Predictive value of SUVmax from initial 18F-FDG PET/CT scans for treatment outcomes in endometrial cancer patients undergoing fertility sparing management.

OBJECTIVE: To evaluate whether the maximum standardized uptake value (SUVmax) from initial 18F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) scans could be a predictor of complete response and recurrence in patients with endometrial cancer who are undergoing fertility sparing management. METHODS: We conducted a retrospective review of patients who were diagnosed with endometrial cancer through biopsy and chose to undergo fertility sparing management using progestin at the Asan Medical Center, from January 2011 to December 2020. Of these, 113 patients who had an 18-FDG-PET/CT scan before starting treatment were included in our study. We measured SUVmax and examined its correlation with complete response and time to progression after achieving complete response to progestin therapy. RESULTS: Of 113 patients, 73 (64.6%) achieved a complete response through fertility sparing management. The receiver operating characteristic curve analysis revealed that the optimal cut-off value of SUVmax for predicting complete response was 6.2 (sensitivity 79.5%, specificity 57.5%, p=0.006). After analyzing recurrence in the 73 patients who achieved complete response, we found that patients with an SUVmax value >6.2 had a significantly shorter time to progression compared with those with a value <6.2. (p=0.04). CONCLUSIONS: SUVmax values of PET-CT, along with other clinicopathological parameters, could be used to predict treatment response and recurrence risk in patients with stage I endometrial cancer undergoing fertility sparing management.

Genome-Wide Association Study to Identify Marker-Trait Associations for Seed Color in Colored Wheat (Triticum aestivum L.).

This study conducted phenotypic evaluations on a wheat F3 population derived from 155 F2 plants. Traits related to seed color, including chlorophyll a, chlorophyll b, carotenoid, anthocyanin, L*, a*, and b*, were assessed, revealing highly significant correlations among various traits. Genotyping using 81,587 SNP markers resulted in 3969 high-quality markers, revealing a genome-wide distribution with varying densities across chromosomes. A genome-wide association study using fixed and random model circulating probability unification (FarmCPU) and Bayesian-information and linkage-disequilibrium iteratively nested keyway (BLINK) identified 11 significant marker-trait associations (MTAs) associated with L*, a*, and b*, and chromosomal distribution patterns revealed predominant locations on chromosomes 2A, 2B, and 4B. A comprehensive annotation uncovered 69 genes within the genomic vicinity of each MTA, providing potential functional insights. Gene expression analysis during seed development identified greater than 2-fold increases or decreases in expression in colored wheat for 16 of 69 genes. Among these, eight genes, including transcription factors and genes related to flavonoid and ubiquitination pathways, exhibited distinct expression patterns during seed development, providing further approaches for exploring seed coloration. This comprehensive exploration expands our understanding of the genetic basis of seed color and paves the way for informed discussions on the molecular intricacies contributing to this phenotypic trait.

Genome-wide identification and characterization of the lettuce GASA family in response to abiotic stresses.

BACKGROUND: Lettuce is one of the most extensively farmed vegetables in the world, and it prefers cool growing conditions. High temperatures promote premature bolt formation, reducing quality and yield. The gibberellic acid-stimulated Arabidopsis (GASA) family genes play critical roles in plant growth, development, and stress responses. However, the biological functions of GASA proteins in lettuce have yet to be thoroughly investigated. RESULTS: Using genome-wide analysis, 20 GASAs were identified in lettuce including, three groups of LsGASA proteins based on the phylogenetic analysis. Except for one, all GASA proteins included a conserved GASA domain with 12 cysteine residues. Cis-element analysis showed that LsGASAs were closely associated with light, phytohormones, and stress resistance. Five segmental and three tandem duplication events were observed in the LsGASA family based on duplication analysis. GASA synteny analysis among lettuce, Arabidopsis, tobacco, and rice revealed that LsGASA5 is highly collinear with all species. Six of the 20 LsGASA showed increased expression patterns at specific time points in the shoot apical meristem when subjected to heat stress. According to gene expression analysis, the majority of GASA were highly expressed in flowers compared to other organs, and six GASA exhibited highly increased expression levels in response to NaCl, abscisic acid, and gibberellin treatment. Furthermore, LsGASA proteins are predominantly found in the plasma membrane and/or the cytosol. CONCLUSIONS: This study provides a comprehensive characterization of LsGASA genes for their diversity and biological functions. Moreover, our results will be useful for further studies on the function of lettuce GASA in abiotic stress- and heat-induced bolting signaling.

