Clinicopathologic significance of mismatch repair protein expression in endometrioid endometrial cancer.

OBJECTIVE: To evaluate the association between mismatch repair (MMR) protein expression and clinico-pathologic outcomes in patients with endometrioid endometrial cancer (EC). MATERIALS AND METHODS: A retrospective review of the clinico-pathologic outcomes was performed on patients who were diagnosed with EC and had results of MMR protein immunohistochemistry. MMR-deficient (MMR-d) was defined as absence of expression in any of the 4 MMR proteins (MLH1, MSH2, MSH6, and PMS2). Demographics, pathologic variables, and survival outcomes were compared according to the MMR status. RESULTS: A total of 193 EC patients with available MMR expression data were included, of whom 163 patients had endometrioid type EC. Overall, 44 patients (27.0%) were classified as MMR-d. Compared with MMR-proficient (MMR-p) group, MMR-d group was associated with more frequent lymphovascular space invasion (LVSI, p = 0.001). MMR-d was also related with higher risk of lymph node (LN) metastasis in endometrioid type EC (p = 0.008), especially para-aortic LN metastasis. During the median follow-up period of 19.1 months (1-44.5), MMR-d group, especially MLH1/PMS2 subgroup, showed a tendency of reduced PFS (p = 0.036 and p = 0.008, respectively). On Cox regression analysis, however, LN metastasis remained as the only independent risk factor for PFS (p = 0.004) in endometrioid EC, and MLH1/PMS2 loss showed a marginally significant association (p = 0.054). CONCLUSION: Our findings of the associations between MMR deficiency and poor prognostic factors, such as LVSI and LN metastasis, may suggest the prognostic value of MMR status in EC and need further prospective validation studies.

Uncertainty Estimation of the Dose Rate in Real-Time Applications Using Gaussian Process Regression.

Major standard organizations have addressed the issue of reporting uncertainties in dose rate estimations. There are, however, challenges in estimating uncertainties when the radiation environment is considered, especially in real-time dosimetry. This study reports on the implementation of Gaussian process regression based on a spectrum-to-dose conversion operator (i.e., G(E) function), the aim of which is to deal with uncertainty in dose rate estimation based on various irradiation geometries. Results show that the proposed approach provides the dose rate estimation as a probability distribution in a single measurement, thereby increasing its real-time applications. In particular, under various irradiation geometries, the mean values of the dose rate were closer to the true values than the point estimates calculated by a G(E) function obtained from the anterior-posterior irradiation geometry that is intended to provide conservative estimates. In most cases, the 95% confidence intervals of uncertainties included those conservative estimates and the true values over the range of 50-3000 keV. The proposed method, therefore, not only conforms to the concept of operational quantities (i.e., conservative estimates) but also provides more reliable results.

A Bayesian Approach for Remote Depth Estimation of Buried Low-Level Radioactive Waste with a NaI(Tl) Detector.

This study reports on the implementation of Bayesian inference to improve the estimation of remote-depth profiling for low-level radioactive contaminants with a low-resolution NaI(Tl) detector. In particular, we demonstrate that this approach offers results that are more reliable because it provides a mean value with a 95% credible interval by determining the probability distributions of the burial depth and activity of a radioisotope in a single measurement. To evaluate the proposed method, the simulation was compared with experimental measurements. The simulation showed that the proposed method was able to detect the depth of a Cs-137 point source buried below 60 cm in sand, with a 95% credible interval. The experiment also showed that the maximum detectable depths for weakly active 0.94-µCi Cs-137 and 0.69-µCi Co-60 sources buried in sand was 21 cm, providing an improved performance compared to existing methods. In addition, the maximum detectable depths hardly degraded, even with a reduced acquisition time of less than 60 s or with gain-shift effects; therefore, the proposed method is appropriate for the accurate and rapid non-intrusive localization of buried low-level radioactive contaminants during in situ measurement.

Radioisotope Identification and Nonintrusive Depth Estimation of Localized Low-Level Radioactive Contaminants Using Bayesian Inference.

