Isolation of azole-resistant Aspergillus spp. from food products.

The prevalence of azole-resistant Aspergillus fumigatus is increasing worldwide and is speculated to be related to the use of azole pesticides. Aspergillus spp., the causative agent of aspergillosis, could be brought into domestic dwellings through food. However, studies on azole-resistant Aspergillus spp. in food products are limited. Therefore, we aimed to isolate Aspergillus spp. from processed foods and commercial agricultural products and performed drug susceptibility tests for azoles. Among 692 food samples, we isolated 99 strains of Aspergillus spp. from 50 food samples, including vegetables (22.9%), citrus fruits (26.3%), cereals (25.5%), and processed foods (1.8%). The isolates belonged to 18 species across eight sections: Aspergillus, Candidi, Clavati, Flavi, Fumigati, Nidulantes, Nigri, and Terrei. The most frequently isolated section was Fumigati with 39 strains, followed by Nigri with 28 strains. Aspergillus fumigatus and A. welwitschiae were the predominant species. Ten A. fumigatus and four cryptic strains, four A. niger cryptic strains, two A. flavus, and four A. terreus strains exceeded epidemiological cutoff values for azoles. Aspergillus tubingensis, A. pseudoviridinutans, A. lentulus, A. terreus, and N. hiratsukae showed low susceptibility to multi-azoles. Foods containing agricultural products were found to be contaminated with Aspergillus spp., with 65.3% of isolates having minimal inhibitory concentrations below epidemiological cutoff values. Additionally, some samples harbored azole-resistant strains of Aspergillus spp. Our study serves as a basis for elucidating the relationship between food, environment, and clinically important Aspergillus spp.

Technology for dementia care: what would good technology look like and do, from carers' perspectives?

BACKGROUND: The development of technology in dementia care has largely been without consultation with carers, and has primarily focused on safety, monitoring devices, and supporting activities of daily living. Further, while involving end-users in the design of technology has been recommended, this is yet to become common practice. METHOD: We conducted a mixed methods study with the aim of investigating carers' values and priorities for technology development, including prior experiences, barriers to use, and what they would like technology to do. Importantly, we asked carers for their design ideas and bespoke technology solutions for future development. RESULTS: Carers of people living with dementia (N = 127), including both unpaid (n = 102) and paid carers (n = 25) residing in Australia, completed an online survey. In addition, a subsample of carers (n = 23) participated in semi-structured interviews. Findings demonstrate that carers want technology to be person-centred, customisable, and to increase opportunities for meaningful social connection. Findings also demonstrate the ability of carers to generate creative design solutions for dementia care. CONCLUSIONS: These findings and implications will be discussed in relation to the importance of co-design with carers and engineers during the design phase of assistive technology. Also, the importance of technology to enhance, not replace, human-to-human social interactions is highlighted.

Combined Neutrophil-to-Lymphocyte Ratio Score Is Associated With Chemotherapeutic Response and Predicts Prognosis in Patients With Advanced Pancreatic Cancer.

BACKGROUND/AIM: Neutrophil-to-lymphocyte ratio (NLR) is a prognostic indicator for several malignancies, including pancreatic cancer. We developed a novel combined NLR score (cNLRS) based on baseline NLR and change in NLR after chemotherapy (ΔNLR), and examined its prognostic value and role in chemotherapeutic response in patients with advanced pancreatic cancer. PATIENTS AND METHODS: This study retrospectively assessed 210 advanced pancreatic cancer patients receiving chemotherapy between 2010 and 2021. The cNLRS was developed and its association with chemotherapeutic response and prognosis was investigated. RESULTS: The cNLRS consisted of baseline NLR ≥2.5 and ΔNLR ≥0, both of which were remained as independent poor predictors of prognosis adjusting for other traditional clinicopathological features. A high cNLRS served as an independent prognostic factor of reduced overall survival. Of note, the cNLRS was significantly associated with disease control rate and treatment duration not only in 1st line treatment but also in 2nd line treatment. CONCLUSION: The cNLRS established as a useful prognostic biomarker might be associated with chemotherapeutic response and could predict survival in advanced patients with pancreatic ductal adenocarcinoma treated with chemotherapy.

