The effect of nintedanib on health-related quality of life in Japanese patients with progressive fibrosing interstitial lung diseases: A subset analysis of the INBUILD trial.

BACKGROUND: In previous Japanese subgroup/subset analyses of the global INBUILD trial, nintedanib reduced the annual rate of forced vital capacity (FVC) decline and the risk of disease progression in patients with progressive fibrosing interstitial lung diseases (PF-ILDs). This exploratory subset analysis assessed the effect of nintedanib on symptoms and impacts of pulmonary fibrosis in Japanese patients with PF-ILDs, including those with usual interstitial pneumonia (UIP)-like fibrotic pattern on high-resolution computed tomography (HRCT). METHODS: This analysis included Japanese patients who received at least one dose of study treatment in the randomized, double-blind, placebo-controlled INBUILD trial. The Living with Pulmonary Fibrosis (L-PF) questionnaire was used to assess pulmonary fibrosis symptoms and impacts (higher scores indicated greater impairment) at baseline and weeks 12-52. RESULTS: In total, 108 Japanese patients (nintedanib: n = 52; placebo: n = 56) were included; 84 patients had UIP-like fibrotic pattern on HRCT. In the total Japanese subgroup and in those with UIP-like fibrotic pattern, numerically greater increases in L-PF total, symptoms total, symptoms fatigue domain, and impacts scores were observed in the placebo group than in the nintedanib group at all timepoints, starting from week 12. A numerically greater increase in the symptoms dyspnea domain score was observed with placebo versus nintedanib starting from week 36. Throughout the study, the symptoms cough domain score increased in the placebo group but decreased in the nintedanib group. CONCLUSIONS: Our findings demonstrate that nintedanib has the potential to reduce the worsening of symptoms and impacts of pulmonary fibrosis in Japanese patients with PF-ILDs.

Clinical Prediction of Retained Products of Conception: Combining Obstetric History and Ultrasound for Improved Accuracy in Severe Postpartum Hemorrhage.

Background The current challenge is how to improve the management of postpartum hemorrhage (PPH) to reduce the maternal mortality rate further. This study aimed to investigate whether a combined specific obstetric history and ultrasonographic findings can improve the predictive accuracy of retained products of conception (RPOC) with severe PPH. Methods This retrospective study included 56 patients who were diagnosed with RPOC. We extracted the following clinical data: obstetric history of second-trimester miscarriage, the time at which there was clinical suspicion of RPOC after the previous pregnancy (TIME), grayscale ultrasonographic finding (RPOC long-axis length [SIZE]), and color Doppler ultrasonographic finding based on the Gutenberg classification (RPOC hypervascularity). In this study, we defined cases requiring blood transfusion therapy or transcatheter arterial embolization as severe PPH. The patients were divided into two groups according to the presence or absence of severe PPH. The predictors of severe PPH were evaluated using logistic regression models. Model A comprised a combination of second-trimester miscarriage and TIME, Model B comprised a combination of Model A and long-axis SIZE, and Model C comprised a combination of Model B and RPOC hypervascularity. Results The multivariable analysis showed that long-axis SIZE was the only significant predictor of severe PPH (odds ratio [OR], 10.38; 95% confidence interval [CI], 2.06-63.86) independent of second-trimester miscarriage, TIME, and RPOC hypervascularity. The c-statistic was higher in Model C (OR, 0.863; 95% CI, 0.731-0.936) than in Model A (OR, 0.723; 95% CI, 0.551-0.847) and Model B (OR, 0.834; 95% CI, 0.677-0.923). Conclusion Combining a specific obstetric history (second-trimester miscarriage and TIME) and ultrasonographic findings (long-axis SIZE and RPOC hypervascularity) improves the predictive accuracy of RPOC with severe PPH. This prediction model may be a useful clinical screening tool for RPOC with severe PPH.