Obtaining the in-depth information of radioactive contaminants is crucial for determining the most cost-effective decommissioning strategy. The main limitations of a burial depth analysis lie in the assumptions that foreknowledge of buried radioisotopes present at the site is always available and that only a single radioisotope is present. We present an advanced depth estimation method using Bayesian inference, which does not rely on those assumptions. Thus, we identified low-level radioactive contaminants buried in a substance and then estimated their depths and activities. To evaluate the performance of the proposed method, several spectra were obtained using a 3 × 3 inch hand-held NaI (Tl) detector exposed to Cs-137, Co-60, Na-22, Am-241, Eu-152, and Eu-154 sources (less than 1µCi) that were buried in a sandbox at depths of up to 15 cm. The experimental results showed that this method is capable of correctly detecting not only a single but also multiple radioisotopes that are buried in sand. Furthermore, it can provide a good approximation of the burial depth and activity of the identified sources in terms of the mean and 95% credible interval in a single measurement. Lastly, we demonstrate that the proposed technique is rarely susceptible to short acquisition time and gain-shift effects.

A rare case of gastric-type mucinous adenocarcinoma in a woman with Peutz-Jeghers syndrome.

Adenocarcinoma of the cervix is less common than squamous cell carcinoma. Minimal deviation adenocarcinoma (adenoma malignum) is considered an extremely well-differentiated variant of GAS. An association exists between GAS and Peutz-Jeghers syndrome, which is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation and multiple hamartomatous polyps in the gastrointestinal tracts. The incidence of GAS in patients with Peutz-Jeghers syndrome is estimated to be 11-17%. We present a rare case of adenoma malignum, diagnosed using colposcopic biopsy in a woman with Peutz-Jeghers syndrome, which was histopathologically confirmed to be GAS after surgery.

Currarino syndrome in an adult woman.

Currarino syndrome is a hereditary disease characterized by the triad of sacral agenesis, anorectal malformation, and presacral mass. Most patients are diagnosed in childhood, and this condition rarely manifests in adulthood. In women, gynecological malformations associated with Currarino syndrome have been reported, such as bicornuate uterus, rectovaginal fistula, and septate uterus. We present a rare case of a 29-year-old woman with a suspected pelvic mass who was diagnosed with Currarino syndrome.

Clinical outcome of high-grade cervical intraepithelial neoplasia during pregnancy: A 10-year experience.

OBJECTIVE: To investigate the clinical outcome of high-grade cervical intraepithelial neoplasia (CIN) diagnosed by colposcopy-directed biopsy during pregnancy and to evaluate the risk factors for persistent disease. STUDY DESIGN: This retrospective study included pregnant women who were diagnosed with CIN2+ by colposcopy-directed biopsy from January 2005 to December 2014. The clinical characteristics, histopathologic results, and human papillomavirus (HPV) test results were reviewed. The final histopathologic result after delivery was compared with the initial diagnosis to determine disease progression, persistence, or regression. RESULTS: During the 10-year period, 215 pregnant women were diagnosed with high-grade CIN (75 CIN2, 140 CIN3) by colposcopy-directed biopsy. The mean age of the patients was 30.4 years. A total of 187 patients (87.0%) had high-risk HPV infections, with 76 (35.3%) infections identified as HPV genotype 16 or 18. Excisional procedures for diagnosis and treatment were not performed during pregnancy. The histopathologic results of 160 patients (normal in 43, CIN1 in 10, CIN2 in 15, CIN3 in 89, and invasive cancer in 3) were evaluated during the postpartum period. Multivariate logistic regression analysis was performed, and postpartum high-risk HPV infection (OR 5.09; 95% CI 2.15-12.05; P < 0.001) was identified as a significant independent predictor of CIN2+ persistence. CONCLUSIONS: Conservative management of CIN2-3 during pregnancy is acceptable. However, persistent high-risk HPV infection is a major risk factor for CIN2+ persistence. Close follow-up with HPV testing, and postpartum colposcopy evaluation are necessary.

Clinicopathological significance of atypical glandular cells on cervicovaginal Pap smears.

