, some cases do not respond as predicted. METHODS: In this case, the same operator treated 2 teeth similarly according to the principles laid out by Banch and Trope. The tooth that according to our expectations was more likely to be revitalized successfully failed to do so, whereas the second tooth that, in our estimation, was less likely to succeed was successful. In the tooth that failed to revitalize, auto-apexification occurred. CONCLUSIONS: Complete understanding for the criteria for predictable revitalization and apexification is still lacking.


Assuntos
Necrose da Polpa Dentária/terapia , Incisivo/lesões , Tratamento do Canal Radicular/métodos , Fraturas dos Dentes/complicações , Compostos de Alumínio/uso terapêutico , Apexificação/métodos , Compostos de Cálcio/uso terapêutico , Criança , Tomografia Computadorizada de Feixe Cônico , Combinação de Medicamentos , Seguimentos , Humanos , Masculino , Óxidos/uso terapêutico , Radiografia Interproximal , Materiais Restauradores do Canal Radicular/uso terapêutico , Preparo de Canal Radicular/métodos , Silicatos/uso terapêutico , Ápice Dentário/patologia , Ápice Dentário/fisiopatologia , Coroa do Dente/lesões , Dente não Vital/terapia , Resultado do Tratamento
8.
Support Care Cancer ; 20(5): 1073-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21573770

RESUMO

PURPOSE: This study was designed to determine if differences exist in the speaking rate and pitch of healthcare providers when discussing bad news versus neutral topics, and to assess listeners' ability to perceive voice differences in the absence of speech content. METHODS: Participants were oncology healthcare providers seeing patients with cancer of unknown primary. The encounters were audio recorded; the information communicated by the oncologist to the patient was identified as neutral or bad news. At least 30 seconds of both bad news and neutral utterances were analyzed; provider voice pitch and speaking rate were measured. The same utterances were subjected to low pass filtering that maintained pitch contours and speaking rate, but eliminated acoustic energy associated with consonants making the samples unintelligible, but with unchanged intonation. Twenty-seven listeners (graduate students in a voice disorders class) listened to the samples and rated them on three features: caring, sympathetic, and competent. RESULTS: All but one provider reduced speaking rate, the majority also reduced pitch in the bad news condition. Listeners perceived a significant difference between the nonverbal characteristics of the providers' voice when performing the two tasks and rated speech produced with the reduced rate and lower pitch as more caring and sympathetic. CONCLUSIONS: These results suggest that simultaneous assessment of verbal content and multiparameter prosodic analysis of speech is necessary for a more thorough understanding of the expression and perception of empathy. This information has the potential to contribute to the enhancement of communication training design and of oncologists' communication effectiveness.


Assuntos
Comunicação , Percepção da Altura Sonora , Percepção da Fala , Revelação da Verdade , Adulto , Empatia , Feminino , Humanos , Masculino , Oncologia/métodos , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/psicologia , Comunicação não Verbal , Médicos/psicologia , Voz , Adulto Jovem
9.
J Natl Compr Canc Netw ; 9(12): 1358-95, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22157556

RESUMO

Occult primary tumors, or cancers of unknown primary (CUPs), are defined as histologically proven metastatic malignant tumors whose primary site cannot be identified during pretreatment evaluation. They have a wide variety of clinical presentations and a poor prognosis in most patients. Patients with occult primary tumors often present with general complaints, such as anorexia and weight loss. Clinical absence of primary tumor, early dissemination, aggressiveness, and unpredictability of metastatic pattern are characteristic of these tumors. Life expectancy is very short, with a median survival of 6 to 9 months. In most patients, occult primary tumors are refractory to systemic treatments, and chemotherapy is only palliative and does not significantly improve long-term survival. However, certain clinical presentations of these tumors are associated with a better prognosis. Special pathologic studies can identify subsets of patients with tumor types that are more responsive to chemotherapy. Treatment options should be individualized for this selected group of patients to achieve improved response and survival rates.


