Clients' experiences of empathy in genetic counseling for hereditary breast and ovarian cancer: A qualitative study in Japan.

Empathy is a significant element in genetic counseling for building relationships with the clients and addressing their issues. However, there are few reports on the experiences of the clients about their perceived empathy in genetic counseling. Cancer genetic counseling needs have been rapidly evolving with the expansion of clinical comprehensive genomic profiling and genetic diagnosis approaches for hereditary cancers. Therefore, this study aimed to reveal empathy perceptions of the clients during cancer genetic counseling. Semi-structured interviews were conducted, and a grounded theory approach was used for data analysis. A total of 13 participants were recruited from organizations for patients with cancer, among whom 11 were patients with hereditary breast and ovarian cancer (HBOC) and two were relatives of patients with HBOC. Data analysis was organized into five categories related to experiences with empathy: (i) prior context to perceive empathy (ii) understanding and consideration, (iii) bedside manner, and (iv) impacted area of perceived empathy; and (v) no empathy. This study highlights the fact that empathy experiences of the clients differ depending on the situation and state of mind. Taken together, this study provides new insights on how to deliver empathic care.

Courtesy stigma of parents of children with Down syndrome: Adaptation process and transcendent stage.

Courtesy stigma, which arises from close connections to people with stigmatized characteristics, negatively affects interpersonal relations. This study aimed to evaluate courtesy stigma and the adaptation process of parents of children with Down syndrome based on semi-structured interviews with 23 Japanese parents. The interview themes were (a) negatively perceived interpersonal experiences and coping strategies; (b) information disclosure and others' responses; and (c) positively perceived interpersonal experiences. The interview data were transcribed and analyzed based on a grounded theory approach. The results suggested that parents perceived and experienced multidimensional courtesy stigma, and they used various coping strategies categorized in combinations of passive-active and internal-external. All parents disclosed information about their child's diagnosis to others, and reverse disclosure (i.e., revealing own relations with people with disabilities) was characteristically observed thereafter. Through active interaction and reflection, the parents cultivated social relationships, compassion, world views, and community involvement, which led to the transcendent stage. However, internal conflict as a mediator between people with and without Down syndrome re-emerged even after achieving the transcendent stage. These findings could help to develop interventions in genetic counseling for parents to deal with interpersonal relationship difficulties.

Empathy experiences of Japanese certified genetic counselors: A qualitative investigation and proposed framework.

Empathy is an important element of genetic counseling. Most genetic counselors acknowledge the significance of empathically engaging clients. However, few empirical studies have focused on the empathy experience of genetic counselors, especially in non-Western countries. This study aimed to investigate Japanese genetic counselors' perspectives on the concept of empathy in clinical practice. The study conducted semi-structured interviews with Japanese certified genetic counselors who had approximately 10 years of clinical experience. Fourteen participants were interviewed about their thoughts on empathy and their experiences wherein they had deeply understood clients or felt closer to them. The interview data were analyzed using grounded theory. As a result, 17 categories were extracted, of which 13 were integrated into three themes of empathy: the empathic cycle in the relationships between genetic counselors and clients (cycling), the process of forming a deeper understanding of a client's perspectives (feeling), and the process of developing skills to understand clients with empathy (developing). The remaining four categories were grouped into the theme of "challenges of empathy." The categories included in the first three themes were similar to previous findings in Western countries, whereas some categories of challenges of empathy were unique to this study, which was conducted in a non-Western country. This might be attributed to the influence of Japanese culture, in which people emphasize self-regulation and an interdependent-self model. To our knowledge, this study is the first to report on Japanese certified genetic counselors' experiences of empathy. This study concludes with some suggestions for future research, including focusing on ways to overcome challenges of empathy in countries or healthcare systems.

Clinical significance of TP53 variants as possible secondary findings in tumor-only next-generation sequencing.