OBJECTIVE: To evaluate the histologic correlation and clinical significance of atypical glandular cells (AGC) detected on Pap tests. METHODS: Pap tests interpreted as AGC were retrieved from an institutional cytopathology database. The AGC subcategories according to the Bethesda system 2001 include atypical glandular cells, not otherwise specified (AGC-NOS), atypical endometrial cells (AEM), and atypical endocervical cells (AEC). Clinicopathologic variables were collected from medical records retrospectively, and histologic follow-up diagnoses were correlated with AGC subcategories. RESULTS: From January 2009 to December 2014, 741 (0.17%) of 435 778 cervical smears were interpreted as AGC. Of 713 cases included in the study analysis, the distribution of AGC subcategories was as follows: AGC 15.3%, AEM 59.6%, and AEC 25.1%. Of 508 cases with histologic follow-up results, 33.9% of cases were diagnosed to have clinically significant lesions, which include cervical squamous or glandular neoplasia (1.4% and 10.0%), endometrial neoplasia (21.5%), and other metastatic carcinoma (1.0%). Endometrial neoplasia was the most common significant pathology in women aged ≥40 years (28.4%), whereas cervical glandular neoplasia was the most commonly diagnosed lesion in women aged <40 years (14.5%, P < 0.001). When considering past histories which could affect the Pap results, IUD use (10.3%) and pregnancy (7.3%) were most frequently documented. Although IUD users showed low prevalence of significant pathology (2.6%), AGC cases related with pregnancy preceded significant pathologic lesions in 14.3%. CONCLUSIONS: The relatively high incidence of significant neoplasia linked to AGC emphasizes the importance of adherence to the AGC management guidelines which recommend early and intensive investigation using multiple testing modalities.

PLASTIC SCINTILLATOR FOR RADIATION DOSIMETRY.

Inorganic scintillators, composed of high-atomic-number materials such as the CsI(Tl) scintillator, are commonly used in commercially available a silicon diode and a scintillator embedded indirect-type electronic personal dosimeters because the light yield of the inorganic scintillator is higher than that of an organic scintillator. However, when it comes to tissue-equivalent dose measurements, a plastic scintillator such as polyvinyl toluene (PVT) is a more appropriate material than an inorganic scintillator because of the mass energy absorption coefficient. To verify the difference in the absorbed doses for each scintillator, absorbed doses from the energy spectrum and the calculated absorbed dose were compared. From the results, the absorbed dose of the plastic scintillator was almost the same as that of the tissue for the overall photon energy. However, in the case of CsI, it was similar to that of the tissue only for a photon energy from 500 to 4000 keV. Thus, the values and tendency of the mass energy absorption coefficient of the PVT are much more similar to those of human tissue than those of the CsI.

Toxicity of intraperitoneal chemotherapy and risk factors for severe toxicity in optimally debulked ovarian cancer patients.

OBJECTIVE: To assess the effect and toxicity of intraperitoneal (IP) chemotherapy for epithelial ovarian cancer and to determine the risk factors for severe toxicity. MATERIALS AND METHODS: Patients who received IP chemotherapy after optimal debulking surgery for ovarian cancer between 2006 and 2012 were retrospectively reviewed. Clinical characteristics were compared between patients with none/Grade 1 or Grade 2 toxicity and those with Grade 3 or Grade 4 toxicity. RESULTS: In 41 patients, the mean number of IP cycles administered was 5.6 and most patients (80.5%) completed at least six cycles. The reasons for discontinuation were catheter-related problems (30%), disease progression (20%), or drug-related adverse effects (30%). Grade 3 or Grade 4 toxicity was observed in 30 patients (73.2%). The rate of neoadjuvant chemotherapy was higher in the patients with Grade 3 or Grade 4 toxicity (37%) than in the patients without Grade 3 or Grade 4 toxicity (9%), however, this difference was not significant (p = 0.128). During a mean follow-up period of 33.6 months, tumor recurrence occurred in 20 (48.8%) patients and the median progression-free survival was 30.0 months. CONCLUSION: Despite the high rate of adverse events, IP chemotherapy can be delivered with a high completion rate and manageable toxicity to patients with optimally debulked ovarian cancer. Toxicity should be closely monitored in patients who have received neoadjuvant chemotherapy until a large prospective study can be performed to determine its influence.

Pregnancy Outcomes and Risk Factors for Uterine Rupture After Laparoscopic Myomectomy: A Single-Center Experience and Literature Review.

