RESUMO
Pancreatic ductal adenocarcinoma (PDAC) is a disease marked by high rates of mortality; it is mostly incurable at the time of diagnosis. Only about 7% of patients survive 5 years after diagnosis. Diagnosis at a late stage and rapid progression with minimal response to available treatments are the main reasons for this poor outcome. It is crucial to identify individuals at high risk of developing PDAC so preventive and early detection measures can be employed. Approximately 10% to 15% of PDAC cases have a hereditary or familial basis. In the majority of PDAC cases, no main causative gene has been identified, but several known germline pathogenic mutations have been shown to be related to an increased risk of this cancer. The presence of 2 or more patients with pancreatic cancer within the circle of first-degree relatives, without the presence of a causative germline mutation, is defined as familial pancreatic cancer; this accounts for 4% to 10% of PDAC. Based on the growing evidence supporting the benefit of germline genetic testing in patients with PDAC, both the American Society of Clinical Oncology and the National Comprehensive Cancer Network recently updated their guidelines to include recommendations around genetic testing for patients with pancreatic cancer. However, there is no general consensus on the group of patients and individuals who should be studied and screened. We present a demonstrative case and review the available data on hereditary and familial PDAC.
Assuntos
Carcinoma Ductal Pancreático/genética , Carcinoma/genética , Mutação em Linhagem Germinativa , Neoplasias Pancreáticas/genética , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/diagnóstico por imagem , Carcinoma/terapia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/terapia , Testes Genéticos/métodos , Humanos , Masculino , Síndromes Neoplásicas Hereditárias/diagnóstico por imagem , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/patologia , Pancreatectomia/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/terapia , Fatores de RiscoRESUMO
Organic chromophores have been well developed for multimodality imaging-guided photothermal therapy (PTT) due to their outstanding optical properties and excellent designability. However, the theranostic efficiencies of most currently available organic chromophores are restricted intrinsically, owing to their poor photostability or complex synthesis procedures. These drawbacks not only increase their cost of synthesis, but also cause side effects in PTT. Method: We presented a facile strategy for constructing a near-infrared (NIR)-absorbing perylenediimide structured with pH-responsive piperazine ring at the bay region. The chromophore was conjugated with carboxyl-end-capped PEG as side chains that can self-assemble into nanoparticles (NPs) in aqueous solution. The NIR optical properties and photothermal conversation ability of PPDI-NPs were investigated. We then studied the imaging-guided PTT of PPDI-NPs under NIR light illumination in 4T1 cells and mice respectively. Results: The excellent photostable PPDI-NPs had near-infrared fluorescence (NIRF) emission and high photothermal conversion efficiency in acidic microenvironment. Importantly, PPDI-NPs can be utilized for the precise detection of tumors by NIRF/photoacoustic/thermal trimodality imaging. Efficient PTT of PPDI-NPs was applied in vitro and in vivo with high biosafety. Conclusion: In summary, we developed pH-responsive perylenediimide nanoparticles as multifunctional phototheranostic agent with high stability and simple synthesis procedures. This study offers a promising organic chromophore for developing phototheranostics in cancer therapy.
Assuntos
Neoplasias da Mama , Carcinoma , Imidas/uso terapêutico , Perileno/análogos & derivados , Terapia Fototérmica , Animais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Carcinoma/diagnóstico por imagem , Carcinoma/terapia , Linhagem Celular Tumoral , Feminino , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Imagem Multimodal , Nanopartículas , Perileno/uso terapêutico , Técnicas Fotoacústicas , Nanomedicina TeranósticaRESUMO
BACKGROUND: It was hitherto common practice to analyse each removed gallbladder for the presence of gall bladder cancer (GBC) although this approach may be questioned. The aim of this study was to determine whether a policy of selective histopathological analysis (Sel-HPA) is oncologically safe and cost effective. METHODS: This retrospective study was conducted in a single Dutch teaching hospital. Immediately following cholecystectomy, the surgeon decided on the basis of inspection and palpation whether histological examination was indicated. The Dutch Comprehensive Cancer Organisation (IKNL) registry was used to identify the number of GBC during this time period. RESULTS: Of 2271 patients who underwent a cholecystectomy in our institution between January 2012 and December 2017, 1083 (47.7%) were deemed indicated for histopathological analysis. Sixteen pathological gallbladders (1.5%) were identified in that period (intestinal metaplasia, nâ¯=â¯3; low grade dysplasia nâ¯=â¯7; carcinoma nâ¯=â¯6). During follow-up, no patient was found to have GBC recurrence in the population whose gallbladder was not sent for pathology (52.3%, nâ¯=â¯1188, median 49 months of follow up). The percentage of gallbladders that were analysed decreased over the six years of observation from 83% to 38%. Our policy of Sel-HP saved over 65 000. CONCLUSIONS: A policy of selective histopathology after cholecystectomy is oncologically safe and reduces costs.
