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1.
ESMO Open ; 7(4): 100531, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35810556

RESUMO

BACKGROUND: Pathogenic variants (PVs) in BRCA1/2 genes account for ∼6% of breast and 20% of ovarian cancers. Most breast tumors developed by BRCA1 carriers are triple negative. BRCA2 tumors have similar rates of estrogen receptor positivity as sporadic controls but are less likely to be human epidermal growth factor receptor 2 (HER2)-positive. Prevalence of HER2 positivity among breast cancers (BCs) in BRCA1/2 mutation carriers is poorly and variably described, ranging from 0% to 10% and 0% to 13% in BRCA1 and BRCA2 carriers, respectively. PATIENTS AND METHODS: We assessed the prevalence of HER2 positivity among a single institutional cohort of 398 BCs developed in carriers of BRCA1/2 PVs (240 BRCA1, 158 BRCA2). Subsequently, a systematic review of the literature and pooled analysis was carried out. RESULTS: In our series we found a 7% HER2 positivity rate among all first BRCA1/2 BCs overall. In BRCA1 carriers, 5.4% of BCs were HER2-positive compared with 9.5% in BRCA2-mutated patients. Among bilateral BCs, HER2-positive cases were 15.2% in the BRCA1 group and 23.1% in the BRCA2 group. Notably, six BRCA1 and eight BRCA2 carriers showed discordant HER2 status between BC and bilateral BC (23.7%, 14/59). The systematic review included 21 083 BRCA1/2 patients from 73 eligible studies. The pooled rate of BRCAmut/HER2-positive BCs is 9.1% (95% confidence interval 7.3% to 11.2%). BRCA1 and BRCA2 when reported as separate data ranged from 0% to 33.3% (mean 8.3%) and from 0% to 86% (mean 10.3%), respectively. CONCLUSIONS: As compared with sporadic cases, BCs occurring in BRCA1 and/or BRCA2 PVs carriers are less frequently HER2-positive. Prevalence of HER2 positivity in our series was consistent with pooled analysis and did not exceed 10%. Although not common, co-existence of BRCA mutations and HER2 overexpression and/or gene amplification should be acknowledged. More research is needed to better characterize this subgroup of patients who should not be excluded a priori from clinical trials of targeted therapy for BRCA1/2-driven cancers.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/genética , Feminino , Genes BRCA2 , Humanos , Receptor ErbB-2/genética
2.
Behav Brain Res ; 429: 113887, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35405174

RESUMO

BACKGROUND: Preclinical rodent models of Parkinson's aim to recapitulate some of the hallmarks of the disease as it presents in humans, including the progressive neuronal loss of dopaminergic neurons in the midbrain as well as the development of a behavioral phenotype. AAV vector-based models of alpha-synuclein overexpression are a promising tool to achieve such animal models with high face and predictive validity. OBJECTIVE: We have developed a preclinical rodent model of Parkinson's disease using an AAV-vector based overexpression of human alpha-synuclein. In the present work we characterize this model on a behavioral and histopathological level. METHODS: We use a AAV9 vector for transgene delivery to overexpress human alpha-synuclein under a CBA promoter. We compare the behavioral and histopathological changes to a AAV vector control group where the transgene was omitted and to that of a 6-OHDA lesion control. We assessed the behavioral performance of these three groups on a series of tests (Cylinder, Stepping, Corridor) at baseline and up to 22 weeks post-injection at which point we performed electrochemical recordings of dopamine kinetics. RESULTS: The overexpression of human alpha-synuclein led to the progressive manifestation of behavioral deficits on all three behavioral tests. This was accompanied with impaired dopamine release and reuptake kinetics as demonstrated by electrochemical detection methods. Histopathological quantifications corroborated the findings that we induced a moderate cell loss with remaining cells displaying pathological markers which are abundant in the brains of human PD patients. CONCLUSIONS: In the present work we developed a characterized a rat model of PD that closely mimics human disease development and pathology. Such model will be of great use for investigation of disease mechanisms and early therapeutic interventions.


