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1.
Clin Oncol (R Coll Radiol) ; 35(10): 682-693, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37558548

RESUMO

AIMS: To report toxicity profile, outcomes and quality of life (QoL) data in patients with recurrent gynaecological cancer who underwent stereotactic body radiotherapy (SBRT) retreatment. MATERIALS AND METHODS: Data from patients' folders were retrospectively extracted, focusing on the primary neoplasm, previous systemic therapies and previous radiotherapy. Concerning SBRT, the total dose (five daily fractions) was delivered with a linear accelerator using intensity-modulated radiotherapy techniques. Acute and late toxicities were assessed by the CTCAE 4.03 scale. QoL was evaluated according to the Cancer Linear Analogue Scale [CLAS1 (fatigue), CLAS2 (energy level), CLAS3 (daily activities)]. RESULTS: Between December 2005 and August 2021, 23 patients (median age 71 years, range 48-80) with 27 lesions were treated. Most patients had endometrial (34.8%), ovarian (26.1%) and cervical cancer (26.1%) as the primary tumour. The most common SBRT schedules in five fractions were 30 Gy (33.3%), 35 Gy (29.6%) and 40 Gy (29.6%). The median follow-up was 32 months (range 3-128). There were no patients reporting acute or late toxicities higher than grade 2, except for a bone fracture. One- and 2-year local control was 77.9% and 70.8%, respectively. One- and 2-year overall survival was 82.6% and 75.1%, respectively. The overall response rate was 96.0%. Regarding QoL, no statistically significant difference was identified between the baseline and follow-up values: the median CLAS1, CLAS2 and CLAS3 scores for each category were 6 (range 4-10) at baseline and 6 (range 3-10) 1 month after SBRT. CONCLUSIONS: This preliminary experience suggests that SBRT retreatment for recurrent gynaecological cancer is a highly feasible and safe treatment with limited side-effects and no short-term QoL impairment.


Assuntos
Neoplasias , Radiocirurgia , Reirradiação , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Qualidade de Vida , Reirradiação/efeitos adversos , Reirradiação/métodos , Estudos Retrospectivos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Recidiva Local de Neoplasia/cirurgia
2.
ESMO Open ; 8(1): 100748, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36603521

RESUMO

BACKGROUND: Maintaining angiogenesis inhibition and switching the chemotherapy backbone represent the current second-line therapy in patients with RAS-mutant metastatic colorectal cancer (mCRC). Regorafenib, an oral multikinase inhibitor, prolonged overall survival (OS) in the chemorefractory setting. MATERIALS AND METHODS: STREAM was an academic, multicenter, single-arm phase II trial, evaluating the activity of regorafenib in RAS-mutant mCRC, in terms of the rate of patients who were progression-free after 6 months from study entry (6mo-PF). Patients were pretreated with fluoropyrimidine, oxaliplatin, and bevacizumab. According to Simon's two-stage design, ≥18 patients 6mo-PF were needed in the overall population (N = 46). Secondary endpoints were safety, objective response rate (ORR), progression-free survival (PFS), and OS. Early metabolic response by [18F]2-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography ([18F]-FDG PET/CT) scan was an exploratory endpoint. EudraCT Number: 2015-001105-13. RESULTS: The number of patients 6mo-PF was 8/22 at the first stage and 14/46 in the overall population. The ORR was 10.9%, disease control rate was 54.6%, median (m)PFS was 3.6 months [95% confidence interval (CI) 1.9-6.7 months], mOS was 18.9 months (95% CI 10.3-35.3 months), and mPFS2 (from study entry to subsequent-line progression) was 13.3 months (95% CI 8.4-19.7 months). Long benefiter patients (>6mo-PF) significantly more often had a single metastatic site and lung-limited disease. No unexpected toxicity was reported. Grade ≥3 events occurred in 39.1% of patients, with hand-foot syndrome (13%), fatigue, and hyperbilirubinemia (6.5%) occurring mostly. Baseline metabolic assessment was associated with OS in the multivariate analysis, while early metabolic response was not associated with clinical outcomes. CONCLUSIONS: The study did not meet its primary endpoint. However, regorafenib was well tolerated and did not preclude subsequent treatments. Patients with good prognostic features (single metastatic site and lung-limited disease) reported clinical benefit with regorafenib. The exploratory metabolic analysis suggests that baseline [18F]-FDG PET/CT might be useful to select patients with a favorable outcome. A chemotherapy-free interval with regorafenib was associated with durable disease control in a selected group of patients with favorable clinical characteristics.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Fluordesoxiglucose F18/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Piridinas/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico
3.
Clin Oncol (R Coll Radiol) ; 35(1): e30-e39, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36207236