Assuntos
Carcinoma/diagnóstico , Colecistectomia , Doenças da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico , Vesícula Biliar/patologia , Pólipos/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Colecistectomia Laparoscópica , Colecistite Aguda/cirurgia , Colecistolitíase/cirurgia , Análise Custo-Benefício , Feminino , Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Metaplasia , Pessoa de Meia-Idade , Países Baixos , Seleção de Pacientes , Pólipos/diagnóstico por imagem , Pólipos/patologia , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Although multiphoton microscopy (MPM) can visualize both cell and extracellular matrix (ECM) structures of the skin in high-contrast without exogenous labeling, label-free MPM is usually too slow to image clinically relevant large regions. A high-speed MPM method would be beneficial for evaluating clinical skin specimens by increasing the imaging area. In this study, moxifloxacin labeling-based MPM (moxifloxacin MPM) was characterized in various human skin cancer specimens. STUDY DESIGN/MATERIALS AND METHODS: Moxifloxacin ophthalmic solution was used for cell-labeling and MPM imaging was conducted afterwards. Moxifloxacin MPM was characterized in ex vivo normal human skin and skin cancer specimens in comparison with the label-free MPM and fluorescence confocal microscopy (FCM) using acridine orange as a labeling agent. Then, moxifloxacin MPM was applied to various ex vivo human skin cancer specimens including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), dermatofibrosarcoma protuberans (DFSP). Results of moxifloxacin MPM were compared with bright-field clinical and histopathologic findings. RESULTS: Moxifloxacin MPM imaged both cells and collagen in the skin, similarly to label-free MPM, but with enhanced fluorescence intensities in cells and enhanced imaging speeds. Moxifloxacin MPM imaged cells in the skin similarly to acridine orange-based FCM. Moxifloxacin MPM of various human skin cancer specimens imaged their specific cellular features. The microscopic features detected in moxifloxacin MPM were confirmed with histological images. CONCLUSIONS: This observational pilot study demonstrated that moxifloxacin MPM could detect specific cellular features of various skin cancers in good correlation with histopathological images in Asian patients at the higher imaging speed than label-free MPM. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Assuntos
Povo Asiático , Carcinoma/diagnóstico por imagem , Microscopia de Fluorescência por Excitação Multifotônica , Moxifloxacina/uso terapêutico , Neoplasias Cutâneas/diagnóstico por imagem , Inibidores da Topoisomerase II/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/etnologia , Carcinoma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/patologia , Técnicas de Cultura de TecidosRESUMO
PURPOSE: To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats. METHODS: We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500µg/kg injected i.p; DMBA+ACE+Vincristine 250µg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, hematology and histopathology were used to validate the treatments. RESULTS: All animals survived. A gradual weight gain in all groups was observed, with no significant difference (p>0.05). The oral administration of ACE and ACE+vincristine 50% significantly reduced breast tumors incidence examined with PET-18FDG and fluorescence (p<0.001). Significant reduction of serum transaminases, oxidative stress and hematological toxicity were observed in these groups. Antioxidant enzyme levels in breast tissue were significantly higher compared to the DMBA and DMBA+vincristine groups. CONCLUSION: These results demonstrate for the first time that ACE positively influences the treatment of DMBA-induced breast cancer in animal model, inducing a reduction in oxidative stress and chemotherapy toxicity, meaning that ACE may have clinical implication in further studies.
Assuntos
Antineoplásicos/farmacologia , Bignoniaceae/química , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Neoplasias Experimentais/tratamento farmacológico , Extratos Vegetais/farmacologia , 9,10-Dimetil-1,2-benzantraceno , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinógenos , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Catalase/análise , Feminino , Fluordesoxiglucose F18 , Glutationa Peroxidase/análise , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/patologia , Imagem Óptica/métodos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Ratos Wistar , Reprodutibilidade dos Testes , Superóxido Dismutase/análise , Fatores de Tempo , Resultado do Tratamento , Vincristina/farmacologia , Vincristina/uso terapêuticoRESUMO
Abstract Purpose: To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats. Methods: We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500μg/kg injected i.p; DMBA+ACE+Vincristine 250μg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, hematology and histopathology were used to validate the treatments. Results: All animals survived. A gradual weight gain in all groups was observed, with no significant difference (p>0.05). The oral administration of ACE and ACE+vincristine 50% significantly reduced breast tumors incidence examined with PET-18FDG and fluorescence (p<0.001). Significant reduction of serum transaminases, oxidative stress and hematological toxicity were observed in these groups. Antioxidant enzyme levels in breast tissue were significantly higher compared to the DMBA and DMBA+vincristine groups. Conclusion: These results demonstrate for the first time that ACE positively influences the treatment of DMBA-induced breast cancer in animal model, inducing a reduction in oxidative stress and chemotherapy toxicity, meaning that ACE may have clinical implication in further studies.
