PM2.5 exposure and risk of lung adenocarcinoma in women of Taiwan: A case-control study with density sampling.

BACKGROUND AND OBJECTIVE: The prevalence of smoking among women in Taiwan is <5%, but the incidence of lung cancer remains high. This study determined the association between PM2.5 (fine particulate matter with an aerodynamic diameter of ≤2.5 µm) exposure and lung cancer among women in Taiwan. METHODS: In total, 21,301 female lung cancer cases nationwide were newly diagnosed between 2012 and 2017. Each case was age-, sex- and calendar year-matched with four controls randomly selected from the general population. Allowing a latent period of 5 years, we estimated the PM2.5 and nitrogen dioxide (NO2 ) exposures for each individual according to the residential changes from 2000. We adopted self-reported smoking statuses for the cases, while those of controls were estimated using annual surveys in each residential county. We performed multiple logistic regression analyses to examine the associations between PM2.5 and NO2 exposures and incident lung cancer cases. RESULTS: The ORs of lung adenocarcinoma for the third (30.5-35.1 µg/m3 ), fourth (35.1-39.3 µg/m3 ) and fifth PM2.5 exposure quintiles (39.3-48.1 µg/m3 ) relative to the first quintile were 1.10 (95% CI: 1.04-1.16), 1.12 (95% CI: 1.06-1.19) and 1.10 (95% CI: 1.04-1.16), respectively, after adjusting for smoking, residence and comorbidities. A dose-response relationship (p = 0.004) was found. The associations persisted with a 10-year latency and were not detected for small-cell and squamous cell carcinoma after control for smoking. We did not observe a similar effect for NO2 exposure. CONCLUSION: Residential PM2.5 exposure higher than 30 µg/m3 was associated with an increased risk of lung adenocarcinoma in women of Taiwan.

The impacts of baseline ventilator parameters on hospital mortality in acute respiratory distress syndrome treated with venovenous extracorporeal membrane oxygenation: a retrospective cohort study.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a valuable life support in acute respiratory distress syndrome (ARDS) in adult patients. However, the success of VV-ECMO is known to be influenced by the baseline settings of mechanical ventilation (MV) before its institution. This study was aimed at identifying the baseline ventilator parameters which were independently associated with hospital mortality in non-trauma patients receiving VV-ECMO for severe ARDS. METHODS: This retrospective study included 106 non-trauma patients (mean age: 53 years) who received VV-ECMO for ARDS in a single medical center from 2007 to 2016. The indication of VV-ECMO was severe hypoxemia (PaO2/ FiO2 ratio < 70 mmHg) under pressure-controlled MV with peak inspiratory pressure (PIP) > 35 cmH2O, positive end-expiratory pressure (PEEP) > 5 cmH2O, and FiO2 > 0.8. Important demographic and clinical data before and during VV-ECMO were collected for analysis of hospital mortality. RESULTS: The causes of ARDS were bacterial pneumonia (n = 41), viral pneumonia (n = 24), aspiration pneumonitis (n = 3), and others (n = 38). The median duration of MV before ECMO institution was 3 days and the overall hospital mortality was 53% (n = 56). The medians of PaO2/ FiO2 ratio, PIP, PEEP, and dynamic pulmonary compliance (PCdyn) at the beginning of MV were 84 mmHg, 32 cmH2O, 10 cmH2O, and 21 mL/cmH2O, respectively. However, before the beginning of VV-ECMO, the medians of PaO2/ FiO2 ratio, PIP, PEEP, and PCdyn became 69 mmHg, 36 cmH2O, 14 cmH2O, and 19 mL/cmH2O, respectively. The escalation of PIP and the declines in PaO2/ FiO2 ratio and PCdyn were significantly correlated with the duration of MV before ECMO institution. Finally, the duration of MV (OR: 1.184, 95% CI: 1.079-1.565, p < 0.001) was found to be the only baseline ventilator parameter that independently affected the hospital mortality in these ECMO-treated patients. CONCLUSION: Since the duration of MV before ECMO institution was strongly correlated to the outcome of adult respiratory ECMO, medical centers are suggested to find a suitable prognosticating tool to determine the starting point of respiratory ECMO among their candidates with different duration of MV. TRIAL REGISTRATION: This study reported a health care intervention on human participants and was retrospectively registered. The Chang Gung Medical Foundation Institutional Review Board approved the study (no. 201601483B0 ) on November 23, 2016. All of the data were extracted from December 1, 2016, to January 31, 2017.