RESUMO

AIMS: To report the final results of a dose-escalation study of volumetric intensity-modulated arc stereotactic radiosurgery (VMAT-SRS) boost after three-dimensional conformal radiation therapy in patients with spine metastases. MATERIALS AND METHODS: Oligometastatic cancer patients bearing up to five synchronous metastases (visceral or bone, including vertebral ones) and candidates for surgery or radiosurgery were considered for inclusion. 25 Gy was delivered in 10 daily fractions (2 weeks) to the metastatic lesion, affected vertebrae and adjacent ones (one cranial and one caudal vertebra). Sequentially, the dose to spinal metastases was progressively increased (8 Gy, 10 Gy, 12 Gy) in the patient cohorts. Dose-limiting toxicities were defined as any treatment-related non-hematologic acute adverse effects rated as grade ≥3 or any acute haematological toxicity rated as ≥ 4 by the Radiation Therapy Oncology Group scale. RESULTS: Fifty-two lesions accounting for 40 consecutive patients (male/female: 29/11; median age: 71 years; range 40-85) were treated from April 2011 to September 2020. Most patients had a primary prostate (65.0%) or breast cancer (22.5%). Thirty-two patients received 8 Gy VMAT-SRS boost (total BED α/ß10: 45.6 Gy), 14 patients received 10 Gy (total BED α/ß10: 51.2 Gy) and six patients received 12 Gy (total BED α/ß10: 57.6 Gy). The median follow-up time was over 70 months (range 2-240 months). No acute toxicities > grade 2 and no late toxicities > grade 1 were recorded. The overall response rate based on computed tomography/positron emission tomography-computed tomography/magnetic resonance was 78.8%. The 24-month actuarial local control, distant metastases-free survival and overall survival rates were 88.5%, 27.1% and 90.3%, respectively. CONCLUSION: A 12 Gy spine metastasis SRS boost following 25 Gy to the affected and adjacent vertebrae was feasible with an excellent local control rate and toxicity profile.


Assuntos
Radiocirurgia , Radioterapia de Intensidade Modulada , Neoplasias da Coluna Vertebral , Idoso , Feminino , Humanos , Masculino , Neoplasias da Mama , Imageamento por Ressonância Magnética , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Radioterapia Conformacional , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/terapia
4.
Clin Transl Oncol ; 24(6): 1177-1183, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34984604

RESUMO

INTRODUCTION: Aim of this analysis was to report toxicity and clinical outcomes in oligorecurrent prostate cancer (PCa) patients treated with single fraction stereotactic radiosurgery (SRS) for bone metastases. METHODS: We separately analyzed clinical data of PCa patients with bone oligometastases enrolled in a prospective phase I trial (DESTROY-2). DESTROY-2 was based on SRS delivered using volumetric modulated arc therapy in patients with primary or metastatic tumors in several extra-cranial body sites. Acute and late toxicity, biochemical tumor response, local control (LC), distant metastases-free (DPFS), progression-free (PFS), time to next-line systemic treatment-free (NEST-FS), and overall survival (OS) were calculated. RESULTS: Data on 37 PCa patients, carrying out 50 bone metastases, candidates for curative-intent treatment and treated with SRS at our Institution were collected. SRS dose ranged between 12 and 24 Gy. One grade 1 acute skin toxicity in one patient treated on the hip (24 Gy) and one grade 1 late skin toxicity in a patient with a scapular lesion (24 Gy) were recorded. No cases of bone fracture were registered in the treated population. With a median follow-up of 25 months (range 3-72 months) 2-year actuarial LC, DPFS, PFS, and OS were 96.7%, 58.1%, 58.1%, and 95.8%, respectively. Median and 2-year NEST-FS were 30 months (range 1-69 months) and 51.2%, respectively. CONCLUSIONS: Data analysis showed few toxicity events, high local control rate and prolonged NEST-FS after linear accelerator-based radiosurgery of bone oligometastases from PCa. The possibility of postponing systemic treatments in patients with oligometastatic PCa by means of SRS should be taken into account. Further prospective studies on larger series are needed to confirm the reported results.