Assuntos
Dopamina , alfa-Sinucleína , Animais , Escala de Avaliação Comportamental , Dependovirus/genética , Modelos Animais de Doenças , Vetores Genéticos , Humanos , Mesencéfalo/metabolismo , Ratos , Ratos Sprague-Dawley , Substância Negra/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
3.
ESMO Open ; 6(6): 100293, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34689001

RESUMO

BACKGROUND: TRIBE and TRIBE-2 studies demonstrated higher benefit from FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan)/bevacizumab compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) or FOLFOX/bevacizumab as an upfront option for metastatic colorectal cancer patients, with more toxicities. We focused on the incidence and longitudinal dynamics of neutropenia and febrile neutropenia (FN) in the two studies, to evaluate their clinical relevance, the magnitude of impact of FOLFOXIRI/bevacizumab, and the role of risk factors in predicting their occurrence. METHODS: The overall incidence of grade 3-4 (G3-4) neutropenia and FN, the time to their onset, the use of granulocyte colony-stimulating factor, and the association with risk factors were evaluated in the overall population and according to treatment arm. FN episodes were assessed by Multinational Association for Supportive Care in Cancer (MASCC) score. RESULTS: Among 1155 patients, 568 (49%) received FOLFOXIRI/bevacizumab. Overall, 410 (35%) experienced G3-4 neutropenia and 70 (6%) FN, 21 (2%) at high risk. FOLFOXIRI/bevacizumab was associated with higher incidence of neutropenia (51% versus 21%, P < 0.001), FN (8% versus 4%, P = 0.02), and high-risk FN [18 (3%) versus 3 (1%), P = 0.015]. No related deaths were observed. The first episode of G3-4 neutropenia and FN occurred mainly in the first 2 months in both arms. Longitudinal analysis showed different patterns of evolution over cycles between the arms (P < 0.001) G3-4 neutropenia being more frequent in the first cycles with FOLFOXIRI/bevacizumab. Older patients (P = 0.01) and females (P < 0.001) had a significantly higher risk of G3-4 neutropenia. No significant interaction effect between arm and analysed risk factors in terms of risk of G3-4 neutropenia or FN was observed. The incidence of FN among older females receiving FOLFOXIRI/bevacizumab was 12%. Neither G3-4 neutropenia nor FN impaired efficacy in terms of overall response rate, progression-free survival, and overall survival. CONCLUSIONS: FOLFOXIRI/bevacizumab has a higher risk of G3-4 neutropenia and FN than doublets/bevacizumab. FN occurred in <10% of patients, mostly as low-risk episodes. A closer monitoring during the first 2 months is recommended; prophylactic use of granulocyte colony-stimulating factor may be considered for older females.


Assuntos
Neoplasias Colorretais , Neutropenia Febril , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Camptotecina/análogos & derivados , Neoplasias Colorretais/patologia , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/epidemiologia , Feminino , Fluoruracila , Humanos , Leucovorina , Compostos Organoplatínicos
4.
Clin Transl Oncol ; 22(7): 1004-1012, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31599376

RESUMO

BACKGROUND: Incidence of gastric cancer (GC) shows different distribution in Italy, with higher incidence in the north and center. We retrospectively analyzed the clinical data of patients resected at the Hospital of Cremona between January 2007 and December 2016. Available clinical variables were linked with survival to identify possible prognostic factors. MATERIALS AND METHODS: Variables analyzed were age, sex, type of surgery, site, histology, invasion, nodal status, resection margins, grade, HER2 status, Helicobacter pylori infection (neo)adjuvant chemotherapy, adjuvant chemoradiotherapy, neutrophil-to-lymphocyte ratio, number of nodes removed and type of lymphadenectomy. Overall survival (OS) was estimated by the Kaplan-Meier method and differences between groups by the log-rank test. Data on OS were analyzed by Cox regression and the final model was obtained using the step-wise method. RESULTS: 379 patients were considered, out of which 195 were operated from 2007 to 2011 and 184 from 2012 to 2016. Median follow-up was 25.5 months, median OS 31.3 months and time to recurrence 23.2 months. D2 resection rate increased from 36% (period 2007-2011) to 74% in 2012-2016 (p = 0.01) with a higher mean number of nodes collected (20.98 for 2007-2011 and 23.53 for 2012-2016, p = 0.040). Only 37% of patients received a postoperative treatment. At multivariate analysis, variables associated with OS were age (p = 0.002), stage (p < 0.001), resection margins status (p < 0.001), adjuvant chemotherapy (p < 0.010) and tumor location (cardia vs non-cardia) (p = 0.029). CONCLUSIONS: Our analysis shows that completeness of resection and lower stage are strong predictors of long-term survival in GC, providing the rationale for adjuvant and neoadjuvant approaches (chemotherapy, radiotherapy or combined). Cardial GC has worse prognosis compared to distal cancers. TRIAL REGISTRATION NUMBER: Service evaluation number 256, protocol 16821/17, date 05 June 2017.


