Search

To evaluate safety and clinical outcomes of uterine artery embolisation (UAE) for bleeding after dilatation and curettage (DC) performed for abortion or termination.The outcomes were analysed in 11 patients who underwent UAE for bleeding after DC for missed abortions (n=8), caesarean scar pregnancies (n=2), or planned termination (n=1) between October 2001 and December 2013. Angiograms and medical records were retrospectively reviewed in order to obtain the patients' baseline characteristics, technical/clinical success rate, complications, and follow-up data regarding menstruation.Technical success, defined as successful catheterisation of both uterine arteries with embolisation to haemostasis, was 100%, whereas clinical success, defined as cessation of bleeding after the initial session of UAE and without the need for additional UAE or surgery for the purpose of haemostasis, was 81.8% (nine of 11). In the two patients with clinical failure due to recurrent vaginal bleeding after UAE, one patient underwent repeat UAE and showed a successful outcome, whilst the other patient required hysterectomy with pathological results of placenta increta. Two other patients underwent hysterectomy for placenta percreta or hydatidiform mole-mimicking remnant placenta. None of the patients included in the present series had procedure-related complications. Menstruation resumed in all eight patients with an intact uterus during the mean follow-up period.UAE may be a safe and effective treatment for bleeding after DC, especially for women who wish to preserve their fertility; however, hysterectomy may be indicated for patients with a placental abnormality.

The Jra antigen of the JR blood group system is a highly prevalent red blood cell antigen. Although anti-Jra-associated hemolytic disease of the fetus and newborn (HDFN) is generally considered mild-to-moderate, a rare fatal case was recently reported. We report the third example of HDFN-related anti-Jra with fatal outcomes. The clinical significance of anti-Jra antibody as a cause of HDFN should be reassessed.

The microRNA-200 (miR-200) family plays a major role in specifying epithelial phenotype by preventing expression of the transcription repressors ZEB1 and ZEB2, which are well-known regulators of the epithelial-to-mesenchymal transition (EMT) in epithelial tumors including oral squamous cell carcinoma (OSCC). Here, we elucidated whether miR-200 family members control RNA-binding protein quaking (QKI), a newly identified tumor suppressor that is regulated during EMT. We predicted that miR-200a and miR-200b could recognize QKI 3'-UTR by analyzing TargetScan and The Cancer Genome Atlas head and neck squamous cell carcinoma (HNSCC) dataset. Forced expression of miR-200b/a/429 inhibited expression of ZEB1/2 and decreased cell migration in OSCC cell lines CAL27 and HSC3. QKI expression was also suppressed by miR-200 overexpression, and the 3'-UTR of QKI mRNA was directly targeted by miR-200 in luciferase reporter assays. Interestingly, shRNA-mediated knockdown of QKI led to pronounced EMT and protumor effects in both in vitro and in vivo studies of OSCC. Furthermore, high expression of QKI protein is associated with favorable prognosis in surgically resected HNSCC and lung adenocarcinoma. In conclusion, QKI increases during EMT and is targeted by miR-200; while, it suppresses EMT and tumorigenesis. We suggest that QKI and miR-200 form a negative feedback loop to maintain homeostatic responses to EMT-inducing signals.

Objective This study was conducted to demonstrate the temporal trends in perinatal outcomes of triplet pregnancies over the last two decades. Methods The medical records of patients with triplet pregnancies at two Korean tertiary-care hospitals from 1992 to 2012 were retrospectively reviewed in regard to maternal and neonatal outcomes. The study was divided into two periods for analysis: period I (1992-2001) and period II (2003-2012). Results Over a 21-year period, 65 women with triplet pregnancies and 185 neonates were analyzed. Period II, when compared with period I, was associated with improved maternal outcomes, characterized by a decreased incidence of preeclampsia (31.8% vs. 2.3%, P=0.002) and anemia (68.2% vs. 30.2%, P=0.003) during pregnancy. Regarding neonatal aspects, the composite morbidity of period II was significantly decreased compared with that of period I, as assessed with a generalized estimating equation for logistic regression (26.2% vs. 8.1%, P=0.03). Multivariable analysis revealed that the gestational age at delivery and the period were significantly associated with the composite neonatal morbidity (P

Objectives: To evaluate the usefulness of chromosomal microarray analysis (CMA) in fetuses with dextro-transposition of the great arteries (d-TGA).Methods: Thirty-two fetuses with d-TGA were examined for submicroscopic copy number variations (CNVs) using CMA.Results: Among the 32 d-TGA fetuses, 23 had isolated lesions (71.9%) and nine had other cardiac or extracardiac anomalies (28.1%). CNVs were detected in 16/32 (50%) of the fetuses, including benign CNVs detected in nine fetuses (28.1%), pathogenic CNVs detected in three fetuses (9.4%), and variants of unknown significance (VOUS) detected in four fetuses (12.5%). There was no significant difference in the detection rates of pathogenic CNVs between the isolated and nonisolated groups. All four VOUS were found in the nonisolated group.Conclusion: CMA might be an effective tool for identifying submicroscopic chromosomal aberrations in fetuses with d-TGA.

Purpose Prenatal maternal stress affects offspring's atopic dermatitis (AD) development, which is thought to be mediated by the oxidative stress. We aimed to evaluate the difference in leukocyte telomere length (LTL), a marker for exposure to oxidative stress, according to the prenatal stress exposure and the later AD development. Methods From a birth cohort (the COhort for Childhood Origin of Asthma and allergic diseases) that had displayed a good epidemiologic association between the exposure to prenatal stress and AD development in the offspring, we selected 68 pairs of samples from 4 subject groups based on the level of prenatal maternal stress and later AD development. The LTL was measured from both cord blood and 1-year peripheral blood, and their LTLs were compared between subject groups. Finally, the proportion of AD development was examined in the subject groups that are reclassified based on subjects' exposure to prenatal stress and there LTL. Results Cord-blood LTL was shorter in prenatally stressed infants than in unstressed ones (P = 0.026), which difference was still significant when subjects became 1 year old (P = 0.008). LTL of cord blood, as well as one of the 1-year peripheral blood, was not different according to later AD development at 1 year (P = 0.915 and 0.174, respectively). Shorter LTL made no increase in the proportion of later AD development in either prenatally high-stressed or low-stressed groups (P = 1.000 and 0.473, respectively). Conclusions Cord-blood LTL may reflect subjects' exposure to maternal prenatal stress. However, the LTL shortening is not a risk factor of increasing AD development until the age of 1, and a longer investigation may be necessary for validation. Currently, the results doubt the role of LTL shortening as a marker for risk assessment tool for the prenatal stress associated with AD development in the offspring.