Assuntos
Neoplasias Ósseas , Neoplasias da Próstata , Radiocirurgia , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Humanos , Masculino , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Estudos Retrospectivos , Resultado do Tratamento
5.
Pediatr Surg Int ; 38(1): 59-68, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34586484

RESUMO

PURPOSE: Total proctocolectomy with ileal J-pouch-anorectal anastomosis (IPAA) remains the preferred surgical treatment for ulcerative colitis (UC) in children. Considering the well-known advantages of minimally invasive approach, and its main application for the deep pelvis, robotic surgery may be used in UC reconstructive procedures. The aim of the study is to report our experience with Robotic IPAA in children. METHODS: Single surgeon experience on Robotic IPAA were prospectively included. Data on patient demographics, surgical details, complications, and length of stay (LOS), were collected. RESULTS: Fifteen patients were included. Median age was 13.2 years, median body weight 45 kg. Median operative time was 240 min. Median LOS was 7 days and mean follow-up time 1 year. No intraoperative complication occurred. Five postoperative complications happened: 3 minors treated conservatively (CD I-II), 2 majors needing reintervention under anesthesia (CD IIIb). No mortality was observed. CONCLUSION: Our preliminary experience reveals that Robotic IPAA is a safe and feasible option for the surgical treatment of UC in children. A bigger patient sample and a long-term follow-up are needed to confirm our findings.


Assuntos
Colite Ulcerativa , Bolsas Cólicas , Laparoscopia , Proctocolectomia Restauradora , Procedimentos Cirúrgicos Robóticos , Adolescente , Canal Anal/cirurgia , Anastomose Cirúrgica , Criança , Colite Ulcerativa/cirurgia , Humanos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
6.
Clin Exp Metastasis ; 38(6): 519-526, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34651242

RESUMO

The prognosis of prostate cancer (PC) is generally favorable but the incidence of metastases is relatively high after the treatment of the primary tumor, especially in high-risk patients. Fractionated stereotactic body radiotherapy (SBRT) or single fraction stereotactic body radiosurgery (SRS) are emerging treatment options in this setting. However, data on SBRT/SRS in patients with metastatic castration-resistant PC (mCRPC) are largely lacking, particularly in subjects with nodal lesions. Therefore, we evaluated outcomes and toxicity recorded in mCRPC patients with nodal oligoprogression. Patients included in this analysis had ≤ 5 metastatic sites without visceral lesions and underwent SBRT/SRS on nodal metastases. Thirty-eight patients carrying out 61 nodal metastases were analyzed. The median SRS dose was 20 Gy (range 12-24 Gy) and the most common schedule was 20 Gy (44.8%). The median SBRT dose was 45 Gy (range 20-50 Gy) and the most common regimen was 45 Gy in 5 fractions (37.9%). Thirty-seven patients (97.4%) showed only grade 0-1 acute toxicity while one patient reported grade 2 dysphagia. In terms of late toxicity, one grade 2 laryngeal, one grade 1 skin and one grade 1 gastrointestinal toxicities were recorded. Two-year actuarial local control (LC), distant progression-free survival, progression-free survival (PFS) and overall survival were 94.0, 47.2, 47.2, and 90.2%, respectively. Two-year next line systemic therapy-free survival (NEST-FS) was 67.7%. In conclusion, the efficacy in terms of LC of SBRT/SRS in patients with nodal metastases from PC was confirmed. Moreover, this analysis suggests the efficacy in terms of PFS and NEST-FS also in the setting of oligoprogressive PC. In fact, about one-third of patients were free from progressive disease and two-third of subjects did not require hormonal therapy switch or discontinuation three years after treatment.