Advanced Cholangiocarcinoma With High Tumor Mutation Burden Achieving Complete Response to Immune Check Point Inhibitor.

BACKGROUND/AIM: Genomic examination of tumor tissue has been clinically accepted, and the identification of actionable mutations for molecular-targeted therapy may provide substantial survival benefit for patients with advanced malignancies. CASE REPORT: A female patient in her 60s showed a stenosis of the afferent loop of the small intestine because of circumferential metastatic tumor 14 months after curative surgery for hilar cholangiocarcinoma. Chemotherapy with gemcitabine plus cisplatin was administered for 18 months. An oncopanel examination was performed during chemotherapy, and a high tumor mutation burden was revealed. At 38 months after surgery, a new recurrent tumor, 2.7 cm in size, was observed in the abdominal wall, which was histologically proven to be metastatic adenocarcinoma. Atezolizumab was administered. After three cycles of treatment, treatment was switched to pembrolizumab because of its acceptance by healthcare insurance. The recurrent tumors in the abdominal wall and small intestine disappeared 6 months after the administration of immune checkpoint inhibitor, and the patient has continued pembrolizumab, surviving for 76 months after surgery without any clinical evidence of tumor. CONCLUSION: Immune checkpoint blockade successfully prolonged the survival of a patient with advanced hilar cholangiocarcinoma with high tumor mutation burden, although the optimal number of mutations for such a successful response needs to be clarified.

Diagnostic accuracy of preoperative adhesion mapping by ultrasonography for laparoscopic surgery in patients with past abdominal surgery with special reference to loose adhesion.

PURPOSE: Endoscopic surgery is widely accepted for both elective and emergent abdominal surgery. This study was performed to assess the accuracy of preoperative adhesion mapping by abdominal ultrasonography (US). METHODS: Intra-abdominal intestinal adhesions on the abdominal wall in 50 patients with a history of abdominal surgery were prospectively assessed by the visceral slide test with US before laparoscopic surgery from 2019 to 2022. Adhesion was assessed in six separate abdominal zones during US. Actual adhesion on the abdominal wall was confirmed during laparoscopic surgery. RESULTS: The sliding distances in upper right, upper central, upper left, lower right, lower central, and lower left zones in patients with versus without intestinal adhesion were 4.4 versus 1.4 cm (P = .004), 3.4 versus 2.5 cm, 4.3 versus 1.3 cm (P = .011), 3.1 versus 1.5 cm (P = .0014), 3.3 versus 1.1 cm (P = .013), and 3.4 versus 0.8 cm (P = .0061), respectively. Receiver operating characteristic analysis revealed the optimal value of sliding distance as 2.5 cm and the area under the curve as 0.86. The specificity of US assessment of adhesion was lower in the central zone than in lateral zones. Loose adhesion mostly seen around the scar was attributed to either filmy tissue or omental adhesion, leading to visceral sliding during US. CONCLUSION: This study revealed the reason for insufficient accuracy of preoperative US assessment of intestinal adhesion around the scar area because of loose adhesion. The upper lateral area might be optimal for first port insertion.

A case of accessory hepatic duct entering cystic duct successfully treated by laparoscopic cholecystectomy for cholecystolithiasis.

Although laparoscopic cholecystectomy is a well-established surgical procedure, an accessory hepatic duct (AcHD) entering the cystic duct is poorly understood. A 77-year-old woman with symptomatic cholecystlithiasis was referred to our hospital. Abdominal ultrasonography indicated several small stones in the gall bladder. Magnetic resonance cholangiopancreatography (MRCP) did not reveal an anomalous cystic duct. Dissecting the gall bladder bed at operation, AcHD entering the cystic duct was suspected. Intraoperative cholangiography revealed that B5 branch entered the cystic duct. We ligated the AcHD, and divided it. Laparoscopic cholecystectomy was completed, and the patient was discharged without any complication. A week after the operation, MRCP showed that ventral branch of B5 was dilated. The patient showed no symptom for more than a year. The present case exhibited extremely rare AcHD entering the cystic duct, which was hardly recognized before surgery. It is possible to recognize such anomalous variants with standard laparoscopic approach based on 2018 Tokyo Guidelines and with attention to the possibilities of AcHD entering the cystic duct.