Assuntos
Adenocarcinoma/cirurgia , Quimiorradioterapia Adjuvante , Gastrectomia/métodos , Terapia Neoadjuvante , Neoplasias Gástricas/cirurgia , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Amplificação de Genes , Infecções por Helicobacter , Humanos , Itália , Estimativa de Kaplan-Meier , Excisão de Linfonodo/métodos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Estudos Retrospectivos , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida
5.
Clin Ter ; 170(5): e328-e331, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612187

RESUMO

Primary perianal fistulous pathology represents a painful condition often noticeable in patients affected by Crohn's disease or Ulcerative colitis. It causes difficult defecation and can evolve in perianal abscess that should be urgently ascertained and drained. The present work aims to propose Argentum-Quartz® as valid non-surgical therapeutic treatment in order to reach a more comfortable perianal fistula healing. In fact, our preliminary data allow us to consider Argentum Quartz® ideally employable for treatment of perianal fistulas associated or not with IBDs, representing a reliable sphincter-sparing solution.


Assuntos
Canal Anal/patologia , Doença de Crohn/terapia , Quartzo/administração & dosagem , Fístula Retal/terapia , Adulto , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão , Resultado do Tratamento , Cicatrização/efeitos dos fármacos
6.
G Chir ; 40(3): 170-173, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31484004

RESUMO

INTRODUCTION: Prolonged air leak (PAL) is one of the most common postoperative complications after lung surgery. It is associated with increased significant morbidity, lower quality of life, longer hospital stay and higher hospital costs. Since its great clinical and economic burden, it is important to establish the feasibility and the effectiveness of the routinary preventive use of a fibrin sealant in order to reduce the incidence of prolonged air leaks. PATIENTS AND METHODS: This is a randomized study on 189 adult patients - 118 men (62.4%) and 71 women (37.6%) aged from 39 to 87 y.o. (mean age 68.3 y.o.) - who underwent lung surgery (lobectomy or bilobectomy) with intraoperatory detection of air leakage, from January 2013 to December 2017, at Department of Thoracic Surgery in "Ospedale Maggiore Carlo Alberto Pizzardi" (Bologna, Italy) and Department of Thoracic Surgery in "Paolo Giaccone" Teaching Hospital (Palermo, Italy). Patients were randomly assigned to the "Glue" arm (90 patients) or the "Control" group (99 patients). We only used stapler or manual suture to achieve aerostasis. In addition, we used a fibrin sealant ("glue") to cover the suture line on patients in the "Glue" arm. The primary endpoints were incidence of prolonged air leaks, days with chest tube and mean hospital stay. RESULTS: In the "Glue" arm we experienced only 1 prolonged air leak (1.1%), while in the "Control" group there were 8 leaks (8.1%). Patients kept chest tube for average 4.15 days in the "Glue" arm and 4.45 days in the "Control" group. The mean hospital stay was average 7.4 days for the "Glue" arm, while 9.1 days in the "Control" group. CONCLUSIONS: According to our experience it seems that the routinary preventive use of a fibrin sealant results in a lower incidence of prolonged air leaks, a shorter hospital stay with lower hospital costs, representing a cost-effective, feasible and effective system to decrease morbility and mortality among surgical patients.


Assuntos
Ar , Fístula Anastomótica/prevenção & controle , Adesivo Tecidual de Fibrina/uso terapêutico , Pneumonectomia/efeitos adversos , Adesivos Teciduais/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Tubos Torácicos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pneumonectomia/métodos , Qualidade de Vida , Técnicas de Sutura
7.
G Chir ; 40(3): 208-212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31484010

RESUMO

Primary leiomyosarcomas of the lung are tumors. We report a case of 49-year old female with history of cough, breathless at rest, right sided chest pain. Chest CT showed a huge (16 cm) mediastinal mass located on the right mediastinum encasing the right main pulmonary artery and infiltrating the main right bronchus and pericardium. The tumor was resected with combined pericardiectomy and pnemonectomy via hemiclamshell incision. This surgical access provided an adequate exposure of the chest "blind zones" and it allowed a radical and safe surgical resection of lung, pleura, pericardium and diaphragm. The final diagnosis showed a low grade differentiation leiomyosarcoma.


