Effects of leuprorelin for the treatment of recurrent gynecological cancer by assessment including self-administered quality-of-life questionnaire.

AIM: To investigate the effects of leuprorelin using a self-administered quality-of-life (QOL) questionnaire in patients with recurrent gynecological cancer. METHODS: Records of patients who received 3.75 mg leuprorelin every 4 weeks for the treatment of recurrent gynecological cancer were retrospectively reviewed. The physical domain of the QOL questionnaire, Care Notebook, was used to assess physical symptoms. Symptom deterioration was defined as a ≥10-point increase in baseline score; otherwise, symptoms were defined as controlled. Radiological and serological responses were evaluated according to the 2011 Gynecological Cancer Intergroup criteria. RESULTS: From 2007 to 2015, 25 patients were administered leuprorelin for the treatment of epithelial ovarian cancer, granulosa cell tumor, endometrial cancer, endometrial stromal sarcoma and clear cell cervical cancer (in 13, 3, 6, 2 and 1 patients, respectively). Twenty patients had received a median of three lines (range 1-12 lines) of chemotherapy. Ten patients had progressive disease during their previous round of chemotherapy. Twenty patients completed the questionnaire every 4 weeks. Following leuprorelin treatment for 8 weeks, the symptom and disease control rates were 65% (13/20) and 44% (11/25), respectively. Two patients, one each with granulosa cell tumor and endometrial cancer, had stable disease at 6 months. Among the 20 patients who completed the QOL questionnaire, symptom control and disease control at 8 weeks showed a significant correlation (P = 0.016). CONCLUSION: Leuprorelin had minimal anticancer activity. The physical domain of the QOL questionnaire could be used to assess effects of hormonal treatment.

Baerveldt surgery outcomes: anterior chamber insertion versus vitreous cavity insertion.

PURPOSE: We compared the outcomes of Baerveldt glaucoma implant (BGI) surgery between vitreous cavity and anterior chamber insertion. METHODS: We retrospectively analyzed a total of 105 consecutive eyes that underwent BGI surgery and were followed up for ≥ 12 months. BGI surgery was performed via the anterior chamber (AC group 48 eyes) or the pars plana into the vitreous cavity (VC group 57 eyes). Patients' data were examined at 3, 6, and 12 months, and then every 6 months after surgery. We compared the groups' intraocular pressure (IOP), success ratio, visual acuity, number of glaucoma medications, central corneal endothelial cell density (CCECD), reduction ratio of CCECD, and postoperative complications. RESULTS: The mean preoperative and postoperative IOP values were not significantly different between the two groups. In the Kaplan-Meier survival plots, there was no significant between-group difference in the success rate (p = 0.333). The postoperative mean CCECD decreased significantly faster in the AC group than the VC group at all time points. The cases of postoperative corneal edema were 12.5% in AC group and 1.8% in VC group. The risk of postoperative corneal edema was significantly higher in the AC group (p = 0.0136). Risk factors for the rapid reduction of CCECD were "history of trabeculectomy" (p = 0.00283), "insertion into the anterior chamber" (p = 0.001), and "shorter distance between the tube and corneal endothelium" (p = 0.0137). CONCLUSION: There was no significant between-group difference in postoperative IOP, medications, or success rate. Considering the reduction of corneal endothelial cells, insertion into the vitreous cavity seems safer than insertion into the anterior chamber.

Results of the Baerveldt® Glaucoma Implant for Neovascular Glaucoma Patients.

Purpose: To evaluate the efficacy and safety of the Baerveldt® glaucoma implant (BGI) for eyes with neovascular glaucoma (NVG). Methods: This was a retrospective study. Thirty-five eyes (31 patients) diagnosed with refractory NVG at Toyama University Hospital were enrolled from January 2012 to December 2015. All patients underwent BGI and were followed up for more than 6 months. Results: The mean age of patients was 62.7±13.9 years old. The mean postoperative follow-up periods was 22.0±12.7 months. The mean preoperative IOP was 35.5±9.6 mmHg and the mean postoperative IOP at 6, 12, 24, 36, 48 month were 12.7±5.9, 12.8±3.7, 12.2±3.3, 13.1±3.3, 15.0±1.4 mmHg respectively. Postoperative visual acuity was not significantly improved. Complications were Hoffmann Elbow erosion in 2 patients who needed additional surgery. The success rate at one year was 82.7%. Postoperative intervention was not required. Conclusion: BGI surgery should be considered a useful treatment to lower the IOP for NVG.