Conversion Surgery After Atezolizumab Plus Bevacizumab for Primary and Peritoneal Metastasis After Hepatocellular Carcinoma Rupture.

BACKGROUND/AIM: Conversion surgery (CS) following atezolizumab plus bevacizumab (Atez+Bev) is a treatment strategy for unresectable hepatocellular carcinoma (UR-HCC). Herein, we report a case of CS after transcatheter arterial embolization (TAE) and Atez+Bev for primary HCC with peritoneal metastases and multiple liver metastasis after HCC rupture. CASE REPORT: A 75-year-old man with a suspected ruptured HCC in segment 4b was referred to the National Hospital Organization Kumamoto Medical Center. TAE was performed to stop the bleeding. Subsequently, 15 courses of Atez+Bev were administered for UR-HCC with primary tumor, peritoneal metastasis, and multiple liver metastases. Multiple liver metastases and peritoneal metastasis resolved 7 months after initiation of Atez+Bev. The primary HCC had shrunk, but the patient decided not to continue treatment because of severe numbness in his fingers. Six months after stopping Atez+Bev, CS was performed because no new lesions were observed, and the patient wished to become cancer-free by resection of the remaining tumor. HCC was successfully resected, and he was discharged without any complications. The pathological findings demonstrated that there was no remnant viable HCC. CONCLUSION: We herein present a case of CS following TAE and Atez+Bev for unresectable and ruptured HCC. The patient did not require chemotherapy after CS and is alive and recurrence-free for 7 months.

Shanghai fever, a fatal enteric illness, in an adult patient with neutropenia caused by treatment-related myelodysplastic syndrome: a case report.

BACKGROUND: Shanghai fever is a rare community-acquired enteric illness with sepsis caused by Pseudomonas aeruginosa. Cases of Shanghai fever in pediatric patients have been reported; however, to the best of our knowledge, there are no reports of adult cases. CASE PRESENTATION: A 65-year-old man visited the emergency department with sudden onset of abdominal pain. He was diagnosed as treatment-related myelodysplastic syndrome after treatment of follicular lymphoma. Moderate tenderness in the middle right abdominal quadrants was noted. Computed tomography showed abdominal free air with a small amount of effusion to the surrounding edematous small intestine, and we performed emergency exploration. During operation, we found multiple bowel perforations with patchy necrotic lesions. The patient was admitted to an intensive care unit postoperatively. Blood culture showed Pseudomonas aeruginosa. His condition improved; however, on the 8th postoperative day, the abdominal drain tube showed turbid drainage. We performed re-operation and found anastomotic leakage with two new bowel perforations. After the re-operation, the patient showed signs of septic shock and his general condition got worse, and the patient died due to multiple organ failure on the 12th postoperative day. CONCLUSION: Shanghai fever may occur in an adult patient with neutropenia.

A case of primary nonleukemic myeloid sarcoma of the spleen, successfully treated by surgery and hematopoietic stem cell transplantation.

BACKGROUND: Myeloid sarcoma (MS) is a rare disease, mostly found in conjunction with acute myelogenous leukemia or other diseases, and primary nonleukemic MS of the spleen is particularly rare. CASE PRESENTATION: We report a 57-year-old male who presented with a spleen mass that was found incidentally, and was enlarged. As a result of various examinations, he was diagnosed with primary MS of the spleen with suspected involvement of the transverse colon, left kidney, pancreatic tail, and left diaphragm. He underwent a total splenectomy, partial pancreatectomy, partial colectomy, left nephrectomy, and left diaphragm partial resection. Histological examination revealed splenic primary MS. Bone marrow biopsy and immunophenotypic flow cytometry revealed no evidence of myeloid leukemia. He underwent umbilical cord blood transplantation, and he is currently living without a sign of recurrence at 10 months after surgery. CONCLUSIONS: We experienced a very rare case of primary spleen MS that was discovered without a hematologic malignancy. Two cases of surgically resected primary splenic MS have been reported, including the present case.