Background Dickkopf-1 (DKK1) is a Wnt/ß-catenin pathway antagonist related to gastric cancer (GC) carcinogenesis. However, the prognostic role of combined DKK1 and ß-catenin expression in advanced GC (AGC) is not clear. Methods In total, 158 patients with AGC who underwent gastric resection were enrolled in this study. DKK1 and ß-catenin expression was evaluated in whole tumor sections by immunohistochemistry. Results DKK1 expression was high in 73 (46.2%) patients, while ß-catenin expression was positive in 51 (32.3%) patients. The expression of DKK1 was positively correlated with that of ß-catenin (P

Objective The aim is to evaluate perinatal outcomes of fetal pleural effusion after thoracoamniotic shunting. Methods This was a retrospective study of 68 singleton pregnancies with massive fetal pleural effusion that underwent thoracoamniotic shunting between 1999 and 2012 at Asan Medical Center, Seoul, Korea. Through a review of medical records, we investigated perinatal outcomes according to the presence of fetal hydrops and identified prognostic factors by stepwise multivariate logistic regression analysis. Results Of the 68 pregnancies, three were lost to follow-up and two fetuses died in utero. The median gestational age at shunting was 28.3 weeks (range, 18.5-34.1 weeks). Of the 65 fetuses, 50 (76.9%) were hydropic, of which hydrops resolved following shunting in 29 fetuses (58.0%). Among the 63 live births, the median gestational age at delivery was 33.6 weeks (range, 26.2-40.0 weeks), with 36 fetuses (57.1%) delivered preterm. The overall survival rate was 75.4% (49/65), and in a subgroup analysis, the survival rate was highest for non-hydropic fetuses (14/15, 93.3%), followed by fetuses whose hydrops resolved (25/29, 86.2%) and remained after shunting (10/21, 47.6%). Conclusion Thoracoamniotic shunting can be helpful for fetuses with massive pleural effusion. While fetal hydrops can occur in such cases, perinatal outcomes can be improved by successful shunting.

The purpose of this paper is to discuss the minimal requirements of the routine mid-trimester anomaly scan in Asian countries after taking into account various factors, including local circumstances, medical practice, guidelines, and availability of experienced sonographers and high-resolution ultrasound machines, which affect the prenatal detection rate of fetal anomalies. In general, a routine mid-trimester anomaly scan includes the assessment of the number of fetuses, fetal cardiac activity, size, anatomy, liquor and placental location. The most controversial issue is which fetal structures should at least be examined. We discussed the requirements of a basic routine scan, as well as the optional views, which can be obtained if feasible to improve the detection of fetal, placental or maternal abnormalities. Routine anomaly scan remains a clinical challenge.