Structural basis for Arf6-MKLP1 complex formation on the Flemming body responsible for cytokinesis.

A small GTPase, Arf6, is involved in cytokinesis by localizing to the Flemming body (the midbody). However, it remains unknown how Arf6 contributes to cytokinesis. Here, we demonstrate that Arf6 directly interacts with mitotic kinesin-like protein 1 (MKLP1), a Flemming body-localizing protein essential for cytokinesis. The crystal structure of the Arf6-MKLP1 complex reveals that MKLP1 forms a homodimer flanked by two Arf6 molecules, forming a 2:2 heterotetramer containing an extended ß-sheet composed of 22 ß-strands that spans the entire heterotetramer, suitable for interaction with a concave membrane surface at the cleavage furrow. We show that, during cytokinesis, Arf6 is first accumulated around the cleavage furrow and, prior to abscission, recruited onto the Flemming body via interaction with MKLP1. We also show by structure-based mutagenesis and siRNA-mediated knockdowns that the complex formation is required for completion of cytokinesis. A model based on these results suggests that the Arf6-MKLP1 complex plays a crucial role in cytokinesis by connecting the microtubule bundle and membranes at the cleavage plane.

Mitosis-coupled, microtubule-dependent clustering of endosomal vesicles around centrosomes.

Upon cell division, not only cells themselves but also their organelles undergo drastic shape changes, although the behaviors of organelles other than the Golgi apparatus remain poorly understood. We followed the spatiotemporal changes in the localization of transferrin receptor (TfnR) and other proteins. In early mitotic phases, a population of proteins cycling through the endocytic recycling compartment (ERC) exhibits a distinct spatiotemporal change from that of Golgi proteins. In prophase/prometaphase, when the cell surface-to-volume ratio is reaching its minimum, the ERC proteins are transiently assembled around the centrated centrosome in a microtubule- and dynein-dependent manner, and soon separated polewards into two clusters concomitant with separation of duplicated centrosomes. Electron microscopic analysis revealed that endosomal vesicles containing endocytosed transferrin cluster tightly around centrosomes without fusing with one another. As cytokinesis proceeds, the clusters gradually collapse, and the ERC proteins reassemble around the furrowing equatorial region. FRAP (fluorescence recovery after photobleaching) analyses of EGFP-TfnR-expressing cells revealed minimal membrane exchange between the endosomal clusters and other cellular compartments until anaphase/telophase, when membrane traffic resumes. Our observations indicate that ERC clustering around centrosomes plays a fundamental role in restricting membrane delivery to the plasma membrane during early mitotic phases, when the cell surface-to-volume ratio reaches its minimum.

Itraconazole Modulates Phospholipid Levels in Tumor-associated Macrophages.

BACKGROUND/AIM: Itraconazole, an antifungal drug, repolarizes pro-tumorigenic M2 tumor-associated macrophages to anti-tumorigenic M1-like phenotypes, thereby inhibiting the proliferation of cancer cells; however, the underlying mechanism remains unclear. Therefore, we investigated the effect of itraconazole on membrane-associated lipids in tumor-associated macrophages (TAM). MATERIALS AND METHODS: M1 and M2 macrophages were derived from the human monocyte leukemia cell line (THP-1) and cultured with or without 10 µM itraconazole. Cells were homogenized and subjected to liquid chromatography/mass spectrometry (LC/MS) analysis to estimate the glycerophospholipid levels in the cells. RESULTS: Lipidomic analysis results, displayed on a volcano plot, revealed that itraconazole-induced altered phospholipid composition, with more pronounced changes in M2 macrophages than in M1. Notably, itraconazole significantly increased intracellular phosphatidylinositol and lysophosphatidylcholine levels in M2 macrophages. CONCLUSION: Itraconazole modulates the lipid metabolism of TAMs, which could have implications for the development of novel cancer therapies.

Weight-Loss Interventions and Levonorgestrel Intrauterine System Implantation for Early-Stage Endometrial Cancer and Atypical Endometrial Hyperplasia to Reduce Perioperative Risk of Severely Obese Patients.

Endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) are associated with obesity, which increases the perioperative morbidity and surgical difficulties in laparoscopic and robotic surgery. Weight-loss interventions (WLIs) are likely to reduce morbidity; however, delayed surgery may cause cancer progression. To minimize the tumor progression, levonorgestrel intrauterine system (LNG-IUS) with minimal side effects was used until the planned surgery. During 2016 and 2021, we conducted preoperative management of WLI using LNG-IUS for seven highly obese women with a body mass index (BMI) ≥35 kg/m2 who had AEH and EC with Grade 1 and no myometrial invasion on magnetic resonance imaging. In three of the seven patients, the BMI decreased by more than 5. Two patients with AEH achieved remission after LNG-IUS placement and requested conservative management. Five patients with EC underwent laparoscopic hysterectomy, without perioperative complications.

