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BACKGROUND: The primary aim of this study was to compare the quality of life between women with obstetric anal sphincter injury (OASI) and women with intact perineum or minor vaginal tears following their first vaginal birth through a validated urogynaecological questionnaire. As a secondary aim, we wanted to identify the specific symptoms for pelvic floor dysfunction after a vaginal birth. METHODS: One hundred thirty-three cases (III- and IV-degree vaginal tears) and 133 controls (intact perineum or I- and II-degree vaginal tear) were asked to fill the PFDI-20 condition-specific and quality of life survey at three and 12 months after vaginal delivery. The survey evaluates pelvic floor dysfunction symptoms through three subsections: the Pelvic Organ Prolapse Distress Inventory (POPDI), the Colorectal-Anal Distress Inventory (CRADI), and Urinary Distress Inventory, (UDI). The scoring system ranges from 0 (no distress) to 100 (maximum distress) for each subsection, subsequently summed up to obtain the summary score (0 to 300). The patients recruited were asked to complete the survey at 3- and 12-months follow-up visit. Accordingly, data collection started. Categorical variables were subjected to Chi-square test or Fisher's Exact test. Quantitative variables were compared through Student's t-test or Mann-Whitney test. RESULTS: All surveys have shown statistically significant differences when comparing the cases to the control group. Consequently, PFDI-20 has shown a strong correlation between III- and IV-grade lacerations and pelvic floor dysfunction persistence at 12 months after delivery. Intestinal symptoms were the most reported disturbances among women with previous OASI. CONCLUSIONS: Major vaginal tears have demonstrated to have a strong impact on women's quality of life up to a follow-up of 12 months. The use of PFDI-20 questionnaire is a useful and valid tool in the diagnosis and follow-up of genital prolapse, fecal and urinary incontinence in primiparous women with a history of OASI. Thus, its application in clinical practice can help offering the most adequate rehabilitative treatment.
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Incontinência Fecal , Lacerações , Diafragma da Pelve , Doenças Vaginais , Feminino , Humanos , Gravidez , Estudos de Casos e Controles , Incontinência Fecal/etiologia , Diafragma da Pelve/patologia , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Mild hyponatremia is frequently encountered in the pediatric emergency department (PED). Although usually of little clinical concern, its prognostic meaning as a possible marker of more severe disease has not yet been well established. METHODS: We retrospectively analyzed data from children and adolescents who performed a blood sample with plasmatic sodium measurement on admission to the PED of IRCCS "Burlo Garofolo" Pediatric Hospital in Trieste, Italy, in 2019. We compared the rate, length of admissions and laboratory characteristics of patients with hyponatremia to those with normal sodium. RESULTS: Among 807 subjects, hyponatremia (sodium < 135 mEq/L) was present in 17.6%, being mild (between 130 and 134 mEq/L) in 16.5%. Hyponatremic patients were younger, more frequently males, with an infection diagnosis, mainly of the respiratory tract and viral aetiology. They presented higher C-reactive protein (CRP) levels and erythrocyte sedimentation rates (ESR). Compared to normonatremic individuals, hyponatremic patients presented a higher risk of underlying infection (aOR 2.02; 95%CI 1.33-3.08), hospital admission (aOR 1.72; 95%CI 1.06-2.48), and a hospital stay of > 5 days (aOR 1.99; 95%CI 1.03-3.85). When considering only subjects with mild hyponatremia, we found similar results. CONCLUSION: Hyponatremia and mild hyponatremia in the PED are associated with an increased admission rate and extended hospital stays. Mild hyponatremia should be considered a warning sign for a possibly more serious condition.