Clinical utility of QRS duration normalized to left ventricular volume for predicting cardiac resynchronization therapy efficacy in patients with "mid-range" QRS duration.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective for patients with heart failure with QRS duration (QRSd) ≥150 ms. However, its beneficial effect seems to be limited for those with "mid-range" QRSd (120-149 ms). Recent studies have demonstrated that modifying QRSd to left ventricular end-diastolic volume (LVEDV)-modified QRSd-improves the prediction of clinical outcomes of CRT. OBJECTIVE: The purpose of this study was to investigate the clinical impact of the modified QRSd on the efficacy of CRT in patients with "mid-range" QRSd. METHODS: We conducted a retrospective, multicenter, observational study, with heart failure hospitalization (HFH) after CRT as the primary endpoint. Modified QRSd is defined as QRSd divided by LVEDV, determined through the Teichholtz method of echocardiography. RESULTS: Among the 506 consecutive patients considered, 119 (mean age 61 ± 15 years; 80% male, QRSd 135 ± 9 ms) with a "mid-range" QRSd who underwent de novo CRT device implantation were included for analysis. During median follow-up of 878 days [interquartile range 381-1663 days], HFH occurred in 45 patients (37%). Fine-Gray analysis revealed modified QRSd was an independent predictor of HFH (hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.96-0.99; P <.01). Receiver operating characteristic curve analysis revealed a cutoff value of 0.65 ms/mL for the modified QRSd in predicting HFH. Patients above the threshold exhibited a significantly lower incidence of HFH than patients below the threshold (HR 0.46; 95% CI 0.25-0.86; P = .01). CONCLUSION: Modified QRSd can effectively predict the efficacy of CRT in patients with a "mid-range" QRSd.

Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids.

The effects of low-dose radiation on undifferentiated cells carry important implications. However, the effects on developing retinal cells remain unclear. Here, we analyzed the gene expression characteristics of neuronal organoids containing immature human retinal cells under low-dose radiation and predicted their changes. Developing retinal cells generated from human induced pluripotent stem cells (iPSCs) were irradiated with either 30 or 180 mGy on days 4-5 of development for 24 h. Genome-wide gene expression was observed until day 35. A knowledge-based pathway analysis algorithm revealed fluctuations in Rho signaling and many other pathways. After a month, the levels of an essential transcription factor of eye development, the proportion of paired box 6 (PAX6)-positive cells, and the proportion of retinal ganglion cell (RGC)-specific transcription factor POU class 4 homeobox 2 (POU4F2)-positive cells increased with 30 mGy of irradiation. In contrast, they decreased after 180 mGy of irradiation. Activation of the "development of neurons" pathway after 180 mGy indicated the dedifferentiation and development of other neural cells. Fluctuating effects after low-dose radiation exposure suggest that developing retinal cells employ hormesis and dedifferentiation mechanisms in response to stress.

iGEM as a human iPS cell-based global epigenetic modulation detection assay provides throughput characterization of chemicals affecting DNA methylation.

Chemical-induced dysregulation of DNA methylation during the fetal period is known to contribute to developmental disorders or increase the risk of certain diseases later in life. In this study, we developed an iGEM (iPS cell-based global epigenetic modulation) detection assay using human induced pluripotent stem (hiPS) cells that express a fluorescently labeled methyl-CpG-binding domain (MBD), which enables a high-throughput screening of epigenetic teratogens/mutagens. 135 chemicals with known cardiotoxicity and carcinogenicity were categorized according to the MBD signal intensity, which reflects the degree of nuclear spatial distribution/concentration of DNA methylation. Further biological characterization through machine-learning analysis that integrated genome-wide DNA methylation, gene expression profiling, and knowledge-based pathway analysis revealed that chemicals with hyperactive MBD signals strongly associated their effects on DNA methylation and expression of genes involved in cell cycle and development. These results demonstrated that our MBD-based integrated analytical system is a powerful framework for detecting epigenetic compounds and providing mechanism insights of pharmaceutical development for sustainable human health.

Effects of nintedanib on disease progression and safety in Japanese patients with progressive fibrosing interstitial lung diseases: Further subset analysis from the whole INBUILD trial.

BACKGROUND: A previous subgroup analysis of data from the INBUILD trial showed that nintedanib reduced the annual rate of decline in forced vital capacity (FVC) in Japanese patients with progressive fibrosing interstitial lung diseases (PF-ILDs). The safety profile of nintedanib over 52 weeks in Japanese patients was similar to that of the overall population. METHODS: Using data from 108 Japanese patients with PF-ILDs who had received at least 1 dose of study medication in the INBUILD trial, we evaluated the effect of nintedanib on disease progression and assessed the safety profile over the whole trial period (i.e., a longer duration than the prior analysis) compared with placebo. ILD progression was defined as an absolute decline in FVC ≥10% predicted vs baseline. RESULTS: Over the whole trial, in Japanese patients with PF-ILDs, nintedanib numerically lowered the risk of progression of ILD or death (hazard ratio [HR], 0.66; 95% confidence intervals [CI]: 0.37, 1.16), acute exacerbation of ILD or death (HR, 0.28; 95% CI: 0.09, 0.83), and death (HR, 0.41; 95% CI: 0.11, 1.51). The most common adverse event over the whole trial in nintedanib-treated Japanese patients was diarrhea, which was manageable for most patients by dose reduction and interruption. The safety profile of nintedanib in this longer duration analysis was consistent with that previously reported. CONCLUSIONS: In this analysis of data from Japanese patients with PF-ILDs, nintedanib nominally reduced the risk of clinically meaningful outcomes reflecting disease progression, including death, over the whole trial, and no new safety concerns were observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02999178.