In tumor-only next-generation sequencing (NGS), identified variants have the potential to be secondary findings (SFs), but they require verification through additional germline testing. In the present study, 194 patients with advanced cancer who underwent tumor-only NGS between April 2015 and March 2018 were enrolled, and the incidences of possible and true SFs were evaluated. Among them, 120 patients (61.9%) harbored at least one possible SF. TP53 was the most frequent gene in which 97 variants were found in 91 patients (49.5%). Nine patients provided informed consent to undergo additional germline testing, and a total of 14 variants (BRCA1, n = 1; BRCA2, n = 2; PTEN, n = 2; RB1, n = 1; SMAD4, n = 1; STK11, n = 1; TP53, n = 6) were analyzed. Three variants (BRCA1, n = 1; BRCA2, n = 2) were confirmed to be SFs, whereas TP53 variants were confirmed to be somatic variants. To confirm the low prevalence of SFs in TP53, we analyzed 24 patients with TP53 variants who underwent a paired tumor-normal NGS assay. As expected, all TP53 variants were confirmed to be somatic variants. A total of 30 patients were tested for germline variants in TP53, but none of them resulted in true SFs, suggesting the low prevalence of SFs in this gene. Therefore, the significance of additional germline testing for TP53 variants appears to be relatively low in daily clinical practice using a tumor-only NGS assay, unless patients have any relevant medical or family history.

Correction: Nationwide survey for current clinical status of amniocentesis and maternal serum marker test in Japan.

Since the publication of this paper, the authors noticed that Yosuke Fujii was assigned to the incorrect affiliation. The affiliation information is provided correctly, above.

Performance and outcomes of noninvasive prenatal testing for twin pregnancies in Japan.

AIM: The purpose of this study was to describe the characteristics of women with twin pregnancies who undergo noninvasive prenatal testing (NIPT) as well as the post-partum and neonatal outcomes of such cases in Japan. METHODS: The study population consisted of women who were pregnant with twins and who underwent NIPT using massively parallel sequencing (MPS) at Nagoya City University Hospital between April 2013 and June 2016. Questionnaires were completed pre-NIPT and post-partum. RESULTS: Among 4009 women who underwent NIPT during the study period, 75 women (1.9%) were pregnant with twins. Fifteen women (20%) experienced vanishing twin/intrauterine fetal deaths at <22 weeks, and 60 women (80%) had normal twin pregnancies at the time of genetic counseling for NIPT. The use of NIPT was correlated with increased proportions of women using assisted reproductive technology (ART). The test had a high performance, with a false-positive rate of 1.7% and no false negatives. CONCLUSION: In this study, NIPT had a high performance, with a false positive rate of 1.7% and no false negatives. When treating women with twin pregnancies, the efficacy of NIPT should be explained during genetic counseling. Further larger studies are required to assess the reliability and validity of NIPT in twin pregnancies.

Clinical sequencing using a next-generation sequencing-based multiplex gene assay in patients with advanced solid tumors.

Advances in next-generation sequencing (NGS) technologies have enabled physicians to test for genomic alterations in multiple cancer-related genes at once in daily clinical practice. In April 2015, we introduced clinical sequencing using an NGS-based multiplex gene assay (OncoPrime) certified by the Clinical Laboratory Improvement Amendment. This assay covers the entire coding regions of 215 genes and the rearrangement of 17 frequently rearranged genes with clinical relevance in human cancers. The principal indications for the assay were cancers of unknown primary site, rare tumors, and any solid tumors that were refractory to standard chemotherapy. A total of 85 patients underwent testing with multiplex gene assay between April 2015 and July 2016. The most common solid tumor types tested were pancreatic (n = 19; 22.4%), followed by biliary tract (n = 14; 16.5%), and tumors of unknown primary site (n = 13; 15.3%). Samples from 80 patients (94.1%) were successfully sequenced. The median turnaround time was 40 days (range, 18-70 days). Potentially actionable mutations were identified in 69 of 80 patients (86.3%) and were most commonly found in TP53 (46.3%), KRAS (23.8%), APC (18.8%), STK11 (7.5%), and ATR (7.5%). Nine patients (13.0%) received a subsequent therapy based on the NGS assay results. Implementation of clinical sequencing using an NGS-based multiplex gene assay was feasible in the clinical setting and identified potentially actionable mutations in more than 80% of patients. Current challenges are to incorporate this genomic information into better therapeutic decision making.

Cerebral amyloid angiopathy in a young man with a history of traumatic brain injury: a case report and review of the literature.