Assuntos
Linfonodos/efeitos da radiação , Neoplasias de Próstata Resistentes à Castração/radioterapia , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos Fase I como Assunto , Progressão da Doença , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Radiocirurgia/efeitos adversos , Radiocirurgia/mortalidade , Dosagem Radioterapêutica , Fatores de Tempo
7.
Cancers (Basel) ; 13(20)2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34680372

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a devastating condition characterised by vague symptomatology and delayed diagnosis. About 30% of PDAC patients report a history of new onset diabetes, usually diagnosed within 3 years prior to the diagnosis of cancer. Thus, new onset diabetes, which is also known as pancreatic cancer-related diabetes (PCRD), could be a harbinger of PDAC. Diabetes is driven by progressive ß cell loss/dysfunction and insulin resistance, two key features that are also found in PCRD. Experimental studies suggest that PDAC cell-derived exosomes carry factors that are detrimental to ß cell function and insulin sensitivity. However, the role of stromal cells, particularly pancreatic stellate cells (PSCs), in the pathogenesis of PCRD is not known. PSCs are present around the earliest neoplastic lesions and around islets. Given that PSCs interact closely with cancer cells to drive cancer progression, it is possible that exosomal cargo from both cancer cells and PSCs plays a role in modulating ß cell function and peripheral insulin resistance. Identification of such mediators may help elucidate the mechanisms of PCRD and aid early detection of PDAC. This paper discusses the concept of a novel role of PSCs in the pathogenesis of PCRD.

8.
Pancreatology ; 21(1): 103-114, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33309014

RESUMO

BACKGROUND: The detection and quantification of circulating tumour cells (CTCs) in pancreatic cancer (PC) has the potential to provide prognostic information. The aim of this review was to provide an overview of the literature surrounding CTCs in PC. METHODS: A systematic literature review on CTCs in PC between 2005-2020 was performed. Data based on peripheral vein samples were used to determine the positivity rate of CTCs, their prognostic significance and their relative numbers compared to portal vein (PV) samples. RESULTS: The overall CTC detection rate in forty-four articles was 65% (95%CI: 55-75%). Detection rate for CellSearch was 26% (95%CI: 14-38%), which was lower than for both filtration and microfluidic techniques. In nine studies with >50 patients, overall survival was worse with CTC positivity (HR 1.82; 95%CI: 1.61-2.05). Five of seven studies which described PV CTC collection provided patient-level data. PV CTC yield was 7.7-fold (95%CI 1.35-43.9) that of peripheral blood. CONCLUSIONS: CTCs were detected in the peripheral circulation of most patients with PC and may be related to prognosis and disease stage. PV blood contains more CTCs than peripheral blood sampling. This review points to the maturation of techniques of CTC enrichment, and its evidence base for eventual clinical deployment.


Assuntos
Células Neoplásicas Circulantes/patologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Humanos
9.
J Crohns Colitis ; 15(3): 367-374, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33022055

RESUMO

BACKGROUND: The aim of this study was to define clusters of activity in a population-based cohort during the first 5 years after diagnosis in children with ulcerative colitis [UC] and to identify early prognostic risk factors. METHODS: All UC patients from the SIGENP IBD registry with a complete follow-up of at least 5 years were included. Active disease was defined every 6 months in the presence of at least one of the following: clinical activity [Paediatric Ulcerative Colitis Activity Index ≥ 35]; endoscopic activity [Mayo score ≥ 1]; faecal calprotectin > 250 µg/g; hospitalization; surgery; or treatment escalation. Formula-based clusters were generated based on four published questionnaire-based activity patterns in adults, plus one additional cluster. RESULTS: In total, 226 patients were identified. Forty-two [19%] had moderate-severe chronically active disease, 31 [14%] chronic-intermittent, 75 [33%] quiescent, 54 [24%] active disease in the first 2 years after the diagnosis, then sustained remission, and 24 [11%] a remission in the first 2 years then an active disease. Mild disease onset along with a lower clinical severity not requiring the use of corticosteroids at 6 months were related to a quiescent disease course at the next follow-up (logistic model area under the curve 0.86 [95% confidence interval 0.78-0.94]; positive predictive value 67%; negative predictive value 70%). Eight per cent of patients needed surgery, none in the quiescent group [p = 0.04]. CONCLUSIONS: More than one-third of children with UC present with a chronically active or intermittent course during the first 5 years of follow-up. A significant group of patients has active disease in the first 2 years and then sustained remission. Interestingly, after initial treatment, one-third of patients have well-controlled disease throughout.