Cumulative Summation Analysis of Learning Curve for Robotic-assisted Hysterectomy in Patients With Gynecologic Tumors.

BACKGROUND/AIM: This study aimed to evaluate the learning curve and perioperative outcomes of robot-assisted hysterectomy (RAH). PATIENTS AND METHODS: We retrospectively analyzed data from 45 patients who underwent RAH using the da Vinci Xi surgical system. The learning curve was evaluated using the cumulative summation method. Demographic data and various perioperative parameters, including total operative time, docking time, and console time, were obtained from the medical records. RESULTS: Cumulative summation analysis indicated that proficiency regarding hysterectomy time was reached after 33 cases. There were two unique phases of the learning curve for console time: the introduction phase identified by the bottom point in the curve, and the proficient phase, identified by an upward line after the bottom point in the curve. There were no significant differences between the two phases in terms of patient age and body mass index. Total operative time, docking time, and console time were significantly decreased in the proficient phase compared with those in the introduction phase. There was a significant reduction in blood loss during operation in the proficient phase. The perioperative complication rates were 12.1% in the introduction phase and 0% in the proficient phase (p=0.5606). No blood transfusion or conversion to laparotomy was required in either phase. CONCLUSION: The introduction and proficient phases identified by cumulative summation analysis demonstrated progressive improvement of surgical performance in surgeons carrying out RAH.

Plant hvu-MIR168-3p enhances expression of glucose transporter 1 (SLC2A1) in human cells by silencing genes related to mitochondrial electron transport chain complex I.

Diet is a crucial factor for preventing most diseases. Edible plant extracts are known to contain exosome-like nanoparticles, in which food-derived plant microRNAs are included and may serve as a novel functional component in human health. Here, we demonstrated that hvu-MIR168-3p included in the nanoparticles of rice aleurone cells down-regulated the expression of the genes related to mitochondrial electron transport chain complex I in human cells. Subsequently, hvu-MIR168-3p enhanced protein and RNA expression levels of glucose transporter I and caused a decrease in the blood glucose level, which findings were obtained by in vitro and in vivo experiments, respectively. These findings suggest that a cross-kingdom relationship between plants and humans with respect to hvu-MIR168-3p exists and may contribute to preventive medicine for GLUT1-related dysfunctions including glucose metabolism, aging, and tumor immunology.

Pulmonary Tumor Thrombotic Microangiopathy with Administration of Pulmonary Vasodilator Resulting in Clinical Improvement Prior to Final Diagnosis.

BACKGROUND The pathophysiology of pulmonary tumor thrombotic microangiopathy (PTTM) was recently revealed by autopsy. Considered rare, we suggest that this fatal disease is not rare, but has not been diagnosed pre-mortem. Some patients with pulmonary thromboembolism with unknown thrombus source or with sudden death have been treated for malignant carcinoma. We report a patient with PTTM who was successfully rescued acutely by treatment with soluble guanylate cyclase (sGC), resulting in appropriate palliative care. CASE REPORT An 80-year-old Japanese woman was transferred to our emergency room for severe dyspnea owing to type I respiratory failure. Her clinical findings indicated pulmonary thromboembolism, but we found no thrombus in either the pulmonary artery or inferior vena cava. However, we incidentally found gallbladder cancer with peritoneal metastases. These findings raised the suspicion of PTTM. We began concurrent sGC and direct oral anticoagulant (DOAC) on the assumption that PTTM had occurred, while performing peripheral pulmonary artery sampling for cytology, and pulmonary perfusion scintigraphy. Cytology revealed several aplastic cells; consequently, we finally diagnosed PTTM. Because she did not wish to undergo examination and active treatment for carcinoma, we initiated palliative care while continuing sGC. She was able to spend time with her family for more than 100 days, without dyspnea. CONCLUSIONS We must recognize PTTM, which is a lesser-known disease, and introduce diagnostic therapy with a pulmonary vasodilator, such as sGC, immediately, when we suspect PTTM, leading to appropriate clinical care.

