In the nonclassical form (NC), good correlation has been observed between genotypes and 17OH-progesterone (17-OHP) levels. However, this correlation was not identified with regard to the severity of ...hyperandrogenic manifestations, which could depend on interindividual variability in peripheral androgen sensitivity. Androgen action is modulated by the polymorphic CAG tract (nCAG) of the androgen receptor (AR) gene and by polymorphisms in 5α-reductase type 2 (SRD5A2) enzyme, both of which are involved in the severity of hyperandrogenic disorders.
To analyze whether nCAG-AR and SRD5A2 polymorphisms influence the severity of the nonclassical phenotype.
NC patients (n = 114) diagnosed by stimulated-17OHP ≥10 ng/mL were divided into groups according to the beginning of hyperandrogenic manifestations (pediatric and adolescent/adult) and CYP21A2 genotypes (C/C: homozygosis for mild mutations; A/C: compound heterozygosis for severe/mild mutations).
CYP21A2 mutations were screened by allelic-specific PCR, MLPA and/or sequencing. HpaII-digested and HpaII-undigested DNA samples underwent GeneScan analysis to study nCAG, and the SRD5A2 polymorphisms were screened by RLFP.
Mean nCAG did not differ among pediatric, adolescent/adult and asymptomatic subjects. In the C/C genotype, we observed a significantly lower frequency of longer CAG alleles in pediatric patients than in adolescent/adults (p = 0.01). In patients carrying the A/C genotype, the frequencies of shorter and longer CAG alleles did not differ between pediatric patients and adolescent/adults (p>0.05). Patients with clitoromegaly had significantly lower weighted CAG biallelic mean than those without it: 19.1±2.7 and 21.6±2.5, respectively (p = 0.007), independent of the CYP21A2 genotype's severity. The SRD5A2 polymorphisms were not associated with the variability of hyperandrogenic NC phenotypes.
In this series, we observed a modulatory effect of the CAG-AR tract on clinical manifestations of the NC form. Although the NC form is a monogenic disorder, our preliminary data suggested that the interindividual variability of the hyperandrogenic phenotype could arise from polygenic interactions.
FLOT regimen became the standard perioperative treatment in several centers around the world for esophagogastric tumors despite concerns about toxicity. In addition, FLOT has never been compared with ...other docetaxel-based regimens. To address this question, we conducted a systematic review of PubMed, Embase and Web of Science including prospective or retrospective studies of docetaxel based perioperative regimen in gastric and esophagogastric tumors. Data regarding chemotherapy regimens, efficacy and toxicity were extracted. Outcomes were compared using a random effects model. Of 548 abstracts, 16 were considered eligible. Comparing the studies with meta-analysis we can see that the regimens are similar in terms of pathological complete response, resection rate, progression free survival and overall survival in one year, without significant heterogeneity. The meta-regression of docetaxel dose failed to show any association with dose ranging between 120-450 mg/m². Regarding the toxicity of the regimens it is noted that the regimens are quite toxic (up to 50-70% of grade 3-4 neutropenia). The results of this meta-analysis with a combined sample size of more than 1,000 patients suggest that docetaxel perioperative regimens are equivalent in outcomes. Prospective trials addressing modified regimens should be performed to provide less toxic strategies and be applicable to all patients.
This study is a meta-analysis of prior publications evaluating the impact of time-to-chemotherapy (TTC) on disease recurrence and survival 3 years after the original surgery.
We performed a ...meta-analysis of studies published in PubMed (1950-2016) as of April 2016. Inclusion criteria were as follows: randomized controlled trials and prospective or retrospective cohorts that included patients with ovarian cancer who had undergone surgery with curative intent and use of adjuvant chemotherapy. We compared rates of disease recurrence and death according to the TTC ("early" vs "delayed") using a random-effects model and performed a metaregression to evaluate the impact of covariates on these outcomes.
Of 239 abstracts in the original search, 12 were considered eligible. The cutoffs used for TTC were between 20 and 40 days. All studies used a platinum-based chemotherapy, and the rates of patients with suboptimal resection varied from 33% to 70%. A longer TTC was not associated with higher rates of disease recurrence (odds ratio, 0.89; 95% confidence interval, 0.63-1.24) or death at 3 years (odds ratio, 1.06; 95% confidence interval, 0.9-1.24). There was no evidence of significant publication bias (Egger test P = 0.472), but data were heterogeneous (I = 64.3%). Metaregression showed that the percentage of patients with suboptimal surgery and values used as cutoff to define "delayed" chemotherapy combined were a significant source of bias (residual I = 0%).
In our analysis, TTC after surgery for ovarian cancer with curative intent was not associated with higher risk of disease recurrence or death. However, this association was influenced by the rate of optimal debulking and definition of "late" initiation of chemotherapy, so we must be careful when applying these data to patients with complete resection.
Palliative sedation (PS) is an intervention to treat refractory symptoms and to relieve suffering at the end of life. Its prevalence and practice patterns vary widely worldwide. The aim of our study ...was to evaluate the frequency, clinical indications and outcomes of PS in advanced cancer patients admitted to our tertiary comprehensive cancer center.