Assuntos
Colite Ulcerativa/epidemiologia , Índice de Gravidade de Doença , Adolescente , Criança , Colectomia/estatística & dados numéricos , Colite Ulcerativa/terapia , Progressão da Doença , Uso de Medicamentos/tendências , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Itália/epidemiologia , Masculino , Sistema de Registros , Indução de Remissão
10.
Int J Mol Sci ; 21(23)2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33271944

RESUMO

Pancreatic cancer (pancreatic ductal adenocarcinoma (PDAC/PC)) has been an aggressive disease that is associated with early metastases. It is characterized by dense and collagenous desmoplasia/stroma, predominantly produced by pancreatic stellate cells (PSCs). PSCs interact with cancer cells as well as other stromal cells, facilitating disease progression. A candidate growth factor pathway that may mediate this interaction is the hepatocyte growth factor (HGF)/c-MET pathway. HGF is produced by PSCs and its receptor c-MET is expressed on pancreatic cancer cells and endothelial cells. The current review discusses the role of the MET/HGF axis in tumour progression and dissemination of pancreatic cancer. Therapeutic approaches that were developed targeting either the ligand (HGF) or the receptor (c-MET) have not been shown to translate well into clinical settings. We discuss a two-pronged approach of targeting both the components of this pathway to interrupt the stromal-tumour interactions, which may represent a potential therapeutic strategy to improve outcomes in PC.


Assuntos
Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Animais , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Humanos , Estadiamento de Neoplasias , Neovascularização Patológica , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Transdução de Sinais , Microambiente Tumoral
11.
J Vis Exp ; (163)2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-33044459

RESUMO

There is a lack of satisfactory animal models to study adjuvant and/or neoadjuvant therapy in patients being considered for surgery of pancreatic cancer (PC). To address this deficiency, we describe a mouse model involving orthotopic implantation of PC followed by distal pancreatectomy and splenectomy. The model has been demonstrated to be safe and suitably flexible for the study of various therapeutic approaches in adjuvant and neo adjuvant settings. In this model, a pancreatic tumor is first generated by implanting a mixture of human pancreatic cancer cells (luciferase-tagged AsPC-1) and human cancer associated pancreatic stellate cells into the distal pancreas of Balb/c athymic nude mice. After three weeks, the cancer is resected by re-laparotomy, distal pancreatectomy and splenectomy. In this model, bioluminescence imaging can be used to follow the progress of cancer development and effects of resection/treatments. Following resection, adjuvant therapy can be given. Alternatively, neoadjuvant treatment can be given prior to resection. Representative data from 45 mice are presented. All mice underwent successful distal pancreatectomy/splenectomy with no issues of hemostasis. A macroscopic proximal pancreatic margin greater than 5 mm was achieved in 43 (96%) mice. The technical success rate of pancreatic resection was 100%, with 0% early mortality and morbidity. None of the animals died during the week after resection. In summary, we describe a robust and reproducible technique for a surgical resection model of pancreatic cancer in mice which mimics the clinical scenario. The model may be useful for the testing of both adjuvant and neoadjuvant treatments.


Assuntos
Neoplasias Pancreáticas/patologia , Animais , Modelos Animais de Doenças , Feminino , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Baço/cirurgia
13.
Clin Ter ; 171(4): e340-e345, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614369