Epigenetic effects of insecticides on early differentiation of mouse embryonic stem cells.

Increasing evidence indicates that many insecticides produce significant epigenetic changes during embryogenesis, leading to developmental toxicities. However, the effects of insecticides on DNA methylation status during early development have not been well studied. We developed a novel nuclear phenotypic approach using mouse embryonic stem cells harboring enhanced green fluorescent protein fused with methyl CpG-binding protein to evaluate global DNA methylation changes via high-content imaging analysis. Exposure to imidacloprid, carbaryl, and o,p'-DDT increased the fluorescent intensity of granules in the nuclei, indicating global DNA methylating effects. However, DNA methylation profiling in cell-cycle-related genes, such as Cdkn2a, Dapk1, Cdh1, Mlh1, Timp3, and Rarb, decreased in imidacloprid treatments, suggesting the potential influence of DNA methylation patterns on cell differentiation. We developed a rapid method for evaluating global DNA methylation and used this approach to show that insecticides pose risks of developmental toxicity through DNA methylation.

Source contributions to multiple toxic potentials of atmospheric organic aerosols.

Fine particulate matter (PM2.5) in the atmosphere is of high priority for air quality management efforts to address adverse health effects in human. We believe that emission control policies, which are traditionally guided by source contributions to PM mass, should also consider source contributions to PM health effects or toxicity. In this study, we estimated source contributions to the toxic potentials of organic aerosols (OA) as measured by a series of chemical and in-vitro biological assays and chemical mass balance model. We selected secondary organic aerosols (SOA), vehicles, biomass open burning, and cooking as possible important OA sources. Fine particulate matter samples from these sources and parallel atmospheric samples from diverse locations and seasons in East Asia were collected for the study. The source and atmospheric samples were analyzed for chemical compositions and toxic potentials, i.e. oxidative potential, inflammatory potential, aryl hydrocarbon receptor (AhR) agonist activity, and DNA-damage, were measured. The toxic potentials per organic carbon (OC) differed greatly among source and ambient particulate samples. The source contributions to oxidative and inflammatory potentials were dominated by naphthalene-derived SOA (NapSOA), followed by open burning and vehicle exhaust. The AhR activity was dominated by open burning, followed by vehicle exhaust and NapSOA. The DNA damage was dominated by vehicle exhaust, followed by open burning. Cooking and biogenic SOA had smaller contributions to all the toxic potentials. Regarding atmospheric OA, urban and roadside samples showed stronger toxic potentials per OC. The toxic potentials of remote samples in summer were consistently very weak, suggesting that atmospheric aging over a long time decreased the toxicity. The toxic potentials of the samples from the forest and the experimentally generated biogenic SOA were low, suggesting that toxicity of biogenic primary and secondary particles is relatively low.

Long-term safety and effectiveness of linagliptin as add-on therapy in Japanese patients with type 2 diabetes: final results of a 3-year post-marketing surveillance.

BACKGROUND: We investigated the long-term safety and effectiveness of linagliptin in Japanese type 2 diabetes (T2D) patients starting linagliptin add-on therapy in routine clinical practice. RESEARCH DESIGN AND METHODS: This 3-year prospective, observational, post-marketing surveillance (PMS) was conducted in Japanese patients starting linagliptin add-on therapy. The primary outcome was the incidence of adverse drug reactions (ADRs). The secondary outcome was the change from baseline in HbA1c. RESULTS: The safety analysis set comprised of 3,372 patients. Mean ± standard deviation (SD) age was 66.5 ± 12.4 years. Most patients (63.2%) received linagliptin in combination with another antidiabetic drug, most commonly a sulfonylurea (38.6%). The incidence of ADRs was 11.39%; the most common ADRs according to MedDRA preferred terms were diabetes mellitus (1.25%), hypertension (0.83%), and hypoglycemia (0.80%). In the effectiveness analysis set (n = 3,029), mean ± SD HbA1c was 7.76 ± 1.37% at baseline and 7.26 ± 1.19% at last observation; mean change from baseline to last observation was - 0.49 ± 1.33%; sustained reductions in HbA1c were observed. These results were consistent across patient subgroups. CONCLUSIONS: In this PMS, linagliptin add-on therapy for Japanese T2D patients had a safety profile consistent with its known profile and HbA1c reductions over 3 years were observed. CLINICALTRIALS.GOV: NCT01904383.