Usefulness of laparoscopy in the management of incidentally discovered retroperitoneal liposarcoma mimicking inguinal hernia: A case report and literature review.

INTRODUCTION: Liposarcomas comprise around 10%-16% of soft tissue sarcomas. The two major sites of liposarcoma are the extremities and retroperitoneum. However, retroperitoneal liposarcomas mimicking inguinal hernia are rare. We present a case of retroperitoneal liposarcoma mimicking inguinal hernia, which was diagnosed after laparoscopic surgery and underwent curative resection. PRESENTATION OF CASE: A 46-year-old man was admitted to our hospital with a right inguinal pain and swelling that had been recognized for 3 years. We diagnosed the inguinal swelling as a right inguinal hernia and planned laparoscopic surgery for inguinal hernia repair. A hernia sac, however, was not found and swollen retroperitoneal fatty tissue near the right internal inguinal ring was observed by laparoscopy. We aborted the surgical procedure and performed computed tomography and magnetic resonance imaging, which revealed an extraperitoneal and lipomatous tumor extending through the inguinal canal to the scrotum. Wide local excision of the tumor, along with right orchidectomy, was performed under laparotomy. Histopathological diagnosis showed well-differentiated liposarcoma of the retroperitoneum and confirmed tumor-free margins. No evidence of recurrence or metastasis was seen in the 9 months after curative resection. DISCUSSION AND CONCLUSION: Laparoscopic surgery for inguinal hernia enables to observation of the inguinal region and management of rare cases, such as retroperitoneal liposarcoma.

[Hormone excretion and peroxisomes of human immortalized extravillous trophoblast cells (TCL-2) derived from first-trimester placenta].

We studied the hormone excretion of human immortalized extravillous trophoblast cells (TCL-2, first-trimester cells) and determined whether peroxisomes are present in TCL-2. The results of TCL-2 were compared with those of TCL-1 (third-trimester cells). Morphologically, TCL-2 cells were fibroblast-like, and the growth rate of TCL-2 was slower than that of TCL-1 during 3 days culture. Progesterone was detected in the medium of TCL-2, and its concentration was approximately one-tenth of that in TCL-1. The activity of the peroxisomal marker enzyme catalase was detected in the TCL-2 homogenate, and it was about one-third the level of that in TCL-1. Fatty acyl-CoA oxidase activity was detected in TCL-2, and it was about one-seventh the level of that in TCL-1. On the other hand, human chorionic gonadotropin (hCG) was detected in the medium of TCL-2, and its concentration after 3 days of culture was about 2-fold that in TCL-1. Using the diaminobenzidine (DAB) method, peroxisomes were found in TCL-2, but only a very small amount of catalase was detected. These results indicate that human immortalized extravillous trophoblast cells (TCL-2) synthesize, secrete hCG and progesterone, and may contain peroxisomes. Because extravillous trophoblast cells are difficult to obtain from the first-trimester placenta, TCL-2 cells are useful for the study of the physiologic functions (including peroxisomal function) of first-trimester cells.

Antiepileptic Drugs Elevate Astrocytic Kir4.1 Expression in the Rat Limbic Region.

Inwardly rectifying potassium (Kir) channel subunits Kir4.1 are specifically expressed in astrocytes and regulate neuronal excitability by mediating spatial potassium buffering. In addition, it is now known that astrocytic Kir4.1 channels are closely involved in the pathogenesis of epilepsy. Here, to explore the role of Kir4.1 channels in the treatment of epilepsy, we evaluated the effects of the antiepileptic drugs, valproate, phenytoin, phenobarbital and ethosuximide, on Kir4.1 expression in astrocytes using immunohistochemical techniques. Repeated treatment of rats with valproate (30-300 mg/kg, i.p., for 1-10 days) significantly elevated the Kir4.1 expression levels in the cerebral cortex, amygdala and hippocampus. Up-regulation of Kir4.1 expression by valproate occurred in a dose- and treatment period-related manner, and did not accompany an increase in the number of astrocytes probed by glial fibrillary acidic protein (GFAP). In addition, repeated treatment with phenytoin (30 mg/kg, i.p., for 10 days) or phenobarbital (30 mg/kg, i.p., for 10 days) also elevated Kir4.1 expression region-specifically in the amygdala. However, ethosuximide (100 mg/kg, i.p., for 10 days), which can alleviate absence but not convulsive seizures, showed no effects on the astrocytic Kir4.1 expression. The present results demonstrated for the first time that the antiepileptic drugs effective for convulsive seizures (valproate, phenytoin, and phenobarbital) commonly elevate the astrocytic Kir4.1 channel expression in the limbic regions, which may be related to their antiepileptic actions.