We retrospectively studied the use of PS in advanced cancer patients who died between March 1st, 2012 and December 31st, 2014. PS was defined as the use of continuous infusion of midazolam or neuroleptics for refractory symptoms in the end of life. This study was approved by the Research Ethics Committee of our institution (project number 2481-15).
During the study period, 552 cancer patients died at the institution and 374 met the inclusion criteria for this study. Main reason for exclusion was death in the Intensive Care Unit. Among all included patients, 54.2% (n = 203) received PS. Patients who received PS as compared to those not sedated were younger (67.8 vs. 76.4 years-old, p < 0.001) and more likely to have a diagnosis of lung cancer (23% vs. 14%, p = 0.028). The most common indications for sedation were dyspnea (55%) and delirium (19.7%) and the most common drugs used were midazolam (52.7%) or midazolam and a neuroleptic (39.4%). Median initial midazolam infusion rate was 0.75 mg/h (interquartile range - IQR - 0.6-1.5) and final rate was 1.5 mg/h (IQR 0.9-3.0). Patient survival (length of hospital stay from admission to death) of those who had PS was more than the double of those who did not (33.6 days vs 16 days, p < 0.001). The palliative care team was involved in the care of 12% (n = 25) of sedated patients.
PS is a relatively common practice in the end-of-life of cancer patients at our hospital and it is not associated with shortening of hospital stay. Involvement of a dedicated palliative care team is strongly recommended if this procedure is being considered. Further research is needed to identify factors that may affect the frequency and outcomes associated with PS.
Breast reduction surgery is a common procedure and the rate of incidental findings in the removed specimens varies between 0% and 4.6%. There are no guidelines about pathological evaluation of breast ...reduction surgery. We reviewed all pathology reports of patients undergoing breast reduction surgery in a single tertiary institution in Brazil from January 2008 to August 2014. Exclusion criteria were a personal history of breast cancer, unclear reason for mastectomy and incomplete data on the pathology report. We considered “relevant findings” flat epithelial atypia, atypical hyperplasia, carcinomas in situ and invasive carcinoma. Of 1672 specimens from breast reduction surgery, 783 met inclusion criteria. Median patient age was 40 (8–77), 91% underwent bilateral mastectomy and 57% of the specimens weighted less than 200 g. In 55% of cases, 4 or more paraffin blocks were sampled. There were 40 (5.1%) relevant findings and the most common was atypical lobular hyperplasia (16–2%). There were 3 invasive carcinomas (0.38%). In multivariate analysis, the only variables associated with a higher odds of relevant pathological findings were patient age ≥ 40 (OR 4.73 CI95% 1.98–11.3
p
< 0.001) and sampling of ≥4 paraffin blocks from each specimen (OR 6.69 95% CI 2.25–19.9
p
< 0.001). The incidence of pre-malignant and malignant lesions in specimens from breast reduction surgery is around 5%, but this risk is significantly higher for patients older than 40 years-old. Sampling at least 4 paraffin blocks from each specimen significantly increases detection rates.
Frantz tumors or solid pseudopapillary pancreatic neoplasm (SPN) are rare exocrine neoplasms that carry a favorable prognosis; they represent up to 3% of all tumors located in the region of the ...pancreas and have specific age and gender predispositions. In recent years, the rising curve of diagnosis is entitled to the evolution and access of diagnostic imaging. In this paper, we have retrospectively reviewed and described the clinical course of 40 patients with SPN from three institutions in Brazil, who had their diagnosis between 2005 and 2020, and analyzed the clinicopathological, genetic, and surgical aspects of these individuals. In accordance with the literature, most patients were women, 60% with unspecified symptoms at diagnosis, with tumors mainly located in the body and tail of the pancreas, of whom 70% underwent a distal pancreatectomy with sparing splenectomy as a standard procedure, and none of the cases have experienced recurrence to date. Surgery still remains the mainstay of treatment given the low metastatic potential, but more conservative approaches as observed in this cohort are evolving to become the standard of care. Herein, we present an in-depth analysis of cases focusing on the latest literature and report some of the smallest tumor cases in the literature. To our knowledge, this is the first report evaluating germline genetic testing and presenting a case of detected Li-Fraumeni syndrome.
A comparative analysis of the association between sedentary behavior versus physical activity levels and tumor staging in women with breast cancer.
The present research adopted a cross-sectional ...study design to recruit a total of 55 adult and elderly women newly diagnosed with breast cancer for data collection and analysis. Inclusion criteria involved patients in procession of a formal approval for participation in the study by the treating physician and those not hitherto subjected to the first cycle of chemotherapy.
Physical activity levels did not influence the pathological stage of breast cancer (p=0.26) or histological tumor grade (p=0.07) in the analyzed subjects. However, there was a significant association between physical activity levels and responsiveness to hormones (epidermal growth factor receptor (HER2), p<0.05) in the analyzed subjects. Significant difference was detected in the histological tumor grade in relation to the mean time spent sitting during the weekend (p<0.05). However, sedentary behavior had no influence on the tumor stage (p>0.05).