Cerebral amyloid angiopathy (CAA), a cause of recurrent and multiple lobar hemorrhages, characteristically occurs in persons aged ≥55 years. We report a case of a 32-year-old male who had recurrent hemorrhage in the left multiple lobes, with a history of traumatic brain injury and hematoma evacuation at the age of 1 year. He underwent surgical treatment and was histopathologically diagnosed as having CAA. The literature review yielded six CAA cases, including ours, aged less than 55 years. All were male and four had histories of severe TBI, suggesting that male sex and TBI may be associated with CAA in young persons.

Nationwide survey for current clinical status of amniocentesis and maternal serum marker test in Japan.

Prenatal testing has been provided in Japan over the past several decades. However, it is difficult to assess the clinical status of amniocentesis (AC) and maternal serum markers (MSM) because obstetricians can perform these tests without registration. This study aims to investigate the current clinical status of AC and MSM in Japan. We conducted a questionnaire study that was intended for a total of 5622 Japanese obstetrics/gynecology facilities during October 2013 to January 2014. The response rate was 40.8% (2295/5622). Of the 2295 facilities, 864 performed MSM (37.7%), 619 performed AC (27.0%) and 412 performed both (18.0%). The average number of MSM tests was 2.0 per month (range 0-52), and the average number of AC tests was 2.4 per month (range 0-30). Involvement of genetic professionals, such as clinical geneticists (CGs) and certified genetic counselors (CGCs), contribute to a content-rich explanation and management of difficult issues and lengthened the explanation time. Nevertheless, relatively few facilities employed these specialists (MSM: 96/864 and AC: 128/619). This is the first study to highlight the current clinical status of AC and MSM tests in Japan. Active involvement of CGs and CGCs can provide more appropriate genetic counseling for prenatal tests.

Clients' and genetic counselors' perceptions of empathy in Japan: A pilot study of simulated consultations of genetic counseling.

The rapidly increasing availability of genetic testing is driving the acceleration of genetic counseling implementation. Empathy is important in medical encounters in general and forms a core component of a successful genetic counseling session; however, empirical evidence on empathy in genetic counseling is minimal. This study aimed to explore the perceptions of empathy in simulated genetic counseling consultations from the perspectives of clients and genetic counselors. Semi-structured interviews and interpersonal process recall were used with participants of simulated genetic counseling consultations to elicit their experiences of empathy. A constructivist grounded theory was used for data analysis. A total of 15 participants, including 10 clients and 5 genetic counselors, participated in 10 simulated counseling sessions. The genetic counselors attempted to demonstrate empathy and were sensitive toward detecting changes in clients. Meanwhile, the clients' perceptions represented their feelings and thoughts elicited through the counselors' empathic approaches. This was the first process study to examine empathy in simulated genetic counseling sessions. Our model of communication of empathy is a process in which counselors try to address implicit aspects of clients, and clients are provided with time and a safe place for introspection, which contributes to discussions on building good relationships with patients. There is also a suggestion of the utility of simulated consultations for healthcare providers to learn empathic communication.

Human genetics education as part of the Japanese Cancer Education Comprehensive Support Project.

In Japan, cancer education has been initiated with children as a measure against cancer. Cancer genome medicine, which is a social implementation, includes aspects of genetic medicine. For this reason, it is assumed that content related to "genetics" is also necessary in cancer education. To investigate the actual situation regarding the teaching of genetics in cancer education, we conducted a questionnaire survey of schoolteachers involved in cancer education; these schoolteachers belonged to the model school of the Cancer Education Comprehensive Support Project. Regarding genetic content, we asked questions related to two aspects: "the molecular genetic mechanisms of cancer" and "the phenomenon of sharing cancer in the family." The results showed that about 60% of the teachers had experience teaching content related to the molecular genetic mechanisms of cancer and the phenomenon of sharing cancer in the family. While many teachers felt that teaching genetics in cancer education was necessary, they also felt that there were difficulties in doing so: 65.2% for content related to the molecular genetic mechanisms of cancer and 70.8% for that related to the phenomenon of sharing cancer in the family. It is important to properly treat cancer as a genetic disease, and it is necessary to examine government curriculum guidelines and establish a collaborative system among other subjects. In addition, the involvement of specialists in genetic medicine and psychosocial support is expected to improve teachers' genetic literacy as well as to communicate with students with consideration for their family history.