To the Editor, Breast cancer is not a single disease entity but rather a heterogeneous disease with various biological behaviors. Breast cancer subtypes can be identified by gene or protein expression profiling using immunohistochemistry (IHC). The expression patterns of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) as detected by IHC are important factors in determining treatment modalities such as hormone therapy, HER2-targeted therapy, and cytotoxic chemotherapy. In recent years, discordance in ER, PR, and HER2 statuses between primary and recurrent breast cancer has been reported, but the discordance rate varies highly. Generally, a change from positive to negative status for ER and PR is more common than a gain of receptor expression, and more patients gain rather than lose HER2 expression [1,2]. Here, we report the unusual case of a patient who was diagnosed initially with triple-negative breast cancer (TNBC) but whose cancer progressed as ER-positive diffuse skin metastases after a short time. A 38-year-old female visited our hospital with a palpable right breast mass in July of 2011. Breast magnetic resonance imaging (MRI) showed a nodular mass with a diameter of 4.0 cm in the upper outer quadrant of the right breast and multiple enlarged lymph nodes in the right axillary region. A core needle biopsy of the breast mass was performed. Pathological examination revealed a poorly differentiated invasive ductal carcinoma, which was negative for ER, PR, and HER2. F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) also showed a nodular mass and multiple lymph nodes with high FDG uptake (maximum standardized uptake value [SUVmax] 4.7) in the right breast and axillary region. There was no evidence of any other distant metastases. On the basis of these results, the patient was diagnosed with TNBC (cT2N3M0) and received three cycles of neoadjuvant chemotherapy with docetaxel and epirubicin. After the three cycles of chemotherapy, a partial response was confirmed by a breast CT scan, and the patient underwent a modified radical mastectomy in November of 2011. Histopathological examination revealed an invasive ductal carcinoma with necrosis and 11 metastatic lymph nodes among the 11 dissected axillary lymph nodes. We found lymphovascular invasion and tumor emboli in dermal lymphatic vessels combined with skin invasion. Immunohistochemical analyses showed negative staining for ER, PR, and HER2. The patient received an additional three cycles of adjuvant chemotherapy with docetaxel and epirubicin, and adjuvant radiotherapy of the right chest wall and regional lymphatics. In September of 2012, a surveillance PET-CT scan showed multiple enlarged lymph nodes with high FDG uptake (SUVmax 6.0) in the left supraclavicular, cervical, and internal mammary lymph nodes, and small nodular lesions with focal FDG uptake (SUVmax 1.9) in the right upper lung and left lower lung fields. A chest CT scan also showed a few tiny peripheral nodules in the right upper lung and left lower lung fields. On physical examination, there were several palpable masses in the left neck. An ultrasound-guided core needle biopsy of the cervical lymph node was performed, and pathological examination revealed an invasive ductal carcinoma. The expression of ER, PR, and HER2 was concordant with the prior right breast cancer, which was negative for ER, PR, and HER2. Subsequently, the patient received six cycles of palliative chemotherapy with docetaxel and cisplatin until January 2013. A follow-up PET-CT scan and chest CT scan showed a near-complete radiological response in the previous multiple metastatic lymph nodes and tiny lung lesions, and there was no evidence of active lesions with abnormal FDG uptake. Therefore, we planned to stop the chemotherapy and to follow up with the patient regularly. Two months later, the patient complained of multiple reddish nodules on her right chest wall, shoulder, and upper arm (Fig. 1A). Breast MRI showed skin enhancement of the right chest wall with an even thickness, and postoperative or postradiation skin changes were suspected (Fig. 1B). A skin biopsy was performed, and the slides were independently reviewed by two pathologists. ER and PR expression was scored using the semiquantitative Allred system, which takes into account the proportion of positive cells (graded from 0 to 5) and the staining intensity (graded from 0 to 3). Pathological examination showed an invasive ductal carcinoma with diffuse lymphatic invasion (Fig. 2A) that was positive for ER (intensity score, 3; proportion score, 3) and negative for PR and HER2 (Fig. 2B). A PET-CT scan showed heterogeneous hypermetabolic activity of the skin throughout the right chest wall and small hypermetabolic nodular lesions in the parasternal area, but there were no other visceral metastases. The patient, who was premenopausal, was administered hormone therapy comprised of a gonadotropin-releasing hormone agonist and tamoxifen (20 mg daily). After three cycles of hormone therapy, follow-up breast MRI showed stable disease for the skin enhancement of the right chest wall. Figure 1 (A) Skin metastases. Ulcerated nodules were noted with erythematous infiltration in the operation bed. (B) Breast magnetic resonance imaging revealed diffuse skin enhancement of the right chest wall with an even thickness. Figure 2 (A) Metastatic carcinoma cells with diffuse lymphatic invasion (asterisks) in the dermis were observed (H&E, ×200). (B) Positive immunohistochemical staining for the estrogen receptor was detected ( ×400). TNBC is defined as a tumor that does not express ER, PR, or HER2; it accounts for 15% to 20% of all breast cancers. TNBC is clearly a distinct clinical subtype but a heterogeneous subgroup with diversity in both tumor biology and prognosis [3]. Over the last decade, the following characteristics of TNBC have been identified: younger patient age, BRCA1-associated cancer, higher incidence of brain metastasis, platinum sensitivity, and poor prognosis [3]. Although the metastatic potential of TNBC is similar to that of other breast cancer subtypes, TNBC is more likely to cause early visceral metastases and is associated with a shorter median time to relapse and death [3]. Our patient experienced relapse with multiple metastases in the cervical lymph nodes and lung within 14 months after diagnosis. She achieved a near-complete radiological response to docetaxel and cisplatin chemotherapy but experienced progression as skin metastases only 2 months after the termination of chemotherapy. Skin metastases from visceral malignancies are uncommon; the reported incidence ranges from 0.7% to 9% [4]. Breast cancer is the most common cancer to metastasize to the skin, followed by lung, melanoma, colon, kidney, and ovarian malignancies. Few studies have investigated the patterns or characteristics of skin metastases in patients with TNBC. Kong et al. [5] evaluated whether the patterns of skin metastases differ according to breast cancer subtype. A retrospective analysis of 125 patients with skin metastases from breast cancer showed that such metastases were more common in hormone receptor-positive breast cancer than in TNBC (42.4% vs. 23.2%, respectively), and that erythematous infiltrations were more frequent in TNBC patients. Our patient presented with ulcerative nodular skin lesions combined with erythematous infiltration in the operation bed, and a change in subtype from TNBC to ER-positive breast cancer was found. Growing evidence of discordance in ER, PR, and HER2 expression between primary and recurrent breast cancer has been reported. The discordance rate varies between studies and can be as high as 40%. The switch to a different tumor phenotype leads to a change in treatment for approximately 20% of cases [1]. According to previous studies, a change from a positive to negative (receptor loss) status is more common than a change from a negative to positive (receptor gain) status. A loss of PR expression is the most frequent change, and changes in ER, PR, and HER2 expression in primary TNBC are relatively rare. Heitz et al. [1] reported that 44 (80.0%) of 55 patients with primary TNBC experienced recurrence of the same triple-negative phenotype, and that only two patients (3.6%) became positive for ER and negative for HER2. The mechanisms responsible for changes in biomarker expression between primary and recurrent breast cancer are not clearly understood, but several possibilities have been proposed, including methodological and technical errors, intratumoral heterogeneity, clonal selection caused by previous treatment, and a switch in tumor biology during progression [1,2]. In our case, we initially confirmed the negativity of the tumor for ER, PR, and HER2 and skin invasion combined with tumor emboli within dermal lymphatic channels in the primary breast cancer obtained from a surgical specimen. Considering that skin metastases occurred in the operation bed and that dermal lymphatic invasion was observed in both primary and recurrent tumor tissues, it is likely that the remaining tumor cells in the lymphatic system had progressed and spread out along the skin. This suggests a change in tumor biology during disease progression or intratumoral heterogeneity in ER expression in the primary breast tumor. Subpopulations of cancer cells in the same patient may exist across different geographical regions of a tumor or evolve over time, which is known as intratumoral heterogeneity. Another lesson from our case is that these biomarkers can change even with a short time to progression. Further study is needed to identify the mechanisms responsible for receptor gain in TNBC, the prognostic impact of a change in tumor phenotype, and the optimal therapeutic strategies.