RESUMO

BACKGROUND AND AIMS: Elderly may suffer from different pathologies during their detention in jail because of their age. Conditions in jails were tough and adapting to that life could be problematic for the elder population. This article aimed to analyse the pathologies and health conditions in a sample of elder inmates from Italy. METHODS: The sample was composed by 94 elderly inmates. The research is multicentric. We selected jails from the cities of Bari, Taranto, Foggia, Lecce, Brescia, Bergamo, Cremona and Mantua. The study was conducted by interviewing the prisoners over 60 years of age, in the period between September and December 2017. RESULTS: 64% of the sample was in a "Not Optimal" health status. Most of pathologies were Cardiac pathologies (23.4%), Diabetes (12.8 %) and Surgery (9.6%). Statistically significant differences were found for heart disease (p=0.02) and Neoplasia (p=0.025) in the prison of Bari compared to all the other prisons. Statistically significant differences were found for Hypertension in Foggia and Taranto prisons compared to all the other (p=0.023). Furthermore, 18.1% of inmates ended up having an addiction. CONCLUSIONS: Our analysis showed that in our sample physical problems were more frequent than psychological one. In fact, in spite of in the literature there was a high prevalence of mental health problems among elderly inmates, we did not find this result. However, stress conditions may increase the risk of pathologies: for example, being in jail and adapt to new hard environment may increase the risk of getting sick. Heart disease pathologies and diabetes were very common in our sample as confirmed by the literature.


Assuntos
Envelhecimento , Nível de Saúde , Prisioneiros , Idoso , Estudos Transversais , Doença , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estresse Psicológico
14.
BMC Oral Health ; 20(1): 99, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32264867

RESUMO

BACKGROUND: The aim of this case report was to use a surgical technique for autotransplantation of tooth using virtually planned 3D printed surgical templates for guided osteotomy preparation of the recipient of donor tooth. CASE PRESENTATION: An 18-year-old male patient received autotransplantation of the right mandibular third molar to replace an included right second molar. This procedure was based on guided implant surgery methods by superimposition of DICOM files and 3D data sets of the jaws. In order to design a 3D-printed template with the aid of a fully digital workflow; the third molar was conserved in PRGF during the surgical procedure and the tooth socket was prepared with a template and the help of a 3D-printed donor tooth copy in order to prevent iatrogenic damage to the donor tooth. This template and replica were manufactured using 3D-printing techniques. The transplanted tooth was placed in infra-occlusion and fixed with a suture splint and root canal therapy was performed 15 days later. The intervention was be accomplished by performing preplanned virtual transplantations with guided osteotomies to ensure accurate donor tooth placement in the new recipient site. The 24 months follow-up showed physiological clinical and radiologic results compatible with healing periradicular tissues. CONCLUSIONS: This approach enables the planning and production of a 3D printed surgical template using the latest diagnostic methods and techniques of guided implant surgery. These accurate virtually predesigned surgical templates and printed analogues of the donor tooth could facilitate autotransplantation, ensuring an atraumatic surgical protocol.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Implantação Dentária/métodos , Dente Serotino/diagnóstico por imagem , Dente Serotino/transplante , Impressão Tridimensional , Cirurgia Assistida por Computador/métodos , Transplante Autólogo/métodos , Adolescente , Implantação Dentária/instrumentação , Implantes Dentários , Humanos , Masculino , Duração da Cirurgia , Radiografia Panorâmica , Resultado do Tratamento
15.
Br J Cancer ; 122(10): 1486-1495, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32203220

RESUMO

BACKGROUND: Stromal-tumour interactions facilitate pancreatic cancer (PC) progression. The hepatocyte growth factor (HGF)/c-MET pathway is upregulated in PC and mediates the interaction between cancer cells and stromal pancreatic stellate cells (PSCs). This study assessed the effect of HGF/c-MET inhibition plus gemcitabine (G) on the progression of advanced PC. METHODS: Orthotopic PC was produced by implantation of luciferase-tagged human cancer cells + human PSCs into mouse pancreas. Tumours were allowed to develop without treatment for 4 weeks. Mice were then treated for 6 weeks with one of the following: IgG, G, HGF inhibitor (Hi), c-MET inhibitor (Ci), Hi + Ci, Hi + G, Ci + G, or Hi + Ci + G. RESULTS: Bioluminescence imaging showed similar tumour sizes in all mice at the initiation of treatments. Triple therapy (Hi + Ci + G): (1) completely eliminated metastasis; (2) significantly reduced tumour size as assessed by bioluminescence and at necropsy; (3) significantly reduced proliferating cancer cell density and stem cell marker DCLK1 expression in tumours. In vitro 3D culture studies supported our in vivo findings. CONCLUSION: Even at an advanced disease stage, a two-pronged approach, targeting (a) HGF/c-MET with relevant inhibitors and (b) cancer cells with chemotherapy, completely eliminated metastasis and significantly decreased tumour growth, suggesting that this is a promising treatment approach for PC.