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Hiponatremia , Masculino , Adolescente , Humanos , Criança , Hiponatremia/diagnóstico , Hiponatremia/epidemiologia , Hiponatremia/etiologia , Estudos Retrospectivos , Hospitalização , Sódio , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND: The aim of our study is to evaluate the outcome of patients affected by brain metastases from colorectal cancer and to correlate the outcome with prognostic factors. METHODS: Patients were retrospectively evaluated. Survival distributions were estimated by using the Kaplan-Meier method. The log-rank test was used to assess the impact on survival of individual factors. RESULTS: Among 41 patients (25M and 16F; median age 58), 58.5 % had rectal cancer and 39 % synchronous metastatic disease; 95 % had extracranial metastases, most common site was lung (87.8 %). Seven patients had synchronous brain metastases. Median overall survival after diagnosis of brain metastases was 5 months [95 % confidence interval 3-12 months]. Median survival from brain metastases diagnosis was 4.2 months in patients treated with radiotherapy (29.3 %), 11.9 months in those with radio- and chemotherapy (21.9 %) and 21.4 months in those with surgery with/without radiotherapy or chemotherapy (29.3 %) (P < 0.0001). On multivariate analysis, no independent prognostic factors were found for disease-free interval from diagnosis to brain metastases and overall survival; amount of chemotherapy before brain metastases have no statistically significant relation to brain-metastases-free-interval even if patients who received more than one line of chemotherapy have a longer median brain-metastases-free-interval than those who received less than one. KRAS was found mutated in 17/28 patients without statistically significant correlation to outcome due to the small sample size. CONCLUSIONS: Prognosis of brain-metastases-patients is poor. An interesting tool is to evaluate the correlation of KRAS status and brain metastases with aim to tailor treatment and follow-up.
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Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias Colorretais/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Circulating tumor cells (CTCs) represent an independent prognostic factor in metastatic colorectal cancer, while their significance in early stages is still an open issue. The aim of the study is to investigate the role of CTCs in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (CT-RT). METHODS: In this prospective single institutional study, cT3-4 and/or N+ rectal cancer was treated with neoadjuvant CT-RT. The primary endpoints were as follows: evaluation of CTCs at baseline (t0), after CT-RT (t1), within 7 days after surgery (t2), and at 6 months from surgery (t3) and correlation with main patient/tumor characteristics, CEA, response to neoadjuvant therapy, and disease-free survival (DFS). CTCs were enumerated with the CellSearch System in 22.5 ml peripheral blood. A repeated measure analysis for binary outcome was used to evaluate over time changes in the percentage of CTCs detectable in blood samples. RESULTS: Of the 90 patients enrolled in this study, 85 were eligible consisting of 52 males and 33 females. Median age was 63 years and median follow-up was 38 months. CTCs were available for all patients at t0, for 67 at t1, for 68 at t2, and for 62 at t3. CTCs >0 were reported on 16 (19%) at t0, on 5 (7.5%) at t1, on 6 (9%) at t2, and on 3 (5%) at t3 (P value for trend 0.039). Only for CT-RT responders, CTCs reduced from t0 to t1. No statistically significant association was found between CTCs and main patient/tumor characteristics and DFS. CONCLUSIONS: Sixteen patients (19%) had CTCs ≥1 at t0 with reduction in CTC number in case of objective remissions. The proportion of patients with CTCs ≥1 decreased over the time as the therapeutic course proceeded. Much effort should be oriented toward increasing CTC detection rate by enhancing technical tests and achieving better patient characterization.
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Quimiorradioterapia Adjuvante , Terapia Neoadjuvante , Células Neoplásicas Circulantes/metabolismo , Neoplasias Retais/sangue , Neoplasias Retais/cirurgia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Análise de SobrevidaRESUMO
Chronic school absenteeism is a common problem in childhood and adolescence, and it is frequently observed in patients with somatic symptom and related disorders (SSRDs). This study aimed to determine whether and to what extent the presence of school absenteeism may be a risk factor for the diagnosis of SSRDs in hospitalised patients. This matched cohort study included children and adolescents aged between 8 and 17 years, admitted to the paediatric ward of the IRCCS Burlo Garofolo in Trieste from 2021 to 2023, who were divided into two groups, the first including children with at least 15 days of absence from school for medical reasons and the second including children with regular school attendance, matched to the former group by age and sex. We consecutively enrolled 70 patients, 35 in the absentee group and 35 in the control group. In the absentee group, 30/35 (85.7%) patients were diagnosed with an SSRD, while in the control group, 1/35 (2.9%) was diagnosed with an SSRD. The absentee group had a 30-fold higher risk of being diagnosed with SSRDs than the control group (RR = 30 [95% CI = 4.3-208]; p < 0.001). This study shows that in hospitalised children, a history of school absenteeism of more than two weeks is an important risk factor for the diagnosis of SSRDs.