Expressional analysis of the astrocytic Kir4.1 channel in a pilocarpine-induced temporal lobe epilepsy model.

The inwardly rectifying potassium (Kir) channel Kir4.1 in brain astrocytes mediates spatial K(+) buffering and regulates neural activities. Recent studies have shown that loss-of-function mutations in the human gene KCNJ10 encoding Kir4.1 cause epileptic seizures, suggesting a close relationship between the Kir4.1 channel function and epileptogenesis. Here, we performed expressional analysis of Kir4.1 in a pilocarpine-induced rat model of temporal lobe epilepsy (TLE) to explore the role of Kir4.1 channels in modifying TLE epileptogenesis. Treatment of rats with pilocarpine (350 mg/kg, i.p.) induced acute status epilepticus, which subsequently caused spontaneous seizures 7-8 weeks after the pilocarpine treatment. Western blot analysis revealed that TLE rats (interictal condition) showed significantly higher levels of Kir4.1 than the control animals in the cerebral cortex, striatum, and hypothalamus. However, the expression of other Kir subunits, Kir5.1 and Kir2.1, remained unaltered. Immunohistochemical analysis illustrated that Kir4.1-immunoreactivity-positive astrocytes in the pilocarpine-induced TLE model were markedly increased in most of the brain regions examined, concomitant with an increase in the number of glial fibrillary acidic protein (GFAP)-positive astrocytes. In addition, Kir4.1 expression ratios relative to the number of astrocytes (Kir4.1-positive cells/GFAP-positive cells) were region-specifically elevated in the amygdala (i.e., medial and cortical amygdaloid nuclei) and sensory cortex. The present study demonstrated for the first time that the expression of astrocytic Kir4.1 channels was elevated in a pilocarpine-induced TLE model, especially in the amygdala, suggesting that astrocytic Kir4.1 channels play a role in modifying TLE epileptogenesis, possibly by acting as an inhibitory compensatory mechanism.

Preferential suppression of limbic Fos expression by intermittent hypoxia in obese diabetic mice.

Sleep apnea (SA) causes not only sleep disturbances, but also neurocognitive impairments and/or psychoemotional disorders. Here, we studied the effects of intermittent hypoxia (IH) on forebrain Fos expression using obese diabetic db/db mice to explore the pathophysiological alterations in neural activities and the brain regions related to SA syndrome. Male db/db mice were exposed to IH stimuli (repetitive 6-min cycles of 1min with 5% oxygen followed by 5min with 21% oxygen) for 8h (80 cycles) per day or normoxic condition (control group) for 14 days. Fos protein expression was immunohistochemically examined a day after the last IH exposure. Mapping analysis revealed a significant reduction of Fos expression by IH in limbic and paralimbic structures, including the cingulate and piriform cortices, the core part of the nucleus accumbens and most parts of the amygdala (i.e., the basolateral and basomedial amygdaloid nuclei, cortical amygdaloid area and medial amygdaloid nucleus). In the brain stem regions, Fos expression was region-specifically reduced in the ventral tegmental area while other regions including the striatum, thalamus and hypothalamus, were relatively resistant against IH. In addition, db/db mice exposed to IH showed a trend of sedative and/or depressive behavioral signs in the open field and forced swim tests. The present results illustrate that SA in the obese diabetic model causes neural suppression preferentially in the limbic and paralimbic regions, which may be related to the neuropsychological disturbances associated with SA.