Assuntos
Carcinogênese/efeitos dos fármacos , Fator de Crescimento de Hepatócito/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pancreáticas/tratamento farmacológico , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Quinases Semelhantes a Duplacortina , Fator de Crescimento de Hepatócito/genética , Humanos , Imunoglobulina G/farmacologia , Camundongos , Metástase Neoplásica , Estadiamento de Neoplasias , Células-Tronco Neoplásicas , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Células Estreladas do Pâncreas/efeitos dos fármacos , Células Estreladas do Pâncreas/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
16.
Pancreatology ; 20(3): 409-418, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31928917

RESUMO

Tumour-stromal interactions have now been acknowledged to play a major role in pancreatic cancer (PC) progression. The abundant collagenous stroma is produced by a specific cell type in the pancreas-the pancreatic stellate cell (PSC). Pancreatic stellate cells (PSCs) are a unique resident cell type of pancreas and with a critical role in both healthy and diseased pancreas. Accumulating evidence indicates that PSCs interact closely with cancer cells as well as with other cell types of the stroma such as immune cells, endothelial cells and neuronal cells, to set up a growth permissive microenvironment for pancreatic tumours, which facilitates local tumour growth as well as distant metastasis. Consequently, recent work in the field has focused on the development of novel therapeutic approaches targeting the stroma to inhibit PC progression. Such a multi-pronged approach targeting both tumour and stromal elements of PC has been successfully applied in pre-clinical settings. The challenge now is to translate the pre-clinical findings into the clinical setting to achieve better outcomes for pancreatic cancer patients.


Assuntos
Neoplasias Pancreáticas/patologia , Células Estreladas do Pâncreas/patologia , Progressão da Doença , Humanos , Microambiente Tumoral
17.
Braz. j. med. biol. res ; 53(9): e10475, 2020. tab
Artigo em Inglês | LILACS, ColecionaSUS | ID: biblio-1132550

RESUMO

SARS-CoV-2 has recently emerged, becoming a global threat, affecting directly all human beings owing to its morbidity and mortality and indirectly, due to the enormous economic and psychological impact produced by social isolation, the most effective measure so far, but unsustainable for a long period. The scientific effort to understand and control SARS-CoV-2 transmission and clinical impact has been huge, and important achievements are highlighted in this review. Diagnosis is central and is the first step in recognizing and fighting any infectious agent. Instrumental to that is the quality of the data, relying on serological and molecular surveys in addition to trustworthy clinical records. However, the fast spread of a virus adapted for human-to-human respiratory transmission raised a demand for millions of molecular tests that are simply not available. Several candidate drugs are under evaluation in clinical trials. Those with an already recognized safety profile are more auspicious, since, if proven effective, can cut several steps of production and phase 2 and 3 trials. More than one hundred vaccine prototypes are in different stages of development, however, safety and efficacy evaluations cannot be obviated, implicating, most optimistically, in at least months for us to have an effective immunization, the definite measure to allow a safe return to the pre-pandemic lifestyle. Science has never been more necessary and present in daily life. Relying on the best of human wit is the only way out to this pandemic, saving as many lives as possible.


Assuntos
Humanos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/epidemiologia , Pandemias , Antivirais/farmacologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Pneumonia Viral/epidemiologia , Vacinas Virais , Ensaios Clínicos como Assunto , Avaliação de Medicamentos , Betacoronavirus , Vacinas contra COVID-19 , COVID-19
18.
Rev. cir. (Impr.) ; 71(5): 398-404, oct. 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1058293