Medical Needs of Adults with Down Syndrome Presenting at a Regional Medical and Rehabilitation Center in Japan.

BACKGROUND: Down syndrome (DS) is the most frequent chromosomal aberration; however, knowledge of associated health issues in adulthood is inadequate. We analyzed health data from Japanese adults with DS. METHODS: We conducted a retrospective chart review of 151 patients with DS who visited the Internal Medicine Outpatient Department of the Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled. RESULTS: Endocrine disorders such as obesity, hyperlipidemia, and hyperuricemia were most common in adulthood (≤40 years) and senescence (>40 years); neurological diseases were more prevalent in senescence. Multimorbidity was noted even patients with DS who were younger than 30 years, and the prevalence increased with age. Only 21 patients (13.9%) with DS visited our hospital with referral letters from pediatricians; 94 patients (62.3%) visited without such referrals from other medical institutions. Patients without a referral letter had a mean of 3.1 comorbidities per patient. Moreover, medical care for some people with DS was interrupted during childhood. CONCLUSIONS: Prevention and detection of comorbidities in patients with DS requires continuous medical care from childhood through adulthood. Recently, DS has been diagnosed by chromosome testing and genetic counseling. Clinical geneticists and genetic counselors can help patients with DS, and their caregivers, to obtain appropriate health care and achieve well-being on their own by seamlessly engaging them throughout childhood and adulthood.

Risk factors for postpartum hemorrhage requiring transfusion in cesarean deliveries for Japanese twins: comparison with those for singletons.

OBJECTIVE: The aim of this study was to identify the factors associated with the increased risk of postpartum hemorrhage requiring transfusion in Japanese twin pregnancies in comparison with those in Japanese singleton pregnancies. METHODS: We reviewed the obstetric records of all singleton and twin deliveries after 22 weeks' gestation at the Japanese Red Cross Katsushika Maternity Hospital from 2003 through 2011. Potential risk factors for transfusion due to hemorrhage after cesarean delivery were selected according to previous studies of postpartum hemorrhage or transfusion or both after delivery: maternal age, parity, previous cesarean deliveries, history of infertility therapies such as in vitro fertilization, gestational age at delivery, neonatal birth weight, placenta previa, uterine myoma≥6 cm, hypertensive disorders, placental abruption, emergency cesarean deliveries and general anesthesia. RESULTS: Using multiple logistic regression, the independent risk factors for postpartum hemorrhage requiring transfusion in singleton pregnancies were preterm delivery [odds ratio (OR) 2.40, 95% confidence interval (CI) 1.2-4.6, p<0.01], placenta previa (OR 8.08, 95% CI 3.9-16, p<0.01) and placental abruption (OR 12.8, 95% CI 2.3-76, p<0.01). In twin pregnancies, however, the independent risk factors for postpartum hemorrhage requiring transfusion were gestational age at ≥41 weeks (OR 8.20, 95% CI 1.3-40, p<0.01) and hypertensive disorders (OR 5.45, 95% CI 2.2-14, p<0.01). CONCLUSIONS: The factors associated with postpartum hemorrhage requiring transfusion in cesarean deliveries of twins seemed to be different from those in singleton cesarean deliveries.

Outcomes of 8 Years of Noninvasive Prenatal Testing at Nippon Medical School Hospital.