Assuntos
Animais , Feminino , Neoplasias da Mama/tratamento farmacológico , Extratos Vegetais/farmacologia , Carcinoma/tratamento farmacológico , Bignoniaceae/química , Neoplasias Experimentais/tratamento farmacológico , Antineoplásicos/farmacologia , Vincristina/farmacologia , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Carcinógenos , Carcinoma/patologia , Carcinoma/diagnóstico por imagem , Catalase/análise , Resultado do Tratamento , Ratos Wistar , Fluordesoxiglucose F18 , 9,10-Dimetil-1,2-benzantraceno , Glutationa Peroxidase/análise , Antineoplásicos/uso terapêuticoRESUMO
Individuals at high risk for pancreatic cancer are recommended surveillance and healthy lifestyle behaviours and patient experience with recommendations are understudied. To describe engagement and experience with surveillance, tobacco and alcohol use, health beliefs and motivation (Champion Health Belief Measure) and the relationship with personal, psychosocial (Impact of Event Scale), and familial characteristics. Interest in integrative therapies (complementary therapies) are described. A multi-site cross-sectional survey including individuals at high risk for pancreatic cancer with no diagnosis of pancreatic cancer who have been evaluated at a comprehensive cancer center. Descriptive statistics and Wilcoxon rank sum test and Fisher's exact test were used to assess univariate associations. Of the 132 respondents (72% response rate), 92 (70%) reported undergoing surveillance which was associated with older age (p = 0.001). Of which, 36% and 51% report that magnetic resonance imaging (MRI) or endoscopic ultrasound (EUS), respectively, were uncomfortable; 22% and 30% dread the next MRI or EUS, respectively. Of those who reported alcohol consumption (n = 88); 15% consumed 1 or more drinks daily and no alcohol consumption was associated with higher Impact of Event scale scores (p = 0.024). A total of six participants were currently smoking every day or some days. Participants reported high motivation to engage in heathy behaviours and 92% were interested in integrative therapies. In these select participants, most were engaging in pancreatic cancer surveillance, alcohol intake was moderate, and tobacco intake was minimal. Modifiable factors, such as experience and comfort with surveillance could be addressed. The sample is motivated to engage in behavioural health intervention.
Assuntos
Carcinoma/psicologia , Neoplasias Pancreáticas/psicologia , Adulto , Consumo de Bebidas Alcoólicas , Atitude Frente a Saúde , Carcinoma/diagnóstico por imagem , Carcinoma/prevenção & controle , Estudos Transversais , Endossonografia , Feminino , Predisposição Genética para Doença , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/prevenção & controle , Fatores de Risco , Fatores Socioeconômicos , Uso de TabacoRESUMO
BACKGROUND: A remarkable therapeutic efficacy has been demonstrated with 225Ac-prostate-specific membrane antigen (PSMA)-617 in heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC) patients. We report our experience with 225Ac-PSMA-617 therapy in chemotherapy-naïve patients with advanced metastatic prostate carcinoma. METHODS: Seventeen patients with advanced prostate cancer were selected for treatment with 225Ac-PSMA-617 in 2-month intervals, with initial activity of 8 MBq, then de-escalation to 7 MBq, 6 MBq or 4 MBq in cases of good response. In one patient, activity was escalated to 13 MBq in the third cycle. Fourteen patients had three treatment cycles administered, while in three patients treatment was discontinued after two cycles due to good response. Six out of 17 patients received additional treatments after the third cycle. Prostate-specific antigen (PSA) was measured every 4 weeks for PSA response assessment. 68Ga-PSMA-PET/CT was used for functional response assessment before each subsequent treatment cycle. Serial full blood count, renal function test, and liver function were obtained to determine treatment-related side effects. RESULTS: Good antitumor activity assessed by serum PSA level and 68Ga-PSMA-PET/CT was seen in 16/17 patients. In 14/17 patients, PSA decline ≥90% was seen after treatment, including seven patients with undetectable serum PSA following two (2/7) or three cycles (5/7) cycles of 225Ac-PSMA-617. Fifteen of 17 patients had a > 50% decline in lesions avidity for tracer on 68Ga-PSMA-PET/CT including 11 patients with complete resolution (PET-negative and either stable sclerosis on CT for bone or resolution of lymph node metastases) of all metastatic lesions. Grade 1/2 xerostomia was seen in all patients, and none was severe enough to lead to discontinuation of treatment. One patient had with extensive bone marrow metastases and a background anemia developed a grade 3 anemia while another patient with solitary kidney and pre-treatment grade 3 renal failure developed grade 4 renal toxicity following treatment. The group presented with significant palliation of bone pain and reduced toxicity to salivary glands due to de-escalation. CONCLUSIONS: 225Ac-PSMA-617 RLT of chemotherapy-naïve patients with advanced metastatic prostate carcinoma led to a ≥ 90% decline in serum PSA in 82% of patients including 41% of patients with undetectable serum PSA who remained in remission 12 months after therapy. The remarkable therapeutic efficacy reported in this study could be achieved with reduced toxicity to salivary glands due to de-escalation of administered activities in subsequent treatment cycles. This necessitates further exploration for informing clinical practice and clinical trial design.
