ABSTRACT
OBJECTIVE: To investigate whether isolated oligohydramnios at term is associated with increased rates of perinatal morbidity and mortality and whether induction of labor in term pregnancies with isolated oligohydramnios is superior to conservative management in reducing perinatal morbidity and mortality. STUDY DESIGN: We searched databases from inception to May 2015. We included studies that evaluated isolated oligohydramnios at term and perinatal outcome. Each outcome was analyzed separately, performing a comparative analysis between the study and control groups. RESULTS: Twelve studies were included with 35,999 women: 2,414 (6.7%) with isolated oligohydramnios and 33,585 (93.29%) with normal amniotic fluid index. Patients with isolated oligohydramnios had significantly higher rates of labor induction [odds ratio (OR) 7.56, confidence interval (CI) 4.58-12.48] and Cesarean sections (OR 2.07, CI 1.77-2.41). There were higher rates of an Apgar score <7 at 1 and 5 min (OR 1.53, CI 1.03-2.26, and OR 2.01, CI 1.3-3.09, respectively) and admission to the neonatal intensive care unit (OR 1.47, CI 1.17-1.84). There were no significant differences in cord pH <7.1 and meconium-stained amniotic fluid. In the single randomized trial comparing induction of labor with expectant management, no differences were found in any significant maternal or neonatal outcomes. CONCLUSION: Isolated oligohydramnios at term is associated with significantly higher rates of labor induction, Cesarean sections, and short-term neonatal morbidity.
Subject(s)
Labor, Induced , Oligohydramnios/diagnostic imaging , Adult , Amniotic Fluid , Cesarean Section , Delivery, Obstetric , Female , Humans , Odds Ratio , Oligohydramnios/mortality , Pregnancy , Pregnancy Outcome , Pregnancy Trimester, Third , Term BirthABSTRACT
Different tumor types vary greatly in their distribution of driver substitutions. Here, we analyzed how mutation and natural selection contribute to differences in the distribution of KRAS driver substitutions between lung, colon and pancreatic adenocarcinomas. We were able to demonstrate that both differences in mutation and differences in selection drive variation in the distribution of KRAS driver substitutions between tumor types. By accounting for the effects of mutation on the distribution of KRAS driver substitutions, we could identify specific KRAS driver substitutions that are more favored by selection in specific tumor types. Such driver substitutions likely improve fitness most when they occur within the context of the tumor type in which they are preferentially favored. Fitting with this, we found that driver substitutions that are more favored by natural selection in a specific type of tumor tend to associate with worse clinical outcomes specifically in that type of tumor.
Subject(s)
Adenocarcinoma/genetics , Colonic Neoplasms/genetics , Lung Neoplasms/genetics , Mutation Rate , Pancreatic Neoplasms/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Adenocarcinoma/pathology , Amino Acid Substitution , Codon , Colonic Neoplasms/pathology , Gene Expression , Humans , Lung Neoplasms/pathology , Organ Specificity , Pancreatic Neoplasms/pathology , Polymorphism, Genetic , Risk Factors , Selection, Genetic , Smoking/genetics , Smoking/physiopathologyABSTRACT
OBJECTIVES: Recent studies have demonstrated intratumor heterogeneity (ITH) for genetic mutations in various tumors and suggest that ITH might have significant clinical impact. Because KRAS is the most commonly mutated oncogene in pancreatic ductal adenocarcinoma and has an important role in pancreatic carcinogenesis, the purpose of this study was to evaluate ITH for KRAS gene mutation and its clinical significance. METHODS: Deep sequencing of 47 pancreatic ductal adenocarcinoma cases was used to determine the fraction of KRAS mutant alleles. In addition, computerized morphometry was used to calculate the fraction of tumor cells. After analysis of both results, cases were classified as ITH or as having amplification of mutant KRAS. The presence of ITH was correlated with clinical and pathological factors. RESULTS: KRAS mutation was found in 38 (81%) cases, of which 12 (32%) showed ITH and 9 (23%) were found to have KRAS mutant allele amplification. The presence of ITH was associated with smaller tumors, whereas amplification was associated with higher tumor diameter. CONCLUSIONS: In pancreatic ductal adenocarcinoma, ITH for KRAS gene mutation was associated with smaller tumors. It is possible that, as the tumor progresses, more cells carry this mutation, which leads to more aggressive tumor features.