Assuntos
Leiomiossarcoma/cirurgia , Neoplasias do Mediastino/cirurgia , Feminino , Humanos , Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/patologia , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/patologia , Ilustração Médica , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Carga Tumoral
8.
G Chir ; 40(2): 115-119, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31131810

RESUMO

AIM: Thoracoscopic lobectomy is superior to thoracotomy, but the evidence for this assumption is low. We present a comparison between thoracotomy and thoracoscopy in term of postoperative complications, mortality, postoperative pain, hospital stay and quality of life. PATIENTS AND METHODS: This is a retrospective analysis of 224 lobectomies in 24-months. 128 patients (57.1%) were operated by thoracotomy; 96 patients (42.9%) by videothoracoscopy. RESULTS: Major complications were observed in 4/128 (3.1%) in thoracotomy group and in 1/96 (1%) in thoracoscopy. Minor complications were observed in 38/128 patients (29.7%) in the thoracotomy, and in 16/96 (16.7%) thoracoscopy. Thoracoscopy patients had a shorter hospital stay. CONCLUSION: Our study shows an advantage of thoracoscopy over thoracotomy but further studies are needed.


Assuntos
Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Cirurgia Torácica Vídeoassistida , Toracotomia , Humanos , Dor Pós-Operatória/epidemiologia , Estudos Retrospectivos
9.
G Chir ; 40(2): 137-140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31131814

RESUMO

The choroid is the most common site for intraocular metastatic di sease. Orbital metastasis as metastatic site of lung adenocarcinoma is very rare and in literature a very exiguous number of cases is present. This is a case report of a woman with history of lung adenocarcinoma and, after surgery, detection of a choroidal mass described as lung metastasis, responding to Gefinitib therapy. However a biopsy was not performed. After two years there was a great dimension decrement of the lung metastasis but she is still suffering from recurrent pleural effusion, with pleural thickenings biopsied and diagnosed as recurrences of disease.


Assuntos
Adenocarcinoma de Pulmão/secundário , Neoplasias da Coroide/secundário , Feminino , Humanos , Pessoa de Meia-Idade
10.
BMC Cancer ; 19(1): 212, 2019 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-30849945

RESUMO

BACKGROUND: The gastric cancer incidence rate differs widely across geographical areas. In Italy, in the province of Cremona the incidence is high, compared to the national situation. For this reason a specialized population-based registry was set up. METHODS: The collection encompasses all gastric cancers diagnosed in the three districts of the province since January 1, 2010. The main data sources were the pathological and Hospital Discharge Records and patient clinical charts. Only diagnoses of primary gastric cancer were considered. For each case the following variables were registered: personal data, medical history and symptoms at diagnosis; imaging assessments performed, details on surgery and other treatments received; genetic background and biomolecular characteristics; social and environmental factors. RESULTS: As of November 2017, 1087 cases were collected; of which 876, diagnosed up to December 2015, were analyzed. Male/female ratio was 1.4. The European Age-standardized Incidence Rate was 41.4 for males and 28.3 for females as compared to a national average of 33.3 and 17.0 respectively. Median age at diagnosis was 73 for male and 78 for female. Helicobacter Pylori infection was present in fewer than 20% of cases. HER-2 gene was amplified in about 25% of cases. Primary tumour location was the gastro-esophageal junction or cardia in 17.5% in males and 8.3% in females. The majority of cases (58.3%) were diagnosed at an advanced stage and overall only 41.2% underwent surgery. Median overall survival was 14.8 months for men and 18.5 for women. Age standardized 5-year relative survival was 31.4% for men and 40.5% for females. Neoadjuvant treatment was performed in fewer than 10% of patients who underwent surgery, and the rate of postoperative therapy adherence was low. DISCUSSION: This study shows a high gastric cancer incidence in the province of Cremona, with a geographical spread across different districts. Moreover, a high percentage of gastric cancers were detected at an advanced stage of disease and a low rate of 5-year relative survival was registered. Based on these findings, effective preventive interventional health strategies and screening procedures need to be implemented to reduce the impact of this pathology in this geographical area.