Medroxyprogesterone as the Initial Systemic Treatment of Recurrent Endometrial Cancer: A Single Institutional Study.

BACKGROUND/AIM: Hormonal treatment is the preferred initial systemic therapy for patients with advanced or recurrent G1 or G2 endometrial cancer (EC) in terms of efficacy, toxicity, and economy. Few reports are available on the topic and we, therefore, conducted a retrospective study. PATIENTS AND METHODS: Patients with EC who received high-dose medroxyprogesterone (MPA) at our Hospital between January 2010 and December 2022 were reviewed. Patients who were treated for fertility preservation or had a history of systemic chemotherapy other than adjuvant therapy were excluded. RESULTS: Sixteen patients who were eligible for study inclusion had recurrent G1 or G2 EC. Their median age was 65 years (range=51-82 years), median body mass index was 22.6 kg/m2 (range=15.3-43.2 kg/m2), and all patients had an ECOG Performance Status of 0. All patients received 200 mg/day of MPA, and eight patients concomitantly received 100 mg/day of aspirin. None of the patients experienced severe adverse events. One patient had grade 2 deep vein thrombosis. Two patients discontinued MPA treatment because of adverse events. The response rate was 44% [95% confidence interval (CI)=20-68%] and median progression-free survival (PFS) was 6.9 months (95% CI=7.5-26 months). Four of 16 patients had PFS longer than 12 months, all of whom had positive tissue estrogen receptor (ER) and progesterone receptor (PR), and PFS at 2 years was 35% (95% CI=10.2-59.8%). CONCLUSION: Hormone therapy is effective long-term in ER- and PR-positive EC and can be recommended as initial systemic therapy. Toxicity is mild and manageable.

Itraconazole Repolarizes Tumor-associated Macrophages and Suppresses Cervical Cancer Cell Growth.

BACKGROUND/AIM: Itraconazole (ITZ), an antifungal agent, has been reported to have anti-tumor effects in patients with multiple cancer types. We investigated the involvement of tumor-associated macrophages (TAMs) in its tumor-agnostic mechanism. MATERIALS AND METHODS: M1 and M2 macrophages were established from human monocyte leukemia cell line (THP-1) and their phenotypes were determined morphologically. Cell membrane antigens and secreted proteins were evaluated by western blots and enzyme-linked immunosorbent assay, respectively. The proteomic profiling of cells was done by liquid chromatography with tandem mass spectrometry and analyzed. Viability of cervical cancer cells (CaSki) was evaluated after addition of the supernatant of M2 macrophages and during co-culture with M2 macrophages, with or without 10-5 M ITZ. RESULTS: Co-culture of M1 macrophages inhibited the proliferation of CaSki cells (p=0.012), while that of M2 macrophages promoted their proliferation (p<0.0001). After treatment of M2 macrophages with ITZ for 24 h, they changed into M1-like shape with decreased expression of cluster of differentiation 163 (CD163) and chemokine ligand 18 (CCL18). The M1-like shape was maintained for 7 weeks of ITZ treatment and reverted to original after ITZ removal. Proteomic analysis of ITZ treated-M2 macrophages also demonstrated M1-like signature including the elevated levels of tumor necrosis factor (TNF)-related proteins. After treatment with ITZ, both the supernatant of the M2 macrophages and the co-culture with M2 macrophages significantly inhibited the proliferation of CaSki cells (each, p<0.0001). CONCLUSION: ITZ repolarized M2 macrophages to M1 type and suppressed cervical cancer cell growth demonstrating TAM-mediated anti-cancer activity of ITZ.

Comprehensive Genomic Profiling Detects Hereditary Cancers and Confers Survival Advantage in Patients With Gynaecological Cancers.