Immune checkpoint inhibitors with chemotherapy for primary advanced mismatch repair-deficient endometrial cancer: A cost-effectiveness analysis.

OBJECTIVE: The addition of immune checkpoint inhibitors (ICIs), pembrolizumab or dostarlimab, to paclitaxel and carboplatin (TC) has shown better response rates and survival outcomes for patients with primary advanced mismatch repair-deficient (MMRd) endometrial cancer (EC) in NRG-GY018 and RUBY, respectively. Nonetheless, the high cost of ICIs remains a major concern when implementing this strategy in the real world. This study aimed to determine the cost-effectiveness of pembrolizumab and dostarlimab with chemotherapy compared to TC for primary advanced MMRd EC. METHODS: We developed a Markov model including 6600 patients with primary advanced MMRd EC to simulate treatment outcomes. The initial decision points in the model were treatment with pembrolizumab with TC (PEM-TC), dostarlimab with TC (DOS-TC), and TC. Model probabilities, costs, and health utility values were derived with assumptions from published literature. Effectiveness was determined as average quality-adjusted life years (QALYs) gained. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: TC was the least costly strategy, whereas PEM-TC was the most effective strategy for primary advanced MMRd EC. TC was cost-effective based on a willingness-to-pay (WTP) threshold of $100,000/QALY compared with PEM-TC (ICER, $377,718/QALY), and DOS-TC exhibited absolute dominance (ICER, $401,859/QALY). PEM-TC was cost-effective when the cost of pembrolizumab 200 mg was reduced to $4361 (61% reduction). PEM-TC was selected in 16.5% with a WTP threshold of $300,000/QALY, but in <1% with a WTP threshold range of $100,000-200,000/QALY. CONCLUSION: PEM-TC can become cost-effective for primary advanced MMRd EC when the cost of pembrolizumab substantially decreases.

Conization before radical hysterectomy in patients with early-stage cervical cancer: A Korean multicenter study (COBRA-R).

OBJECTIVE: To investigate the impact of conization on survival outcomes and to identify a specific population that might benefit from conization before radical hysterectomy (RH) in patients with early-stage cervical cancer. METHODS: From six institutions in Korea, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who underwent primary type C RH between 2006 and 2021. The patients were divided into multiple groups based on tumor size, surgical approach, and histology. We performed a series of independent 1:1 propensity score matching and compared the survival outcomes between the conization and non-conization groups. RESULTS: In total, 1254 patients were included: conization (n = 355) and non-conization (n = 899). Among the matched patients with a tumor size of >2 cm, the conization group showed a significantly better 3-year disease-free survival (DFS) rate compared with the non-conization group when RH was conducted via minimally invasive surgery (MIS), in those with squamous cell carcinoma (96.3% vs. 87.4%, P = 0.007) and non-squamous cell carcinoma (97.0% vs. 74.8%, P = 0.021). However, no difference in DFS was observed between the two groups among the matched patients with a tumor size of ≤2 cm, regardless of surgical approach or histological type. In patients who underwent MIS RH, DFS significantly worsened as the residual tumor size increased (P < 0.001). CONCLUSION: Cervical conization was associated with a lower recurrence rate in patients with early-stage cervical cancer with a tumor size of >2 cm who underwent primary MIS RH. Cervical conization may be performed prior to MIS RH to minimize the uterine residual tumor.

Pathological findings and long-term prognosis in Korean BRCA1/2 mutation carriers undergoing risk-reducing salpingo-oophorectomy.