Assuntos
Neoplasias Gástricas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Feminino , Humanos , Incidência , Itália/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Avaliação de Resultados da Assistência ao Paciente , Vigilância da População , Prognóstico , Sistema de Registros , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/mortalidade , Avaliação de Sintomas
11.
Ann Oncol ; 29(7): 1528-1534, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29873679

RESUMO

Background: Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status. Patients and methods: Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined as right- or left-sided if they originated from the caecum to the transverse colon or within the splenic flexure and beyond, respectively. Patients with available information about both primary sidedness and RAS and BRAF status were included in the present analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumor location and RAS and BRAF mutational status. Results: Information about primary sidedness and RAS and BRAF status was available for 358 (70.5%) out of 508 randomized patients. Patients with right-sided tumors (N = 173) presented shorter OS [23.7 versus 31.0 months, HR = 1.42 (95% CI 1.09-1.84), P = 0.010] and a trend toward shorter PFS [10.2 versus 11.5 months, HR = 1.24 (95% CI: 0.98-1.56), P = 0.083] than those with left-sided tumors (N = 185), but these associations were no longer evident when adjusting for RAS and BRAF status. Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS (HR = 0.59 versus 0.89, P for interaction = 0.099) and OS (HR = 0.56 versus 0.99, P for interaction = 0.030) and this advantage was independent of their RAS and BRAF status. Conclusions: FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status. Trial registration: clinicaltrials.gov identifier NCT00719797.

12.
J Biol Regul Homeost Agents ; 32(2): 415-423, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29685027

RESUMO

Few data are available about the clinical course of severe colonic Crohn’s disease (CD). The aim of this study is to describe the clinical course of severe Crohn’s colitis in a patient cohort with isolated colonic or ileocolonic CD, and to compare it with the clinical course of patients with severe ulcerative colitis (UC). Thirty-four patients with severe Crohn’s colitis were prospectively identified in our cohort of 593 consecutive hospitalized patients through evaluation of the Crohn’s Disease Activity Index score and the Harvey-Bradshaw Index. One hundred sixty-nine patients with severe ulcerative colitis were prospectively identified in our cohort of 449 consecutive hospitalized patients through evaluation of the Lichtiger score and the Truelove-Witts score. We evaluated the following data/aspects: response to steroids, response to biologics, colectomy rate in acute, colectomy rate during follow-up, megacolon and cytomegalovirus infection rate. We did not find significant differences in the response to steroids and to biologics, in the percentage of cytomegalovirus infection and of megacolon, while the rate of colectomy in acute turned out to be greater in patients with severe Crohn’s colitis compared to patients with severe UC, and this difference appeared to be the limit of statistical significance (Chi-squared 3.31, p = 0.069, OR 0.39); the difference between the colectomy rates at the end of the follow-up was also not significant. In the whole population, by univariate analysis, according to the linear regression model, a young age at diagnosis is associated with a higher overall colectomy rate (p = 0.024) and a higher elective colectomy rate (p = 0.022), but not with a higher acute colectomy rate, and an elevated ESR is correlated with a higher overall colectomy rate (p = 0.014) and a higher acute colectomy rate (p = 0.032), but not with a higher elective colectomy rate. This correlation was significant on multivariate analysis. The overall rate of colectomy in the cohort of patients with severe Crohn’s colitis was greater than that of the cohort of patients with severe UC, but this figure is not supported by a different clinical response to steroid therapy or rescue therapy with biologics. The clinical course of severe Crohn’s colitis requires to be clarified by prospective studies that include a larger number of patients in this subgroup of disease.


