Simultaneous bilateral mastectomy and RRSO for BRCA2-positive non-invasive breast cancer in Japan: a case report and analysis of initial experience.

BACKGROUND: In Japan, genetic testing, surveillance, and risk-reducing surgery for hereditary breast and ovarian cancer (HBOC) syndrome have been covered by the Japanese national insurance system since April 2020. On the other hand, the current situation is that medical care, including surveillance of undiagnosed (cancer-free) patients, is self-funded even for individuals with HBOC. We report a case in which breast cancer was diagnosed at an early stage during surveillance for cancer-free HBOC at the patient's own expense, and risk-reducing surgery was performed at the same time as treatment for breast cancer. CASE PRESENTATION: The patient was a 63-year-old woman. Her sister had a history of breast cancer in her 30s and was found to be a BRCA2 pathogenic variant carrier by genetic testing. The patient therefore presented to the genetic department of our hospital and underwent genetic testing (out-of-pocket). A pathogenic variant was found at the same site. During annual breast and ovarian surveillance at the patient's own expense, a physician with sufficient expertise in contrast-enhanced breast magnetic resonance imaging (MRI) noticed a change in the contrast enhancement pattern on breast MRI and performed needle biopsy, revealing ductal carcinoma in situ. At the request of the patient, she underwent concurrent contralateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy in addition to breast cancer treatment. CONCLUSIONS: We encountered a case in which cancer treatment and risk-reducing surgery were performed at the same time for a pathogenic variant carrier who was very anxious about developing cancer. Surveillance of cancer-free BRCA1/2 mutation carriers and expansion of insurance coverage for surgery are important future issues.

Polaprezinc for prevention of oral mucositis in patients receiving chemotherapy followed by hematopoietic stem cell transplantation: A multi-institutional randomized controlled trial.

Oral mucositis is a common and distressing complication in patients receiving high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT). We reported previously in a single-center retrospective analysis that zinc-L-carnosine (polaprezinc [PZ]) reduced the incidence of oral mucositis associated with HSCT. To verify the accuracy of the prophylactic effect of PZ against oral mucositis, we carried out a multi-institutional prospective randomized controlled study. Patients were randomly allocated to either the prevention group, in which PZ lozenge treatment was started before chemotherapy, or the control group, in which administration of PZ lozenges was initiated immediately after the onset of Grade 2 oral mucositis. Oral mucositis was evaluated daily from the start of chemotherapy to 35 days after transplantation. A total of 91 patients were enrolled, and 88 patients (47 in the control group and 41 in the prevention group) were eligible for data analysis. The incidence of Grade ≥2 but not Grade ≥3 oral mucositis was significantly reduced in the prevention group compared to the control group (44.7% in control group vs 22.0% in the prevention group, P = .025). There were no significant differences in the incidence rates of other adverse events or the rate of engraftment (95.6% vs 97.2%, P = .693) between the two groups. These findings suggest that PZ lozenge is effective for prophylaxis against Grade ≥2 oral mucositis associated with chemotherapy in patients undergoing HSCT without any influence on the HSCT outcome.

Real-world data of the association between quality of life using the EuroQol 5 Dimension 5 Level utility value and adverse events for outpatient cancer chemotherapy.

BACKGROUND: Outpatient cancer chemotherapy may lead to improved quality of life (QOL) by allowing treatment to continue without impairing the social lives of patients compared with hospitalization. However, the occurrence of serious adverse events may cause a decline in QOL. We investigated the relationship between outpatient chemotherapy-induced adverse events and QOL. METHODS: A single-center retrospective descriptive study was conducted in patients who received outpatient chemotherapy at Gifu University Hospital (Gifu, Japan) between September 2017 and December 2018. The utility values of QOL, type and severity of adverse events, type of cancer, chemotherapy regimen, and other patient demographics were analyzed. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. QOL was evaluated using the Japanese version of the EuroQol 5 Dimension 5 Level (EQ-5D-5L). Associations between the EQ-5D-5L utility value and serious adverse events were assessed using adjusted (age and sex) odds ratios obtained with a proportional odds logistic regression model. RESULTS: Data from 1008 patients who received 4695 chemotherapy cycles were analyzed. According to proportional odds logistic regression, the adverse events that significantly correlated with a decreased EQ-5D-5L utility value were malaise, edema of the limbs, peripheral neuropathy, pruritus, and dry skin. Based on the proportional odds logistic analysis, neither cancer type nor anticancer drugs were significantly correlated with the EQ-5D-5L utility value in patients who received chemotherapy. Pharmaceutical care for peripheral neuropathy significantly improved patients' EQ-5D-5L utility value from 0.747 to 0.776 (P < 0.01). CONCLUSIONS: Adverse events (i.e., peripheral neuropathy, malaise, and edema of the limbs) are significantly correlated with a decrease in QOL, regardless of the type of cancer or anticancer drugs used. Pharmaceutical care provided by pharmacists in collaboration with physicians may improve QOL.