Physical activity levels did not influence the tumor stage and histological tumor grade. Sedentary behavior had a significant influence on the histological tumor grade.
Immunotherapy-induced pneumonitis: cases report Helber, Henrique Alkalay; Hada, Aline Lury; Pio, Raquel Baptista ...
Einstein (São Paulo, Brazil),
06/2018, Letnik:
16, Številka:
2
Journal Article
Odprti dostop
Immunotherapy-induced pneumonitis is a rare complication with incidence estimated around 3%. This disease is difficult to diagnose and has great morbidity. For this reason, it became a challenge for ...oncologists and emergencists. We reviewed the case of five patients who used anti-PD1 (program cell death receptor antagonist 1) for antineoplastic treatment and developed treatment-induced pneumonitis. All patients had respiratory problems because of immunotherapy and presence of ground-glass radiologic change. Among all patients, only one had grade 5 pneumonitis, and delaying to begin corticosteroid therapy and worsening in clinical picture led to patient death. Other four patients with symptomatic grade 2 pneumonitis underwent corticosteroid therapy and had improvement in clinical and radiologic picture. Two patients were treated after an episode of pneumonitis, and no new pulmonary complications were observed until the end of this study. Immunotherapy-induced pneumonitis, although uncommon, can be potentially fatal. Medical team has the responsibility to pay attention for most common symptoms of the disease such as cough and dyspnea and conduct an early diagnosis and effective early treatment with corticosteroids.
Chemotherapy is the currently recommended first-line treatment for metastatic pancreatic cancer; however, few patients are eligible for aggressive treatment. We performed a meta-analysis with a ...combined sample size of 1461 patients and found that mFIO (modified FOLFIRINOX; leucovorin, 5-fluorouracil, irinotecan, oxaliplatin) regimens are associated with outcomes similar to those with regular FOLFIRINOX. The analysis results suggest that it is reasonable to consider mFIO for patients with metastatic pancreatic adenocarcinoma, increasing the patient population eligible for this regimen.
We performed a meta-analysis of previous reports evaluating the effect of mFIO (modified FOLFIRINOX; leucovorin, 5-fluorouracil, irinotecan, oxaliplatin) regimens in advanced pancreatic cancer.
We performed a meta-analysis of reported studies in PubMed, Scopus, and Web of Science (1950-2016) in December 2016. The inclusion criteria were randomized trials, prospective or retrospective cohorts, patients with metastatic pancreatic adenocarcinoma, the use of mFIO or FOLFIRINOX (FIO) chemotherapy, and available information for ≥ 1 efficacy endpoint (response rate, progression-free survival, and/or overall survival). The outcomes were compared according to the chemotherapy regimen using a random effects model. We also performed a meta-regression analysis to evaluate the effect of dose reductions on outcomes.
Of 2525 abstracts, 32 were considered eligible. Modifications in the FIO regimen included omission of the 5-fluorouracil bolus and/or dose reductions in infusional 5-fluorouracil, irinotecan, and/or oxaliplatin. mFIO was not associated with inferior response rates (32% vs. 33%; P = .879), lower rates of survival at 11 months (47% vs. 50%; P = .38), or lower 6-month progression-free survival rates (47% vs. 53%; P = .38). The meta-regression of the percentage of dose reduction failed to show any association.
The results of the present meta-analysis with a combined sample size of 1461 patients suggest that it is reasonable to consider mFIO regimens for patients with metastatic pancreatic adenocarcinoma.
Intravenous infusion of crystalloid solutions is a cornerstone of the treatment of hemorrhagic shock. However, crystalloid solutions can have variable metabolic acid-base effects, perpetuating or ...even aggravating shock-induced metabolic acidosis. The aim of this study was to compare, in a controlled volume–driven porcine model of hemorrhagic shock, the effects of three different crystalloid solutions on the hemodynamics and acid-base balance.
Controlled hemorrhagic shock (40% of the total blood volume was removed) was induced in 18 animals, which were then treated with normal saline (0.9% NaCl), Lactated Ringer's Solution or Plasma-Lyte pH 7.4, in a blinded fashion (n = 6 for each group). Using a predefined protocol, the animals received three times the volume of blood removed.
The three different crystalloid infusions were equally capable of reversing the hemorrhage-induced low cardiac output and anuria. The Lactated Ringer's Solution and Plasma-Lyte pH 7.4 infusions resulted in an increased standard base excess and a decreased serum chloride level, whereas treatment with normal saline resulted in a decreased standard base excess and an increased serum chloride level. The Plasma-Lyte pH 7.4 infusions did not change the level of the unmeasured anions.
Although the three tested crystalloid solutions were equally able to attenuate the hemodynamic and tissue perfusion disturbances, only the normal saline induced hyperchloremia and metabolic acidosis.
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