Assuntos
Colite Ulcerativa , Doença de Crohn , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
J Biol Regul Homeost Agents ; 32(1): 7-11, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29504359

RESUMO

Crohn’s disease (CD) is an inflammatory bowel disease with a multifactorial etiology. Clinical features include mucosal erosion, diarrhea, weight loss and other complications such as formation of granuloma. In CD, granuloma is a non-neoplastic epithelioid lesion, formed by a compact aggregate of histiocytes with the absence of a central necrosis, however, the correlation among CD and the formation of granulomas is unknown. Many cases of granulomas in the extracellular site, related to CD, have been reported in the literature. These granulomas, at times, represented the only visible manifestation of the pathology. Extra intestinal granulomas have been found on ovaries, lungs, male genitalia, female genitalia, orofacial regions and skin. From the data in the literature it could be hypothesized that there is a cross-reaction of the immune system with similar antigenic epitopes belonging to different sites. This hypothesis, if checked, can place CD not only among inflammatory bowel disease but also among inflammatory diseases with systemic involvement.


Assuntos
Doença de Crohn/metabolismo , Doença de Crohn/patologia , Doença de Crohn/fisiopatologia , Granuloma/metabolismo , Granuloma/patologia , Granuloma/fisiopatologia , Humanos , Especificidade de Órgãos
14.
Ann Oncol ; 29(4): 924-930, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29324972

RESUMO

Background: Neutrophil/lymphocyte ratio (NLR), defined as absolute neutrophils count divided by absolute lymphocytes count, has been reported as poor prognostic factor in several neoplastic diseases but only a few data are available about unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our study was to evaluate the prognostic and predictive role of NLR in the TRIBE trial. Patients and methods: Pts enrolled in TRIBE trial were included. TRIBE is a multicentre phase III trial randomizing unresectable and previously untreated mCRC pts to receive FOLFOXIRI or FOLFIRI plus bevacizumab. A cut-off value of 3 was adopted to discriminate pts with low (NLR < 3) versus high (NLR ≥ 3) NLR, as primary analysis. As secondary analysis, NLR was treated as an ordinal variable with three levels based on terciles distribution. Results: NLR at baseline was available for 413 patients. After multiple imputation at univariate analysis, patients with high NLR had significantly shorter progression-free survival (PFS) [hazard ratio (HR) 1.27 (95% CI 1.05-1.55), P = 0.017] and overall survival (OS) [HR 1.56 (95% CI 1.25-1.95), P < 0.001] than patients with low NLR. In the multivariable model, NLR retained a significant association with OS [HR 1.44 (95% CI 1.14-1.82), P = 0.014] but not with PFS [HR 1.18 (95% CI 0.95-1.46), P = 0.375]. No interaction effect between treatment arm and NLR was evident in terms of PFS (P for interaction = 0.536) or OS (P for interaction = 0.831). Patients with low [HR 0.84 (95% CI 0.64-1.08)] and high [HR 0.73 (95% CI 0.54-0.97)] NLR achieved similar PFS benefit from the triplet and consistent results were obtained in terms of OS [HR 0.83 (95% CI 0.62-1.12) for low NLR; HR 0.82 (95% CI 0.59-1.12) for high NLR]. Conclusion: This study confirmed the prognostic role of NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line, showing the worse prognosis of pts with high NLR. The advantage of the triplet is independent of NLR at baseline.


Assuntos
Neoplasias Colorretais/sangue , Contagem de Linfócitos , Metástase Neoplásica , Neutrófilos/citologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Prognóstico , Estudos Retrospectivos
15.
J Biol Regul Homeost Agents ; 31(4): 1101-1107, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29254321

RESUMO

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC). The aim of the study is to evaluate the prevalence of CRC in a cohort of Caucasian patients with T2DM and the association with other variables previously known to be related with increased risk of CRC. We retrospectively evaluated the data of 741 consecutive Caucasian patients with T2DM who underwent colonoscopic screening in our tertiary referral center. A control cohort of 333 patients with thyroid disease was selected to evaluate the difference in the incidence of CRC. At a median follow-up of 132.5 months (range 33.3-175.7), 67 cases of cancer (prevalence 9%) occurred; among these, 14 cases of CRC were reported (prevalence 1.88%) among the diabetic patients, while only two case (one of these was a CRC) (overall prevalence 0.006%, prevalence of CRC 0.003%) occurred in the control group; the difference between the prevalence of CRC was statistically significant (chi-square 4.21, p=0.04). The median duration of T2DM to CRC diagnosis was 168 months (range 12-768). At the univariate analysis, older age (p=0.001, r 0.138) and diabetes duration (p=0.001, r 0.138) were related to higher risk of cancer, while metformin seems to be protective towards cancer (p=0.07, r -0.098). In the subset of patients with CRC, the age (RR = 2.25; 95% CI: 0.30 - 17.31; p less than 0.001), the diabetes duration (RR = 1.93; 95% CI: 0.25 – 14.77; p = 0.001) and the sulphonylureas treatment (RR = 2.33; 95% CI: 0.78 – 7.38; p = 0.007) were independently correlated with CRC. In our study, the prevalence of CRC in the cohort of patients with T2DM was higher compared to that from the National Tumor Register in 2010 (0.5%). Furthermore, we could speculate that sulphonylureas may play a role in CRC carcinogenesis impairing the physiological insulin secretion.