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Objective: Pain's causes in children with severe cognitive impairment may be challenging to diagnose. This study aimed to investigate if there is a relationship between pain causes and the age of children. Methods: We conducted a multicenter retrospective study in three Italian Pediatric Units. Eligible subjects were patients from 1 to 18 years with severe neurological impairment. We collected data regarding diagnoses, pain causes and medical or surgical procedures. The timing of pain episodes was categorized into age-related periods: infants and toddlers (0-24 months), preschool children (3-5 years), schoolchildren (6-12 years), and adolescents (13-17 years). Results: Eighty children with severe neurological impairment were enrolled. The mean age was 11 years (±5.8). Gastroenterological pain was most common in the first years of life (p = 0.004), while orthopaedic and tooth pain was the most typical in schoolchildren and adolescents (p = 0.001 and p = 0.02). Concerning surgical procedures, PEG placement and gastric fundoplication were significantly more common in the first 5 years of age (p = 0.03), and heart surgery was typical of infants (p = 0.04). Orthopaedic surgery was more commonly reported in older children and adolescents (p < 0.001). Conclusions: Some causes of pain are more frequent in children with severe neurological impairment in defined age-related periods. Specific age-related pain frequencies may help physicians in the diagnostic approach.
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BACKGROUND AND PURPOSE: For patients with Stage II colon cancer, the use of adjuvant chemotherapy remains controversial. The purpose of this study was to identify clinical and/or pathological findings related to a worse prognosis in this category of patients. PATIENTS AND METHODS: We retrospectively analyzed the data of consecutive patients, extracted by an institutional Tumour Registry, admitted to an affiliated University Hospital in Milan (European Institute of Oncology) for adenocarcinoma of the colon (all sites), between 2000 and 2005, and having a final pT3 N0 pathology staging after curative surgery. Adjuvant chemotherapy was decided as a result of a medical decision within a multidisciplinary Tumor Board. RESULTS: Data of 137 patients were obtained, with a median follow-up of 77 months (range 6-131). Patients who received chemotherapy were younger than patients who did not. Nine patients out of 137 (6.5 %) died as a consequence of colon cancer recurrence; four of them had received adjuvant chemotherapy. Only histological grade III and mucinous histotype were found to impact on cumulative incidence of colon-related events (p 0.03 and 0.02, respectively); no impact was found on cumulative incidence of colonic neoplasm recurrence-related deaths (p 0.74 and 0.74, respectively). Number of analyzed LNs (lymph nodes) emerged as a factor possibly affecting the cumulative incidence of colon-related events (p 0.09) as well as the cumulative incidence of colonic neoplasm recurrence-related deaths (p 0.10). The risk of events was inversely proportional to the number of dissected LNs, even over 20 up to about 25 LNs. Never-smokers exhibited a lower incidence of colon-related events, although the difference was not statistically significant (p 0.09). All other analyzed variables did not show any impact on survival rate, including age, gender, ASA score, BMI, site of colonic neoplasm, multifocality, perivascular invasion, and use of adjuvant chemotherapy. CONCLUSIONS: Histology grading G3 and mucinous histotype were predictors of worse outcome. Efforts to improve LN evaluation should result in clinically significant improvements in outcome, and also the quality of care for patients with radically resected stage II colon cancer.
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Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Idoso , Colo/patologia , Feminino , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Análise de Sobrevida , Fatores de TempoRESUMO
Objective: To assess newborn hearing screening (NHS) impact on timing of cochlear implant (CI) surgery of patients with prelingual bilateral profound hearing impairment (BPHI), in order to evaluate whether the NHS ultimately serves the needs of the target population in Italy. Methods: An online questionnaire was created to survey subjects affected by prelingual BPHL born between 1990 and 2018. Questions focused on age at BPHI diagnosis, first and second CI surgery (if performed), and the region in which the surgery was performed. The survey was distributed to potential participants via social media communities used by hearing impaired people or their family members for sharing advice and offering support. Responses were analyzed using descriptive statistics. Results: Among the 318 respondents who completed the questionnaire, 276 (87%) reported having chosen CI surgery, 2/3 of them bilaterally. In the vast majority (97%) of cases the CI is used on a daily basis. Most of the people residing in the center (65%) and southern Italy (71%) had to move from their region of residence to perform the surgery. Late CI surgery was associated with failure to perform NHS (p = 0.007), birth before 2011 (p = 0.009), definitive diagnosis of BPHI after 6 months of life (p = 0.002), and progressive hearing impairment (p < 0.001). Conclusion: The worldwide scientific approval of the NHS as the current best opportunity for early diagnosis and CI treatment for prelingual BPHI is confirmed by what patients and families reported via the online questionnaire used for this study. In recent years, early bilateral cochlear implantation has become increasingly available in Italy, but late diagnosis, progressive hearing loss, failure to perform the NHS and lack of follow-up are still open questions. A large proportion of families had to move from the region of residence to have their child undergo CI surgery, revealing inequalities in terms of geographical disparities. Social media has proved to be a valuable, fast and inexpensive tool for gathering information on the effectiveness of health prevention programs, involving a large sample of individuals in a short amount of time.