Thyroid hormone enhanced human hepatoma cell motility involves brain-specific serine protease 4 activation via ERK signaling.

BACKGROUND: The thyroid hormone, 3, 3', 5-triiodo-L-thyronine (T3), has been shown to modulate cellular processes via interactions with thyroid hormone receptors (TRs), but the secretory proteins that are regulated to exert these effects remain to be characterized. Brain-specific serine protease 4 (BSSP4), a member of the human serine protease family, participates in extracellular matrix remodeling. However, the physiological role and underlying mechanism of T3-mediated regulation of BSSP4 in hepatocellular carcinogenesis are yet to be established. METHODS: The thyroid hormone response element was identified by reporter and chromatin immunoprecipitation assays. The cell motility was analyzed via transwell and SCID mice. The BSSP4 expression in clinical specimens was examined by Western blot and quantitative reverse transcription polymerase chain reaction. RESULTS: Upregulation of BSSP4 at mRNA and protein levels after T3 stimulation is a time- and dose-dependent manner in hepatoma cell lines. Additionally, the regulatory region of the BSSP4 promoter stimulated by T3 was identified at positions -609/-594. BSSP4 overexpression enhanced tumor cell migration and invasion, both in vitro and in vivo. Subsequently, BSSP4-induced migration occurs through the ERK 1/2-C/EBPß-VEGF cascade, similar to that observed in HepG2-TRα1 and J7-TRα1 cells. BSSP4 was overexpressed in clinical hepatocellular carcinoma (HCC) patients, compared with normal subjects, and positively associated with TRα1 and VEGF to a significant extent. Importantly, a mild association between BSSP4 expression and distant metastasis was observed. CONCLUSIONS: Our findings collectively support a potential role of T3 in cancer cell progression through regulation of the BSSP4 protease via the ERK 1/2-C/EBPß-VEGF cascade. BSSP4 may thus be effectively utilized as a novel marker and anti-cancer therapeutic target in HCC.

Glucose-regulated protein 58 modulates ß-catenin protein stability in a cervical adenocarcinoma cell line.

BACKGROUND: Cervical cancer continues to threaten women's health worldwide, and the incidence of cervical adenocarcinoma (AD) is rising in the developed countries. Previously, we showed that glucose-regulated protein 58 (Grp58) served as an independent factor predictive of poor prognosis of patients with cervical AD. However, the molecular mechanism underlying the involvement of Grp58 in cervical carcinogenesis is currently unknown. METHODS: DNA microarray and enrichment analysis were used to identify the pathways disrupted by knockdown of Grp58 expression. RESULTS: Among the pathway identified, the WNT signaling pathway was one of those that were significantly associated with knockdown of Grp58 expression in HeLa cells. Our experiments showed that ß-catenin, a critical effector of WNT signaling, was stabilized thereby accumulated in stable Grp58 knockdown cells. Membrane localization of ß-catenin was observed in Grp58 knockdown, but not control cells. Using a transwell assay, we found that accumulated ß-catenin induced by Grp58 knockdown or lithium chloride treatment inhibited the migration ability of HeLa cells. Furthermore, an inverse expression pattern of Grp58 and ß-catenin was observed in cervical tissues. CONCLUSIONS: Our results demonstrate that ß-catenin stability is negatively regulated by Grp58 in HeLa cells. Overexpression of Grp58 may be responsible for the loss of or decrease in membranous ß-catenin expression in cervical AD.

Possible overdiagnosis of early-stage lung adenocarcinoma among never-smokers in Taiwan.

10-year survival for never-smokers with >1 cm but ≤3 cm AIS/BAC/MIA was not inferior to that of the matched referents, pointing to possible overdiagnosis. Clinicians might consider adhering to Lung-RADS and watchful waiting for these non-solid nodules. https://bit.ly/41U6kxs.