Implementation of a standardised pharmacist check of medical orders prior to preparation of anticancer drugs to reduce drug wastage.

BACKGROUND: The increasing cost of anticancer drugs is now being recognised as a global problem, and measures against drug wastage are among the most important cost containment strategies for anticancer drugs. OBJECTIVE: When blood examination results or changes to a patient's condition necessitate dose reduction or discontinuation of anticancer drugs after their preparation, the compounded anticancer drugs are discarded. To reduce anticancer drug wastage after preparation, we developed a protocol that set the eligibility, start of treatment, dose reduction and discontinuation criteria for injectable anticancer drugs and assessed the effect of pharmacists' checks of these criteria based on the present protocol prior to preparation of injectable anticancer drugs. METHOD: Observations before and after introduction of the protocol were conducted at Gifu University Hospital. We recorded the number, type and cost of anticancer drugs discarded after preparation and the reason for discarding these drugs in our dedicated database. RESULTS: Checking the criteria for anticancer drug administration before preparation significantly reduced the rate at which anticancer drugs within a chemotherapy cycle were discarded after preparation compared with that prior to the protocol's introduction (0.367% [18/4909] vs 0.032% [2/6248], P < .001). Additionally, the total cost of anticancer drugs discarded after preparation was reduced from JPY 2 041 786 (USD 18 562) to JPY 398 414 (USD 3622). CONCLUSION: Pharmacists' checks of the eligibility, start of treatment, dose reduction and discontinuation criteria for anticancer drugs based on the present protocol prior to preparation of injectable anticancer drugs was useful for reducing drug wastage after preparation.

Comparative efficacy and safety of vancomycin versus teicoplanin in febrile neutropenic patients receiving hematopoietic stem cell transplantation.

WHAT IS KNOWN AND OBJECTIVE: Patients who receive hematopoietic stem cell transplantation (HSCT) are usually administered a calcineurin inhibitor. Because vancomycin is associated with an increased incidence of nephrotoxicity, neutropenic patients receiving HSCT are considered a high-risk population for nephrotoxicity with vancomycin. We retrospectively compared the efficacy and safety of vancomycin and teicoplanin in febrile neutropenic patients receiving HSCT. METHODS: A single-centre, retrospective cohort study was conducted at the 614-bed Gifu University Hospital in Japan. Patients who received HSCT and were administered vancomycin or teicoplanin by injection for febrile neutropenia from 1 January 2012 to 31 August 2017 were enrolled. Time to attain an effective trough concentration, clinical efficacy and adverse events were compared between the two groups. RESULTS: Time to attain an effective trough concentration of over 10 µg/mL tended to be shorter in the teicoplanin group than in the vancomycin group (median 3, 95% confidence interval [CI] 2.4-3.6 days vs median 6, 95% CI 1.5-10.5 days; hazard ratio [HR] 0.4, 95% CI 0.15-1.06; P = .066). The rate of clinical failure was lower in the teicoplanin group than in the vancomycin group (18.8% vs 53.8%, P = .113). In addition, the overall incidence of nephrotoxicity was significantly lower in the teicoplanin group (0% vs 46.2%, P = .004). WHAT IS NEW AND CONCLUSION: Our findings suggest that administration of teicoplanin may lead to early attainment of the effective concentration with a lower rate of clinical failure and incidence of nephrotoxicity compared to vancomycin in febrile neutropenic patients receiving HSCT.

Rapid attainment of target trough concentrations of tacrolimus for early improvement of clinical symptoms in patients with ulcerative colitis.