Assuntos
Actínio/uso terapêutico , Carcinoma/radioterapia , Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Actínio/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Dipeptídeos/efeitos adversos , Ácido Edético/análogos & derivados , Isótopos de Gálio , Radioisótopos de Gálio , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Oligopeptídeos , Projetos Piloto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/patologia , Compostos Radiofarmacêuticos/efeitos adversosRESUMO
BACKGROUND: Complete macroscopic cytoreduction in patients with peritoneal carcinomatosis (PC) is the basic requirement for long-term survival. Diagnostic laparoscopy (DL) can be difficult and of limited clinical value secondary to postoperative or tumor-induced adhesions. The aim of this study was to evaluate the role of DL in patients with prior surgery and PC. METHODS: The database of the surgical department of the University Medical Center of Regensburg was reviewed (9/2010-10/2014) selecting for DL in patients with PC. The operative report had a standardized format allowing for the determination of the extent of the intra-abdominal visible area and the extent of tumor on the surface of the small intestine. For the classification we used our own developed score. RESULTS: DL was performed in 102 patients. The complete abdominal cavity was evaluable in 48%. At least two quadrants and the largest part of the small intestine could be assessed in 70%. 37% of the patients had massive tumor manifestation on the small intestine or its mesentery. PCI (Peritoneal Cancer Index) could not be calculated in 71% of the patients due to incomplete visualization of the abdominal cavity and/or multiple tumor manifestations on the small intestine. 54% of patients were classified as non-resectable and 85% who seemed suitable for cytoreductive surgery underwent a CCR-0 resection and HIPEC. CONCLUSIONS: In spite of prior surgery and PC, DL is frequently possible and a useful tool to define the extent of tumor spread. Lots of patients can be prevented from needless open laparotomy. The extent of tumor involvement of the small intestine seems to be more relevant than calculation of the PCI to determine the potential for complete resection. Therefore, in the presence of adhesions, inspection of the complete abdominal cavity does not offer added clinical benefit and further adhesiolysis can be avoided.
Assuntos
Carcinoma/diagnóstico por imagem , Carcinoma/secundário , Laparoscopia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/secundário , Adulto , Idoso , Carcinoma/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Hipertermia Induzida , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/terapia , Estudos RetrospectivosRESUMO
The development of nanoscaled theranostic agents for cancer combination therapies has received intensive attention in recent years. In this report, a degradable hollow mesoporous PEG-Si/C-DOX NP is designed and fabricated for pH-responsive, photoacoustic imaging-guided highly effective chemo-thermal combination therapy. The intrinsic hollow mesoporous structure endows the as-synthesized nanoparticles (NPs) with a high drug loading capacity (31.1%). Under NIR (808 nm) irradiation, the photothermal conversion efficiency of the Si/C NPs is as high as 40.7%. Preferential accumulation of the PEG-Si/C-DOX NPs around tumor tissue was demonstrated with photoacoustic images. Cellular internalization of the NPs and release of the DOX in nuclei are shown with fluorescent images. With efficient NIR photothermal conversion and high DOX loading capacity, the PEG-Si/C-DOX NPs are demonstrated to have remarkable cancer-cell-killing ability and to achieve complete in vivo tumor elimination via combinational chemo-thermal therapy. Last but not least, the NPs show good biodegradability and biosafety, making them a promising candidate for multifunctional drug delivery and cancer theranostic.