Salpingectomy for ectopic pregnancy reduces ovarian cancer risk-a nationwide study.

Recent studies propose fallopian tubes as the tissue origin for many ovarian epithelial cancers. To further support this paradigm, we assessed whether salpingectomy for treating ectopic pregnancy had a protective effect using the Taiwan Longitudinal National Health Research Database. We identified 316 882 women with surgical treatment for ectopic pregnancy and 3 168 820 age- and index-date-matched controls from 2000 to 2016. In a nested cohort, 91.5% of cases underwent unilateral salpingectomy, suggesting that most surgically managed patients have salpingectomy. Over a follow-up period of 17 years, the ovarian carcinoma incidence was 0.0069 (95% confidence interval [CI] = 0.0060 to 0.0079) and 0.0089 (95% CI = 0.0086 to 0.0092) in the ectopic pregnancy and the control groups, respectively (P < .001). After adjusting the events to per 100 person-years, the hazard ratio (HR) in the ectopic pregnancy group was 0.70 (95% CI = 0.61 to 0.80). The risk reduction occurred only in epithelial ovarian cancer (HR = 0.73, 95% CI = 0.63 to 0.86) and not in non-epithelial subtypes. These findings show a decrease in ovarian carcinoma incidence after salpingectomy for treating ectopic pregnancy.

Thyroid hormone receptor inhibits hepatoma cell migration through transcriptional activation of Dickkopf 4.

Triiodothyronine (T3) is a potent form of thyroid hormone mediates several physiological processes including cellular growth, development, and differentiation via binding to the nuclear thyroid hormone receptor (TR). Recent studies have demonstrated critical roles of T3/TR in tumor progression. Moreover, long-term hypothyroidism appears to be associated with the incidence of human hepatocellular carcinoma (HCC), independent of other major HCC risk factors. Dickkopf (DKK) 4, a secreted protein that antagonizes the canonical Wnt signaling pathway, is induced by T3 at both mRNA and protein levels in HCC cell lines. However, the mechanism underlying T3-mediated regulation of DKK4 remains unknown. In the present study, the 5' promoter region of DKK4 was serially deleted, and the reporter assay performed to localize the T3 response element (TRE). Consequently, we identified an atypical direct repeat TRE between nucleotides -1645 and -1629 conferring T3 responsiveness to the DKK4 gene. This region was further validated using chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA). Stable DKK4 overexpression in SK-Hep-1 cells suppressed cell invasion and metastatic potential, both in vivo andin vitro, via reduction of matrix metalloproteinase-2 (MMP-2) expression. Our findings collectively suggest that DKK4 upregulated by T3/TR antagonizes the Wnt signal pathway to suppress tumor cell progression, thus providing new insights into the molecular mechanism underlying thyroid hormone activity in HCC.

Potential of an age-stratified CA125 cut-off value to improve the prognostic classification of patients with endometrial cancer.

OBJECTIVE: It is not clear whether the prognostic value of pretreatment serum CA125 levels is independent or through association with other clinicopathological features in endometrial cancer. METHODS: All patients with endometrial cancer treated between 2000 and 2010 were retrospectively reviewed. The correlation of clinicopathological characteristics, CA125 and treatment outcomes was analyzed. Receiver operating characteristics (ROC) curves were used to determine the CA125 cut-off values. Cox proportional hazard regression was used for multivariate analysis. RESULTS: Of the 923 eligible patients, 757 had serum CA125 levels measured before treatment. We identified 264 (34.9%) patients with pretreatment serum CA125>35 U/mL. By multivariate analysis, advanced stage (P=0.001), serous or clear cell carcinoma (P=0.008), positive peritoneal cytology (P=0.042), and lymph node metastases (P=0.004) were significant risk factors for cancer-specific survival (CSS), while serum CA125>35 U/mL (P=0.067) was of borderline statistical significance. Using ROC curve stratified by age, we found that a serum CA125>35 U/mL was significant for CSS (HR=2.34, 95% CI=1.04-5.29) among patients >49 years old. After adjustment for confounding factors, serum CA125>105 U/mL was significant (HR=6.03, 95% CI=1.19-30.63) in patients ≤49 years old. CONCLUSIONS: These results suggest that an age-stratified cut-off level for CA125 (35 U/mL in patients >49 years old and 105 U/mL in patients ≤49 years old) can improve the prognostic stratification of patients with endometrial cancer.