Assuntos
Oncologia/legislação & jurisprudência , Neoplasias Primárias Desconhecidas/terapia , Guias de Prática Clínica como Assunto , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Algoritmos , Anticorpos/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/diagnóstico , Carcinoma/epidemiologia , Carcinoma/patologia , Carcinoma/terapia , Feminino , Humanos , Metástase Linfática , Masculino , Oncologia/organização & administração , Técnicas de Diagnóstico Molecular/métodos , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/epidemiologia , Sociedades Médicas/legislação & jurisprudência , Sociedades Médicas/organização & administração , Estados Unidos
10.
Clin Cancer Res ; 17(12): 4063-70, 2011 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-21531815

RESUMO

PURPOSE: Accurate identification of tissue of origin (ToO) for patients with carcinoma of unknown primary (CUP) may help customize therapy to the putative primary and thereby improve the clinical outcome. We prospectively studied the performance of a microRNA-based assay to identify the ToO in CUP patients. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded (FFPE) metastatic tissue from 104 patients was reviewed and 87 of these contained sufficient tumor for testing. The assay quantitates 48 microRNAs and assigns one of 25 tumor diagnoses by using a biologically motivated binary decision tree and a K-nearest neighbors (KNN). The assay predictions were compared with clinicopathologic features and, where suitable, to therapeutic response. RESULTS: Seventy-four of the 87 cases were processed successfully. The assay result was consistent or compatible with the clinicopathologic features in 84% of cases processed successfully (71% of all samples attempted). In 65 patients, pathology and immunohistochemistry (IHC) suggested a diagnosis or (more often) a differential diagnosis. Out of those, the assay was consistent or compatible with the clinicopathologic presentation in 55 (85%) cases. Of the 9 patients with noncontributory IHC, the assay provided a ToO prediction that was compatible with the clinical presentation in 7 cases. CONCLUSIONS: In this prospective study, the microRNA diagnosis was compatible with the clinicopathologic picture in the majority of cases. Comparative effectiveness research trials evaluating the added benefit of molecular profiling in appropriate CUP subsets are warranted. MicroRNA profiling may be particularly helpful in patients in whom the IHC profile of the metastasis is nondiagnostic or leaves a large differential diagnosis.


Assuntos
Carcinoma/diagnóstico , Carcinoma/secundário , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Primárias Desconhecidas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma/genética , Árvores de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Neoplasias Primárias Desconhecidas/genética , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
11.
J Cancer Educ ; 24(3): 180-5, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19526404

RESUMO

BACKGROUND: In many countries, physicians are reluctant to disclose unfavorable medical information to patients with advanced cancer and instead give the bad news to the family. METHODS: The authors modified standard communication workshops to help Italian senior oncologists overcome cultural, social, and attitudinal barriers to disclosure of diagnosis and prognosis. RESULTS: Fifty-seven physicians participated; 88% believed the workshops would improve their medical practice. Many pursued further training and organized communication skills programs of their own. CONCLUSIONS: Communication skills workshops can be modified to meet educational and social norms and help clinicians acquire the interpersonal skills needed for honest communication with patients.


Assuntos
Barreiras de Comunicação , Características Culturais , Educação Médica Continuada , Oncologia/educação , Neoplasias/diagnóstico , Revelação da Verdade , Humanos , Relações Médico-Paciente
12.
J Clin Oncol ; 26(27): 4442-8, 2008 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-18802157