Assuntos
Carcinoma/diagnóstico por imagem , Carcinoma/terapia , Tratamento Farmacológico/métodos , Hipertermia Induzida/métodos , Nanopartículas/administração & dosagem , Técnicas Fotoacústicas/métodos , Animais , Antineoplásicos/administração & dosagem , Carbono/administração & dosagem , Linhagem Celular Tumoral , Modelos Animais de Doenças , Doxorrubicina/administração & dosagem , Xenoenxertos , Histocitoquímica , Humanos , Camundongos Nus , Transplante de Neoplasias , Silício/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: In Japan, preoperative chemotherapy is considered essential for resectable stage II or III esophageal cancers. It is important to identify nonresponders for preoperative chemotherapy because continuing ineffective chemotherapy is not beneficial for them. We investigated the correlation between the computed tomography number of tumor and the effect of preoperative chemotherapy in patients with esophageal cancer. METHODS: This retrospective study included 50 patients receiving preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for stage II or III esophageal cancer. The computed tomography number of tumor was measured as the mean of Hounsfield Units of the primary lesion on a plain computed tomography measured within a freehand region of interest drawn around the tumor border. For analysis, the patients were classified into responders and nonresponders to chemotherapy, with the pathologic response evaluated using the Japanese and Mandard classification. We analyzed the associations between the computed tomography number of tumor and clinical factors; histopathologic features, including the tumor size, depth of tumor invasion, capillary invasion, Ki-67, p53, and CK5/6 expression; the pathologic response to chemotherapy and prognosis. RESULTS: There was a significant association between the computed tomography number of tumor and the response to chemotherapy. The cut-off value of the computed tomography number of tumor in predicting responders to chemotherapy was 40 Hounsfield Units (area under the receiver operating characteristic curve = 0.73, P = .009); patients with computed tomography number of tumor greater than this value significantly responded to chemotherapy (P = .02 in the Japanese and P = .009 in the Mandard classification) with good postoperative prognosis (P = .04). Only Ki-67 expression among the histopathogic features were associated with the computed tomography number of tumor in histopathologic features (P = .01). CONCLUSION: The computed tomography number of tumor may be useful to predict the efficacy of preoperative chemotherapy and subsequent prognosis for patients with advanced esophageal cancer.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma/diagnóstico por imagem , Carcinoma/terapia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Tomografia Computadorizada por Raios X , Idoso , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Docetaxel , Esofagectomia , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: We studied the presenting symptoms, time intervals, and workup involved in the diagnosis of nasopharyngeal carcinoma in an integrated health care system. METHODS: A retrospective chart review of all patients with a nasopharyngeal carcinoma diagnosis between 2007 and 2010 at Kaiser Permanente Northern California. Main outcome measures included diagnostic time intervals, presenting symptoms, diagnostic accuracy of nasal endoscopy, imaging, and diagnosis at first otolaryngologist (Oto-HNS) visit. RESULTS: This study included 101 patients: 70 (70%) were of Chinese or of Southeast Asian descent. The median time intervals along the diagnostic pathway were symptom onset to primary care physician visit, 6.0 weeks; primary care physician to Oto-HNS, 2.4 weeks; Oto-HNS to pathologic diagnosis, 1.1 weeks; and diagnosis to treatment onset, 5.5 weeks. The most common presenting symptoms were otologic issues (41, 41%), neck mass (39, 39%), nasal issues (32, 32%), and headache/cranial neuropathy (16, 16%). A nasopharyngeal lesion was detected in 54 (53%) patients after the first Oto-HNS visit. Among the initial nasal endoscopy reports, 32 (32%) did not reveal a nasopharyngeal lesion; 32 (32%) initial imaging studies also did not reveal a nasopharyngeal lesion. There was no correlation between diagnostic delay and disease stage. CONCLUSION: Nasopharyngeal carcinoma presenting symptoms are extremely variable, and initial misdiagnosis is common. Median time from symptom onset to treatment was almost six months among patients studied. Nearly one-third of nasopharyngeal cancers were missed with nasal endoscopy and imaging. An understanding of the risk factors, presenting symptoms, and limitations associated with these diagnostic tests is necessary to support earlier detection of this insidious cancer.