Clinicopathologic parameters and immunohistochemical study of endometrial stromal sarcomas.

We aimed to investigate the clinicopathologic features, immunohistochemical studies, and prognosis in patients with endometrial stromal sarcoma (ESS). Clinical information was reviewed retrospectively for cases of ESS (1985-2009). A histologic review and immunohistochemical staining for the estrogen receptor, progesterone receptor, c-Kit, CD-10, Ki-67, and m-TOR were performed. Sixty-one patients (median age, 44 y; range, 22-71) were eligible for analysis (1988 International Federation of Gynecology and Obstetrics Stage I, 43; Stage II, 2; Stage III, 11; Sage IV, 4; unstaged, 1). The median follow-up period for survivors was 73 mo. Of those, the patients who underwent an adnexectomy and a pelvic lymphadenectomy, 15% and 13%, respectively, revealed metastasis. There were 20 relapses/persistence, including 13 (65%) in the pelvis and abdomen and 7 (35%) in distant sites. Eight patients died from ESS at a median duration of 14.5 mo (range, 2-50 mo) after relapse. Five- and 10-yr cancer-specific survival (CSS) rates were 88% and 85%, respectively; and 5- and 10-yr progression-free survival rates were 69% and 57%, respectively. Stage, residual disease, and high proliferative index of Ki-67 were significant prognostic factors for both progression-free survival and CSS in a univariate analysis, in addition to mitotic index for CSS. Multivariate analysis selected only residual disease as an independent variable for progression-free survival and stage and residual disease for CSS. Our results support using clinical Stage I, no residual disease, low proliferative index of Ki-67, and estrogen receptor/progesterone receptor overexpression as potential biomarkers to select patients with ESS for fertility-preservation surgery (5 such patients were alive and free).

Estimation of disability free life expectancy in non small cell lung cancer based on real world data.

To quantify the societal impact of disability in patients with non-small cell lung cancer (NSCLC), this study estimated the disability-free life expectancy (DFLE), loss-of-DFLE and explored their associations with quality-adjusted life expectancy (QALE) and loss-of-QALE. We interlinked national databases and applied a rolling-over algorithm to estimate the lifetime survival function for patients with NSCLC. Using the EuroQOL-5 Dimension (EQ-5D) and Barthel index (BI), we repeatedly measured the quality-of-life and disability functions of NSCLC patients who visited our hospital from 2011 to 2020. Age-, sex-matched referents were simulated from lifetables of the same calendar year of diagnosis. We categorized BI scores ≤ 70 as in need of long-term care and constructed linear mixed models to estimate the utility values and disability scores. We collected 960 cases and 3088 measurements. The proportions of measurements without disability at age 50-64 and in stage I-IIIa, 50-64 and stage IIIb-IV, 65-89 and stage I-IIIa and 65-89 and stage IIIb-IV were 97.3%, 89.3%, 94.8%,78.3%, corresponding to DFLEs of 15.3, 2.4, 6.8, 1.2 years and losses-of-DFLE of 8.1, 20.7, 4.0, 8.6 years, respectively, indicating that advanced stage had a stronger effect than old age. Survivors in advanced stages showed increased demands for assistance in almost all subitems. The DFLEs seemed to be approximate to the QALEs and the latter were shorter than the former due to discomfort and depression. From a societal perspective, future health technology assessment should consider the impact of lifetime duration of functional disability. Early diagnosis of NSCLC may decrease the burden of long-term care.

Losses of lifetime employment duration and productivity for patients with different subtypes and stages of lung cancer.