WHAT IS KNOWN AND OBJECTIVE: The target trough concentration of tacrolimus for ulcerative colitis is recommended to be 10-15 ng/mL in the initial two weeks and 5-10 ng/mL in the later phase. However, the effectiveness of rapid attainment of these target trough concentrations of tacrolimus in patients with ulcerative colitis is still unclear. In the present study, we evaluated the clinical efficacy and safety of rapid attainment of target trough concentrations of tacrolimus in patients with ulcerative colitis. METHODS: A prospective cohort was conducted at Gifu University Hospital in Gifu, Japan. Hospitalized patients who received tacrolimus for the treatment of ulcerative colitis between April 2009 and March 2017 were enrolled. Since June 2011, the initial loading dose of tacrolimus increased from 0.05 to 0.1-0.2 mg/kg/d, and the maintenance dose to achieve the target trough concentration was determined to be 12.5 ng/mL by proportional calculation with measured blood concentration. The period required to attain target trough concentration and the clinical efficacy before and after dosage modification was compared. RESULTS: The initial dose after dosage modification was significantly increased compared to that before dosage modification (0.10 [0.04-0.22], median [range] mg/kg/d vs 0.05 [0.03-0.05] mg/kg/d, P < 0.001). The period required to attain a target trough concentration over 10 ng/mL was significantly shortened by dosage modification (6 [4-14] days before dosage modification vs 4.5 [2-8] days after modification, P = 0.048). Further, stool frequency score was significantly improved after dosage modification, without affecting the incidence of adverse events. WHAT IS NEW AND CONCLUSION: Our findings suggest that rapid attainment of the target trough concentration of tacrolimus improves clinical symptoms in patients with ulcerative colitis.

GALT carcinoma: three case reports with glycoprotein 2 immunohistochemistry and electron microscopic observations.

AIMS: Gut-associated lymphoid tissue (GALT) carcinoma is a rare colorectal tumour that arises in the epithelium covering GALT. GALT carcinoma is a differentiated tubular adenocarcinoma with dense lymphoid tissue with a characteristically well-demarcated margin. To date, 26 cases of GALT carcinoma, including the three cases discussed here, have been reported. Most (24 of 26) were discovered at early stages and none of the cases have documented any metastases. This suggests that GALT carcinoma may have a favourable prognosis. It is hypothesised that GALT carcinoma originates from M cells in specialised epithelia covering GALT. However, this hypothesis has yet to be confirmed. METHODS AND RESULTS: In this study, we examined three cases of GALT carcinoma by immunohistochemistry detection of glycoprotein 2, a specific marker for M cells, and electron microscopy. Our findings showed that the tumour cells of GALT carcinoma in all three cases were negative for M cells. We thus concluded that GALT carcinoma may be a tubular adenocarcinoma arising by chance in the GALT. This unique carcinoma is a diferentiated adenocarcinoma that grows slowly with the development of GALT. CONCLUSIONS: We propose that GALT carcinoma should be classified separately because of its histological setting and good prognosis.

Gastrointestinal bleeding associated with chronic excessive use overdosing with topical ketoprofen patch in elderly patient.

PURPOSE: Topical ketoprofen patch has been developed to reduce the risk of systemic adverse effects such as gastrointestinal injury and renal toxicity. MATERIALS AND METHODS: We reported here a case of lower intestinal bleeding associated with chronic excessive use of topical ketoprofen patch in an elderly patient. RESULTS: A 74-year-old female visited to the outpatient clinic of the Gifu University Hospital and admitted thereafter. She had fecal occult blood and anemia. Enteroscopic examination showed several ulcerative lesions and a protruded lesion accompanied with redness in the small intestinal mucosa. She used 8 sheets of 20 mg ketoprofen patch every day for a long period to relieve pain in the shoulder, lower back and lower limb. She had no diseases that are related to the initiation of gastrointestinal bleeding, including infection, inflammatory bowel disease, autoimmune disease and malignant disease. Thus, the present lower intestinal bleeding was concluded to be due to the use of topical ketoprofen patch. The symptoms were recovered after cessation of the patch. CONCLUSIONS: Extensive care should be taken to avoid ulcerative intestinal hemorrhage to elderly patients receiving multiple doses of non-steroidal anti-inflammatory drug patch for multiple days.