Assuntos
Neoplasias Colorretais/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Hipoglicemiantes/uso terapêutico , Compostos de Sulfonilureia/efeitos adversos , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Insulina/metabolismo , Secreção de Insulina , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , População Branca
16.
J Biol Regul Homeost Agents ; 31(4): 1119-1125, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29254324

RESUMO

The term focal active colitis (FAC) is conventionally used to describe the presence of isolated cryptitis, characterized by an inflammatory infiltrate consisting of intraepithelial neutrophils and/or neutrophils invading the lumen of the criptae, with no other microscopic alteration of the colonic mucosa and, in particular, without the presence of signs of chronic inflammation. To date, only four studies, including one conducted in a pediatric population, have been performed to evaluate the clinical significance of this disease. The aim of this retrospective study on prospectively-collected data is to evaluate the clinical implications of the focal active colitis, since there still remains a marked uncertainty regarding this topic and about how often such a diagnosis will presage a diagnosis of inflammatory bowel disease (IBD). Clinical, endoscopic, and pathological data were retrospectively reviewed from 30 patients with focal active colitis, who had no other diagnostic findings on colorectal biopsy and no history of chronic inflammatory bowel disease. The histological findings were correlated with clinical diagnoses. Thirty patients (11 males, 19 females; age 24-80 years, median 56 years) (0.5%) out of 5,600 undergoing colonoscopy between January 2012 and December 2016 presented a definitive diagnosis of FAC. Follow-up ranged from 6 to 60 months (median 24 months). At endoscopy, 19 patients (63%) had mild and non-specific changes, such as mild mucosal erythema, while 11 (37%) had normal findings. Eight patients were documented as having irritable bowel syndrome, while nine cases could be attributed to the effects of drugs, five presented FAC as incidental finding, one a diagnosis of infectious colitis, and seven a diagnosis of IBD (4 with Crohn’s disease). FAC was confirmed to be a more significant predictor of IBD than the previous literature would indicate, even if larger prospective studies, targeted to study this relationship, are needed to understand more clearly its clinical significance.


Assuntos
Centros Médicos Acadêmicos , Colite/diagnóstico , Colo/patologia , Doenças Inflamatórias Intestinais/diagnóstico , Mucosa Intestinal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colite/patologia , Colonoscopia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Achados Incidentais , Doenças Inflamatórias Intestinais/patologia , Itália , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
17.
J Biol Regul Homeost Agents ; 31(3): 769-774, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28685524

RESUMO

Colorectal cancer (CRC) is one of the most common cancers worldwide. Various factors, including oxidative stress, where excessive productions of reactive oxygen species (ROS) and reactive nitrogen species (RNS) occur, contribute to its pathogenesis. Numerous studies have investigated the effect of antioxidant substances derived from food such as fruits and vegetables; however, data on Lycopene are still rare. Studies on HT-29 colorectal cancer cells and on animal models have shown that lycopene has effects on cell proliferation and on the progression of the CRC by interacting with various cellular signaling pathways. This analysis of the literature focused on the antioxidant effect of lycopene, a substance that is found in the tomato.