OBJECTIVE: Our study aimed to evaluate the incidence of pathological findings in asymptomatic Korean patients with BRCA1/2 pathogenic variants who underwent risk-reducing salpingo-oophorectomy and to assess their long-term prognosis. METHODS: We retrospectively analyzed the medical records of patients with a germinal BRCA1/2 pathologic variant who had undergone risk-reducing salpingo-oophorectomy at Asan Medical Center (Seoul, Korea) between January 2013 and December 2020. All pathologic reports were made based on the sectioning and extensively examining the fimbriated end of the fallopian tube (SEE/FIM) protocol. RESULTS: Out of 243 patients who underwent risk-reducing salpingo-oophorectomy, 121 (49.8%) had a BRCA1 mutation, 119 (48.9%) had a BRCA2 mutation, and three (1.2%) had both mutations. During the procedure, four (3.3%) patients with a BRCA1 mutation were diagnosed with serous tubal intraepithelial carcinoma (STIC) or serous tubal intraepithelial lesion (STIL), and another four patients (3.3%) were diagnosed with occult cancer despite no evidence of malignancy on preoperative ultrasound. In the BRCA2 mutation group, we found one (0.8%) case of STIC, but no cases of STIL or occult cancer. During the median follow-up period of 98 months (range, 44-104) for STIC and 54 months (range, 52-56) for STIL, none of the patients diagnosed with these precursor lesions developed primary peritoneal carcinomatosis. CONCLUSIONS: Risk-reducing salpingo-oophorectomy, in asymptomatic Korean patients with BRCA1/2 pathogenic variants, detected ovarian cancer and precursor lesions, including STIC or STIL. Furthermore, our follow-up period did not reveal any instances of primary peritoneal carcinomatosis, suggesting a limited body of evidence supporting the imperative need for adjuvant treatment in patients diagnosed with these precursor lesions during risk-reducing salpingo-oophorectomy.

Recent Improvement in Survival Outcomes and Reappraisal of Prognostic Factors in Pediatric Living Donor Liver Transplantation.

Living donor liver transplantation (LDLT) is a significant advancement for the treatment of children with end-stage liver disease given the shortage of deceased donors. The ultimate goal of pediatric LDLT is to achieve complete donor safety and zero recipient mortality. We conducted a retrospective, single-center assessment of the outcomes as well as the clinical factors that may influence graft and patient survival after primary LDLTs performed between 1994 and 2020. A Cox proportional hazards model was used for multivariate analyses. The trends for independent prognostic factors were analyzed according to the following treatment eras: 1, 1994 to 2002; 2, 2003 to 2011; and 3, 2012 to 2020. Primary LDLTs were performed on 287 children during the study period. Biliary atresia (BA; 52%), acute liver failure (ALF; 26%), and monogenic liver disease (11%) were the leading indications. There were 45 graft losses (16%) and 27 patient deaths (7%) in this population during the study period. During era 1 (n = 81), the cumulative survival rates at 1 and 5 years after LDLT were 90.1% and 81.5% for patients and 86.4% and 77.8% for grafts, respectively. During era 2 (n = 113), the corresponding rates were 92.9% and 92% for patients and 89.4% and 86.7% for grafts, respectively. During era 3 (n = 93), the corresponding rates were 100% and 98.6% for patients and 98.9% and 95.4% for grafts, respectively. In the multivariate analyses, primary diagnosis ALF, bloodstream infection, posttransplant lymphoproliferative disease, and chronic rejection were found to be negative prognostic indicators for patient survival. Based on generalized care guidelines and center-oriented experiences, comprehensive advances in appropriate donor selection, refinement of surgical techniques, and meticulous medical management may eventually realize a zero-mortality rate in pediatric LDLT.

Postnatal Imaging for Prediction of Outcome in Patients with Left-sided Congenital Diaphragmatic Hernia.