RESUMO

PURPOSE: To evaluate the feasibility of a 10-gene reverse transcriptase polymerase chain reaction assay to identify the tissue of origin in patients with carcinoma of unknown primary (CUP) site. PATIENTS AND METHODS: Diagnostic biopsy formalin-fixed, paraffin-embedded (FFPE) specimens from 120 patients with CUP were collected retrospectively from Sarah Cannon Research Institute, Nashville, TN, and prospectively from The University of Texas M. D. Anderson Cancer Center, Houston, TX. Tissue of origin assignments by the assay were correlated with clinical and pathologic features and with response to therapy. RESULTS: The assay was successfully performed in 104 patients (87%), and a tissue of origin was assigned in 63 patients (61%). In the remaining 41 patients (39%), the molecular profiles were not specific for the six tumor types detectable by this assay. The tissues of origin most commonly identified were lung, pancreas, and colon; most of these patients had clinical and pathologic features consistent with these diagnoses. Patients with lung and pancreas profiles had poor response to treatment. Patients with colon cancer profiles had better response to colon cancer-specific therapies than they did to empiric CUP therapy with taxane/platinum regimens. Patients with ovarian cancer profiles were atypical, with widespread visceral metastases and a paucity of overt peritoneal involvement. CONCLUSION: This gene expression profiling assay was feasible using FFPE biopsy specimens and identified a putative tissue of origin in 61% of patients with CUP. In most patients, the assigned tissue of origin was compatible with clinicopathologic features and response to treatment. Prospective studies in which assay results are used to direct therapy are indicated.


Assuntos
Carcinoma/diagnóstico , Carcinoma/secundário , Perfilação da Expressão Gênica/métodos , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Carcinoma/genética , Carcinoma/patologia , Diagnóstico Diferencial , Estudos de Viabilidade , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/classificação , Valor Preditivo dos Testes , Estudos Retrospectivos
13.
J Clin Oncol ; 26(21): 3496-502, 2008 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-18640930

RESUMO

PURPOSE: We conducted a phase II trial to assess the outcomes of patients who received preoperative gemcitabine-based chemoradiation and pancreaticoduodenectomy (PD) for stage I/II pancreatic adenocarcinoma. PATIENTS AND METHODS: Eligible patients with pancreatic head/uncinate process adenocarcinoma and radiographically defined potentially resectable disease received chemoradiation with 7 weekly intravenous (IV) infusions of gemcitabine (400 mg/m(2) IV over 30 minutes) plus radiation therapy (30 Gy in 10 fractions over 2 weeks). Patients underwent restaging 4 to 6 weeks after completion of chemoradiation and, in the absence of disease progression, were taken to surgery. RESULTS: The study enrolled 86 patients. At the time of restaging, disease progression or a decline in performance status precluded 13 patients from surgery. Seventy-three (85%) of 86 patients were taken to surgery, extrapancreatic disease was found in nine, and 64 (74%) of 86 underwent a successful PD. Median overall survival (86 patients) was 22.7 months with a 27% 5-year survival. Median survival was 34 months for the 64 patients who underwent PD and 7 months for the 22 unresected patients (P < .001). The 5-year survival for those who did and did not undergo PD was 36% and 0%, respectively. CONCLUSION: Preoperative gemcitabine-based chemoradiation followed by restaging and evaluation for surgery separated the study population into two different subsets: patients likely to benefit from PD (n = 64) and those in whom surgery would be unlikely to provide clinical benefit (n = 22). Furthermore, the encouraging overall survival observed in this large trial supports the continued investigation of gemcitabine-based preoperative therapy in resectable pancreatic cancer.


Assuntos
Adenocarcinoma/terapia , Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Terapia Neoadjuvante/métodos , Neoplasias Pancreáticas/terapia , Cuidados Pré-Operatórios/métodos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Gencitabina
15.
J Transl Med ; 5: 66, 2007 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-18076766