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OBJECTIVES: Current antenatal care largely relies on widely spaced appointments, hence only a fraction of the pregnancy period is subject to monitoring. Continuous monitoring of physiological parameters could represent a paradigm shift in obstetric care. Here, we analyse the data from daily home monitoring in pregnancy and consider the implications of this approach for tracking pregnancy health. METHODS: Prospective feasibility study of continuous home monitoring of blood pressure, weight, heart rate, sleep and activity patterns from the first trimester to 6 weeks postpartum. RESULTS: Fourteen out of 24 women completed the study (58%). Compared to early pregnancy [week 13, median heart rate (HR) 72/min, interquartile range (IQR) 12.8], heart rate increased by week 35 (HR 78/min, IQR 16.6; P â=â0.041) and fell postpartum (HR 66/min, IQR 11.5, P â=â0.021). Both systolic and diastolic blood pressure were lower at mid-gestation (week 20: SBP 103 mmHg, IQR 6.6; DPB 63 mmHg, IQR 5.3 P â=â0.005 and P â=â0.045, respectively) compared to early pregnancy (week 13, SBP 107 mmHg, IQR 12.4; DPB 67 mmHg, IQR 7.1). Weight increased during pregnancy between each time period analyzed, starting from week 15. Smartwatch recordings indicated that activity increased in the prepartum period, while deep sleep declined as pregnancy progressed. CONCLUSION: Home monitoring tracks individual physiological responses to pregnancy in high resolution that routine clinic visits cannot. Changes in the study protocol suggested by the study participants may improve compliance for future studies, which was particularly low in the postpartum period. Future work will investigate whether distinct adaptative patterns predate obstetric complications, or can predict long-term maternal cardiovascular health.
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Sistema Cardiovascular , Período Pós-Parto , Pressão Sanguínea/fisiologia , Feminino , Humanos , Período Pós-Parto/fisiologia , Gravidez , Primeiro Trimestre da Gravidez , Estudos ProspectivosRESUMO
OBJECTIVES: We aimed to identify clinical, anamnestic, and sociodemographic characteristics associated with a positive swab for SARS-CoV2, and to provide a predictive score to identify at risk population in children aged 2-14 years attending school and tested for clinical symptoms of COVID-19. DESIGN: Cross sectional study. SETTING: Outpatient clinic of the IRCCS Burlo Garofolo, a maternal and child health tertiary care hospital and research centre in Italy. DATA COLLECTION AND ANALYSIS: Data were collected through a predefined form, filled out by parents, and gathered information on sociodemographic characteristics, and specific symptoms, which were analysed to determine their association with a positive SARS-CoV-2 swab. The regression coefficients of the variables included in the multivariate analysis were further used in the calculation of a predictive score of the positive or negative test. RESULTS: Between September 20th and December 23rd 2020, from 1484 children included in the study, 127 (8.6%) tested positive. In the multivariate analysis, the variables retained by the model were the presence of contact with a cohabiting, non-cohabiting or unspecified symptomatic case (respectively OR 37.2, 95% CI 20.1-68.7; 5.1, 95% CI 2.7-9.6; 15.6, 95% CI 7.3-33.2); female sex (OR 1.49, 95% CI 1.0-2.3); age (6-10 years old: OR 3.2, 95% CI 1.7-6.1 p<0.001; >10 years old: OR 4.8, 95% CI 2.7-8.8 p<0.001); fever (OR 3.9, 95% CI 2.3-6.4); chills (OR 1.9, 95% CI 1.1-3.3); headache (OR 1.45, 95% CI 0.9-2.4); ageusia (OR 1.3, 95% CI 0.5-4.0); sore throat (OR 0.48, 95% CI 0.3-0.8); earache (OR 0.4, 95% CI 0.1-1.3); rhinorrhoea (OR 0.8, 95% CI 0.5-1.3); and diarrhoea (OR 0.52, 95% CI 0.2-1.1). The predictive score based on these variables generated 93% sensitivity and 99% negative predictive value. CONCLUSIONS: The timely identification of SARS-CoV2 cases among children is useful to reduce the dissemination of the disease and its related burden. The predictive score may be adopted in a public health perspective to rapidly identify at risk children.