OBJECTIVE: To evaluate associations between postnatal imaging features and outcome of left-sided congenital diaphragmatic hernia, as defined by overall survival and a requirement for extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: Newborns diagnosed prenatally with left-sided congenital diaphragmatic hernia between January 2013 and September 2021 were studied retrospectively. The esophageal deviation index was newly defined as the largest diameter from the midline to deviated gastric tube divided by the largest transverse diameter of the thoracic cavity on the radiograph. Regression analyses were performed to identify postnatal imaging features associated with overall survival and a requirement for ECMO. The predictive power (ie, area under the curve [AUC] of a time-dependent receiver operating characteristic curve) of prenatal, postnatal, and intraoperative findings for predicting survival were calculated. RESULTS: Ninety-seven patients (54 males; mean gestational age, 38.3 ± 1.9 weeks; mean birth weight, 2956.5 ± 540.0 g) were analyzed. The esophageal deviation index (adjusted hazard ratio [HR], moderate [≥0.19 to <0.24], 6.427 [P = .029]; severe [≥0.24], 33.007 [P < .001]) and right pneumothorax (adjusted HR, 8.763; P = .002) were associated with overall survival and with a requirement for ECMO. Liver herniation on postnatal ultrasound also was associated with overall survival (P < .001) and need for ECMO (P = .001). In addition, the AUC for prediction of 1-year survival from postnatal ultrasound was comparable with that of prenatally or intraoperatively detected liver herniation (0.93; 95% CI, 0.88-0.97). CONCLUSIONS: The esophageal deviation index, right pneumothorax, and liver herniation observed by postnatal imaging have prognostic value in patients with left-sided congenital diaphragmatic hernia.

Effect of Colloidal Interactions and Hydrodynamic Stress on Particle Deposition in a Single Micropore.

Clogging is ubiquitous. It happens in a wide range of material processing and causes severe performance degradation or process breakdown. In this study, we investigate clogging dynamics in a single micropore by controlling the surface property of the particle and processing condition. Microfluidic observation is conducted to investigate particle deposition in a contraction microchannel where polystyrene suspension is injected as a feed solution. The particle deposition area is quantified using the images taken using a CCD camera in both upstream and downstream of the microchannel. Pressure drop across the microchannel is also measured. When the particle interaction is repulsive, the deposition occurs mostly in downstream, while an opposite tendency is identified when the particle interaction is attractive. More complex deposition characteristics are found as the flow rate is changed. Particle flux density and the ratio of lift force to colloidal force are introduced to explain the clogging dynamics. This study provides a useful insight to alleviate clogging issues by controlling the colloidal interaction and hydrodynamic stress.

Comparison of splenic vessel preserving distal pancreatectomy and the Warshaw technique for solid pseudopapillary neoplasm in children.

PURPOSE: Spleen-preserving distal pancreatectomy (SPDP) such as splenic vessel preservation (SVP) for solid pseudopapillary neoplasms (SPNs) in the body or tail of the pancreas in children prevents post-splenectomy infection and hematologic disorders. However, SVP could be technically challenging, and the Warshaw technique (WT) could be an alternative technique that has been reported to be safe and effective in adults. We, therefore, compared the perioperative outcomes of SVP and WT in pediatric patients. METHODS: We retrospectively reviewed the medical records of pediatric patients with SPN who underwent SPDP using SVP or WT between November 2002 and November 2018 at a large-sized tertiary referral center. RESULTS: Twenty-eight patients were included. Sixteen (57.1%) patients underwent SVP and 12 (42.9%) patients underwent WT. There were no significant differences in the baseline characteristics between the two groups. Postoperative complications occurred in 8 patients each in the SVP (50%), and the WT (66.7%) groups. Two (12.5%) in the SVP group and 1 (8.3%) in the WT group required additional intervention. During a median follow-up duration of 49 months, there were no significant differences in the incidence of splenic infarctions or perigastric varices between the two groups. CONCLUSIONS: There were no significant differences in the surgical outcomes between WT and SVP in pediatric patients with SPN. WT could be a safe and feasible alternative technique for SVP in challenging cases.