PURPOSE We aimed to evaluate the clinical effectiveness and safety of double coaxial self-expandable metallic stent (DCSEMS) in management of malignant colonic obstruction as a bridge to surgery or palliation for inoperable patients. METHODS Between April 2006 and December 2012, 49 patients (27 males and 22 females; median age, 68 years; age range, 38-91 years) were selected to receive decompressive therapy for malignant colonic obstruction by implanting a DCSEMS. Application of DCSEMS was attempted in 49 patients under fluoroscopic guidance. The obstruction was located in the transverse colon (n=2), descending colon (n=7), sigmoid colon (n=24), rectosigmoid junction (n=6), and the rectum (n=10). The intended use of DCSEMS was as a bridge to elective surgery in 23 patients and palliation in 26 patients. RESULTS Clinical success, defined as >50% dilatation of the stent with subsequent symptomatic improvement, was achieved in 48 of 49 patients (98%). The stent was properly inserted in all patients. No immediate major procedure-related complications occurred. One patient in the bridge-to-surgery group had colon perforation three days after DCSEMS application. Four patients had late migrations of the double stent. CONCLUSION Application of DCSEMS is safe and effective in management of malignant colonic obstruction; it prevents stent migration and tumor ingrowth and lowers perforation rate during the stent application.

A 31-year-old pregnant woman was referred to us at 34.6 weeks' menstrual age for sonographic evaluation of a fetal left lower limb abnormality. Sonographic findings revealed shortening of the left tibia and dorsal hyperflexion of the left foot. There was no family history of genetic disease, and the maternal serum alpha-fetoprotein concentration was normal. A male infant was born with extensive skin peeling, mainly on his left leg, associated with muscular dystrophy. Epidermolysis bullosa was confirmed on a skin biopsy; the neonate died 53 days after birth as a result of severe sepsis. Although cutaneous epidermolysis bullosa is difficult to diagnose prenatally, shortening and deformity of extremities may provide a clue to the diagnosis, even when the maternal alpha-fetoprotein concentration is normal. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:319-321, 2016.

To evaluate the perinatal survival and renal function of fetuses with lower urinary tract obstruction (LUTO) who underwent vesicoamniotic shunting using a double-basket catheter METHODS: We retrospectively reviewed 32 fetuses with LUTO who underwent vesicoamniotic shunting using a double-basket catheter between 1998 and 2013.Among the 32 fetuses examined, 5 died because of termination of pregnancy, and 2 died in utero. The median gestational age at diagnosis was 15.5 (range, 10.0-27.3) weeks, and that at initial shunting was 17.1 (range, 12.3-32.2) weeks. Shunt dislocation or occlusion occurred in 18 of 42 procedures (42.8%). The median gestational age at delivery for the 25 live births was 35.5 (range, 28-40) weeks. Postnatal diagnosis revealed posterior urethral valves in 15 fetuses, a cloacal anomaly in 7, and urethral stenosis in 3. Three neonatal deaths occurred, resulting in an overall perinatal survival rate of 68.8% (22 of 32). The rates of normal renal function were 40.6% (13 of 32) at 28 days and 40% (10 of 25) at 2 years after birth. The absence of oligohydramnios after shunting was the only prognostic factor for normal renal function at 2 years (P .05).Vesicoamniotic shunting may be helpful for fetuses with LUTO.

The aim of this study was to evaluate the prevalence of disseminated intravascular coagulation and to determine whether the presence of disseminated intravascular coagulation is associated with major adverse events in patients with primary postpartum hemorrhage who present to the emergency department. This retrospective case-control study was conducted in the emergency department of a university-affiliated, tertiary referral center between January 1, 2004 and December 31, 2013. Patients were classified into disseminated intravascular coagulation (disseminated intravascular coagulation score ≥ 5) and non-disseminated intravascular coagulation groups. The two groups were compared in terms of clinical characteristics and the occurrence of major adverse events, defined as massive transfusion (≥ 10 units of packed red blood cells within 24 hours of emergency department admission), invasive intervention (uterine artery embolization or emergency hysterectomy), hospital days, ventilator-free days, intensive care unit admission, intensive care unit-free days, and in-hospital mortality. Among 255 patients with primary postpartum hemorrhage, 57 patients (22.4%) had overt disseminated intravascular coagulation. The disseminated intravascular coagulation group had significantly lower hemoglobin, hematocrit, platelet counts, and fibrinogen levels than the non-disseminated intravascular coagulation group; in addition, they had higher prothrombin times, and D-dimer levels (P

Objective. Caveolin-1 (Cav-1), as the main component of caveolae, has complex roles in tumourigenesis in human malignancies. We investigated Cav-1 in primary and metastatic tumor cells of gastric cancer (GC) and its association with clinical outcomes. Methods. We retrieved 145 cases of GC who had undergone curative gastrectomy. The expression levels of Cav-1 was evaluated by immunohistochemistry, and its association with clinicopathological parameters and patient survival was analyzed. Results. High expression of Cav-1 protein of the GC in the stomach and metastatic lymph node was 12.4% (18/145) and 16.5% (15/91). In the multivariate analysis, tumoral Cav-1 protein in metastatic lymph node showed prognostic significance for relapse-free survival (RFS, HR, 3.934; 95% CI, 1.882–8.224; P=0.001) and cancer-specific survival outcome (CSS, HR, 2.681; 95% CI, 1.613–8.623; P=0.002). Among the GCs with metastatic lymph node, it remained as a strong indicator of poor prognosis for RFS (HR, 3.136; 95% CI, 1.444–6.810; P=0.004) and CSS (HR, 2.509; 95% CI, 1.078–5.837; P=0.032). Conclusion. High expression of tumoral Cav-1 protein in metastatic lymph node is associated with unfavorable prognosis of curative resected GC, indicating the potential of novel prognostic markers.