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Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , COVID-19/epidemiologia , Adolescente , Fatores Etários , COVID-19/diagnóstico , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Itália , Masculino , Fatores Sexuais , Fatores Socioeconômicos , Centros de Atenção Terciária/estatística & dados numéricosRESUMO
BACKGROUND: To evaluate efficacy and feasibility of chemo-radiotherapy in patients with non-metastatic anal squamous-cell-cancer. METHODS: TNM staged anal squamous-cell cancer patients were treated with pelvic radiotherapy concomitant to continuous infusion fluorouracil plus cisplatin for at least 2 cycles. In T3-T4 or any T - N+ tumours or in "slow-responder" cases, 1-2 chemotherapy courses were subsequently administered. Tumour assessment was performed at baseline and 6-8 weeks after radiotherapy to evaluate response. RESULTS: 29 patients were enrolled: 4 males, 25 females; median age 57 years; baseline T1/T2/T3/T4 2/12/7/8; N involvement 17. Median dose pelvic radiotherapy was 59.4 Gy (range: 54-74). In 5 patients 2 chemotherapy courses, in 12 patients three and in 12 patients four courses were performed. At first evaluation, 27 CR (93.1%; 95% CI: 78% - 98%) and 2 SD were observed. Main grade (G) 3 toxic events were neutropenia (8%), diarrhoea (8%) and dermatitis (62%). Most frequent late events G3-G4 occurred in 14 patients: proctitis (5), dermatitis (4), bladder dysfunctions (2), sexual dysfunctions (9), lower extremity venous thromboses (2), dysuria (1), stenosis (1) and tenesmus (1). Five patients reported G1 leucopoenia. The rate of colostomy was 14%. After a median follow up of 42 months (range: 4-81), 20 patients are still alive without relapse and 3 died due to PD. The estimated 7-year DFS was 83.4% (C.I.: 68.3%-98.5%) and the estimated 7-year OS was 85.7% (C.I.: 70% - 100%). The 1-year and the estimated 7-year colostomy-free survivals were 85.9% (C.I.: 73.1% - 98.7%). CONCLUSIONS: Concurrent cisplatin plus fluorouracil and radiotherapy is associated with favourable local control rates and acute toxicity. Future investigations will be directed towards research into molecular biomarkers related to disease progression and resistance to chemo-radiotherapy and to the evaluation of new cytotoxic agents or targeted drugs, such as anti-epidermal growth factor receptor, concomitant to RT and to determining the role of intensity-modulated radiotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Adulto , Idoso , Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Humanos , Bombas de Infusão , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia de Intensidade Modulada , Indução de Remissão , Análise de SobrevidaRESUMO
OBJECTIVE: To evaluate concordance between prenatal and postnatal diagnosis of congenital talipes equinovarus (cTEV), rates of surgery and postnatal outcomes in relation to the prenatal classification of severity. STUDY DESIGN: This is a retrospective observational cohort study on fetuses with a prenatal diagnosis of cTEV between 2004 and 2018. All cases of isolated cTEV in singleton pregnancies were included. Postnatally, the Ponseti method was applied. Children were followed-up postnatally for at least two years, with a specific focus on neurodevelopmental outcome. RESULTS: The cohort included 81 fetuses with a prenatal diagnosis of cTEV confirmed postnatally in 86.4% of cases. Concordance between prenatal and postnatal assessment was good for both laterality and degree of severity (kâ¯=â¯0.61 and 0.66, respectively). The average Pirani score, number of casts and rates of Achilles tendon tenotomy were higher for III degree cTEV (pâ¯<â¯0.001). Within this group only, the rate of relapse was 11% and the rates of major surgery was 6%. The postnatal outcome was normal in 68.6% newborns, while 14% of cases had a diagnosis of minor additional findings and 17% had an impairment of neurological development. None of the outcome was statistically correlated to the prenatal assessment of laterality or degree. CONCLUSIONS: The accuracy of prenatal ultrasound for isolated cTEV is 86% with a false positive diagnosis of 14%. The grade of cTEV assigned prenatally correlates to postnatal severity and longer orthopedic rehabilitation in terms of number of casts and need of surgery. The assessment of the correlation between cTEV and neurological impairment requires further prospective studies on larger cohorts.