BACKGROUND: Noninvasive prenatal testing (NIPT) is used to screen for fetal chromosomal abnormalities, such as fetal aneuploidy, and has been offered at our hospital since 2013. We analyzed data from our center to determine if NIPT screenees could be given more-accurate information on NIPT outcomes. METHODS: This retrospective observational study included 819 pregnant women who requested NIPT at Nippon Medical School Hospital from November 2013 to October 2021. We examined medical records for data on NIPT results and clinical outcomes. RESULTS: Of the 819 women, 764 (93.2%) underwent NIPT, and 55 (6.7%) did not. Of the 764 women who underwent NIPT, 17 received a positive result (2.2%), of whom 2 (11.8%), 4 (23.5%), and 11 (64.7%) received a positive result for trisomy 13, 18, and 21, respectively. The true-positive rates after definitive diagnoses of trisomy 13, 18, and 21 were 1 (50%), 3 (75%), and 11 (100%), respectively. Of the 17 positive results, there were two false-positive results (11.8%) (for trisomy 13 and trisomy 18). Eleven women with fetal aneuploidy terminated their pregnancies, and four cases resulted in intrauterine fetal death. Five neonates with negative NIPT results had congenital disease without chromosomal abnormality. Two patients had indeterminate results from the first blood sampling, possibly because of treatment with unfractionated heparin. The results of repeat testing after heparin cessation were negative. CONCLUSIONS: Our results were generally similar to nationwide data for Japan. NIPT providers can provide more detailed and individualized genetic counseling for each situation by understanding their own medical facility's data in detail.

Neonatal small-for-gestational age status as a favorable factor for the complete vaginal delivery of both fetuses in Japanese dichorionic twins.

AIM: In singletons, neonatal small-for-gestational age (SGA) status is an unfavorable postpartum outcome leading to cesarean section (CS) and increasing the possibility of maternal operative complications. Perinatal characteristics of SGA newborns in dichorionic (DC) twins were investigated for the prognostic impact on their mothers. METHODS: A retrospective study was performed from 2004 to 2009 on 329 DC twins with two live births. Neonates were classified as SGA if they weighed less than the 10th percentile at birth according to Japanese singleton norms. Statistical differences between DC twins delivering appropriate-for-gestational age (AGA)/AGA pairs (control group) and AGA/SGA, SGA/AGA or SGA/SGA pairs (the first/second twins) were analyzed. RESULTS: The median (range) of the gestational ages at delivery for AGA/AGA, AGA/SGA, SGA/AGA and SGA/SGA pairs were 37.1 (27.1-40.3), 37.2 (29.0-40.9), 37.1 (28.1-40.7) and 37.3 (33.3-40.4) weeks, and the complete vaginal delivery rates of both fetuses were 66.2% (43/65), 84.8% (28/33), 82.4% (14/17) and 70.0% (7/10), respectively. Compared with AGA/AGA pairs, AGA/SGA pairs showed a higher incidence of spontaneous vaginal births of both fetuses (31.3% [26/83] vs 19.9% [37/186], OR 1.84, 95% CI 1.45-4.73) and a lower incidence of emergent CS (25.3% [21/83] vs 38.7% [72/186], OR 0.53, 95% CI 0.30-0.95). CONCLUSION: The relatively small size of SGA fetuses allows both fetuses to remain inside the uterus for a longer time and to easily pass through the maternal parturient canal for complete vaginal delivery. Neonatal SGA status is a favorable factor for avoiding operative complications of CS and optimizing maternal perinatal outcomes.

Maternal risk factors for small-for-gestational age newborns in Japanese dichorionic twins.

AIM: To investigate the maternal risk factors for small-for-gestational age (SGA) newborns in Japanese dichorionic (DC) twins. METHODS: A retrospective study was conducted from 2003 to 2008 on 340 DC twin pregnancies resulting in two live births. Newborns were classified as SGA if their birth weight was below the 10th percentile according to Japanese singleton norms. Statistical differences were evaluated between pregnancies resulting in appropriate-for-gestational age (AGA) pairs and those resulting in at least one SGA neonate. RESULTS: The study population consisted of AGA/AGA (50.8%), AGA/SGA (37.0%) and SGA/SGA pairs (12.0%). Logistic regression analysis identified significant interrelations for SGA with maternal nulliparity (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.30-0.91), smoking (OR 3.25, 95% CI 1.09-9.66), assisted reproductive technology (OR 0.52, 95% CI 0.30-0.89), pregnancy-induced hypertension (OR 2.00, 95% CI 1.01-4.31), pregravid weight (kg) (unitary OR 0.94, 95% CI 0.91-0.97) and monthly weight gain (kg/month) (unitary OR 0.25, 95% CI 0.14-0.44). Bivariable receiver operating characteristic curves were generated for monthly weight gain (area under the curve [AUC] 0.626, cutoff 1.41 kg/month, P<0.001) and total weight gain (AUC 0.615, cutoff 14.0 kg, P<0.001). CONCLUSION: Cigarette smoking and weight gain control are relatively modifiable factors for which interventional management is necessary to avoid perinatal problems arising from SGA pregnancy. Further studies are needed to investigate optimal nutrition, health guidance and subsequent weight gain control that lead to concrete improvement in maternal and infant prognoses.