Human papillomavirus (HPV) infection plays a significant role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Expression of miR-21 has a prognostic role in a wide variety of cancers. The upregulation of miR-21 suppresses a number of target genes, including phosphatase tensin homologue (PTEN) and programmed cell death 4 (PDCD4). We investigated the association between the expression of miR-21 and the clinical features of HNSCC using stratified analysis based on HPV infection status. HPV status and miR-21 expression in HNSCC tissues from 167 patients were evaluated using in situ hybridization. The expression of PDCD4 and PTEN was examined by immunohistochemistry. The up-regulation of stromal miR-21 expression occurred in 40.6% of HPV-negative samples and 28.3% of the HPV-positive group. In HPV-stratified multivariate analysis, high miR-21 expression was associated with poor cancer-specific survival in HPV-negative tumors, but not in HPV-positive tumors. There was a significant association between miR-21 and cytoplasmic PDCD4 overexpression in HPV-negative HNSCCs. We suggest that stromal miR-21 expression is an independent prognostic factor in HPV-negative tumors and miR-21 may play different roles depending on HPV infection status.

Background The purpose of this study was to investigate expression differences of p53, PTEN, PI3K, Akt and mTOR according to the human papillomavirus (HPV) infection and to evaluate clinical significance as prognostic markers in patients with locally advanced tonsillar cancer. Methods Sixty-five patients were reviewed. Tissue microarrays were prepared from surgical specimens and stained with antibodies against p53, PTEN, PIK3CA, Akt and mTOR. Results Twenty-six patients were HPV-positive. Expression of P53 as well as PIK3CA, Akt and mTOR were not significantly different between the 2 groups. However, total PTEN (nuclear and cytoplasmic PTEN) expression was significantly frequent in HPV-positive group. Both overall survival (OS) and disease-free survival (DFS) were significantly different between the 2 groups. Nuclear PTEN expression in the cancer area and pathological nodal stage were significantly correlated with DFS. Conclusion Our study suggests that the presence of PTEN expression with predisposition to nucleus more frequently observed in HPV-positive tonsillar cancers are significantly associated with favorable survival outcome, independent of activated PI3K/Akt/mTOR cell survival pathway. © 2014 Wiley Periodicals, Inc. Head Neck 37: 636–643, 2015

Most thoracopagus twins present with cardiac fusion and associated congenital cardiac defects, and assessment of this anatomy is of critical importance in determining patient care and outcome. Cardiac CT with electrocardiographic triggering provides an accurate and quick morphological assessment of both intracardiac and extracardiac structures in newborns, making it the best imaging modality to assess thoracopagus twins during the neonatal period. In this case report, we highlight the diagnostic value of cardiac CT in thoracopagus twins with an interatrial channel and complex congenital cardiac defects.

The aims of this study were to investigate the correlation between topoisomerase II alpha (TOP2A), microtubule-associated protein-tau (MAP-tau) and other prognostic factors in breast cancer and to evaluate the predictive value of TOP2A and MAP-tau in breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy.Seventy patients with axillary lymph node positive breast cancer who underwent curative surgery between January 2000 and December 2005 were evaluated retrospectively. The levels of protein expression of TOP2A and MAP-tau were assessed using immunohistochemistry.Among the 70 patients, 43 (61.4%) showed TOP2A overexpression and 30 (42.9%) showed MAP-tau positivity. TOP2A overexpression was associated with p53 positivity and high histological grade. MAP-tau positivity was associated with a lower positive lymph node ratio, lower proliferative activity, and hormone receptor positivity. Based on the TOP2A and MAP-tau expression, there was no significant difference in disease-free survival in the breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy.We conclude that immunohistochemical analysis of TOP2A and MAP-tau protein expression may not predict the benefits of adjuvant anthracycline and taxane chemotherapy in axillary node positive breast cancer.

Objective: The purpose of this study was to investigate the clinical outcome of fetal pericardial effusion (PE). Methods: This study involved a retrospective review of prenatally diagnosed PE cases. The criterion for inclusion was pericardial fluid in an area greater than 2 mm in diameter. Results: A total of 276 cases of PE and 252 cases diagnosed with other anomalies were initially reviewed. PE is associated with cardiac malformation, hydrops fetalis, extracardiac abnormalities, infections, anemias, intrauterine growth restriction, and aneuploidy markers in fetuses. Of these reviewed cases, 24 cases of isolated fetal PE were studied. In all cases, pericardial fluid filled an area ranging from 2 to 17 mm in diameter. Four cases of isolated PE had an abnormal postnatal condition, and 3 cases were excluded due to lack of follow-up. The size of the PE was not related to the regression of pericardial fluid, adverse outcomes or mortality rate associated with the isolated PE. All newborns were healthy, and there were no chromosomal abnormalities in the study population. Conclusions: There were no adverse clinical outcomes or chromosomal abnormalities in the fetuses diagnosed with isolated PE. Most cases of isolated PE resolved spontaneously and were associated with a good prognosis.

Purpose Previous studies suggest that the concentration of 25-hydroxyvitamin D [25(OH)D] in cord blood may show an inverse association with respiratory tract infections (RTI) during childhood. The aim of the present study was to examine the influence of 25(OH)D concentrations in cord blood on infant RTI in a Korean birth cohort. Methods The levels of 25(OH)D in cord blood obtained from 525 Korean newborns in the prospective COhort for Childhood Origin of Asthma and allergic diseases were examined. The primary outcome variable of interest was the prevalence of RTI at 6-month follow-up, as diagnosed by pediatricians and pediatric allergy and pulmonology specialists. RTI included acute nasopharyngitis, rhinosinusitis, otitis media, croup, tracheobronchitis, bronchiolitis, and pneumonia. Results The median concentration of 25(OH)D in cord blood was 32.0 nmol/L (interquartile range, 21.4 to 53.2). One hundred and eighty neonates (34.3%) showed 25(OH)D concentrations less than 25.0 nmol/L, 292 (55.6%) showed 25(OH)D concentrations of 25.0-74.9 nmol/L, and 53 (10.1%) showed concentrations of ≥75.0 nmol/L. Adjusting for the season of birth, multivitamin intake during pregnancy, and exposure to passive smoking during pregnancy, 25(OH)D concentrations showed an inverse association with the risk of acquiring acute nasopharyngitis by 6 months of age (P for trend=0.0004). Conclusion The results show that 89.9% of healthy newborns in Korea are born with vitamin D insufficiency or deficiency (55.6% and 34.3%, respectively). Cord blood vitamin D insufficiency or deficiency in healthy neonates is associated with an increased risk of acute nasopharyngitis by 6 months of age. More time spent outdoors and more intensified vitamin D supplementation for pregnant women may be needed to prevent the onset of acute nasopharyngitis in infants.