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Pé Torto Equinovaro , Moldes Cirúrgicos , Criança , Pé Torto Equinovaro/diagnóstico por imagem , Pé Torto Equinovaro/cirurgia , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Diagnóstico Pré-Natal , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The purpose of the study was to evaluate whether the mutational status of Kirsten rat sarcoma viral oncogene homolog (KRAS) or b-viral oncogene homolog B1 (BRAF) could be an independent prognostic factor in the subset of patients with colorectal cancer liver metastases (CRLM) who undergo complete liver resection. MATERIALS AND METHODS: A systematic literature review was performed to identify articles reporting relapse-free survival (RFS) and/or overall survival (OS) of patients who underwent complete liver resection for CRLM, stratified according to KRAS and BRAF mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis. RESULTS: Eleven studies, including 1833 patients, were eligible for the meta-analysis. Nine of them reported OS stratified according to KRAS mutation. The pooled analysis revealed that KRAS mutation was negatively associated with OS (HR, 1.674; 95% confidence interval [CI], 1.341-2.089; P < .001). Nine among 11 studies reported RFS stratified according to KRAS mutation and HRs in multivariate analysis were available in 7. In a pooled analysis, KRAS mutation was negatively associated with RFS (HR, 1.529; 95% CI, 1.287-1.817; P < .001). In 3 studies HRs of the multivariate analysis regarding the OS according to BRAF mutational status were also available, showing a negative association with OS (HR, 3.055; 95% CI, 1.794-5.204; P < .001). CONCLUSION: KRAS mutations are negatively associated with OS and RFS in patients who undergo complete liver resection for CRLM. A similar negative effect on OS was observed also for BRAF mutation, although fewer studies were included. These data support integration of KRAS and BRAF mutational status into a combined predictive score for prospective assessment of outcome after resection of CRLM in clinical studies.
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Neoplasias Colorretais/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Mutação , PrognósticoRESUMO
BACKGROUND: The aim of the study was to evaluate the response to and toxicity of pre-operative radiochemotherapy containing raltitrexed (Tomudex) for resectable rectal adenocarcinoma. PATIENTS AND METHODS: From November 2000 to June 2002, 18 consecutive patients staged T3 NO0N+ were treated with pre-operative chemotherapy (3 mg/m2 of raltitrexed on days 1, 19, 38) and concurrent radiotherapy (RT) (50.4 Gy) in 6 weeks, followed by radical surgery within 8 weeks. RESULTS: The treatment compliance was high. No major acute toxicity was reported. Concerning late toxicity, genitourinary adverse effects were prevalent. A complete response was observed in one patient (6%), partial response in eight (47%), stable disease in seven (41%) and progression in one case. Three-year actuarial disease-free and overall survival rates were 37% and 87.5%, respectively. CONCLUSION: Raltitrexed did not increase the pathological response rate compared with the rates obtained with use of preoperative RT alone and reported in the literature. Acute morbidity was low and acceptable, while late toxicity was considerable, prevalently concerning sexual dysfunction and urinary complications.
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Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Antimetabólitos Antineoplásicos/uso terapêutico , Quinazolinas/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Tiofenos/uso terapêutico , Adenocarcinoma/cirurgia , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Cuidados Pré-Operatórios , Quinazolinas/efeitos adversos , Neoplasias Retais/cirurgia , Tiofenos/efeitos adversosRESUMO
Cetuximab is a monoclonal antibody that is effective in the treatment of metastatic colorectal cancer (mCRC). Cetuximab blocks epidermal growth factor receptor (EGFR)-ligand interaction and inhibits downstream RAS-ERK activation. However, only some activating mutations in RAS affect cetuximab efficacy, and it is not clear what else mediates treatment success. Here we hypothesized that cetuximab induces immunogenic cell death (ICD) that activates a potent antitumor response. We found that cetuximab, in combination with chemotherapy, fostered ICD in CRC cells, which we measured via the endoplasmic reticulum (ER) stress response and an increase in phagocytosis by dendritic cells. ICD induction depended on the mutational status of the EGFR signaling pathway and on the inhibition of the splicing of X-box binding protein 1 (XBP1), an unfolded protein response (UPR) mediator. We confirmed the enhanced immunogenicity elicited by cetuximab in a mouse model of human EGFR-expressing CRC. Overall, we demonstrate a new, immune-related mechanism of action of cetuximab that may help to tailor personalized medicine.