Assuntos
Carcinoma/diagnóstico , Erros de Diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Adulto , California , Carcinoma/complicações , Carcinoma/diagnóstico por imagem , Diagnóstico Tardio , Progressão da Doença , Endoscopia , Feminino , Cabeça/diagnóstico por imagem , Cabeça/patologia , Cefaleia/diagnóstico , Cefaleia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/complicações , Neoplasias Nasofaríngeas/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Pescoço/patologia , Otorrinolaringologistas , Estudos RetrospectivosRESUMO
Perfluorocarbon nanoemulsions (PFCNEs) have recently been undergoing rigorous study to investigate their ability to improve the therapeutic efficacy of tumor ablation by high intensity focused ultrasound (HIFU). For precise control of PFCNE delivery and thermal ablation, their accumulation and distribution in a tumor should be quantitatively analyzed. Here, we used fluorine-19 (19F) magnetic resonance imaging (MRI) to quantitatively track PFCNE accumulation in a tumor, and analyzed how intra-tumoral PFCNE quantities affect the therapeutic efficacy of HIFU treatment. Ablation outcomes were assessed by intra-voxel incoherent motion analysis and bioluminescent imaging up to 14 days after the procedure. Assessment of PFCNE delivery and treatment outcomes showed that 2-3 mg/mL of PFCNE in a tumor produces the largest ablation volume under the same HIFU insonation conditions. Histology showed varying degrees of necrosis depending on the amount of PFCNE delivered. 19F MRI promises to be a valuable platform for precisely guiding PFCNE-enhanced HIFU ablation of tumors.
Assuntos
Técnicas de Ablação/métodos , Carcinoma/diagnóstico por imagem , Carcinoma/terapia , Imagem por Ressonância Magnética de Flúor-19/métodos , Fluorocarbonos/administração & dosagem , Hipertermia Induzida/métodos , Sonicação/métodos , Animais , Carcinoma/patologia , Modelos Animais de Doenças , Emulsões/administração & dosagem , Histocitoquímica , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante Heterólogo , Resultado do TratamentoRESUMO
Early detection and therapy of esophageal cancer is very important for improving the prognosis and survival rate of the patient. A theranostic agent that combines multimodal imaging with cancer therapy may be used for augmenting the visualization and treatment of the cancer. Herein, we report the synthesis of a hollow tantalum oxide (TaOx) nanoparticle that was successfully engineered by encapsulation of polypyrrole (PPy) and doxorubicin (DOX) in the core and conjugation with a near infrared fluorescence dye (NIRDye800) on the shell of the hollow TaOx nanoparticles. The as-prepared core/shell nanoparticles showed multimodal imaging features including computed tomography (CT) (for the preliminary location of the tumor), photoacoustic (for the anatomical localization of the tumor), and fluorescence imaging (for real-time monitoring of the tumor margin) and pH- and thermal-sensitive drug release. Because the early esophageal carcinoma is a type of superficial cancer, a subcutaneous model in the thigh was used for the in vivo study. The core/shell nanoparticles shows high imaging contrast between the tumor and the adjacent tissues and controllable photothermal therapy (PTT) and chemotherapy. Our results indicated that the obtained core/shell nanoparticles had significant potential in the triple-modality imaging guided precisely chemo-thermal synergetic therapy of esophageal cancer. In addition, after aerosol administration, our nanoparticles also exhibited comparable therapeutic efficacy with the intravenous administration, which is more suitable for clinical therapy of esophageal carcinoma.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma/diagnóstico por imagem , Carcinoma/terapia , Meios de Contraste/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Corantes Fluorescentes/administração & dosagem , Imagem Multimodal/métodos , Nanopartículas , Óxidos/administração & dosagem , Fototerapia/métodos , Tantálio/administração & dosagem , Animais , Antibióticos Antineoplásicos/química , Carcinoma/patologia , Linhagem Celular Tumoral , Meios de Contraste/química , Doxorrubicina/química , Liberação Controlada de Fármacos , Neoplasias Esofágicas/patologia , Corantes Fluorescentes/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Concentração de Íons de Hidrogênio , Masculino , Camundongos Endogâmicos BALB C , Imagem Óptica , Óxidos/química , Técnicas Fotoacústicas , Polímeros/química , Valor Preditivo dos Testes , Pirróis/química , Solubilidade , Tantálio/química , Temperatura , Nanomedicina Teranóstica , Fatores de Tempo , Tomografia Computadorizada por Raios X , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
INTRODUCTION: Skull base metastases (SBM) are an infrequent and late type of cancer progression that are associated to poor prognosis. Its clinical manifestations may be grouped in five clinical syndromes and radiotherapy is its more frequent treatment. Because of the improvement in imaging tests and the close follow up of cancer patients, SBM can be diagnosed incidentally. In this group the best option of treatment has not been established. AIM: To analyze the clinical features and outcomes of patients with SBM diagnosed incidentally. PATIENTS AND METHODS: Between January 2012 and December 2015, 31 patients with diagnoses of SBM from solid primary tumor were reviewed. RESULTS: SBM were diagnosed due to skull base syndromes (n = 24) or incidentally (n = 7). Symptomatic patients were treated with radiotherapy. Patients diagnosed incidentally remained without symptoms of craneal base involvement during the follow up, although they frequently had other types of intracranial progression. A statistically significant difference in survival was observed between symptomatic and asymptomatic patients (p = 0.001). CONCLUSIONS: The incidentally diagnosed SBM were frequently associated to other types of intracranial progression, limiting the options of treatment.