The aim of this study was to determine whether initial shock index (SI) was independently associated with the requirement for massive transfusion (MT) in emergency department (ED) patients with primary postpartum hemorrhage (PPH). A retrospective cohort study of ED patients with primary PPH was performed at a university-affiliated, tertiary referral center between January 2004 and May 2012. Patients were classified to two groups: MT group (patients who received ≥10 U of packed red blood cells within 24 h of ED admission) and non-MT group (patients who received

For the pathological evaluation of the chorioamniotic membranes, a membrane roll is made to give an orientation to the sections and to cover more extended planes. We designed a new instrument, Annie's memb-roller, for easy preparation of membrane rolls. Annie's memb-roller has two non-toothed arms which are 2 mm wide, 1 mm thick, and 8 cm long. To test its effectiveness in making a membrane roll, the placentas obtained from pregnant women (n = 10) with various obstetrical conditions were used. Preparation of the membrane rolls using Annie's memb-roller was easy and successful in all cases tested. The lengths of the membranes measured from fresh placentas and paraffin sections showed a very good correlation (p < 0.001; r = 0.941). Application of the memb-roller would be very helpful in the semi-quantitative analysis of the chorioamniotic membranes and the standardization of placental pathology and research practice.

Considering the protumorigenic roles of interleukin-6 (IL-6) transsignaling, we assessed the serum levels of IL-6, soluble interleukin-6 receptor (sIL-6R), and soluble glycoprotein 130 (sgp130) in 143 patients with breast cancer. Serum levels of IL-6 were elevated with advanced T and N stage. Serum levels of sIL-6R were lower in patients with estrogen receptor-positive cancer. The median values of IL-6 and sgp130 did not differ between patients with recurrence and those without recurrence. However, higher serum levels of sIL-6R at diagnosis were associated with significantly shorter relapse-free survival in patients with estrogen receptor-positive breast cancer.

Congenital heart disease is the most common abnormality in the human fetus. Fetal echocardiography has been used to detect the majority of cardiac defects, and it is now part of the routine screening method for fetal evaluation. In this article, we present standard ultrasonographic views of the normal fetal heart obtained during the second trimester, first-trimester fetal echocardiography findings, and a modified myocardial performance index.

This report introduces a method for ultrasound-guided transcervical forceps extraction (UTCE) of unruptured interstitial pregnancies; this method does not necessitate elective caesarean delivery for future pregnancies. This report also compares this technique with conventional methods. A retrospective review was conducted involving 16 women treated for interstitial pregnancies. Among these women, UTCE was successfully performed in six of 16 women, with only one woman requiring additional intervention; conventional treatment was performed in the other ten women. UTCE is a safe, effective and minimally invasive option for treating interstitial pregnancies and should be considered as an alternative treatment modality.

Patients with HPV-positive oropharyngeal cancer show better tumor response to radiation or chemotherapy than patients with HPV-negative cancer. HPV oncoprotein E6 binds and degrades a typically wild-type p53 protein product. However, HPV16 infection and p53 mutation infrequently coexist in a subset of HNSCCs. The purpose of this study was to investigate the mechanisms through which tumor biology and molecular genetic mechanisms change when two HPV-negative, p53-mutated oropharyngeal cell lines (YD8, non-disruptive p53 mutation; YD10B, disruptive p53 mutation) derived from patients with a history of heavy smoking are transfected with HPV E6 and E7 oncogenes in vitro. Transfection with HPV E6 and E7 oncogenes in YD8, reduced the abundance of proteins encoded by tumor suppressor genes, such as p-p53 and p-Rb. Cell proliferative activity was increased in the cells transfected with E6E7 compared to cells transfected with vector alone (P=0.09), whereas the invasiveness of E6E7-transfected cells was significantly reduced (P=0.02). cDNA microarray of the transfected cells with E6E7 showed significant changes in mRNA expression in several signaling pathways, including focal adhesion, JAK-STAT signaling pathway, cell cycle and p53 signaling pathway. Regarding the qPCR array for the p53 signaling pathway, the mRNA expression of STAT1 was remarkably upregulated by 6.47-fold (P

The skeletal muscle is an unusual site for metastasis from breast cancer. We present two cases of breast cancer that relapsed as skeletal muscle metastasis without other distant organ metastasis. We performed the core needle biopsy of metastatic sites and confirmed discordance in estrogen receptor, progesterone receptors, and human epidermal growth factor receptor 2 expression between primary breast cancer and skeletal muscle metastases. In the second case, we found the skeletal muscle metastasis through F-18 fluorodeoxyglucose positron emission tomography/computed tomography scans (PET/CT). Intramuscular hot spots on PET/CT scans should be considered as a sign of metastasis even in the absence of abnormalities on computed tomography scans. Our patients received systemic chemotherapy, and showed a partial response. Further studies are needed to determine the prognosis and proper management of isolated skeletal muscle metastasis in breast cancer.

Excision repair cross complement group 1 (ERCC1) expression is a predictive biomarker for platinum-containing treatment in squamous cell carcinoma of head and neck (SCCHN). However, the prognostic significance after surgical resection is not well understood.Oropharynx (n=143) or oral cavity (n=61) SCCHN patients undergoing surgery were included. ERCC1 protein expression and HPV status were assessed by ERCC1 and p16 immunohistochemistry.The ERCC1, over-expressed in 66.7% of patients, was associated with oral cavity cancer (P0.001), well differentiation (P=0.036), and HPV negativity (P0.001). In TCGA database, ERCC1 mRNA upregulation was enriched in HPV-negative and oral cavity cancers, and associated with HRAS mutation (P0.001). The prognostic role of ERCC1 was not different according to HPV status. High ERCC1 expression showed a trend toward poor prognosis in patients with an advanced stage (P=0.079) with marginal significance.The ERCC1 expression was not prognostic in surgically resected oropharynx/oral cavity SCCHN, irrespective of HPV status. However, it could provide additional prognostic information for advanced stage patients.