RESUMO

BACKGROUND: Pharmacokinetic advantages of intraperitoneal (IP) rhIL-12, tumor response to IP delivery of other cytokines as well as its potential anti-angiogenic effect provided the rationale for further evaluation of IPrhIL-12 in patients with persistent ovarian or peritoneal carcinoma. METHODS: A phase 2 multi-institutional trial (NCI Study #2251) of IP rIL-12 (300 nanogram/Kg weekly) was conducted in patients with ovarian carcinoma or primary peritoneal carcinoma. Patients treated with primary therapy for ovarian cancer who had no extraabdominal/parenchymal disease or bulky peritoneal disease were eligible. Four to 8 weeks from last chemotherapy, eligible patients underwent a laparotomy/laparoscopy. Patients with residual disease < or = 1 cm were registered for the treatment phase 2-5 weeks post surgery. The effect of IP rIL-12 on the expression of TNFalpha , INFalpha , IL-10, IP-10, IL-8, FGF, VEGF was also studied. RESULTS: Thirty-four patients were registered for the first screening phase of the study. Median age was 56.6 years (range: 31-71); 12 completed the second phase and were evaluable for response/toxicity. Performance scores of IL-12 treated patients were 0 (11 pts) and 1 (1 pt). There were no treatment related deaths, peritonitis or significant catheter related complications. Toxicities included grade 4 neutropenia (1), grade 3 fatigue (4), headache (2), myalgia (2), non-neutropenic fever (1), drug fever (1), back pain (1), and dizziness (1). The best response observed was SD. Two patients had SD and 9 had PD, and 1 was evaluable for toxicity only. Peritoneal fluid cytokine measurements demonstrated a > or = 3 fold relative increase post-rhIL-12: IFN-gamma, 5/5 pts; TNF-alpha , 1/5; IL-10, 4/5; IL-8, 5/5; and VEGF, 3/5. IP10 levels were increased in 5/5 patients. Cytokine response profiles suggest either NK or T-cell mediated effects of IP rhIL-12. Cytokine/chemokine results also suggest a pleiotropic response since proteins with potential for either anti-tumor (IFN-gamma , IP-10) or pro-tumor growth effects (VEGF, IL-8) were detected. CONCLUSION: IP IL-12 can safely be administered at this dose and schedule to patients after first line chemotherapy for ovarian/peritoneal carcinoma. The maximum response was stable disease. Future IP therapies with rhIL-12 will require better understanding and control of pleiotropic effects of IL-12.


Assuntos
Interleucina-12/toxicidade , Interleucina-12/uso terapêutico , Neoplasia Residual/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Líquido Ascítico/química , Ensaios Clínicos Fase I como Assunto , Citocinas/análise , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/toxicidade , Segurança
16.
Am J Gastroenterol ; 102(12): 2696-707, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17764494

RESUMO

OBJECTIVES: Although cigarette smoking is the most well-established environmental risk factor for pancreatic cancer, the interaction between smoking and other risk factors has not been assessed. We evaluated the independent effects of multiple risk factors for pancreatic cancer and determined whether the magnitude of cigarette smoking was modified by other risk factors in men and women. METHODS: We conducted a hospital-based case-control study involving 808 patients with pathologically diagnosed pancreatic cancer and 808 healthy frequency-matched controls. Information on risk factors was collected by personal interview, and unconditional logistic regression was used to determine adjusted odds ratios (AORs) by the maximum-likelihood method. RESULTS: Cigarette smoking, family history of pancreatic cancer, heavy alcohol consumption (>60 mL ethanol/day), diabetes mellitus, and history of pancreatitis were significant risk factors for pancreatic cancer. We found synergistic interactions between cigarette smoking and family history of pancreatic cancer (AOR 12.8, 95% confidence interval [CI] 1.6-108.9) and diabetes mellitus (AOR 9.3, 95% CI 2.0-44.1) in women, according to an additive model. Approximately 23%, 9%, 3%, and 5% of pancreatic cancer cases in this study were related to cigarette smoking, diabetes mellitus, heavy alcohol consumption, and family history of pancreatic cancer, respectively. CONCLUSIONS: The significant synergy between these risk factors suggests a common pathway for carcinogenesis of the pancreas. Determining the underlying mechanisms for such synergies may lead to the development of pancreatic cancer prevention strategies for high-risk individuals.