Effect of chilling acclimation on germination and seedlings response to cold in different seed coat colored wheat (Triticum aestivum L.).

BACKGROUND: Flavonoids can protect plants against extreme temperatures and ROS due to their antioxidant activities. We found that deep-purple seed coat color was controlled by two gene interaction (12:3:1) from the cross between yellow and deep-purple seed coat colored inbreds. F2:3 seeds were grouped in 3 by seed coat color and germinated under chilling (4 °C) and non-acclimated conditions (18 °C) for a week, followed by normal conditions (18 °C) for three weeks and a subsequent chilling stress (4 °C) induction. We analyzed mean daily germination in each group. Additionally, to study the acclimation in relationship to the different seed coat colors on the germination ability and seedling performances under the cold temperatures, we measured the chlorophyll content, ROS scavenging activity, and expression levels of genes involved in ROS scavenging, flavonoid biosynthetic pathway, and cold response in seedlings. RESULTS: The results of seed color segregation between yellow and deep purple suggested a two-gene model. In the germination study, normal environmental conditions induced the germination of yellow-seed, while under chilling conditions, the germination ratio of deep purple-seed was higher than that of yellow-colored seeds. We also found that the darker seed coat colors were highly responsive to cold acclimation based on the ROS scavenging enzymes activity and gene expression of ROS scavenging enzymes, flavonoid biosynthetic pathway and cold responsive genes. CONCLUSIONS: We suggest that deep purple colored seed might be in a state of innate pre-acquired stress response state under normal conditions to counteract stresses in a more effective way. Whereas, after the acclimation, another stress should enhance the cold genes expression response, which might result in a more efficient chilling stress response in deep purple seed seedlings. Low temperature has a large impact on the yield of crops. Thus, understanding the benefit of seed coat color response to chilling stress and the identification of limiting factors are useful for developing breeding strategies in order to improve the yield of wheat under chilling stress.

The Clinical Significance and Utility of HPV-DNA Testing in Korean Women with Atypical Glandular Cells in Cervical Pap Tests: An Analysis of 311 Cases at a Single Institution.

The aim of this study is to analyze the correlation between clinically significant histologic results and HPV in women with AGC in pap test. Of the 311 women confirmed as AGC, 111 women (35.7%) was identified as positive for HPV. In the AGC analysis, cervical lesions were significantly more common in HPV positive group compared to HPV negative group (61.2 vs. 10.5%, p < 0.001). In contrast, endometrial lesions were not associated with HPV infection (8.1 vs. 4.5%, p = 0.12). The HPV-DNA testing in women with AGC may be a useful tool for predicting clinically significant cervical lesions.

Continued medical treatment for persistent early endometrial cancer in young women.

OBJECTIVE: We aimed to investigate the effectiveness of continuing medical therapy in patients who did not achieve complete response (CR) despite 9 months of progestin treatment. We also sought to determine the prognostic factors associated with achieving CR among these patients. METHODS: We retrospectively analyzed 51 patients with presumed stage IA, grade 1 or 2 endometrioid adenocarcinoma who had persistent disease on biopsy performed at 9-12 months after at least 9 months of progestin-based therapy. Data on clinicopathological factors and oncological and obstetrical outcomes following continuous hormonal treatment were extracted from the patients' medical records and analyzed. Univariate and multivariate analyses for predicting CR were performed. RESULTS: Thirty-seven (72.5%) of 51 patients achieved CR after prolonged fertility-sparing treatment. Median time to CR from starting initial progestin was 17.3 months (range, 12.1-91.7 months). On univariate analysis, history of polycystic ovarian syndrome, histologic grade 2, and not achieving partial response (PR) until 12 months were significantly associated with failure to CR (odds ratio [OR], 6.188, 95% confidence interval [CI], 1.405-27.244, p = 0.018; OR, 9.722, 95% CI, 1.614-58.581, p = 0.013; and OR, 21.750, 95% CI, 4.016-117.783, p < 0.001, respectively). Multivariate analysis revealed that not achieving PR until 12 months was an independent prognostic factor predicting failure to CR after prolonged progestin therapy (OR, 21.803, 95% CI, 3.601-132.025, p = 0.001). CONCLUSIONS: Continued medical treatment is effective for persistent early endometrial carcinoma after at least 9 months of progestin therapy in young women who want to preserve their fertility.