Clinical significance of singleton pregnancies complicated by placental abruption occurred at preterm compared with those occurred at term.

OBJECTIVE: This study investigated the clinical significance of placental abruption occurred at preterm compared with those that occurred at term. METHODS: We reviewed the obstetric records of 102 singleton deliveries complicated by placental abruption after 22 weeks of gestation. The χ(2) test for categorical variables was used and differences with p < 0.05 were considered significant. Odds ratios (ORs) and 95% confidence intervals (CIs) were also calculated. RESULTS: Of 102 cases of placental abruption, 60 cases (59%) occurred at preterm and 42 (41%) at term. There were no significant differences in perinatal outcomes between the two groups with preterm and term gestations. The incidence of histological chorioamnionitis in the preterm group was significantly higher than that in the term group (crude OR 3.4, 95% CI 1.4-8.2, p < 0.01) while that of placental embolisms and/or infarctions in the preterm group was significantly lower than that in the term group (crude OR 0.35, 95% CI 0.16-0.80, p = 0.01). Using logistic regression, preterm placental abruption was significantly more likely in multiparous patients (adjusted OR 2.5, 95% CI 1.0-6.2, p = 0.046) and those demonstrating histological chorioamnionitis (adjusted OR 3.5, 95% CI 1.4-9.1, p < 0.01), while term placental abruption was significantly more likely in cases of placental embolisms and/or infarctions (adjusted OR 3.5, 95% CI 1.2-10, p = 0.02). CONCLUSION: The current results indicate that the possible processes leading to placental abruption at preterm are different from those at term.

Effect of changes in renal circulation on serum uric acid levels in women with twin pregnancy.

OBJECTIVE: We examined the relationship between serum uric acid levels and changes in renal circulation in women with twin pregnancy compared with those in women with singleton pregnancy. METHODS: The Doppler waveforms of the bilateral maternal main renal arteries were obtained from 15 women at 37-38 weeks of nonpreeclamptic twin pregnancy and 16 healthy women at the same gestational age of singleton pregnancy. The resistance index (RI), pulsatility index (PI), and acceleration time were determined. RESULTS: The mean serum uric acid level in the twin pregnancy group was significantly higher than that in the singleton pregnancy group (5.0 ± 0.9 vs. 3.7 ± 0.6 mg/dl, P < 0.01). Although there were no significant differences in the RI or PI levels between the singleton and twin pregnancy groups, the acceleration time in the twin pregnancy group was significantly prolonged compared with that in the singleton pregnancy group (82.2 ± 29 vs. 59.9 ± 17 ms, P = 0.01). There was a significant correlation between serum uric acid levels and acceleration times (r(2) = 0.55, P < 0.01). CONCLUSION: The changes in renal circulation may be one of the possible mechanisms leading to hyperuricemia in women with twin pregnancies.

Hemodynamic changes in maternal renal arteries in twin pregnancy.

AIM: We examined whether the Doppler waveforms of the maternal renal main arteries are altered in women with twin pregnancy compared with those in singleton pregnancy. METHODS: The indices of vascular resistance and acceleration time of the maternal main renal arteries were obtained from 19 healthy women at 37-38 weeks of singleton gestation and 17 women at the same gestational age with non-preeclamptic twin gestation. RESULTS: There were no significant differences in the indices of vascular resistance between the singleton and twin groups. However, the acceleration time was significantly prolonged in the twin pregnancy group compared with that in the singleton pregnancy group (83.7 +/- 24 vs. 59.8 +/- 12 ms, p < 0.01). CONCLUSION: The current results imply that maternal renal arteries are more significantly affected by hemodynamic changes in twin pregnancy than in singleton pregnancy.