BACKGROUND/AIM: The clinical benefits of comprehensive genomic profiling (CGP) of tumours in patients with gynaecological cancers remain unknown. We investigated the utility of CGP in assessing patient survival and its efficacy in detecting hereditary cancers in gynaecological patients. PATIENTS AND METHODS: We retrospectively analysed the medical records of 104 gynaecological patients who underwent CGP between August 2018 and December 2022. The detection of actionable and accessible genomic alterations and administration of targeted therapy, as recommended by the molecular tumour board (MTB), were assessed. The overall survival (after second-line treatment in cervical and endometrial carcinomas and after platinum-resistant recurrence in ovarian carcinoma) was compared between patients with or without administration of MTB-recommended genotype-matched therapy. Germline findings were assessed using a variant allele frequency-tumour content graph. RESULTS: Among 104 patients, actionable and accessible genomic alterations were observed in 53 patients. Matched therapy was applied in 21 patients, comprising administration of repurposing itraconazole (n=7), immune checkpoint inhibitors (n=7), poly (ADP-ribose) polymerase inhibitors (n=5), and others (n=2). The median overall survival of patients receiving and not receiving matched therapy were 19.3 months and 11.2 months, respectively (p=0.036, hazard ratio=0.48). Among 12 patients with hereditary cancers, 11 patients were previously undiagnosed. Seven patients had hereditary breast and ovarian cancer, and five had other cancer. CONCLUSION: The implementation of CGP testing prolonged overall survival in gynaecological cancer as well as provided an opportunity for genetic counselling for newly-diagnosed patients with hereditary cancers and their families.

Usefulness of indocyanine green angiography to depict the distant retinal vascular anomalies associated with branch retinal vein occlusion causing serous macular detachment.

PURPOSE: To report the usefulness of indocyanine green angiography (ICGA) to depict the retinal vascular anomalies associated with distant branch retinal vein occlusion resulting in serous retinal detachment at the macula. METHODS: This was a retrospective, case series of 6 patients (6 eyes) with serous retinal detachments. Fluorescein angiography and ICGA showed that those 6 eyes had a distant branch retinal vein occlusion. The characteristics in ophthalmic examinations such as fundus appearance, fluorescein angiography, ICGA, optical coherence tomography, and clinical courses were evaluated. RESULTS: In addition to serous retinal detachments, five eyes exhibited hard exudates around the macula. Fluorescein angiography and ICGA clearly showed the vessel occlusion; however, no apparent abnormalities appeared in the macular area in any of the eyes. In four eyes, early-phase ICGA depicted the retinal vascular anomalies within the area of venous occlusion and those were seen as hyperfluorescent patches on late-phase ICGA. In two eyes, punctate hyperfluorescent spots were seen in the area of venous occlusion on late-phase ICGA. Optical coherence tomography depicted a serous retinal detachment at the macula and retinal swelling in the outer nuclear layer from the macula to the hyperfluorescent abnormalities on ICGA. The macular serous retinal detachments were resolved within 3 months after laser photocoagulation was applied to the hyperfluorescent areas on ICGA. CONCLUSION: Leakage from subsequent vascular anomalies after branch retinal vein occlusion can cause submacular fluid. Indocyanine green angiography is useful for detecting the causative vascular regions of the fluid.

Metronomic chemotherapy using oral cyclophosphamide and bevacizumab for recurrent cervical cancer: A multi-institutional retrospective study.

No standard chemotherapy is available after disease progression or anaphylaxis during platinum chemotherapy among patients with recurrent cervical cancer. Here we report the efficacy and toxicities of metronomic chemotherapy consisting of 50 mg of oral cyclophosphamide (CPA) daily and intravenous 15 mg/kg of bevacizumab (BEV) repeated every 3 weeks (CPA-BEV). Treated patients were retrospectively reviewed. Adverse events and response rates were recorded according to the Common Toxicity Criteria for Adverse Events (CTCAE) ver 5.0 and Response Evaluation Criteria In Solid Tumors ver 1.1, respectively. Eleven patients had been treated with CPA-BEV between 2016 and 2021.The pathologic types were squamous cell carcinoma in seven patients, adenocarcinoma in three, and large cell neuroendocrine carcinoma in one. Nine patients had primary concurrent chemoradiotherapy (CCRT). Five patients received more than one prior chemotherapy (excluding CCRT). Six patients had progressive disease during prior platinum-based chemotherapy, four patients recurred within 6 months of the last platinum administration, and one patient had platinum anaphylaxis. Grade 3 or more hematologic toxicities and grade 2 or more non-hematological toxicities were observed in one with grade 3 neutropenia and in one with grade 2 proteinuria, respectively. The median duration of chemotherapy was 2.8 months (range 0.2-30.6 months). One patient had CR but none had PR. Median progression-free survival was 2.8 months (95 %CI: 2.1-10.7 months), and median overall survival was 13.6 months (95 %CI: 8.4-33.7 months). In conclusion, the CPA-BEV regimen showed favorable antitumor activity with minimal toxicity and is promising candidate for second-line chemotherapy.