To evaluate the reproducibility of the fetal right myocardial performance index determined by simultaneous recording of inflow and outflow using a dual gate pulsed-wave Doppler (DD).This was a prospective study of 39 normal singleton fetuses. Two experienced operators each measured the right myocardial performance index in three ways, twice: (1) separate recording of the inflow and outflow using single-gate pulsed-wave Doppler (PD), (2) simultaneous recordings of the inflow and outflow using tissue Doppler (TD), and (3) simultaneous recordings of the inflow and outflow using DD. Intra- and interoperator reproducibility were assessed with intraclass correlation coefficients. The measurements from all three methods taken by the more experienced operator were compared using Bland-Altman plots and mean differences.For both operators, intra-operator reproducibility was the highest when using DD, followed by PD, and TD. Interoperator agreement was the highest for PD measurements, followed by DD, and TD. The smallest mean difference was between the PD and DD measurements by the more experienced operator. There was a positive correlation between PD and DD values (r = 0.369, P .001).Dual gate pulsed-wave Doppler may be an effective alternative to the PD or TD methods, and can separately evaluate systolic and diastolic myocardial function.

Some recent studies have reported that early intervention by a medical emergency team (MET) for clinical deterioration before intensive care unit (ICU) admission was associated with a survival benefit in critically ill cancer patients. We hypothesized that early MET intervention for an obstetric crisis in the general wards would be related to favorable outcomes in critically ill obstetric patients.Data of obstetric patients who were managed by a MET were collected retrospectively from 1 March 2008 to 30 April 2015. A total of 69 obstetric patients were enrolled. Among them, 48 (69.6%) were treated successfully in the general wards and 21 (30.4%) were transferred to the ICU.Major causes of MET activation were pulmonary edema (n = 23, 33.3%), hypovolemic shock (n = 19, 27.5%), and septic shock (n = 8, 11.6%). Compared with the patients treated in the general ward, the patients transferred to the ICU had significantly higher severity of illness score. Sequential Organ Failure Assessment score was the most useful for prediction of ICU admission of obstetric patients (AUC, 0.810, P0.001), and the ideal cut-off was 4 (sensitivity, 81%; specificity, 60%). During the study period, in-hospital mortality of the obstetric patients was 2.9% (2/69).After MET activation many obstetric patients could be successfully treated in the general wards without mortality. Therefore, MET may reduce ICU admissions in critically ill obstetric patients.

Background Autophagy, a cellular degradation process, has complex roles in tumourigenesis and resistance to cancer treatment in humans. The aim of this study was to explore the expression levels of autophagy-related proteins in patients with rectal cancer and evaluate their clinical role in the neoadjuvant chemoradiotherapy setting. Methods All specimens evaluated were obtained from 101 patients with colorectal cancer who had undergone neoadjuvant chemoradiotherapy and curative surgery. The primary outcomes measured were the expression levels of two autophagy-related proteins (microtubule-associated protein 1 light chain 3 beta (LC3β) and beclin-1) by immunohistochemistry and their association with clinicopathological parameters and patient survival. Results Among the 101 patients, the frequency of high expression of beclin-1 was 31.7 % (32/101) and that of LC3β was 46.5 % (47/101). A pathologic complete response was inversely associated with LC3β expression (P = 0.003) and alterations in the expression of autophagy-related proteins (P = 0.046). In the multivariate analysis, however, autophagy-related protein expression did not show prognostic significance for relapse-free survival or overall survival. Conclusions High expression of autophagy-related proteins shows a strong negative association with the efficacy of neoadjuvant chemoradiotherapy in patients with rectal cancer. Autophagy has clear implications as a therapeutic target with which to improve the efficacy of neoadjuvant chemoradiotherapy.

Summary Objectives The aims of this study were to evaluate the expression of EGFR, PI3K, Akt, mTOR, and PTEN in the oral cavity and oropharyngeal cancers, and to investigate their clinical significance as prognostic markers. Materials and methods One hundred twenty-one patients who underwent curative surgery for oral cavity or oropharyngeal squamous cell carcinoma in Seoul St. Mary’s Hospital between January 1995 and September 2009 were evaluated. The level of protein expression of EGFR, PIK3CA, pAkt, mTOR, and PTEN was assessed by immunohistochemistry. In situ hybridization was used to detect the existence of human papillomavirus (HPV). Results Nineteen of 61 patients with oropharyngeal cancer showed HPV-positive tumors, and two of 60 patients with oral cavity cancer showed HPV-positive tumors. EGFR and pAkt expression was significantly higher in oral cavity cancers than in oropharyngeal cancers. Loss of PTEN occurred significantly more frequently in oral cavity cancers than in oropharyngeal cancers. The expression levels of PIK3CA, mTOR, and p53 did not differ significantly between the two cancers. Overexpression of EGFR and pAkt and loss of PTEN were observed more frequently in HPV-negative tumors. Multivariate Cox regression analysis showed that pAkt expression had a significantly unfavorable impact on relapse-free survival in oropharyngeal cancer. Conclusion We conclude that the expression levels of EGFR, pAkt, and PTEN differ between oropharyngeal and oral cavity cancer and it may be attributed to HPV-related molecular pathogenesis. The expression of pAkt might be an unfavorable prognostic marker for relapse-free survival in oropharyngeal cancer.