Carcinoma of the Lower Uterine Segment (LUS): Clinicopathological Characteristics and Association with Lynch Syndrome.

Endometrial cancer arises from the uterine body and fundus in many cases, but can also originate from the lower region of the uterine body through the upper region of the cervix. Such tumors are referred to as carcinoma of the lower uterine segment (LUS) or isthmus, and account for 3-6.3% of all cases of endometrial cancer. This relatively low incidence has permitted performance of only small-scale studies, but the clinical and pathological characteristics of carcinoma of the LUS in all these reports have differed from those of other endometrial cancers. Generally, endometrial cancer is classified into estrogen-dependent endometrioid adenocarcinoma (designated as type I), and non-endometrioid types that are less associated with estrogen and include poorly differentiated adenocarcinoma (type II). In some reports, carcinoma of the LUS has been found to have type II characteristics. Carcinoma of the LUS has also been associated with Lynch syndrome, a hereditary disease with frequent development of colorectal, endometrial, and ovarian cancers. Lynch syndrome is thought to be induced by mismatch repair gene mutation. The frequency of Lynch syndrome in cases of general endometrial cancer is 1-2%. In contrast, the frequency in patients with carcinoma of the LUS is much higher, with up to 29% of cases diagnosable with Lynch syndrome and a high frequency of hMSH2 mutation found in one study. This suggests that further investigation of the clinical and pathological characteristics of carcinoma of the LUS and the association with Lynch syndrome is required through performance of a large-scale survey.

Narrow band imaging hysteroscopy: a comparative study using randomized video images.

Narrow band imaging (NBI) has been used in the gastrointestinal endoscopy field as a novel endoscopic imaging technique and has contributed to improved qualitative diagnosis and detection of lesions. However, there are only a few studies of use of NBI in the gynecology field. We applied NBI in flexible hysteroscopy at our outpatient clinic and evaluated the utility of NBI hysteroscopy for diagnosis of malignant endometrial lesions by comparison of the sensitivity and specificity between white light alone and white light+NBI using hysteroscopic video images. The subjects were 65 patients with a suspected endometrial lesion in the uterine cavity. These patients underwent flexible hysteroscopy using NBI in addition to conventional white light. Video images from 65 patients were edited into two groups, white light alone (WL group) and white light+NBI (NBI group) (130 images in total). Computerized block randomization of the order was then performed. Four raters independently diagnosed the images without use of other clinical information. Using the pathological diagnosis as the gold standard, we evaluated the sensitivity and specificity of diagnosis of atypical endometrial hyperplasia (AEH) or endometrial carcinoma compared between the WL and NBI groups. The sensitivity of diagnosis of AEH or endometrial carcinoma was numerically higher in the NBI group for all raters, and the average sensitivity was significantly higher in the NBI group compared to the WL group (78.6% vs. 63.7%, P<0.001). The specificity for each rater and the average specificity were comparable between the two groups. Compared to white light hysteroscopy, NBI hysteroscopy had a higher sensitivity for diagnosis of AEH or endometrial carcinoma without loss of specificity. This suggests that NBI hysteroscopy may be more useful than white light hysteroscopy for endoscopic diagnosis of malignant endometrial lesions.

Relationship between DNA Mismatch Repair Deficiency and Endometrial Cancer.

Some cases of endometrial cancer are associated with a familial tumor and are referred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Lynch syndrome is thought to be induced by germline mutation of the DNA mismatch repair (MMR) gene. An aberration in the MMR gene prevents accurate repair of base mismatches produced during DNA replication. This phenomenon can lead to an increased frequency of errors in target genes involved in carcinogenesis, resulting in cancerization of the cell. On the other hand, aberrant DNA methylation is thought to play a key role in sporadic endometrial carcinogenesis. Hypermethylation of unmethylated CpG islands in the promoter regions of cancer-related genes associated with DNA repair leads to the cell becoming cancerous. Thus, both genetic and epigenetic changes are intricately involved in the process through which cells become cancerous. In this review, we introduce the latest findings on the DNA mismatch repair pathway in endometrial cancer.