BACKGROUND: How different subtypes and stages of lung cancer affect morbidity- and mortality-associated productivity have not been investigated. This study quantified the losses of lifetime employment duration and productivity among patients with various subtypes and stages of lung cancer. METHODS: We identified nationwide lung cancer patients diagnosed at the ages of 50-64 between 2011 and 2019. Monthly survival probabilities were weighted by monthly employed-to-population ratios and working salaries to estimate lifetime employment duration and productivity. We compared lifetime employment duration and productivity of patients with those of the age-, sex-, calendar year-matched general population for losses of lifetime employment duration and productivity, which were multiplied by pathology and stage shifts based on the first-round screening of Taiwan Lung Cancer Screening in Never Smoker Trial (TALENT) to calculate the savings of lifetime employment duration and productivity. RESULTS: Lung cancer patients had shorter survival and employment duration than the referents. Patients with lung cancers other than adenocarcinoma experienced greater losses of lifetime employment duration and productivity as compared to adenocarcinoma patients. Applying the estimations of never-smoking patients to 100 lung cancer patients with pathology and stage shifts based on the TALENT, the savings of lifetime employment duration and productivity were 132.2 (95% prediction interval: 116.2-147.4) years and 3353 (95% prediction interval: 2914-3802) thousand US dollars, respectively. CONCLUSIONS: Early diagnosis of lung cancer would save the losses of employment duration and lifetime productivity. Future evaluation of the cost-effectiveness of lung cancer screening could consider incorporating these societal impacts.

Endometrial Cancer Detection Using a Cervical DNA Methylation Assay (MPap) in Women with Abnormal Uterine Bleeding: A Multicenter Hospital-Based Validation Study.

BACKGROUND: We describe a DNA methylation assay, named MPap test, using cervical scraping as an alternative technique for endometrial cancer detection. METHODS: A multicenter hospital-based, two-stage validation study was conducted to validate the cancer detection performance of the MPap test. The MPap value was determined from the DNA methylation status of two genes (BHLHE22, CDO1) and combined with two other clinical variables (age, BMI). The cutoff threshold of the MPap value was established in stage 1 and validated in stage 2. A total of 592 women with abnormal uterine bleeding were enrolled from five medical centers throughout Taiwan. RESULTS: In stage 1, the sensitivity, specificity, and positive and negative predictive values of the MPap test for detecting endometrial cancer were 92.9%, 71.5%, 39.8%, and 98.0%, respectively. These values were validated in stage 2, being 92.5%, 73.8%, 40.2%, and 98.1%. Moreover, MPap outperformed transvaginal ultrasound in sensitivity and negative predictive values for detecting endometrial cancer. When we applied the algorithm for triage of endometrial cancer detection by MPap in the Taiwan National Health Insurance dataset, we found that it may reduce invasive procedures by 69~73%. CONCLUSIONS: MPap may provide a feasible alternative for endometrial cancer detection and can be considered as a triage test to reduce unnecessary invasive procedures.

Glucose-regulated protein 58 modulates cell invasiveness and serves as a prognostic marker for cervical cancer.

Human papilloma virus infection is critical but not sufficient to cause cervical cancer. Molecular markers of cervical carcinogenesis are essential. The aim of this study was to identify aberrantly expressed proteins in cervical cancer and determine their clinical significance. A two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomic strategy was used for screening candidate proteins. Immunoblotting and immunohistochemical (IHC) analyses were performed to confirm the results of 2-DE, and the clinical significance was estimated. Glucose-regulated protein 58 (Grp58) was overexpressed in 73% of cancers. The IHC staining showed that the Grp58 histoscore was significantly higher in patients with adenocarcinoma (AD) compared with squamous cell carcinoma (P < 0.05). Grp58 staining was intense in AD with a penetration depth greater than half of the cervical stroma (P = 0.033). High Grp58 expression was associated with low overall survival and recurrence-free survival (RFS) rates (P = 0.007 and P = 0.013, respectively). In multivariate analysis, high Grp58 expression (P = 0.042) and lymph node metastasis (P = 0.026) were determined as independent prognostic factors for RFS. Patients exhibiting both high Grp58 expression and lymph node metastasis displayed poorer outcomes than the other patient groups. In functional studies, knockdown of Grp58 in HeLa cells led to decreased cell invasiveness and inhibition of lung metastasis in a xenograft mouse model. In conclusion, Grp58 serves as a potent prognostic factor of cervical AD. Estimation of the Grp58 index in conjunction with the lymph node metastasis status might aid in predicting the prognosis of cervical AD.

