Uterine-fundal hypoechoic mass: a possible ultrasound sign for cesarean scar pregnancy.

PURPOSE OF INVESTIGATION: Cesarean scar pregnancy (CSP) is a life-threatening condition that requires early pregnancy termination. Its early ultrasound diagnosis is clinically important; however, previous studies focused on the CSP site itself. The present study was conducted to investigate the authors' clinical impression that a uterine-fundal hypoechoic mass is more frequently observed in CSP. Such a finding, if confirmed, may contribute to ultrasound diagnosis of CSP. The authors also determined the relationship between the treatment strategy and outcome, with special emphasis on conditions eventually requiring uterine artery embolization (UAE). MATERIALS AND METHODS: This was a case-control study of CSP, and the authors analyzed all 14 women that were treated in this single tertiary institute over a period of ten years. Control subjects consisted of all pregnant women with prior cesarean section (CS) but no CSP. RESULTS: Patients with CSP were significantly more likely to have a hypoechoic mass than controls (42.9 vs. 15.4%, respectively; p = 0.028). On confining results to a "fundal" hypoechoic mass, only CSP(+) patients showed it (CSP vs. control: 28.6 vs. 0%, respectively; p < 0.001). Six (43%: 6/14) received UAE: four following vaginal evacuation (artificial or spontaneous), and two for bleeding after methotrexate (MTX) treatment. CONCLUSION: Patients with CSP more frequently had a uterine-fundal hypoechoic mass, whose detection may trigger a detailed observation of the CSP site, possibly leading to CSP diagnosis.

Comprehensive analyses using next-generation sequencing and immunohistochemistry enable precise treatment in advanced gastric cancer.

BACKGROUND: In advanced gastric cancer (AGC), most clinical trials are designed on the basis of protein expression or gene amplification of specific genes. Recently, next-generation sequencing (NGS) allowed us to comprehensively profile the tumor gene status. This study aimed to elucidate the profiling between gene alterations and protein expression in AGC to aid in future clinical trials on AGC. PATIENTS AND METHODS: Formalin-fixed, paraffin-embedded tumor samples from 121 stage III/IV gastric cancer patients were examined for protein expression of tyrosine kinase receptors (RTKs; ERBB2, EGFR, c-MET, and FGFR2) using immunohistochemistry (IHC). Furthermore, 409 cancer-related genes were sequenced to detect mutations and copy number variations using NGS. RESULTS: Most ERBB2 overexpression (IHC 3+) cases (80.0%) had ERBB2 amplification and did not have other RTK amplification or oncogene mutations. However, one-fourth of MET overexpression cases (25.0%) had ERBB2 alterations. EGFR and FGFR2 overexpression cases had ERBB2 alterations or other gene alterations such as KRAS or PIK3CA. On the other hand, most of the four RTK amplification cases (88.2%) were mutually exclusive with each amplification. However, RTK amplification did not simply correlate with protein overexpression, whereas cases with RTK high-level amplification had protein overexpression and rarely showed other co-existing gene alterations. CONCLUSION: AGC involves a complicated arrangement of protein expression and gene alterations. Comprehensive analyses of NGS and IHC will be necessary to design the optimal therapy for treating the appropriate population of patients in future clinical trials.

Congenital mesoblastic nephroma: Its diverse clinical features - A literature review with a case report.

To characterise congenital mesoblastic nephroma (CMN), with special emphasis on polyhydramnios and the neonatal prognosis, we summarise 31 CMN patients (30 reported patients and the present patient). CMN was detected at a median of 30 weeks' gestation, and infants were delivered at a median of 34 weeks' gestation. Of 27 patients with available data, 19 (70%) had polyhydramnios, of which 8 required amnio- drainage. Women with amnio-drainage gave birth significantly earlier (30.4 weeks' gestation) than those without polyhydramnios (36.7 weeks' gestation). Thus, CMN was frequently associated with polyhydramnios and this polyhydramnios was associated with a significant increase in the risk of preterm birth. Of 20 patients with available data, the affected-side kidney was 'compressed' in 16 and 'replaced' in 4: polyhydramnios was present in a half vs 100%, respectively, suggesting that a 'replaced' kidney may suggest a more aggressive tumour and may be associated with a poorer prognosis. Univariate analysis showed that early gestational week at diagnosis was the only feature significantly associated with poor prognosis. Thus, polyhydramnios, 'replaced' kidney and early gestational week at diagnosis, may indicate poor prognosis, to which obstetricians should pay attention.

Changes in standing body sway of pregnant women after long-term bed rest.

Pregnant women tend to fall and increased body postural instability, namely body sway, may be one of the causative factors. We had a clinical impression that pregnant women after long-term bed rest tend to fall. We hypothesised that such women may show increased body sway, which we attempted to determine. Pregnant women (n = 161) were divided into three groups: (i) women with preterm labour after 2-week bed rest, (ii) those after 4-week bed rest, and (iii) those without bed rest or preterm labour. Body sway was analysed using stabilometry, that is, computed analysis of movement of the centre of gravity. The 3 groups fundamentally showed the same stabilometric measurements. Women with oedema showed greater medial-lateral sway than those without it. Factors other than oedema yielded no differences in stabilometric parameters. Long-term bed rest fundamentally did not increase body sway to the extent that stabilometry could reveal it. It may be prudent to consider that pregnant women with oedema tend to fall.

Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer.

BACKGROUND: We conducted comprehensive clinical and molecular characterization of claudin 18.2 expression (CLDN18.2) in advanced gastric or gastroesophageal junction cancer (GC/GEJC). PATIENTS AND METHODS: Patients with advanced GC/GEJC who received systemic chemotherapy from October 2015 to December 2019 with available tumor specimens were analyzed. We evaluated clinicopathological features of CLDN18.2 expression with four molecular subtypes: mismatch repair deficient, Epstein-Barr virus-positive, human epidermal growth factor receptor 2-positive, and others. In addition, programmed death-ligand 1 (PD-L1) combined positive score (CPS), genomic alterations, and the expression of immune cell markers were assessed. Clinical outcomes of standard first- or second-line chemotherapy and subsequent anti-programmed cell death protein 1 (anti-PD-1) therapy were also investigated according to CLDN18.2 expression. RESULTS: Among 408 patients, CLDN18.2-positive (moderate-to-strong expression in ≥75%) was identified in 98 patients (24.0%) with almost equal distribution in the four molecular subtypes or CPS subgroups. CLDN18.2-positive was associated with Borrmann type 4, KRAS amplification, low CD16, and high CD68 expression. Overall survival with first-line chemotherapy was not significantly different between CLDN18.2-positive and -negative groups [median 18.4 versus 20.1 months; hazard ratio 1.26 (95% confidence interval 0.89-1.78); P = 0.191] regardless of stratification by PD-L1 CPS ≥5. Progression-free survival and objective response rates of first- and second-line chemotherapy, and anti-PD-1 therapy also showed no significant differences according to CLDN18.2 status. CONCLUSIONS: CLDN18.2 expression in advanced GC/GEJC was associated with some clinical and molecular features but had no impact on treatment outcomes with chemotherapy or checkpoint inhibition. CLDN18.2-positive also had no impact on overall survival. This information could be useful to interpret the results from currently ongoing clinical trials of CLDN18.2-targeted therapies for advanced GC/GEJC and to consider a treatment strategy for CLDN18.2-positive GC/GEJC.

[Stanford type A acute aortic dissection with congenital complete absence of the left pericardium; report of a case].

A 52-year-old woman who presented with acute onset of chest pain was diagnosed with Stanford type A acute aortic dissection by computed tomography at another hospital. She was referred to our department for emergency surgery. The left pericardium visualized via a median sternotomy was clearly defective, and the left phrenic nerve was located ventral to the defect. The ascending aorta and total arch were replaced with an aortic valve and a prosthetic graft, respectively. Postoperative chest radiography excluded left phrenic nerve palsy. The postoperative course was uneventful and the patient was discharged on postoperative day 17.

[Surgical treatment of left ventricular pseudoaneurysm after acute myocardial infarction in subacute phase; report of a case].

A 81-year-old man who was complaining of chest pain was admitted. He was diagnosed as acute myocardial infarction. Coronary angiogram was performed and an occlusion of the circumflex coronary artery (#13) was diagnosed. Percutaneous coronary intervention (PCI) was done successfully. Cardiac tamponade was showed on the 3rd day after PCI. Percutaneous pericardial drainage was done and his hemodynamic was improved. Transthoracic echocardiogram showed left ventricular pseudoaneurysm with 2 cm in diameter and expanding to 5 cm in diameter after 3 weeks. Patch closure was carried out under cardiopulmonary bypass on subacute phase. His postoperative recovery was uneventful. Left ventricular pseudoaneurysm is a rare complication of acute myocardial infarction (AMI) and surgical treatment of this disease was discussed.

Transcription factor Egr1 acts as an upstream regulator of beta-catenin signalling through up-regulation of TCF4 and p300 expression during trans-differentiation of endometrial carcinoma cells.

The beta-catenin/TCF4/p300 pathway is involved in early signalling for trans-differentiation towards the morular phenotype of endometrial carcinoma cells, but little is known about the upstream regulators. Here we show that transcription factor early growth response 1 (Egr1) acts as an initial mediator through up-regulating the expression of TCF4 and p300. In an endometrial carcinoma cell line with abundant oestrogen receptor alpha, Egr1 expression at both mRNA and protein levels was significantly increased by serum and 17beta-oestradiol stimuli. Serum-stimulated cells also showed increased expression of TCF4 and p300, while inhibition of Egr1 by specific siRNAs resulted in decreased expression. Transfection of Egr1 led to transactivation of TCF4 as well as p300 genes, through specific binding to a promoter region, and thus in turn resulted in nuclear accumulation of beta-catenin mediated by the up-regulating TCF4. The overexpression also caused inhibition of beta-catenin/TCF4/p300-mediated transcription, probably through sequestration of p300. Egr1 promoter activity was increased by serum but not 17beta-oestradiol, in contrast to the marked repression associated with TCF4, p300, and Egr1 itself, indicating that the regulation involves several feedback loops. In clinical samples, cells immunopositive for nuclear Egr1, as well as beta-catenin and TCF4, were found to be sporadically distributed in glandular components of endometrial carcinoma with morules. A significant positive correlation between nuclear beta-catenin and TCF4 was observed, but no such link was evident for Egr1, probably due to the existence of negative feedback regulation. Together, these data indicate that Egr1 may participate in modulation of the beta-catenin/TCF4/p300 signalling pathway as an initial event during trans-differentiation of endometrial carcinoma cells, through its impact on several signalling networks.