Early Transcriptomic Changes upon Thalidomide Exposure Influence the Later Neuronal Development in Human Embryonic Stem Cell-Derived Spheres.

Stress in early life has been linked with the development of late-life neurological disorders. Early developmental age is potentially sensitive to several environmental chemicals such as alcohol, drugs, food contaminants, or air pollutants. The recent advances using three-dimensional neural sphere cultures derived from pluripotent stem cells have provided insights into the etiology of neurological diseases and new therapeutic strategies for assessing chemical safety. In this study, we investigated the neurodevelopmental effects of exposure to thalidomide (TMD); 2,2',4,4'-tetrabromodiphenyl ether; bisphenol A; and 4-hydroxy-2,2',3,4',5,5',6-heptachlorobiphenyl using a human embryonic stem cell (hESC)-derived sphere model. We exposed each chemical to the spheres and conducted a combinational analysis of global gene expression profiling using microarray at the early stage and morphological examination of neural differentiation at the later stage to understand the molecular events underlying the development of hESC-derived spheres. Among the four chemicals, TMD exposure especially influenced the differentiation of spheres into neuronal cells. Transcriptomic analysis and functional annotation identified specific genes that are TMD-induced and associated with ERK and synaptic signaling pathways. Computational network analysis predicted that TMD induced the expression of DNA-binding protein inhibitor ID2, which plays an important role in neuronal development. These findings provide direct evidence that early transcriptomic changes during differentiation of hESCs upon exposure to TMD influence neuronal development in the later stages.

Clinical Features of Recurrence in Patients Without Residual Tumour in Endometrial Cancer.

BACKGROUND/AIM: Initial treatment of endometrial cancer with surgery and platinum and taxane-based chemotherapy is often successful, but it remains unclear as to whether certain types of the disease relapse. The aim of this study was to identify the clinical features of recurrence in patients without residual tumour in endometrial cancer. PATIENTS AND METHODS: Clinical features, histological type, and time to recurrence were analyzed in 640 endometrial cancer patients without residual tumours. RESULTS: Of 640 patients, 517 were type I and 123 were type II. For type I, early recurrent (ER) disease and late recurrent (LR) disease were noted in 80 and 8 patients, respectively, and 97.5% of ER occurred within 2 years. After recurrence, 76.2% of ER and 50% of LR patients died. In type II, ER and LR were noted in 41 and 1 patients, respectively, and 97.6% of ER occurred within 2 years, of which 75.6% died after recurrence. One LR case died of disease. CONCLUSION: Most patients recurred within 2 years irrespective of clinical stage or type.

Investigation of inflammation inducing substances in PM2.5 particles by an elimination method using thermal decomposition.

The substances associated with PM2.5-induced inflammatory response were investigated using an elimination method. PM2.5 were heated at temperatures of 120, 250, and 360°C. The results demonstrated microbial substances such as LPS and b-glucan, and chemicals including BaP, 1,2-NQ, and 9,10-PQ were reduced drastically in PM2.5 heated at 120°C. On the other hand, DBA, 7,12-BAQ, and BaP-1,6-Q were not noticeably reduced. Most of these substances had disappeared in PM2.5 heated at 250°C and 360°C. Metals (eg, Fe, Cu, Cr, Ni) in PM2.5 exhibited a slight thermo-dependent increase. RAW264.7 macrophages with or without NAC were exposed to unheated PM2.5, oxidative stress-related and unrelated inflammatory responses were induced. PM2.5-induced lung inflammation in mice is caused mainly by thermo-sensitive substances (LPS, b-glucan, BaP, 1,2-NQ, 9,10-PQ, etc.). Also, a slight involvement of thermo-resistant substances (DBA, 7,12-BAQ, BaP-1,6-Q, etc.) and transition metals was observed. The thermal decomposition method could assist to evaluate the PM2.5-induded lung inflammation.

Efficacy of daikenchuto, a traditional Japanese Kampo medicine, for postoperative intestinal dysfunction in patients with gastrointestinal cancers: meta-analysis.