Overexpression of gelsolin in human cervical carcinoma and its clinicopathological significance.

OBJECTIVES: Cervical carcinoma is the second most common cause of death from gynecological cancers worldwide. Knowledge of the molecular mechanisms underlying the tumorigenesis of cervical cancer cell, except human papilloma virus infection, is limited. METHODS: A microarray was used to study the differential expression of genes in cancerous tissues to identify new molecular markers for diagnosis and prognosis. Their differential expression was confirmed with Western blotting and immunohistochemical analyses. The clinical correlations and prognostic significance of the aberrantly expressed proteins were evaluated to identify novel biomarkers of cervical cancer. RESULTS: The expression of gelsolin was significantly upregulated in 78% of patients with cervical cancer, and gelsolin was selected for further study. Gelsolin expression was stronger in cervical tumor tissues than in the surrounding noncancerous tissues (P<0.001). Gelsolin expression in the plasma of cervical cancer patients was increased 2.2-fold compared with that of healthy control subjects (P<0.001). The levels of plasma gelsolin in the early and late stages were significantly different (P=0.006). According to immunohistochemical analysis, increased gelsolin expression was associated with histological type and FIGO stage II. The 5-year overall survival and recurrence-free survival rates for the low-expression group (cut-off=115) were significantly higher than those of the high-expression group. Cancer cells with reduced gelsolin expression exhibited reduced migration and proliferation. CONCLUSIONS: These results provide strong evidence that gelsolin plays an important role in cellular proliferation and migration in cervical cancer and suggest that gelsolin is a promising marker for cervical cancer screening and prognosis.

Acute Mesenteric Vein Thrombosis in a Pregnant Patient at 10 Weeks Gestation: A Case Report.

Acute abdominal pain during pregnancy is challenging, both from a diagnostic and management perspective. A non-localized, persistent pain out of proportion to physical examination is a sign that advanced imaging may be necessary. Mesenteric venous thrombosis in a pregnant patient is extremely rare, but if diagnosis is delayed, can be potentially fatal to both the mother and the fetus. We present here a pregnant patient in the tenth week of gestation with classic clinical manifestations of mesenteric vein thrombosis and the corresponding findings on magnetic resonance imaging (MRI) and computed tomography (CT).

(18)F-FDG PET in stage IB/IIB cervical adenocarcinoma/adenosquamous carcinoma.

PURPOSE: The diagnostic and prognostic value of (18)F-FDG PET in cervical adenocarcinoma/adenosquamous carcinoma (AC/ASC) is unclear. The aim of this study was to assess the value of PET in the management of cervical AC/ASC. METHODS: Patients with resectable FIGO stage IB/IIB cervical AC/ASC receiving a preoperative MRI scan and a PET or PET/CT scan before radical surgery were eligible. Diagnostic efficacy was compared by receiver operating characteristic (ROC) analysis. Correlations between clinicopathological parameters and outcome and maximum standardized uptake values (SUVmax) of FDG uptake were evaluated. RESULTS: The study group comprised 83 patients (mean age 48.3 + or - 9.7 years) Five-year overall survival was 85.5%, with a median follow-up time of 38.6 months (range 2.8-87.2 months). Pelvic lymph node (PLN) and paraaortic lymph node (PALN) metastases were seen in 32.5% and 8.4% of patients, respectively. The difference in diagnostic efficacy in identifying metastatic PALN between PET and MRI was significant (PET versus MRI, area under the curve 0.832 versus 0.607, p=0.039). SUVmax in primary tumour was correlated with LN metastasis and deep stromal invasion. Overall survival was significantly related to FIGO stage, PLN metastasis, deep cervical stromal invasion, tumour size measured by MRI, and SUVmax of the primary cervical tumour. CONCLUSION: PET provided significantly better diagnostic efficacy than MRI in detecting PALN metastasis. Poor prognostic factors in cervical AC/ASC were SUVmax of the primary cervical tumour >5.3, stage IIB, deep cervical stromal invasion, tumour size measured by MRI > or = 40 mm, and PLN metastasis.

