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.

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.

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.

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.

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.

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.

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.

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.

Germline mismatch repair gene variants analyzed by universal sequencing in Japanese cancer patients.

BACKGROUND: Lynch syndrome (LS) is the commonest inherited cancer syndrome caused by pathogenic variants of germline DNA mismatch repair (g.MMR) genes. Genome-wide sequencing is now increasingly applied for tumor characterization, but not for g.MMR. The aim of this study was to evaluate the incidence and pathogenicity of g.MMR variants in Japanese cancer patients. METHODS: Four g.MMR genes (MLH1, MSH2, MSH6, and PMS2) were analyzed by next generation sequencing in 1058 cancer patients (614 male, 444 female; mean age 65.6 years) without past diagnosis of LS. The g.MMR variant pathogenicity was classified based on the ClinVar 2015 database. Tumor MMR immunohistochemistry, microsatellite instability (MSI), and BRAF sequencing were also investigated in specific cases. RESULTS: Overall, 46 g.MMR variants were detected in 167 (15.8%) patients, 17 likely benign variants in 119 patients, 24 variants of uncertain significance (VUSs) in 68 patients, two likely pathogenic variants in two patients, and three pathogenic variants in three (0.3%) patients. The three pathogenic variants included two colorectal cancers with MLH1 loss and high MSI and one endometrial cancer with MSH6 loss and microsatellite stability. Two likely pathogenic variants were shifted to VUSs by ClinVar (2018). One colon cancer with a likely benign variant demonstrated MLH1 loss and BRAF mutation, but other nonpathogenic variants showed sustained MMR and microsatellite stability. CONCLUSIONS: Universal sequencing of g.MMR genes demonstrated sundry benign variants, but only a small proportion of cancer patients had pathogenic variants. Pathogenicity evaluation using the ClinVar database agreed with MSI, MMR immunohistochemistry, and BRAF sequencing.

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.

Association between homologous recombination repair gene mutations and response to oxaliplatin in pancreatic cancer.

OBJECTIVES: We aimed to examine the association between homologous recombination repair (HRR)-related gene mutations and efficacy of oxaliplatin-based chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). RESULTS: Non-synonymous mutations in HRR-related genes were found in 13 patients and only one patient had a family history of pancreatic cancer. Eight patients with HRR-related gene mutations (group A) and nine without HRR-related gene mutations (group B) received oxaliplatin-based chemotherapy. Median progression-free survival after initiation of oxaliplatin-based chemotherapy was significantly longer in group A than in group B (20.8 months vs 1.7 months, p = 0.049). Interestingly, two patients with inactivating HRR-related gene mutations who received FOLFIRINOX as first-line treatment showed exceptional responses with respect to progression-free survival for > 24 months. MATERIALS AND METHODS: Complete coding exons of 12 HRR-related genes (ATM, ATR, BAP1, BRCA1, BRCA2, BLM, CHEK1, CHEK2, FANCA, MRE11A, PALB2, and RAD51) were sequenced using a Clinical Laboratory Improvement Amendment-certified multiplex next-generation sequencing assay. Thirty consecutive PDAC patients who underwent this assay between April 2015 and July 2017 were included. CONCLUSIONS: Our results suggest that inactivating HRR-related gene mutations are predictive of response to oxaliplatin-based chemotherapy in patients with PDAC.

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.

Placenta with Old, Diffuse Infarction that Was Difficult to Differentiate from a Placental Tumor.

Placental lesions, including placental infarction, are associated with fetal and neonatal mortality and morbidity. We present a case of fetal growth restriction associated with an old, diffuse placental infarction. Because the placenta had only a single viable cotyledon, the others being atrophic, the lesion appeared to be a placental tumor on prenatal ultrasonography. The patient did not have pregnancy-induced hypertension. At 31 weeks of gestation, a cesarean delivery was performed because of fetal growth arrest and breech presentation. A small-for-gestational age infant was delivered with Apgar scores of 8 at both 1 and 5 minutes, and the infant had cleft palate and cleft lips. Pathological examination of the placenta revealed an old, diffuse infarction without neoplastic change. In cases in which a placental tumor causing fetal growth restriction is strongly suspected, diffuse placental infarction should be considered as part of the differential diagnosis, because placental tumors are associated with poor maternal prognosis.

Trial of labor after cesarean delivery as an independent risk factor for intrapartum asphyxia in singleton deliveries beyond 37 weeks' gestation.

The aim of this study was to determine the factors associated with intrapartum asphyxia in singleton deliveries beyond 37 weeks' gestation. We reviewed the obstetric records of Japanese singleton deliveries after 37 weeks' gestation managed at Japanese Red Cross Katsushika Maternity Hospital from 2005 through 2010. Forty-nine cases were diagnosed as intrapartum asphyxia on the basis of an Apgar score <4 at 5 minutes or umbilical arterial pH <7.0 or both. Cases with umbilical arterial pH ≥7.1 and 1-minute Apgar score ≥7 were examined as controls (n=10,484). Logistic multivariate regression analysis showed that intrapartum asphyxia was independently associated with cases of trial of labor after cesarean delivery (adjusted odds ratio, 3.24; 95% confidence intervals, 1.0-11; p=0.04). Our findings may be encouraging for the counseling of patients regarding a possible attempt at trial of labor after cesarean delivery.

Perinatal outcomes of failed vacuum extraction.

The aims of this study were to compare the perinatal outcomes of successful vacuum extraction (VE) or failed VE and to compare the perinatal outcomes of failed VE followed by forceps delivery (FD) or Cesarean section (CS) from 2000 through 2007. Compared with cases of successful VE, cases of failed VE followed by CS had a significantly higher incidence of neonatal complications, whereas cases of failed VE followed by FD had a significantly higher incidence of maternal injury. Both CS and FD remain important yet distinct treatments for emergency cases of failed VE. Therefore, the decision to use a second instrument (FD) or to proceed to CS should be made in each case on the basis of these differences.