Assessment of bruxism in the clinic.

Bruxism is a much-discussed clinical issue in dentistry. Although bruxism is not a life-threatening disorder, it can influence the quality of human life, especially through dental problems, such as tooth wear, frequent fractures of dental restorations and pain in the oro-facial region. Therefore, various clinical methods have been devised to assess bruxism over the last 70 years. This paper reviews the assessment of bruxism, provides information on various assessment methods which are available in clinical situations and discusses their effectiveness and usefulness. Currently, there is no definitive method for assessing bruxism clinically that has reasonable diagnostic and technical validity, affects therapeutic decisions and is cost effective. One future direction is to refine questionnaire items and clinical examination because they are the easiest to apply in everyday practice. Another possible direction is to establish a method that can measure actual bruxism activity directly using a device that can be applied to patients routinely. More clinical studies should examine the clinical impact of bruxism on oral structures, treatment success and the factors influencing the decision-making process in dental treatment.

Inhibition of DNA synthesis and alteration of cyclic adenosine 3',5'-monophosphate levels in RSa cells by human leukocyte interferon.

Human leukocyte interferon inhibits the proliferation of the virus-transformed human embryonic cells RSa. Incorporation of [3H]thymidine (TdR) into an intracellular pool and the activity of TdR kinase were reduced in the interferon-treated RSa cell culture. High-degree (90%) inhibition of [3H]TdR incorporation was associated with concentrations of added interferon that produced more than a twofold increase in the intracellular cyclic AMP (cAMP) level, and low-degree inhibition was associated with smaller increases in cAMP. In the IFr cell culture, which is relatively resistant to the anticellular action of interferon, considerably less inhibition of TdR incorporation and a slight increase in cAMP were observed. Extracellularly added dibutyryl-cAMP inhibited the proliferation of both RSa and IFr cells to almost the same degree. A decrease in cAMP level and the initiation of DNA synthesis of G1-phase-arrested RSa cells by serum addition were prevented when cells were pretreated with interferon. These results indicated that intracellular cAMP may mediate the inhibitory effect of interferon on DNA synthesis and cell growth.

Inhibition of DNA synthesis of synchronized RSa cells by human leukocyte interferon.

A human leukocyte interferon preparation suppressed DNA synthesis and subsequent mitosis of synchronously growing virus-transformed human RSa cells. DNA synthesis was inhibited completely when interferon was added to cell cultures in late G1 phase, but was not so inhibited when interferon was added in G1/S boundary phase. Overall protein synthesis was reduced only slightly by interferon treatment. The findings suggested that critical events leading to the inhibition of DNA synthesis and subsequent mitosis by interferon action take place in late G1 phase or S phase.

Characteristics of a human cell line successively transformed by Rous sarcoma virus and simian virus 40.

Human enbryo cells were successively transformed by the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) and simian virus 40 (SV40) in vitro, and the double transformant HuE 13 RS was established. From this cell line the two clonal cell lines RSa and RSb were isolated. In both, presence of SV40 T antigens was demonstrated by the fluorescent antibody technique, and the presence of RSV genomes was verified in one RSb clone by focus formation after fusion with chick embryo cells. Growth of these cells was affected by dibutyryl cAMP without marked morphologic changes. Cells were extremely sensitive to the anticellular action of human leukocyte interferon.

Effects of adriamycin on the reverse transcriptase and the production of murine leukemia virus.

Adriamycin inhibited the endogenous RNA-, poly (A)-d(T)12-, and calf thymus DNA-catalyzed reaction of reverse transcriptase from AKR mouse murine leukemia virus (AKR-MLV). This inhibition was found at the reaction levels of endogenous RNA-directed and subsequent DNA-directed DNA synthesis. Although adriamycin and actinomycin D significantly reduced the growth of AKR mouse cells (K3b), the treatment with adriamycin could bot inhibit the AKR-MLV production in these cells. Actinomycin D inhibited AKR-MLV production completely in the same experimental condition. In adriamycin-resistant K3b/Am cells, which were isolated by intermittent treatment of K3b cells with adriamycin, persistence of AKR-MLV was demonstrated. K3b/Am cells showed some altered characteristics such as reduced growth rate and tumorigenicity.