Itraconazole Inhibits Intracellular Cholesterol Trafficking and Decreases Phosphatidylserine Level in Cervical Cancer Cells.

BACKGROUND/AIM: Itraconazole shows anticancer activity in various types of cancer but its underlying mechanism is unclear. We investigated the effect of itraconazole on membrane-associated lipids. MATERIALS AND METHODS: To investigate the influences of itraconazole on cholesterol trafficking, cervical cancer CaSki cells were cultured with itraconazole and analyzed by Filipin staining followed by confocal microscopy. Effect on the glycerophospholipid profiles was analyzed by liquid chromatography/mass spectrometry (LC/MS). RESULTS: After itraconazole treatment, Filipin staining revealed cholesterol accumulation in the intracellular compartments, which was similar to the distribution after treatment of U18666A (cholesterol transport inhibitor). LC/MS analysis showed a significant decrease in phosphatidylserine levels and an increase in lysophosphatidylcholine levels in CaSki cells. CONCLUSION: Itraconazole inhibited cholesterol trafficking and altered the phospholipid composition. Alterations in the cell membrane can potentiate the anticancer activity of itraconazole.

Itraconazole Increases Resolvin E3 Concentration and 12/15-lipoxygenase Inhibitor Attenuates Itraconazole Cytotoxicity in Cervical Cancer Cells.

BACKGROUND/AIM: The anticancer mechanism of itraconazole remains unsolved; therefore, we studied itraconazole-induced alterations in specialized pro-resolving mediators (SPMs) in cancer cells. MATERIALS AND METHODS: The human cervical squamous carcinoma cell line CaSki was cultured with or without 1 µM itraconazole. Liquid chromatography/mass spectrometry analysis was conducted to identify SPMs that were influenced by itraconazole. Cell growth experiments were conducted using itraconazole and inhibitors targeting the metabolic pathways of candidate SPMs. RESULTS: Resolvin E3, resolvin E2, prostaglandin J2 (PGJ2), delta-12-PGJ2, and maresin 2 were identified as candidate SPMs. The 12/15-lipoxygenase inhibitor, which is involved in the conversion of 18-hydroxy-eicosapentaenoic acid to resolvin E3, attenuated the inhibitory effect of itraconazole. Inhibition of the PGJ2 metabolic pathway did not interfere with itraconazole treatment. CONCLUSION: The metabolic pathway of SPMs, including resolving E3, could be proposed as an anticancer target of itraconazole.

Recurrent uterine serous carcinoma with a germline pathogenic BRCA2 variant treated using olaparib: A case report.

A germline pathogenic variant in BRCA2 was secondarily found through genomic sequencing of uterine serous carcinoma. Clinical response to olaparib was observed in recurrent uterine serous carcinoma with a germline BRCA2 mutation. Here, we report, for the first time, a long-term clinical response to olaparib in a patient with uterine serous carcinoma and a germline pathogenic BRCA2 variant.

Bevacizumab with metronomic chemotherapy of low-dose oral cyclophosphamide in recurrent cervical cancer: Four cases.

Standard chemotherapy for women with advanced or recurrent cervical cancer involves a combination of paclitaxel, platinum, and bevacizumab. However, for patients who experience anaphylaxis in response to paclitaxel or platinum, have permanent peripheral neuropathy, or develop early recurrence or progressive disease during first-line chemotherapy, the development of a non-taxane non-platinum regimen is mandatory. Clinical trials using anti-angiogenic treatment demonstrated favorable outcomes in cases of highly vascularized cervical cancer. Metronomic chemotherapy has been considered an anti-angiogenic treatment, although its use in combination with bevacizumab has not been studied in cervical cancer. We treated four patients with recurrent cervical cancer with 50 mg of oral cyclophosphamide daily and 15 mg/kg of intravenous bevacizumab every 3 weeks (CFA-BEV). One patient experienced disease progression after 4 months, whereas the other three patients continued the regimen until their last follow-up at 13, 14, and 15 months, respectively. One patient suffered from grade 3 neutropenia; however, no grade 2 or higher non-hematological toxicities were observed. These cases demonstrate the use of CFA-BEV with minimal toxicity and expected anti-cancer activity and indicate that this regimen should be considered for second-line chemotherapy in advanced recurrent cervical cancer.