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Morte Celular/efeitos dos fármacos , Cetuximab/farmacologia , Neoplasias Colorretais/imunologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Animais , Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Calreticulina/efeitos dos fármacos , Calreticulina/metabolismo , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Morte Celular/imunologia , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/imunologia , Fluoruracila/administração & dosagem , Células HCT116 , Células HT29 , Humanos , Indóis/farmacologia , Irinotecano , Leucovorina/administração & dosagem , Camundongos , Panitumumabe , Fagocitose/imunologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Piridonas/farmacologia , Pirimidinonas/farmacologia , Sulfonamidas/farmacologia , Resposta a Proteínas não Dobradas , Vemurafenib , Proteína 1 de Ligação a X-Box/efeitos dos fármacos , Proteína 1 de Ligação a X-Box/imunologia , Proteína 1 de Ligação a X-Box/metabolismoRESUMO
Elevated levels of circulating chromogranin A (CgA), a protein stored in the secretory granules of many neuroendocrine cells and neurons, have been detected in the blood of patients with neuroendocrine tumors or heart failure. The pathophysiological role of increased secretion of CgA is unknown. Using mice bearing subcutaneous tumors genetically engineered to secrete CgA in circulation, we have found that increased blood levels of this protein prevent vascular leakage induced by tumor necrosis factor-alpha (TNF) in the liver venous system. Structure-activity studies, carried out with CgA fragments administered to normal mice, showed that an active site is located within residues 7-57 of CgA. Accordingly, an anti-CgA antibody directed to residues 53-57 inhibited the effect of circulating CgA, either endogenously produced or exogenously administered, on liver vessels. Studies of the mechanism of action showed that CgA inhibits TNF-induced VE-cadherin down-regulation and barrier alteration of cultured endothelial cells, in an indirect manner. Other effectors, such as thrombin and vascular endothelial growth factor were partially inhibited by CgA N-terminal fragments in in vitro permeability assays. These findings suggest that circulating CgA could help regulate the endothelial barrier function and to protect vessels against TNF-induced plasma leakage in pathological conditions characterized by increased production of TNF and CgA, such as cancer or heart failure.
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Síndrome de Vazamento Capilar/prevenção & controle , Permeabilidade Capilar/efeitos dos fármacos , Cromograninas/fisiologia , Fator de Necrose Tumoral alfa/toxicidade , Animais , Anticorpos Monoclonais/farmacologia , Antígenos CD , Sítios de Ligação , Caderinas/fisiologia , Síndrome de Vazamento Capilar/induzido quimicamente , Permeabilidade Capilar/fisiologia , Células Cultivadas/efeitos dos fármacos , Cromogranina A , Cromograninas/química , Cromograninas/genética , Cromograninas/farmacologia , Endotélio Vascular/citologia , Extravasamento de Materiais Terapêuticos e Diagnósticos/prevenção & controle , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Circulação Hepática/efeitos dos fármacos , Linfoma/metabolismo , Linfoma/patologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neoplasias/fisiopatologia , Fragmentos de Peptídeos/farmacologia , Precursores de Proteínas/metabolismo , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/fisiologia , Trombina/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
PURPOSE: Anal cancer is an uncommon malignancy, but its incidence is increasing worldwide. Chemoradiation is the standard primary treatment for patients with loco-regional limited disease. However, once patients develop metastatic spread, the prognosis is very poor. Human papillomavirus (HPV) is present in around 80 % of anal cancers, but its prognostic and/or predictive value is essentially unknown in this disease. METHODS: We retrospectively evaluated 50 patients with the diagnosis of anal squamous cell carcinoma treated at our institution with combined chemoradiotherapy for loco-regional limited disease. HPV status was evaluated from paraffin-embedded tumor tissues collected at the time of diagnosis by a polymerase chain reaction analysis. RESULTS: Among 50 patients, 42 (84 %) were HPV-positive. Thirty-two (64 %) patients were positive to genotype 16, two (4 %) to genotype 18, and three (6 %) to both 16 and 18. Lymph nodal involvement and clinical stage at diagnosis were more advanced for HPV-positive patients. After a median follow-up of 4 years (range 0.4-13.8), 46 (92 %) patients were alive. Overall, eight patients relapsed: One regional, one loco-regional, and six distant recurrences were observed. Four patients died of metastatic disease. Five-year disease-free survival (DFS) in HPV-positive and HPV-negative patients was 92.5 and 50.0 %, respectively (P < 0.01). In multivariate analysis, HPV-positivity was associated with a statistically significant better 5-year DFS (HR HPV+ vs HPV- 0.10; 95 % CI 0.02-0.50). Five-year overall survival in HPV-positive and HPV-negative patients was 93.3 and 66.7 %, respectively (P = 0.12). CONCLUSIONS: In our study, HPV-positive anal cancers had a statistically significant improved DFS compared to HPV-negative group.