TITLE: Metastasis asintomaticas de la base craneal: evolucion clinica y alternativas terapeuticas.Introduccion. Las metastasis sintomaticas de la base craneal (MBC) son una progresion infrecuente, tardia y de mal pronostico en pacientes con tumores solidos. Sus manifestaciones clinicas pueden agruparse en cinco sindromes caracteristicos, y su tratamiento mas frecuente es la radioterapia. Gracias a los progresos tecnologicos en las pruebas de imagen y al seguimiento estrecho de los pacientes con cancer, las MBC pueden diagnosticarse incidentalmente. En este subgrupo no se conoce la evolucion clinica ni se ha establecido la mejor modalidad de tratamiento. Objetivo. Analizar las caracteristicas clinicas y la evolucion de los pacientes diagnosticados incidentalmente de MBC. Pacientes y metodos. Entre enero de 2012 y diciembre de 2015, 31 pacientes con una neoplasia solida diagnosticados de MBC fueron valorados por nuestro servicio. Resultados. Las MBC se diagnosticaron por la presencia de un sindrome de base craneal (n = 24) o incidentalmente (n = 7). Los pacientes sintomaticos fueron tratados con radioterapia. Todos los pacientes diagnosticados incidentalmente permanecieron sin sintomas relacionados con la afectacion de la base craneal hasta la fecha del fallecimiento, aunque frecuentemente presentaron de forma concomitante otros tipos de progresion intracraneal de mal pronostico. Se observo una diferencia estadisticamente significativa en la supervivencia a favor de los pacientes sintomaticos (p = 0,001). Conclusiones. Las MBC diagnosticadas incidentalmente se asociaron frecuentemente a otros tipos de progresion intracraneal, limitando las opciones terapeuticas.
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Carcinoma/secundário , Neoplasias da Base do Crânio/secundário , Adulto , Idoso , Doenças Assintomáticas , Neoplasias da Mama , Carcinoma/diagnóstico por imagem , Carcinoma/radioterapia , Carcinoma/cirurgia , Feminino , Humanos , Achados Incidentais , Estimativa de Kaplan-Meier , Neoplasias Pulmonares , Imageamento por Ressonância Magnética , Masculino , Cuidados Paliativos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Estudos Retrospectivos , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/radioterapia , Neoplasias da Base do Crânio/cirurgia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Medical imaging plays an important role in selecting patients with metastatic castration-resistant prostate cancer for 223Ra-dichloride therapy of bone metastases. The purpose of this study was to investigate whether 68Ga-PSMA-PET has incremental value over conventional imaging for selecting patients suitable for 223Ra-dichloride therapy. METHODS: In 27 consecutive patients referred for 223Ra-dichloride therapy additional 68Ga-PSMA-PET/CT was performed and tracer distribution was evaluated systematically with respect to the detection of visceral metastases and bone metastases with inadequate uptake on bone scintigraphy. RESULTS: In 4 patients (15 %) 68Ga-PSMA-PET revealed previously unknown visceral metastases (3 liver, 1 adrenal gland), which changed the therapeutic decision in 2 cases. PET revealed more extended tumour involvement in the bone compared to bone scintigraphy in 9 patients (33 %). In 3 of these, the mismatch was extensive enough to question suitability for 223Ra-dichloride therapy. CONCLUSIONS: Additional 68Ga-PSMA-PET as a gatekeeper between conventional staging and 223Ra-dichloride therapy can provide valuable additional information with regard to visceral metastases and tumour manifestations without adequate bone mineral turnover. It may lead to a change in therapeutic management in a significant number of patients and should therefore be considered in future clinical trials.
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Carcinoma/radioterapia , Carcinoma/secundário , Ácido Edético/análogos & derivados , Oligopeptídeos , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Rádio (Elemento)/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma/diagnóstico por imagem , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Pessoa de Meia-Idade , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Nasopharyngeal carcinoma is the predominant tumour type arising in the nasopharynx. Its aetiology is multifactorial; racial and geographical distribution, EBV infection and environmental exposure to specific substances are considered risk factors. This condition is endemic in some Asian areas, where a genetic predisposition in its oncogenesis has been established. There is a strong susceptibility between nasopharyngeal carcinoma and HLA, where related specific haplotypes have been found. In areas where the incidence is low, there are few reported cases of families affected. We report 3 cases of families with nasopharyngeal carcinoma among siblings, in the non-Asian population, probably related to EBV infection.