Assuntos
Neoplasias Pancreáticas/etiologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Comorbidade , Complicações do Diabetes , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos
17.
Cancer ; 109(12): 2547-56, 2007 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-17492688

RESUMO

BACKGROUND: The associations between passive smoking and the use of noncigarette tobacco products with pancreatic cancer are not clear. METHODS: In this case-control study, the authors collected information on passive smoking and the use of noncigarette tobacco products in 808 patients with pancreatic adenocarcinoma and 808 healthy controls by personal interview. Multivariable logistic regression was performed to estimate the adjusted odds ratio (AOR) and 95% confidence interval (95% CI). RESULTS: The results confirmed the previously reported association between active smoking and increased risk for pancreatic cancer. The AOR was 1.7 (95% CI, 1.4-2.2) for regular smokers, 1.8 (95% CI, 1.4-2.4) for long-term smokers, and 3.1 (95% CI, 2.2-4.3) for former smokers. Although passive smoking showed a nonsignificantly elevated risk for pancreatic cancer in the entire study population (AOR, 1.3; 95% CI, 0.9-1.7), the association was present among ever smokers (AOR, 1.7; 95% CI, 1.03-2.6) but was absent among never smokers (AOR, 1.1; 95% CI, 0.8-1.6). Neither intensity nor duration of passive smoking modified the risk of pancreatic cancer among never smokers. The use of chewing tobacco, snuff, and pipes showed no significant risk elevation for pancreatic cancer after controlling for the confounding effects of demographics and other known risk factors. The use of cigars in never smokers showed a borderline significant increase of risk for pancreatic cancer (AOR, 2.2; 95% CI, 1.0-4.7; P = .05). CONCLUSIONS: The current observations did not support a role for passive smoking or the use of noncigarette tobacco products in the etiology of pancreatic cancer. The association between cigar use and the risk of pancreatic cancer needs to be confirmed in other study populations.


Assuntos
Adenocarcinoma/etiologia , Neoplasias Pancreáticas/etiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Tabaco sem Fumaça/efeitos adversos , Adenocarcinoma/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Coleta de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/epidemiologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
18.
Cancer ; 106(7): 1624-33, 2006 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-16518827

RESUMO

BACKGROUND: Unique metastatic patterns cited in the literature often arise from anecdotal clinical observations and autopsy reports. The authors analyzed clinical data from a large number of patients with histologically confirmed, distant-stage adenocarcinoma to evaluate metastatic patterns. METHODS: Tumor registry data were collected between 1994-1996 on 11 primary tumor sites and 15 metastatic sites from 4399 patients. The primary and metastatic sites were cross-tabulated in various ways to identify patterns, and the authors developed algorithms by using multinomial logistic regression analysis to predict the locations of primary tumors based on metastatic patterns. RESULTS: Three primary tumors had single, dominant metastatic sites: ovary to abdominal cavity (91%), prostate to bone (90%), and pancreas to liver (85%). The liver was the dominant metastatic site for gastrointestinal (GI) primary tumors (71% of patients), whereas bone and lung metastases were noted most frequently in non-GI primary tumors (43% and 29%, respectively). In a study of combinations of liver, abdominal cavity, and bone metastases, 86% of prostate primary tumors had only bone metastases, 80% of ovarian primary tumors had only abdominal cavity metastases, and 74% of pancreas primary tumors had only liver metastases. A single organ was the dominant source of metastases in 7 sites: axillary lymph node from the breast (97%), intestinal lymph node from the colon (84%), thoracic lymph node from the lung (66%), brain from the lung (64%), mediastinal lymph node from the lung (62%), supraclavicular lymph node from the breast (51%), and adrenal gland from the lung (51%). CONCLUSIONS: The algorithms that the authors developed achieved a cross-validated accuracy of 64% and an accuracy of 64% on an 1851-patient independent test set, compared with 9% accuracy when a random classifier was used.