BACKGROUND: The Japan Society for Oriental Medicine makes a compilation of structured abstracts of randomized controlled trials (RCTs) of Kampo medicines available on its Evidence Reports of Kampo Treatment (EKAT) website. METHODS: Using EKAT, we conducted a systematic review and meta-analysis on the efficacy of using daikenchuto ( https://mpdb.nibiohn.go.jp/stork ) for bowel dysfunction after surgery for gastrointestinal cancer. The primary outcomes were the time to first postoperative flatus and the time to first postoperative bowel movement (BM). RESULTS: We found nine relevant RCTs. The mean differences between the daikenchuto group and control group (daikenchuto was not administered) were - 0.43 (95% CI: - 0.77 to - 0.09) days for the time to first postoperative flatus, - 0.29 (95% CI: - 0.59 to 0.01) days for the time to first postoperative BM, and - 0.95 (95% CI: - 1.70 to - 0.21) days for the length of postoperative hospital stay, and the risk ratio of the incidence of intestinal obstruction was 0.60 (95% CI: 0.35-1.03). The time to first postoperative flatus and the length of postoperative hospital stay were significantly shorter in the daikenchuto group than those in the control group (P = 0.01). However, only double-blind studies were evaluated; the results turned to be non-significant. CONCLUSION: As a result of meta-analysis by all retrieved according to the registered protocol, daikenchuto was efficacious in improving postoperative bowel dysfunction in patients with gastrointestinal cancers. However, limiting to articles with description of COI and blindness, significance disappeared.

Synthesis of Functionalized Medium-Sized trans-Cycloalkenes by 4π Electrocyclic Ring Opening/Alkylation Sequence.

Development of a novel synthetic method for medium-sized trans-cycloalkenes (TCAs) is described. Functionalized TCAs are readily prepared from simple cycloalkanones in a few steps, namely, enol silyl ether formation, [2+2] cycloaddition, and domino 4π electrocyclic ring opening/alkylation (conjugate addition). The first example of central-to-planar chirality transfer from enantiomerically enriched cyclobutenes to TCAs is also described.

The toxicological analysis of secondary organic aerosol in human lung epithelial cells and macrophages.

Secondary organic aerosol (SOA) is a component of airborne particulate matter in urban areas. However, their toxicities remain incompletely understood. In this study, we investigated the oxidative and inflammatory potency of SOA derived from three different volatile organic compounds (α-pinene, m-xylene, and trimethylbenzene) using human bronchial epithelial cells (BEAS-2B) and macrophages (U937). In BEAS-2B cells, all types of SOA extracts increased the expression of the heme oxygenase 1 (HMOX1) and interleukin-8 (IL8) genes, a typical marker for oxidative stress and inflammatory responses, respectively. Among the three types of SOA, m-xylene-derived SOA showed the strongest induction of the HMOX1 and IL8 genes, and transcriptional activity via the antioxidant response element (ARE). A causal candidate for SOA induction of oxidative stress is 2,6-dimethyl-1,4-benzoquinone (DMBQ) because only this quinone compound increased the transcriptional activity via ARE among components tested in this study. Similar to the case of BEAS-2B cells, SOA extracts increased the expression of HMOX1 and IL8 genes in U937 cells, mainly through oxidative stress, but these responses in U937 cells were prolonged when compared with BEAS-2B cells. Together, these results show that SOA affects lung epithelial cells and macrophages mainly through oxidative stress and inflammation, suggesting their contribution to the development of respiratory diseases.

Association of Serum HB-EGF Value and Response to Chemotherapy in Patients with Recurrent Ovarian Cancer.

BACKGROUND/AIM: Many anticancer agents including molecularly-targeted drugs have been developed for ovarian cancer. However, the prognosis of recurrent ovarian cancer remains extremely poor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is reported as a rational target for ovarian cancer therapy. Moreover, serum HB-EGF expression is recognized as a biomarker in patients with primary ovarian cancer. MATERIALS AND METHODS: We analysed serum samples with recurrent ovarian cancer at the Fukuoka University Hospital from April 2009 to March 2014. To assess the clinical significance of serum HB-EGF in recurrent ovarian cancer, the association between serum HB-EGF levels and prognosis in patients with recurrent ovarian cancer was examined using ELISA. RESULTS: Patients with high serum HB-EGF expression showed a significantly poor response to second-line chemotherapeutic agents compared with patients with low HB-EGF levels. CONCLUSION: HB-EGF expression in serum may be a potential therapeutic indicator for novel HB-EGF-targeted therapy in recurrent ovarian cancer.