Since the risk of developing allergic disease increases in individuals exposed to allergens previously, even during the neonatal period, the immunologic status of a fetus may be important in the subsequent development of allergy. We evaluated the fetal factors to predict atopic dermatitis (AD) at 12 months in 412 infants of a COhort for Childhood Origin of Asthma and Allergic Diseases (COCOA) in the general Korean population. Cord blood mononuclear cells (CBMCs) were stimulated with ovalbumin and phytohemagglutinin and cellular proliferative response and concentrations of interleukin-13 and interferon-γ, were measured. The risk of developing AD was greater in boys than girls (OR 1.97, 95% CI 1.26-3.09), infants delivered by cesarean section than vaginally (OR 1.93, 95% CI 1.14-3.26) and infants with than without parental history of AD (OR 2.34, 95% CI 1.29-4.24). The CBMC proliferative response to phytohemagglutinin stimulation was higher in infants with than without AD (P = 0.048), but no difference was observed in ovalbumin-stimulated cells (P = 0.771). Risk factors for the development of AD at 12 months include male gender, delivery by cesarean section and parental history of AD. Increased CBMC proliferative response to phytohemagglutinin stimulation may predict the development of AD at 12 months.

Pelvic arterial embolization for primary postpartum hemorrhage was safe and effective, although patients with disseminated intravascular coagulation and those who have received a massive transfusion should be carefully monitored during embolization because of the potential need for repeat embolization or additional surgery.

We retrospectively compared the efficacy and toxicity of gemcitabine combination with capecitabine or erlotinib in unresectable pancreatic cancer to know whether the combination with cytotoxic and target agent has more benefit comparing to combination of cytotoxic agents.Fifty-three patients with unresectable pancreatic cancer, treated with gemcitabine and capecitabine (GC) or gemcitabine and erlotinib (GE) as first line between October 2006 and July 2010, were reviewed. In GC group, patients were treated with gemcitabine 1,000 mg/m(2) on days 1, 8, and capecitabine 1,300 mg/m(2) bid was administered on days 1-14, repeated every 21 days. In GE group, gemcitabine was given at 1,000 mg/m(2) I.V for 30 min on days 1,8,15, and erlotinib was taken orally at 100 mg through days 1-28, repeated every 28 days.Response rate was similar, 23.5 % in GE and 21.1 % in GC, but GC had better disease control rate with 73.7 % than GE with 52.9 %. GC also showed longer PFS and OS (5.37 and 14.43 months) than GE (2.63 and 6.23 months) (p = 0.032 for PFS and 0.002 for OS). In toxicity profiles, GC had more hematologic toxicities and GE had more non-hematologic toxicities.The combination with cytotoxic agents seems to have better efficacy and clinical outcome than combination with cytotoxic agent and target agent. The new combination should be developed for the treatment for advanced pancreatic cancer.

Objectives To establish the reference range of intracranial translucency (IT) in the Korean population, and to evaluate whether Volume IT™ is a reliable technique for measuring IT. Methods We retrospectively analyzed the IT of 93 singleton fetuses at 10.5 to 12.6 weeks of gestation using previously obtained three-dimensional volume data. The IT was measured manually and automatically using Volume IT™ in each fetus by one experienced and one beginner operator. We measured the IT values according to the crown–rump length and evaluated whether Volume IT™ can successfully measure the IT. Inter-observer agreement and intra-observer reproducibility were analyzed using the intraclass correlation coefficients (ICC), and the IT measurements obtained by the experienced operator using the manual and automated methods were then compared using the Bland–Altman plot and ICC. Results Among 93 cases, 2 were lost to follow-up after the first trimester scan and were excluded from further evaluation. Both operators identified the fourth ventricle in all 91 cases using Volume IT™. The experienced and beginner operators were able to measure the IT in 89 (98%) fetuses, with 4 and 13, respectively, requiring adjustments. The IT values increased with gestational age (correlation coefficient, r = 0.491, P

Anemia is a common complication in dialysis patients because of their relative erythropoietin deficiency. Despite treatment with erythropoiesis-stimulating agents (ESAs), some patients experienced ESA hyporesponsiveness. We evaluated the clinical and laboratory factors that affect ESA hyporesponsiveness and investigated the relationships between hepcidin, inflammatory markers, and the iron profiles of hemodialysis patients. Sixty-eight patients receiving hemodialysis at a single institution were evaluated in a cross-sectional study. The patients were divided into tertiles based on the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram of body weight divided by the hemoglobin level. The mean EHRI values for each tertile were 3.3 ± 1.2 (T1), 10.2 ± 2.9 (T2), and 24.5 ± 11.6 (T3). The mean serum erythropoietin levels were significantly higher in the Q3 and Q4 groups. Thus, patients with ESA hyporesponsiveness showed relative resistance to erythropoietin therapy. In univariate and multivariate analyses, patients in the third tertile of EHRI showed significantly higher mean interleukin-6 (IL-6) levels. Serum C-reactive protein (CRP) levels showed a similar trend, but the differences were not significant. Serum hepcidin levels tended toward lower mean values in the third tertile of EHRI. No relationship was observed between hepcidin and inflammatory markers or iron status. In conclusion, IL-6, but not CRP, is a strong predictor of ESA hyporesponsiveness in hemodialysis patients who have sufficient iron. It may be difficult to use hepcidin as an independent clinical marker because of the many factors that influence it and their interactions.

To establish normal reference ranges for the fetal left modified myocardial performance index (Mod-MPI) measured by the Auto Mod-MPI system and evaluate Mod-MPI changes in recipients of twin-to-twin transfusion syndrome (TTTS) before and after fetoscopic laser coagulation.This was a prospective longitudinal study of normal singleton fetuses from 12.0 to 40.0 weeks of gestation. TTTS cases treated by laser coagulation were reviewed for Mod-MPI measurements of recipients. All measurements were performed using the Auto Mod-MPI system by a single experienced operator.Among a total 447 examinations from 222 fetuses, we were unable to measure the Mod-MPI in two cases, and therefore, 445 examinations were analyzed. The median Mod-MPI consistently increased from 0.44 to 0.56 throughout gestation. The median isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) also increased with advancing gestational age. The ejection time (ET) increased until 27 weeks of gestation and decreased thereafter. In the 30 recipients, Mod-MPI, ICT, and IRT increased before laser coagulation and significantly decreased after laser coagulation.Normal reference values for left Mod-MPI were established using the Auto Mod-MPI system, and these might be useful for assessing cardiac function in TTTS. © 2016 John WileySons, Ltd.