Outcome of staging chest CT and identification of factors associated with lung metastasis in children with hepatoblastoma.

OBJECTIVES: To evaluate the outcome of staging chest CT and to identify clinicoradiological factors predictive of lung metastasis in patients with hepatoblastoma based on the 2017 PRE-Treatment EXTent of tumor (PRETEXT) system. METHODS: This bi-center study retrospectively identified patients diagnosed with hepatoblastoma between January 1998 and September 2019 in two tertiary hospitals. The primary outcome was the proportion of the patients who had lung metastasis at staging chest CT. The diagnostic accuracy of staging chest CT was calculated based on the 2017 PRETEXT criteria. The secondary outcome was the identification of factors predictive of lung metastasis using multivariable logistic regression. RESULTS: In total, 123 patients (median age, 1 year; interquartile range, 0-4 years; 59 female) were included. Among those, 28% (35/123; 95% confidence interval [CI], 21-37%) had lung metastasis at staging chest CT. The overall accuracy of staging chest CT was 96.8%. The proportion of lung metastasis in patients with stage I, II, III, and IV was 0%, 24% (12 of 49; 95% CI, 14-38%), 23% (9 of 40; 95% CI, 12-38%), and 56% (14 of 25; 95% CI, 37-73%), respectively. Multifocality (adjusted odds ratio, 6.7; 95% CI, 2.7-17.5; p < .001) and male sex (adjusted odds ratio, 3.1; 95% CI, 1.2-8.6; p = .02) were associated with the presence of lung metastasis. CONCLUSIONS: Twenty-eight percent of the patients with hepatoblastoma had lung metastasis at staging chest CT. Multifocality and male sex were predictive factors for lung metastasis on staging chest CT. KEY POINTS: • The proportion of lung metastasis in patients with hepatoblastoma was 28%. • The overall accuracy of staging chest CT was 97% based on the 2017 PRETEXT system. • Hepatic tumor multifocality and male sex were predictors of lung metastasis.

Effect of 5-azacytidine (5-aza) on UCP2 expression in human liver and colon cancer cells.

The function of the uncoupling protein 2 (UCP2) is different for each cancer cell. However, the mechanism of expression is still unclear. DNA methylation affects protein expression and is one factor that transforms normal cells into cancer cells. In this study, the hepatocellular carcinoma Hep3B and HepG2 cells and colorectal cancer HT-29 cells were treated with 5-azacytidine (5-aza), a DNA demethylation agent, to observe the modification of UCP2 expression and the methylation degree in the UCP2 promoter region. Promoter basal activity and degree of UCP2 expression were measured in Hep3B, HepG2, and HT-29 cells. In addition, methylation-specific PCR (MSP) was performed to investigate the degree of methylation in the UCP2 promoter region. The methylation region in the UCP2 promoter was confirmed based on bisulfite sequencing. In Hep3B cells in which UCP2 mRNA was not transcribed, the promoter basal activity was significantly higher than in HT-29 or HepG2 cells in which UCP2 mRNA was transcribed. Treatment with 5-aza increased UCP2 expression in Hep3B and HT-29 cells; however, the expression in HepG2 cells was unchanged. The UCP2 promoter in Hep3B cells has numerous methylated regions compared with HT-29 and HepG2 cells. The results of the present study revealed that inhibition of UCP2 expression in Hep3B cells was due to methylation of the promoter region. Investigating the mechanism that induces UCP2 expression in cancer cells is important to understand the function of UCP2, which could aid in cancer treatment.

Identification and analysis of a differentially expressed wheat RING-type E3 ligase in spike primordia development during post-vernalization.