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Carcinoma/genética , Neoplasias Nasofaríngeas/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/diagnóstico por imagem , Carcinoma/epidemiologia , Carcinoma/terapia , Cisplatino/administração & dosagem , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Fluoruracila/administração & dosagem , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/terapia , Radioterapia Adjuvante , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facilitate the image-guided resection of the disease. While antibodies have proven to be highly effective vectors for the delivery of radioisotopes and fluorophores to malignant tissues, the use of radioimmunoconjugates labeled with long-lived nuclides such as 89Zr poses two important clinical complications: high radiation doses to the patient and the need for significant lag time between imaging and surgery. In vivo pretargeting strategies that decouple the targeting vector from the radioactivity at the time of injection have the potential to circumvent these issues by facilitating the use of positron-emitting radioisotopes with far shorter half-lives. Here, we report the synthesis, characterization, and in vivo validation of a pretargeted strategy for the multimodal PET and NIRF imaging of colorectal carcinoma. This approach is based on the rapid and bioorthogonal ligation between a trans-cyclooctene- and fluorophore-bearing immunoconjugate of the huA33 antibody (huA33-Dye800-TCO) and a 64Cu-labeled tetrazine radioligand (64Cu-Tz-SarAr). In vivo imaging experiments in mice bearing A33 antigen-expressing SW1222 colorectal cancer xenografts clearly demonstrate that this approach enables the non-invasive visualization of tumors and the image-guided resection of malignant tissue, all at only a fraction of the radiation dose created by a directly labeled radioimmunoconjugate. Additional in vivo experiments in peritoneal and patient-derived xenograft models of colorectal carcinoma reinforce the efficacy of this methodology and underscore its potential as an innovative and useful clinical tool.
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Anticorpos Antineoplásicos/administração & dosagem , Carcinoma/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Radioisótopos de Cobre/administração & dosagem , Corantes Fluorescentes/administração & dosagem , Imagem Óptica/métodos , Tomografia por Emissão de Pósitrons/métodos , Animais , Anticorpos Antineoplásicos/química , Radioisótopos de Cobre/química , Modelos Animais de Doenças , Corantes Fluorescentes/química , Xenoenxertos , CamundongosRESUMO
A 66-year-old man with castration-resistant prostate carcinoma and multiple symptomatic bone mestastases was considered for Ra-dichloride (Xofigo) therapy. Staging with Ga-PSMA-PET/CT revealed additional extensive tumor involvement of the spine without relevant uptake in bone scintigraphy. Based on this imaging result, the patient was rescheduled for a PSMA-targeted therapy. Additional Ga-PSMA-PET/CT may have a considerable benefit for patients considered for Xofigo.
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Carcinoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Idoso , Carcinoma/radioterapia , Ácido Edético/análogos & derivados , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Oligopeptídeos , Compostos Organometálicos , Neoplasias de Próstata Resistentes à Castração/radioterapia , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Rádio (Elemento)/uso terapêuticoRESUMO
BACKGROUND: Precision medicine approaches are ideally suited for rare tumors where comprehensive characterization may have diagnostic, prognostic, and therapeutic value. We describe the clinical case and molecular characterization of an adolescent with metastatic poorly differentiated carcinoma (PDC). Given the rarity and poor prognosis associated with PDC in children, we utilized genomic analysis and preclinical models to validate oncogenic drivers and identify molecular vulnerabilities. METHODS: We utilized whole exome sequencing (WES) and transcriptome analysis to identify germline and somatic alterations in the patient's tumor. In silico and in vitro studies were used to determine the functional consequences of genomic alterations. Primary tumor was used to generate a patient-derived xenograft (PDX) model, which was used for in vivo assessment of predicted therapeutic options. RESULTS: WES revealed a novel germline frameshift variant (p.E1554fs) in APC, establishing a diagnosis of Gardner syndrome, along with a somatic nonsense (p.R790*) APC mutation in the tumor. Somatic mutations in TP53, MAX, BRAF, ROS1, and RPTOR were also identified and transcriptome and immunohistochemical analyses suggested hyperactivation of the Wnt/ß-catenin and AKT/mTOR pathways. In silico and biochemical assays demonstrated that the MAX p.R60Q and BRAF p.K483E mutations were activating mutations, whereas the ROS1 and RPTOR mutations were of lower utility for therapeutic targeting. Utilizing a patient-specific PDX model, we demonstrated in vivo activity of mTOR inhibition with temsirolimus and partial response to inhibition of MEK. CONCLUSIONS: This clinical case illustrates the depth of investigation necessary to fully characterize the functional significance of the breadth of alterations identified through genomic analysis.