Assuntos
Adenocarcinoma/secundário , Algoritmos , Metástase Neoplásica , Sistema de Registros/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
19.
Carcinogenesis ; 27(1): 103-11, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15987714

RESUMO

To test the hypothesis that genetic variation in the metabolism of tobacco carcinogens, such as aromatic amines (AA) and heterocyclic amines (HCA), contributes to pancreatic cancer, we have examined genetic polymorphisms of three key enzymes, i.e. cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 1 and 2 (NAT1 and NAT2), in a hospital-based case-control study of 365 patients with pancreatic adenocarcinoma and 379 frequency-matched healthy controls. Genotypes were determined using PCR-restriction fragment length polymorphism (RFLP) and Taqman methods. Smoking information was collected by personal interview. Adjusted odds ratio (AOR) and 95% confidence interval (CI) was estimated by unconditional multivariate logistic regression analysis. We found that the NAT1 'rapid' alleles were associated with a 1.5-fold increased risk of pancreatic cancer (95% CI: 1.0-2.1) with adjustment of potential confounders. This effect was more prominent among never smokers (AOR: 2.4, 95% CI: 1.4-4.3) and females (AOR: 1.8, 95% CI: 1.0-3.1). Some genotypes were significantly associated with increased risk for pancreatic cancer among smokers, especially heavy smokers (<20 pack years). For example, heavy smokers with the CYP1A2*1D (T-2467delT) delT, CYP1A2*1F(A-163C) C allele, NAT1 'rapid' or NAT2 'slow' alleles had an AOR (95% CI) of 1.4 (0.7-2.3), 1.9 (1.1-3.4), 3.0 (1.6-5.4) and 1.5 (0.8-2.6), respectively, compared with never smokers carrying the non-at-risk alleles. These effects were more prominent in females than in males. The corresponding AOR (95% CI) was 3.1 (1.0-8.0), 3.8 (1.5-10.1), 4.5 (1.6-12.7) and 2.0 (0.8-5.1) for females versus 1.0 (0.4-1.9), 1.1 (0.5-2.4), 2.1 (1.0-4.6) and 1.1 (0.5-2.6) for males. A significant synergistic effect of CYP1A2*1F C allele and NAT1"rapid" alleles on the risk for pancreatic cancer was also detected among never smokers (AOR: 2.9, 95% CI: 1.2-6.9) and among females (AOR: 2.5, 95% CI: 1.1-5.7). These data suggest that polymorphisms of the CYP1A2 and NAT1 genes modify the risk of pancreatic cancer.


Assuntos
Arilamina N-Acetiltransferase/genética , Citocromo P-450 CYP1A2/genética , Isoenzimas/genética , Neoplasias Pancreáticas/genética , Polimorfismo Genético/genética , Fumar/efeitos adversos , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Idoso , Carcinoma Ductal Pancreático/enzimologia , Carcinoma Ductal Pancreático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Neoplasias Pancreáticas/enzimologia , Fenótipo , Fatores de Risco
20.
J Cancer Educ ; 20(3): 143-9, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16122361

RESUMO

BACKGROUND: Training in the communication components of cancer care is necessary for the practice of oncology. We conducted a communication course for oncology fellows. METHODS: Teaching methods included lectures, role playing and simulated patient interviews. We used self-reports, knowledge questionnaires and course/faculty evaluations. RESULTS: A total of 17 fellows participated. Skills in dealing with bad news, denial and end-of-life issues improved. We obtained information on communication tasks commonly performed during patient interactions, various aspects of the course and faculty performance. CONCLUSIONS: Fellows' knowledge and self-efficacy improved postcourse. Information on challenges faced by trainees and their feedback may help focus the design of future courses.


Assuntos
Comunicação , Bolsas de Estudo , Oncologia , Avaliação de Programas e Projetos de Saúde , Adulto , Competência Clínica , Docentes de Medicina , Feminino , Seguimentos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Oncologia/educação , Pessoa de Meia-Idade , Simulação de Paciente , Papel do Médico , Aprendizagem Baseada em Problemas , Revelação da Verdade , Estados Unidos
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