KEY MESSAGE: We identified a RING-type E3 ligase (TaBAH1) protein in winter wheat that targets TaSAHH1 for degradation and might be involved in primordia development by regulating targeted protein degradation. Grain yield per spike in wheat (Triticum aestivum), is mainly determined prior to flowering during mature primordia development; however, the genes involved in primordia development have yet to be characterized. In this study, we demonstrated that, after vernalization for 50 days at 4 °C, there was a rapid acceleration in primordia development to the mature stages in the winter wheat cultivars Keumgang and Yeongkwang compared with the Chinese Spring cultivar. Although Yeongkwang flowers later than Keumgang under normal condition, it has the same heading time and reaches the WS9 stage of floral development after vernalization for 50 days. Using RNA sequencing, we identified candidate genes associated with primordia development in cvs. Keumgang and Yeongkwang, that are differentially expressed during wheat reproductive stages. Among these, the RING-type E3 ligase TaBAH1 (TraesCS5B01G373000) was transcriptionally upregulated between the double-ridge (WS2.5) stage and later stages of floret primordia development (WS10) after vernalization. Transient expression analysis indicated that TaBAH1 was localized to the plasma membrane and nucleus and was characterized by self-ubiquitination activity. Furthermore, we found that TaBAH1 interacts with TaSAHH1 to mediate its polyubiquitination and degradation through a 26S proteasomal pathway. Collectively, the findings of this study indicate that TaBAH1 might play a prominent role in post-vernalization floret primordia development.

Prenatal prognostic factors for isolated right congenital diaphragmatic hernia: a single center's experience.

BACKGROUND: Right-sided congenital diaphragmatic hernia (RCDH) is relatively rare compared with left-sided congenital diaphragmatic hernia (LCDH). Clinical data of RCDH, especially with respect to antenatal prediction of neonatal outcome, are lacking. The aim of this study was to report the treatment outcomes of patients with antenatally diagnosed RCDH and to evaluate the predictability of observed-to-expected lung area-to-head circumference ratio (O/E LHR) for perinatal outcomes, focused on mortality or extracorporeal membrane oxygenation (ECMO) requirement. METHODS: We retrospectively reviewed the medical records of newborn infants with isolated RCDH. We analyzed and compared the clinical and prenatal characteristics including the fetal lung volume, which was measured as the O/E LHR, between the survivors and the non-survivors. RESULTS: A total of 26 (66.7%) of 39 patients with isolated RCDH survived to discharge. The O/E LHR was significantly greater in survivors (64.7 ± 21.2) than in non-survivors (40.5 ± 23.4) (P =.027). It was greater in survivors without ECMO requirement (68.3 ± 15.1) than non-survivors or those with ECMO requirement (46.3 ± 19.4; P = .010). The best O/E LHR cut-off value for predicting mortality in isolated RCDH was 50. CONCLUSIONS: The findings in this study suggest that O/E LHR, a well-characterized prognostic indicator in LCDH, could be applied to a fetus with antenatally diagnosed RCDH. A large cohort study is required to verify the association between O/E LHR values and the graded severity of RCDH.

Functional and structural evaluation in the lungs of children with repaired congenital diaphragmatic hernia.

BACKGROUND: To evaluate the long-term functional and structural pulmonary development in children with repaired congenital diaphragmatic hernia (CDH) and to identify the associated perinatal-neonatal risk factors. METHODS: Children with repaired CDH through corrective surgery who were born at gestational age ≥ 35 weeks were included in this analysis. Those who were followed for at least 5 years were subjected to spirometry and chest computed tomography for evaluation of their functional and structural growth. Main bronchus diameters and lung volumes (total, left/right) were measured. According to total lung volume (TLV) relative to body surface area, children were grouped into TLV ≥ 50 group and TLV < 50 group and the associations with perinatal-neonatal factors were analyzed. RESULTS: Of the 28 children (mean age, 6.2 ± 0.2 years) with left-sided CDH, 7 (25%) had abnormal pulmonary function, of whom 6 (87%) showed restrictive patterns. All pulmonary functions except FEF25-75% were worse than those in matched healthy control group. Worse pulmonary function was significantly associated with small head and abdominal circumferences at birth. The mean TLV was 1339.1 ± 363.9 mL and LLV/TLV was 47.9 ± 2.5 mL. Children with abnormal pulmonary function were more likely to have smaller lung volumes. In multivariate analysis, abdominal circumference at birth was significantly associated with abnormal lung volume. CONCLUSIONS: A quarter of children with repaired CDH showed abnormal pulmonary function. Small abdominal circumference at birth was associated with abnormal pulmonary function and lower TLV. .