STUDY OBJECTIVE: To evaluate pregnancy outcomes after laparoscopic myomectomy (LSM), focusing on the risk of uterine rupture. DESIGN: Retrospective cohort study (Canadian Task Force classification III). SETTING: University hospital. PATIENTS: Of 676 women who visited the obstetrics department for a pregnancy after undergoing LSM performed at the same center between 1994 and 2012, we included the 523 women who had follow-up through the end of pregnancy. INTERVENTIONS: All patients underwent LSM, and their medical charts were retrospectively reviewed. MEASUREMENTS AND MAIN RESULTS: Multiple myomas were removed in 35.2% of cases, intramural-type lesions occurred in 46.5% of cases, and the mean myoma diameter was 4.9 cm. Pregnancy outcomes after LSM included 400 (76.5%) full-term deliveries and 100 (19.1%) vaginal deliveries, with other adverse outcomes being no different than the general population. The mean interval between LSM and pregnancy was 14 months, and only 3 (0.6%) cases of uterine rupture occurred during pregnancy. In analysis, by reviewing the published cases of uterine rupture, we found that the mean diameter, myoma number and type, and the rate of uterine suture were similar between the ruptured cases and all of our cases of LSM. CONCLUSION: LSM can be safely used in women of reproductive age who want to become pregnant. Uterine rupture occurs in rare cases, regardless of myoma features, but further large-scale studies are required to ascertain the detailed effects of various surgical techniques.

A multicenter study of the importance of systemic chemotherapy for patients with small-cell neuroendocrine carcinoma of the uterine cervix.

AIMS: We investigated the prognosis of patients with small-cell neuroendocrine carcinoma of the uterine cervix (SCNEC) in relation to treatment modalities. METHODS: We retrospectively reviewed the medical records and pathological reports of 102 patients who were histologically diagnosed with SCNEC at 5 different institutes. Time to progression (TTP) and overall survival (OS) were analyzed for each treatment modality. RESULTS: Of the patients with early-stage [International Federation of Obstetrics and Gynecology (FIGO) stage IB2 or below] SCNEC, 57.8 and 79.3% underwent radical hysterectomy followed by adjuvant therapy. In advanced-stage SCNEC, concurrent chemoradiation therapy was given to 51.4% of the patients. The overall recurrence rate was 51.6%. In early- and advanced-stage SCNEC, the TTP was not different (22.3 vs. 13.3 months, p = 0.104), but the OS was different (40.7 vs. 21.4 months, p = 0.029). Parametrial involvement and lymph vascular space invasion were found to be associated with an unfavorable prognosis. Interestingly, survival was the most unfavorable in patients with early-stage SCNEC who had never received chemotherapy. FIGO stage and use of chemotherapy were identified as independent prognostic factors in SCNEC patients. CONCLUSIONS: SCNEC requires systemic chemotherapy as part of the initial treatment, along with surgery or radiation, even in patients with early-stage disease.

Survival outcomes and toxicity of intraoperative intraperitoneal chemotherapy in advanced epithelial ovarian cancer.

OBJECTIVE: To assess the effect of single-dose cisplatin intraperitoneally administered during cytoreductive surgery in advanced epithelial ovarian cancer. METHODS: Data from patients who underwent surgical management followed by intravenous (IV) chemotherapy for stage III epithelial ovarian cancer from 2003 to 2012 were retrospectively reviewed. Subjects were divided into intraperitoneal (IP) and no-intraperitoneal (NIP) groups according to the administration of IP cisplatin 100 mg during the staging surgery. Clinical results such as survival outcomes and chemotherapeutic toxicity were compared between the two groups. RESULTS: Thirty-seven patients in the IP group and 26 in the NIP group were identified. There were no significant differences between the two groups in basic characteristics such as age, histology, and surgical procedures. After the surgery with or without IP chemotherapy, there was no difference in the rate of either hematologic or gastrointestinal toxicity or in the rate of incompletion of following IV chemotherapy. Tumor recurrence occurred in 67.6% (25 patients) of IP group and 57.7% (15 patients) of NIP group (P=0.423) during the mean follow-up period of 37 months. The 3-year disease free-survival rate was 39.9% in the IP group and 35.8% in the NIP group, and the relative risk of recurrence was 0.864 (95% confidence interval, 0.447-1.673; P=0.665) in the IP group as compared with the NIP group. CONCLUSION: IP chemotherapy with single-dose cisplatin during cytoreductive surgery is safe and feasible with little chemotherapeutic toxicity in advanced epithelial ovarian cancer, but no distinct improvement in survival could be demonstrated in the present study.

Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients.

Here, we demonstrate that electroporation-enhanced immunization with a rationally designed HPV DNA vaccine (GX-188E), preferentially targeting HPV antigens to dendritic cells, elicits a significant E6/E7-specific IFN-γ-producing T-cell response in all nine cervical intraepithelial neoplasia 3 (CIN3) patients. Importantly, eight out of nine patients exhibit an enhanced polyfunctional HPV-specific CD8 T-cell response as shown by an increase in cytolytic activity, proliferative capacity and secretion of effector molecules. Notably, seven out of nine patients display complete regression of their lesions and viral clearance within 36 weeks of follow up. GX-188E administration does not elicit serious vaccine-associated adverse events at all administered doses. These findings indicate that the magnitude of systemic polyfunctional CD8 T-cell response is the main contributing factor for histological, cytological and virological responses, providing valuable insights into the design of therapeutic vaccines for effectively treating persistent infections and cancers in humans.

Clinical experience in ovarian squamous cell carcinoma arising from mature cystic teratoma: A rare entity.

OBJECTIVE: We sought to investigate the clinicopathologic features of ovarian squamous cell carcinomas arising from mature cystic teratomas (MCT) and to report our clinical experience and lessons learned. METHODS: From January 1993 to November 2012, a total of 6,260 women with ovarian MCT were surgically treated at Cheil General Hospital and Women's Healthcare Center. Among them, the cases with malignant transformation to squamous cell carcinoma were included in this analysis. Patient demographic characteristics, surgical findings, and prognosis were evaluated retrospectively. RESULTS: Of the 6,260 ovarian MCT patients, four (0.06%) had ovarian squamous cell carcinoma arising from MCT. The mean patient age was 43 years (range, 35-51 years), and the mean tumor size was 12 cm (range, 9-16 cm), with two patients in the International Federation of Gynecology and Obstetrics stage I and the other two in stage III. Upon preoperative imaging, all cases were expected to be benign ovarian tumors, but the preoperative squamous cell carcinoma antigen level was elevated from 1.5 ng/mL in stage Ia to 11.3 ng/mL in stage IIIc, suggesting malignancy, while the CA-125 level was normal in two of the three patients who received the test. Optimal debulking surgery was performed and adjuvant chemotherapy was used in all patients, but death from the recurrence of disease occurred in one patient, whose overall survival was 10 months. CONCLUSION: Ovarian squamous cell carcinoma arising from MCT is extremely rare, and it is rarely diagnosed preoperatively on imaging workups. Measuring the squamous cell carcinoma antigen level might be a useful diagnostic clue, and it might also be predictive of the tumor stage. An adequate staging surgery should be included in the standard treatment, but multicenter studies are needed to confirm this.

Comparison of laparoscopy and laparotomy for the management of early-stage ovarian cancer: surgical and oncological outcomes.

OBJECTIVE: To investigate the surgical and oncological outcomes of laparoscopic surgery compared with laparotomy for the treatment of early-stage ovarian cancer. METHODS: Data from patients who underwent surgical management for early-stage ovarian cancer between 2006 and 2012 were retrospectively reviewed. All patients presented with stage I or II disease, and underwent comprehensive staging surgery consisting of a total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, omentectomy, and peritoneal cytology. RESULTS: Seventy-seven patients who underwent laparoscopic surgery (24 patients) or laparotomy (53 patients) were identified. Surgery for none of the patients was converted from laparoscopy to laparotomy. The mean operation time was shorter and the estimated blood loss was lower in the laparoscopy group than in the laparotomy group, though the differences were not statistically significant (193 min vs. 224 min, p=0.127; 698 mL vs. 973 mL, p=0.127). There were no differences in the intraoperative or postoperative complications. During a mean follow-up period of 31 months, tumor recurrence occurred in 4 patients: 2 (8.3%) in the laparoscopy group and 2 (3.8%) in the laparotomy group. The mean disease-free survival was 59 months after laparoscopy and 66 months after laparotomy (p=0.367). CONCLUSION: Laparoscopic surgery seems to be adequate and feasible for the treatment of early-stage ovarian cancer with comparable results to laparotomy in terms of the surgical outcomes and oncological safety.