Assuntos
Alphapapillomavirus/genética , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Infecções por Papillomavirus/terapia , Idoso , Alphapapillomavirus/fisiologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/virologia , Carcinoma de Células Escamosas/virologia , Quimiorradioterapia , DNA Viral/genética , Intervalo Livre de Doença , Feminino , Genótipo , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos da radiação , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/fisiologia , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
BACKGROUND: The aim of our study was to evaluate retrospectively in a large single institution setting all cases of lung resections for colorectal metastases from 1998 to 2008 and to assess clinicopathologic factors influencing outcome. METHODS: In all, 199 patients, 125 men and 74 women, with lung metastases of colorectal cancer, 120 colon and 79 rectum, underwent resection with curative intent; mean interval between primary surgery and lung metastasis was 35 months. Carcinoembryonic antigen preoperative value was abnormal in 52 patients; K-RAS wild-type was detected in 60 of 97 examined cases; 75 patients received preoperative or postoperative chemotherapy or both. A solitary lesion was described in 95 patients (47.7%), two or three metastases in 72 (36.2%), and more than three metastases in 26 (13.1%). Nodal status was reported in 130 patients (73%). One hundred twenty patients (60.3%) underwent wedge resection, 27 (13.6%) underwent segmentectomy, and 52 (26.1%) had lobectomy. An R0 resection was achieved in 178 cases (89.4%). RESULTS: Median overall survival was 4.2 years (95% confidence interval: 3.1 to 5.1) with a 5-year overall survival of 43% (95% confidence interval: 36% to 50%). An R1 resection (log rank p = 0.0001), thoracic nodal involvement (log rank p = 0.0002), and preoperative abnormal carcinoembryonic antigen value (log rank p < 0.001) were significantly associated with poor outcome in univariate analysis. In multivariate analysis, the same variables plus the number of lesions (single versus multiple, p = 0.04) were shown to affect outcome. CONCLUSIONS: An R0 resection, preoperative carcinoembryonic antigen, nodal involvement, and number of lesions represent strong prognostic factors in patient with lung metastases of colorectal cancer. The role of systemic treatments and biomolecular tests deserve future prospective investigations.
Assuntos
Neoplasias Colorretais/patologia , Neoplasias Pulmonares/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário/sangue , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Metastasectomia , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
We describe here a case of pure gastric yolk sac tumor (YST). A 62-year-old patient underwent gastrectomy with D2 dissection. The histological report confirmed the diagnosis of YST and that two of the 14 regional lymph nodes removed were metastatic. Three courses of PEB regimen chemotherapy were delivered subsequently. Three months later the patient experienced dysphagia from stenosis of the anastomosis and a computerized tomography scan showed tumor recurrence with peritoneal nodules; the patient died one year after surgery. The origin of gastric YST is unclear but involvement of migrating germ cells during embryonic development or multipotential neoplastic protoepithelial cells of the gastric mucosa have been suggested. Generally the prognosis of gastric YST is poor and the standard therapeutic approach beyond surgery is still uncertain.
RESUMO
PURPOSE: Squamous cell anal carcinoma (SCC) is an uncommon disease comprising only 1-5% of all intestinal tumours. SCC is now considered the prototype for the successful application of conservative treatment as chemoradiation instead of aggressive surgery. The EGFR status and k-ras mutations in SCC of the anal canal has not been well investigated. The purpose of our evaluation was to give information about this issue. METHODS: From June 1999 to December 2008, 32 patients affected by SCC were treated in our institution with chemotherapy containing Fluoropyrimidine and platinum salt concomitant with pelvic radiotherapy. Immunohistochemistry for EGFR and k-ras mutation was retrospectively evaluated. RESULTS: Twenty-six specimens were considered evaluable for biological objectives: K-ras mutation was performed in all cases, while EGFR in 12. In all cases of our series wild-type K-ras was observed. CONCLUSIONS: Such information is, in our knowledge, the Wrst reported in literature on this setting. This observation previously reported in other tumours has supported the effective use of EGFR-inhibitors in recurrent or metastatic disease. This observation could support the role of EGFR-inhibitors in the treatment of SCC.