Assessment of native liver fibrosis using ultrasound elastography and serological fibrosis indices in children with biliary atresia after the Kasai procedure.

BACKGROUND: Validated non-invasive examinations are necessary to monitor liver fibrosis in children with biliary atresia (BA) after the Kasai procedure. PURPOSE: To evaluate the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE), transient elastography (TE), and the serologic biomarkers of aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score for evaluating native liver fibrosis in children with BA. MATERIAL AND METHODS: We retrospectively reviewed same-day 2D-SWE and TE liver stiffness (LS) measurements of 63 patients with BA who underwent the Kasai procedure. The APRI and FIB-4 score were computed. Hepatic fibrosis was categorized into three clinical categories based on the ultrasound (US) hepatic morphology and clinical manifestations of liver cirrhosis: I, pre-cirrhotic liver state (n = 15); II, US and/or clinical signs of liver cirrhosis with compensated liver function (n = 27); and III, liver cirrhosis with decompensated liver function (n = 21). We compared area under the receiver operating characteristic curve (AUC) data among 2D-SWE, TE, APRI, and FIB-4 score. Combined evaluation of serologic fibrosis indices and US elastography was conducted and AUCs of combinations were analyzed. RESULTS: 2D-SWE, TE, APRI, and FIB-4 score showed good to excellent diagnostic accuracy for differentiating clinical categories (AUCs 0.779-0.955). AUC values were significantly increased after adding TE to FIB-4 score for detecting liver cirrhosis (P = 0.02). CONCLUSION: 2D-SWE, TE, APRI, and FIB-4 score are accurate non-invasive markers for monitoring native liver fibrosis in patients with BA. Combined use of serologic markers and US elastography could yield more accurate diagnoses of liver fibrosis than serologic markers alone.

Real-world experience of olaparib as maintenance therapy in BRCA-mutated recurrent ovarian cancer.

PURPOSE: The primary objective of our study was to investigate the effectiveness and safety of olaparib maintenance therapy in patients with BRCA-mutated recurrent ovarian cancer in daily practice. The secondary objective of this study was to identify prognostic factors associated with prolonged progression-free survival (PFS) in such patients. METHODS: We conducted a retrospective analysis of 40 patients who received olaparib maintenance treatment. Data on clinicopathological factors, oncological outcomes, and adverse events were obtained from medical records and analyzed. RESULTS: All patients had high-grade serous recurrent ovarian cancer with BRCA mutation and achieved complete or partial response to the most recent platinum-based chemotherapy. After a median follow-up of 14.3 months, the median PFS was 23.7 months (95% confidence interval, 14.1-33.4); however, the median overall survival was not reached. In the log-rank test, the PFS was significantly longer for patients with most recent platinum-free interval (PFI) ≥ 12 months, complete response to the last platinum-based chemotherapy, and less than three lines of previous chemotherapy (p = 0.005, p = 0.016, and p = 0.023, respectively). Most hematologic and non-hematologic adverse events were of grade 1 or 2, and the common adverse events were mostly related to myelosuppression. CONCLUSION: Olaparib maintenance treatment in BRCA-mutated recurrent ovarian cancer is effective and safe in clinical practice. Most recent PFI, response to the last platinum-based chemotherapy, and the number of previous chemotherapy lines were associated with PFS in patients with BRCA-mutated recurrent ovarian cancer.