Distribution and perinatal transmission of bacterial vaginal infections in pregnant women without vaginal symptoms.

BACKGROUND: We evaluated the distribution and vertical transmission of bacterial vaginal infections in asymptomatic pregnant women. METHODS: We performed multiplex PCR on secretions collected on cervical swabs from pregnant women at over 36 weeks of gestation and on oral secretions collected from their neonates immediately after delivery. We detected sexually transmitted infections (STIs) with the following 6 species: Trichomonas vaginalis, Mycoplasma hominis, Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, and Ureaplasma urealyticum. RESULTS: Infectious agents were detected in 64 of 455 pregnant women (14.1%) and in 11 neonates (2.4%). The rate of vertical transmission was 17.2% and all the infectious agents detected in neonates were concordant with those found in their mothers. U. urealyticum was the most frequently detected in the maternal genitalia, followed by M. hominis. Women who were in labor for a longer period of time had a higher risk of vertically transmitting STI agents to their neonates. CONCLUSIONS: Vertical transmission of bacterial STIs from mothers to their infants is possible at delivery and influenced by the duration of labor. STIs should be diagnosed in pregnant women to prevent vertical transmission from the mother to the infant at the time of delivery.

Endometrial Stromal Sarcomas: A clinico-pathological analysis of 27 patients.

OBJECTIVE: To evaluate clinico-pathological features and prognostic valuses of Endometrial stromal sarcomas (ESS) through comparison of the two grade groups (low- and high-grade disease). METHODOLOGY: We retrospectively analyzed the medical records of 27 patients who were diagnosed with ESS at a single institute between March 1988 and November 2009. Our retrospective chart review was approved by our local institutional Review Board (IRB). RESULTS: The median age of the patients was 44.0 years, the median follow-up period was 101.0 months and the 10-year survival rate was 74.2%. The median uterine weight was 215.0 gm. Twenty-three (70.4%) and four patients (29.6%) had low- and high-grade disease, respectively. As primary treatment, twenty-four (70.4%) and three patients (11.1%) underwent type I hysterectomy and type III hysterectomy, respectively. Total six cases were recurred and two cases of the six-recurred patients were distant metastasis (lung) and four cases were died of the disease. Univariate analysis revealed that the histologic grade and the uterine tumor weight were significantly related with longer disease-free survival (p=0.025 and 0.043 respectively). CONCLUSION: ESSs with high-grade or larger tumor size have to be carefully and sufficiently managed, because of its rarity and aggressive behavior. To determine the proper adjuvant treatment of ESS with high risks, further clinical data should be collected and studied.

Magnetic resonance imaging and intraoperative frozen sectioning for the evaluation of risk factors associated with lymph node metastasis in endometrial cancer.

INTRODUCTION: To analyze the accuracy of magnetic resonance imaging (MRI) and intraoperative frozen sectioning (IFS) for predicting the low- and high-risk patients and risk factors associated with lymph node (LN) metastasis in patients with surgically staged endometrial cancer. METHODS: The medical records of 175 patients with endometrial cancer who underwent comprehensive surgical staging including pelvic and para-aortic LN dissection between January 2008 and July 2011 were retrospectively analyzed. Results of MRI and IFS of the uterus for the evaluation of risk factors were correlated with final pathology. RESULTS: Our results showed a high specificity and negative predictive value of MRI and IFS for the evaluation of myometrial invasion and cervical stromal invasion. Of the 41 patients identified as low risk by both MRI and IFS, none had pelvic or para-aortic LN metastases in the final pathology. CONCLUSIONS: The results indicate that MRI and IFS may be useful for the evaluation of risk factors associated with LN metastasis in patients with endometrial cancer. Magnetic resonance imaging and IFS can be used to accurately identify low-risk patients who do not need comprehensive surgical staging and may prevent unnecessary lymphadenectomy.