Long-term follow up of cervical cancer patients with unexplained squamous cell carcinoma antigen elevation after post-therapy surveillance using positron emission tomography.

AIM: We aimed to define the long-term follow-up results in cervical cancer patients with unexplained squamous cell carcinoma antigen (SCC-Ag) elevation (negative conventional imaging studies, computed tomography or magnetic resonance imaging) after definitive treatment using positron emission tomography (PET). METHODS: Of the 27 women with unexplained SCC-Ag elevation, 13 died or were alive with disease (12 PET true-positive, one PET false-negative) in our previous report. In this study, we reported long-term follow-up results for all the 14 patients remaining cancer-free at cut-off of our previous analysis (seven with true-negative PET and two with false-positive PET, and five with true-positive PET having received successful curative salvage therapy). RESULTS: The seven patients with true-negative PET studies remained recurrence-free (median follow up, 70 months; range, 11-84). Two patients had pelvic inflammatory disease; their SCC-Ag levels returned to the normal range after eradication of infection. Two other patients had recurrent cystitis, and their SCC-Ag levels normalized at 5 and 36 months, respectively. The two patients with false-positive PET/computed tomography were disease-free 73.5 and 70 months from original PET studies, respectively. In contrast, of the five patients with successful salvage, two are alive without disease (at 80 and 86.7 months), one died of radiation cystitis at 54 months, and two died of their cancer subsequent to previous analysis. CONCLUSION: Cystitis or pelvic inflammatory disease may cause unexplained elevation of SCC-Ag after definitive treatment. A negative PET study usually indicates absence of disease. PET is a useful tool to identify curable recurrences, especially when SCC-Ag < 4 ng/mL.

Maintenance of pegylated liposomal doxorubicin/carboplatin in patients with advanced ovarian cancer: randomized study of an Asian Gynecologic Oncology Group.

OBJECTIVES: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. METHODS: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m², n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. RESULTS: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19-0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCA/non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11-1.18; p=0.091). CONCLUSIONS: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.

Myometrial invasion in endometrial cancer: diagnostic accuracy of diffusion-weighted 3.0-T MR imaging--initial experience.

PURPOSE: To assess the diagnostic accuracy of fused T2-weighted and high-b-value diffusion-weighted (DW) magnetic resonance (MR) images at 3 T for evaluation of myometrial invasion in patients with endometrial cancer. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. From May 2006 to October 2007, 48 consecutive patients aged 25-80 years (mean age, 57 years) who had endometrial cancer were prospectively enrolled for preoperative evaluation by using a 3-T MR unit. Two radiologists interpreted the depth of myometrial invasion on T2-weighted images, dynamic contrast material-enhanced MR images, and fused T2-weighted and DW MR images (b = 1000 sec/mm(2)). Statistical methods included kappa statistics for reader agreement, Pearson analysis for pathologic correlation, accuracy assessment, and receiver operating characteristic analysis for diagnostic performance comparison. Surgical pathologic findings were the reference standard. RESULTS: Reader agreement was excellent for fused T2-weighted and DW images (weighted kappa, 0.79), with a significant pathologic correlation regarding the depth of myometrial invasion (r = 0.94, P < .0001). For assessing any myometrial involvement, addition of fused T2-weighted and DW imaging to dynamic contrast-enhanced or dynamic contrast-enhanced and T2-weighted imaging was significantly better compared with dynamic contrast-enhanced imaging alone (P < .001) or dynamic contrast-enhanced and T2-weighted (P = .001) imaging; T2-weighted imaging combined with fused T2-weighted and DW imaging also was better than dynamic contrast-enhanced and T2-weighted imaging (P = .001). Tumor apparent diffusion coefficients were 0.60-1.32 x 10(-3) mm(2)/sec (median, 0.75 x 10(-3) mm(2)/sec), with no significant correlation with the depth of myometrial invasion (P = .31, r = -0.15). CONCLUSION: Fused T2-weighted and high-b-value DW images at 3 T can provide accurate information for preoperative evaluation of myometrial invasion.