RESUMO

Resumen Objetivo: En este estudio, se propuso establecer la relación entre la pérdida de peso y la evolución de las artropatías en un grupo de pacientes obesos sometidos a cirugía bariátrica. Materiales y Método: Investigación correlacional y de corte longitudinal, retrospectivo, donde se revisaron 33 historias de pacientes obesos mórbidos con artralgia en cualquier articulación, sometidos a cirugía bariátrica. Se realizó el análisis descriptivo de las variables numéricas según la distribución de los datos. Como prueba de relación se utilizó la Prueba T de Student para comparación de proporciones, asumiendo un valor p < 0,05. Resultados: 63,3% fueron femeninas, siendo la rodilla la principal articulación afectada (51,5%), con reducción considerable de su índice de masa corporal poscirugía. Al compararse los promedios del IMC inicial, a los 3, 6 y 12 meses, se encontraron diferencias estadísticamente significativas (p < 0,01). La desaparición de la artralgia en la mayoría de los pacientes ocurrió durante los primeros 3 meses, principalmente pacientes con obesidad grado I y II, en contraste con aquellos pacientes con obesidad grado III y IV, quienes requirieron un mayor lapso, para lograr la desaparición total de la artralgia. Conclusiones: La disminución gradual del dolor articular estuvo en relación directa a la reducción de las cifras de peso del paciente ya operado, mejorando la calidad de vida de los pacientes de la muestra.


Aim: In this study it was proposed to establish the relationship between weight loss and the evolution of the joint diseases in a group of obese patients undergoing bariatric surgery. Materials and Method: Cutting longitudinal, retrospective, and correlational research where studied 33 morbidly obese patients histories and arthralgia, in any joint they was undergoing bariatric surgery. It was the descriptive analysis of the numerical variables according to the distribution of the data. As proof of relationship the Student T test was used for comparison of proportions, assuming a P-value < 0.05. Results: 63.3% were female, being the main affected joint (51.5%), with significant reduction in their rate of body mass post surgery knee. To compare the averages of initial IMC, 3, 6 and 12 months statistically significant differences were found (p < 0.01). The disappearance of arthralgia in patients most occurred during the first 3 months, mainly patients with obesity grade I and II, in contrast to those patients with obesity grade III and IV, who required a greater period, to achieve the total disappearance of arthralgia. Conclusion: The gradual decrease in the pain joint was in direct relation to the reduction of the numbers of weight of the patient already operated, improving the quality of life of the patients of the indicated.


Assuntos
Humanos , Masculino , Feminino , Artralgia/reabilitação , Cirurgia Bariátrica/reabilitação , Período Pós-Operatório , Redução de Peso
20.
J Pain Res ; 12: 117-125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30613160

RESUMO

BACKGROUND: Previous studies have shown the efficacy of tapentadol (TP) for chronic cancer pain. We evaluated multiple effectiveness aspects of TP prolonged release on moderate-severe cancer-related pain, neuropathic pain (NeP), patient satisfaction, and quality of life. METHODS: An observational prospective study was conducted on 80 cancer patients. Opioid-naïve patients received a starting dose of prolonged-release TP 50 mg twice daily, and opioid-experienced patients were switched to TP, not to exceed 500 mg/day. Treatment response was evaluated at 3, 6, 30-40, and 60-70 days through response rate, numeric rating-scale scoring, survival analysis (time to event for response), pain-intensity difference, TP escalation-index percentage, and effects on NeP. The drug-sparing effect on concomitant therapies was evaluated. RESULTS: Seventy of 80 patients (88%) were responders to treatment (95% CI 78%-94%). Compared to T0, pain-intensity reductions were statistically significant for all intervals (P<0.01), with better results at T3/T4. NeP was significantly reduced at T4 (P<0.01). The probability of response was low at the initial stages and increased during the study. Pain-intensity differences decreased during the study, though without significance. Two patients (2.5%) left the study for TP-induced side effects. A significant improvement in quality of life was observed after 30-40 days (P<0.01). The majority of patients were "satisfied", "very satisfied", or "extremely satisfied" (T3-T4). CONCLUSION: TP was effective in terms of drug-sparing effect, response rate, TP escalation-index percentage, and NeP management. By comparing data from the survival analysis with the response rate and time to response (numeric rating scale from T0 to T4), we found that although TP induced a quick response, a longer period of therapy and higher doses were needed to improve the positive result.

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