Assuntos
Carotenoides/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais , Neoplasias Experimentais , Transdução de Sinais/efeitos dos fármacos , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Humanos , Licopeno , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Espécies Reativas de Oxigênio/metabolismo
18.
J Biol Regul Homeost Agents ; 31(3): 791-795, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28726358

RESUMO

It is well established that oxidative stress is common in inflammatory bowel diseases (IBDs). Accordingly, antioxidants are recommended for treatment. The aim of this study is to compare the effects of antioxidants contained in the various types of tea on symptoms and evolution of IBD and colorectal cancer (CRC). Analysis of the literature revealed that the theaflavin-3, 30-digallate (TFDG) contained in black tea, and epigallocatechin-3-O-gallate (EGCG) contained in green tea have protective effects against oxidative stress. Moreover, these substances are involved in many biochemical processes responsible for inflammation and proliferation of cancer cells. It is documented that both TFDG and EGCG are able to reduce inflammatory phenomena and symptoms associated with IBD, as well as to reduce the proliferation of CRC cells. Most studies are performed in vitro or in experimental animal models. It is, therefore, advisable to formulate studies that could be carried out on humans or human samples, in order to develop the appropriate therapeutic strategies.


Assuntos
Antioxidantes/uso terapêutico , Biflavonoides/uso terapêutico , Catequina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Dieta , Ácido Gálico/análogos & derivados , Doenças Inflamatórias Intestinais/tratamento farmacológico , Chá/química , Animais , Antioxidantes/química , Biflavonoides/química , Catequina/química , Catequina/uso terapêutico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Ácido Gálico/química , Ácido Gálico/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia
19.
Clin Ter ; 168(2): e133-e135, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28383625

RESUMO

Perineal hernia is the protrusion of an intra-abdominal structure into the perineal area, that could be primitive or secondary to trauma or abdominoperineal resection. Main treatment could be transabdominal, transperineal or combined. Here is a rare case of anterior perineal hernia in a young saxophone male patient, treated with a mininvasive perineal approach. A 25-year-old Caucasian male patient referred 1-year history of perineal pain. The pain was more severe when he played his saxophone. Local exam was negative but a dynamic perineal ultrasonography revealed a small anterior perineal hernia. The defect was repaired with a polypropylene plug and the patient was discharged the day after. At one year, no signs of remission have been signalled. Perineal mesh hernioplasty of primary perineal hernia is technically feasible, is associated with rapid recovery and minimal complications, and has a good long-term outcome. The use of ultrasonography to detect the hernia could be considered the best choice whenever it is of small size. Ultrasonography allow to identify weakness areas, reducing diagnostic time and avoiding further costs.


Assuntos
Hérnia/etiologia , Herniorrafia/métodos , Abdome/patologia , Adulto , Humanos , Masculino , Períneo/patologia , Telas Cirúrgicas
20.
Eur J Surg Oncol ; 43(9): 1607-1616, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28347525

RESUMO

INTRODUCTION: Major pathologic regression after neoadjuvant therapy is a strong and favorable prognostic factor in several types of cancer (breast, rectal and bladder). This information is less clear and has yet to be systematically evaluated in upper gastrointestinal tumors. We performed a meta-analysis to evaluate the prognostic impact of tumor regression after preoperative therapy on disease-free survival (DFS) and overall survival (OS) in gastro-esophageal cancer patients. METHODS: we searched for relevant articles in PubMed, SCOPUS, Web of Science, CINAHL, LILACS, Ovid, Cochrane Library, Google Scholar and Embase up to June 2, 2016. Data of tumor regression (complete or near-complete pathologic response) that independently correlated with OS and DFS in multivariate analysis were extracted, and the proper hazard ratios (HRs) with corresponding 95% confidence intervals (95% CIs) were pooled according to the random effect model. RESULTS: a total of 17 studies-which included 3145 patients-were considered in the final analysis. Major pathologic response was significantly related with better OS (HR 0.46, 95% CI 0.32-0.66, P < 0.001) and DFS (HR = 0.40, 95% CI 0.26-0.62, P < 0.001). Pathologic complete response (pCR) or major tumor regression were associated with the same degree of benefit in outcome compared to no or minimal pathologic regression, regardless of histology. CONCLUSION: major pathologic response is associated with a significant improvement in OS compared to no response or minor pathologic changes after neoadjuvant therapy in gastro-esophageal cancers. This should be considered a robust prognostic factor to guide postoperative treatment and follow-up.


Assuntos
Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Terapia Neoadjuvante , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Intervalo Livre de Doença , Esofagectomia , Gastrectomia , Humanos , Estadiamento de Neoplasias , Taxa de Sobrevida
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