Repurposing itraconazole as an anticancer agent.

Itraconazole, a common anti-fungal agent, has demonstrated potential anticancer activity, including reversing chemoresistance mediated by P-glycoprotein, modulating the signal transduction pathways of Hedgehog, mechanistic target of rapamycin and Wnt/ß-catenin in cancer cells, inhibiting angiogenesis and lymphangiogenesis, and possibly interfering with cancer-stromal cell interactions. Clinical trials have suggested the clinical benefits of itraconazole monotherapy for prostate cancer and basal cell carcinoma, as well as the survival advantage of combination chemotherapy for relapsed non-small cell lung, ovarian, triple negative breast, pancreatic and biliary tract cancer. As drug repurposing is cost-effective and timesaving, a review was conducted of preclinical and clinical data focusing on the anticancer activity of itraconazole, and discusses the future directions for repurposing itraconazole as an anticancer agent.

Itraconazole Modulates Hedgehog, WNT/ß-catenin, as well as Akt Signalling, and Inhibits Proliferation of Cervical Cancer Cells.

BACKGROUND/AIM: Repurposing itraconazole as an anticancer agent has been evaluated in several studies. The present study investigated whether itraconazole exerts an anticancer effect on cervical cancer cells. MATERIALS AND METHODS: CaSki and HeLa cells were cultured in itraconazole and vehicle after which colony-forming and cell viability assays were performed. Transcription and protein expression were assessed by cDNA microarray analysis and immunoblotting, respectively. RESULTS: Itraconazole suppressed proliferation of CaSki and HeLa cells in a dose- and time-dependent manner. Furthermore, CaSki cells were more significantly affected by itraconazole than HeLa cells. The microarray analysis showed an 8-fold down-regulation in the expression of GLI1, WNT4 and WNT10A among itraconazole-treated CaSki cells. Moreover, the transcription of sterol carrier protein-2 and ATP-binding cassette transporter-1 was unaffected by itraconazole. Immunoblots showed suppression in ß-catenin expression and Akt phosphorylation. CONCLUSION: Itraconazole is a multi-targeting anticancer agent and a promising therapeutic agent for cervical cancer.

Itraconazole Inhibits AKT/mTOR Signaling and Proliferation in Endometrial Cancer Cells.

BACKGROUND: Itraconazole is a common antifungal agent that has demonstrated anticancer activity in preclinical and clinical studies. This study investigated whether itraconazole exerts this effect in endometrial cancer (EC) cells. MATERIALS AND METHODS: Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and gene and protein expression were assessed by microarray analysis and immunoblotting, respectively, in five EC cell lines. RESULTS: Itraconazole-suppressed proliferation of AN3-CA, HEC-1A and Ishikawa cells (p<0.05) but not of HEC-50B or SNG-II cells. Itraconazole did not suppress GLI1 or GLI2 transcription but did inhibit the expression of mammalian target of rapamycin (mTOR) signaling components in AN3-CA and HEC-1A cells, while inducing that of microtubule-associated protein 1A/1B-light chain 3-II, a marker of autophagy. ATP-binding cassette transporter A1 gene was down-regulated in Ishikawa, HEC-50B and SNG-II cells. CONCLUSION: Itraconazole treatment suppresses the growth of EC cells by inhibiting AKT/mTOR signalling.

[A case of acute pulmonary thromboembolism accompanied by anomalous inferior vena cava with azygous continuation].

A 38-year-old man with atopic dermatitis presented with right chest pain and dyspnea. Previously, he had received 2mg of betamethasone daily, to prevent rejection of the right transplanted cornea, for 24 days. His body temperature was 37.4 degrees C, peripheral leucocyte count measured 12,000/mm3, and C-reactive protein was 6.3 mg/dl. A computed tomogram of the chest revealed infiltration in the right lower lung field, and he was then treated for pneumonia. The second day he fell down one flight of stairs due to a syncopal attack and received a head injury. At this point his vital blood pressure was 102/55 mmHg, heart rate was 130/min and SpO2 under breathing room air was 76%. These findings indicated possible acute pulmonary thromboembolism. Enhanced computed tomography revealed pulmonary arteries occluded by massive thrombosis and anomalous inferior vena cava with azygous continuation. To decrease the risk of further cerebral bleeding, anti-coagulation therapy was administered with only 24,000 IU/day of heparin. Following treatment, the patient completely recovered. We reported this rare case of acute pulmonary thromboembolism accompanied by anomalous inferior vena cava with azygous continuation.