Flexible hysteroscopy with narrow band imaging (NBI) for endoscopic diagnosis of malignant endometrial lesions.

Narrow band imaging (NBI) for detection of blood vessels and microstructures on the mucosal surface is used in gastrointestinal endoscopy since it can improve qualitative diagnosis and detection of lesion. However, there are no studies on flexible hysteroscopy using NBI. We performed flexible hysteroscopy with NBI for outpatients to investigate the sensitivity and specificity of endoscopic diagnosis of malignant endometrial lesions. Of patients who attended our hospital for suspected lesions in the uterine cavity between April 2009 and May 2010, 104 subjects underwent hysteroscopy with NBI, in addition to white light. Using the pathological diagnosis as the gold-standard, we evaluated the sensitivity and specificity of NBI hysteroscopy for detecting atypical endometrial hyperplasia (AEH) or carcinoma. The results were also compared with historical data (n=209) for conventional hysteroscopy using white light only in 2008. The sensitivities were 97.2% [95% confidence interval (95% CI): 90.3-99.7%] and 82.6% (95% CI: 74.4-89.0%) for NBI hysteroscopy and conventional hysteroscopy, respectively. The 95% CIs for the two methods did not overlap and the sensitivity of lesion detection was higher with NBI hysteroscopy. Specificities were comparable, 90.6% (95% CI: 75.0-98.0%) and 85.1% (95% CI: 76.3-91.6%) between the methods. NBI hysteroscopy has increased sensitivity for detection of atypical endometrial hyperplasia (AEH) or carcinoma. A comparison with historical data suggested that NBI may be useful for diagnosis of malignant endometrial lesions. As far as we are aware, this is the first evaluation of flexible hysteroscopy with NBI for diagnosis of malignant endometrial lesions.

MicroRNA and endometrial cancer: Roles of small RNAs in human tumors and clinical applications (Review).

MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 base pairs that regulate the expression of genes by targeting messenger RNA with complementarity with the miRNA base sequence. Regulation of gene expression by miRNAs is crucial in cellular development and differentiation, and recent studies suggest a relationship between human diseases and the breakdown of gene silencing mechanisms induced by miRNA abnormalities. In particular, abnormal miRNA expression has been detected in various types of cancer and the target genes have been identified. These results indicate that miRNAs act in a manner equivalent to oncogenes or tumor suppressors. miRNAs may also serve as diagnostic biomarkers and therapeutic targets. In this review, we introduce the latest findings on miRNAs in human endometrial cancer, a common malignancy, and discuss the potential of miRNAs as biomarkers and targets for molecular therapy.

Presence and some characteristics of peroxisomes in immortalized human trophoblast cells.

Using morphological and biochemical (Western blot and cell fractionation) methods, we investigated whether peroxisomes are present in human extravillous trophoblast cells. Immortalized extravillous trophoblast cells (TCL-1) were incubated in the presence or absence of 0.5 mM clofibric acid for 3 d. In immunofluorescence staining of trophoblast cells with antibodies anti-catalase and anti-acyl-CoA oxidase (marker enzymes of peroxisomes), electron microscopy and immunoelectron microscopy, peroxisomes were detected in the cells. The size and number of peroxisomes in the trophoblast cells were smaller than those in rat liver. The number of peroxisomes was increased by clofibric acid. In Western blot experiment with antibodies anti-peroxisomal enzymes of beta-oxidation system, densitometric analysis revealed approximately two fold increase in staining by clofibric acid. When we performed cell fractionation experiment using catalase as one of the peroxisomal marker enzymes, the highest activity of catalase was found in the light mitochondrial fraction. Specific activity of catalase in the light mitochondrial fraction was significantly increased to about 1.3 times higher than the control value by clofibric acid treatment. Upon Nycodenz density gradient centrifugation, the catalase activity was concentrated in the density fraction around 1.14-1.15. These findings suggest that microperoxisomes, which have a density smaller than those of rat hepatic peroxisomes, do exist in human extravillous trophoblast cells. It may also be possible to proliferate human peroxisomes in limited quantities using peroxisome proliferator of rodents.