Total resection combined with osteotomy is more effective for orbital solitary fibrous tumor excision: a report of three cases.

A solitary fibrous tumor is a neoplasm generally arising from the mesothelial surfaces of the pleura and mesothelium. In this paper, we describe three cases of rare solitary fibrous tumors arising from the orbit and discuss the management of the tumors, including diagnosis and treatment. All three cases were treated by surgical resection and showed satisfactory aesthetic and functional results. For a definitive diagnosis, immunohistochemical staining for proteins such as vimentin, CD34 and bcl-2 and hematoxylin and eosin (H&E) staining for identifying the morphological characteristics of spindle cell tumors with a partially storiform pattern and staghorn vessels are indispensable. The principle of treatment for orbital solitary fibrous tumor is complete resection because the prognosis depends on controlling tumor progression, which can be difficult with chemotherapy and radiotherapy alone.

Control of Constipation in Patients Receiving CHOP or CHOP-Like Chemotherapy Regimens for Non-Hodgkin's Lymphoma.

Management of constipation in patients receiving cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CHOP-like chemotherapy regimens is important for prevention of paralytic ileus. We reported earlier that the laxative action of magnesium oxide is reversed by the concomitant use of antacids in cancer patients receiving opioid analgesics. Here, we assessed the prevalence of prophylactic laxative medication for the control of constipation in patients receiving CHOP or CHOP-like regimens for non-Hodgkin's lymphoma. Data obtained from 211 eligible patients were retrospectively analyzed. Almost all patients (99%) received anti-ulcer agents such as proton pump inhibitors and H2 receptor antagonists for the prophylaxis of gastric disorders associated with prednisolone. Prophylactic laxatives were prescribed in 86 patients (40.8%), in which magnesium oxide was used most predominantly (88.4%). However, magnesium oxide at doses of ≦2000 mg/d was not effective for prevention of constipation, although the compound totally inhibited the incidence of constipation at doses higher than 2000 mg/d. Therefore, it is important to avoid negative drug interaction between magnesium oxide and antacids in patients receiving CHOP chemotherapy.

Cancer Cell Interaction with Adipose Tissue: Correlation with the Finding of Spiculation at Mammography.

PURPOSE: To investigate the relationship between spiculated masses at mammography and marginal adipose tissue invasion at histologic examination. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and the requirement to obtain informed consent was waived. A total of 478 patients with invasive breast cancer who underwent surgery between 1999 and 2009 were included in this study. Clinical-pathologic findings from patients with spiculated masses on mammograms were compared with those from patients without spiculated masses by using logistic regression models, Cox proportional hazards regression models, and the Kaplan-Meier method. RESULTS: There were 136 spiculated tumors and 342 nonspiculated tumors. All 136 spiculated tumors (100%) were positive for adipose tissue invasion, whereas only 264 of the 342 nonspiculated tumors (77%) were positive for adipose tissue invasion (P < .001). Multivariate analysis revealed that adipose tissue invasion (P < .001), histologic grade (P < .001), dense breast (P = .002), and body mass index (P = .02) were independent factors associated with spiculation. With regard to survival, although many patients with spiculated tumors had a hormone-sensitive (estrogen receptor positive: P = .004; progesterone receptor positive: P = .001) or low-grade (P < .001) tumor, in contrast to the patients without spiculated masses, the prognosis in the two groups was similar (disease-free survival: P = .09; overall survival: P = .23). CONCLUSION: Cancer cell interaction with adipose tissue is crucial for the finding of spiculation at mammography.

Reproductive outcomes following preimplantation genetic diagnosis using fluorescence in situ hybridization for 52 translocation carrier couples with a history of recurrent pregnancy loss.

Forty-six reciprocal and six Robertsonian translocation carrier couples who experienced recurrent pregnancy loss underwent fluorescence in situ hybridization-based preimplantation genetic diagnosis (PGD) for the presence of the two translocated chromosomes. Out of 52 couples, 17 (33%) were undergoing infertility treatment. In total, 239 PGD cycles as oocyte retrieval (OR) were applied. The transferrable rate of negatively diagnosed embryos at the cleavage stage was 26.3%; 71 embryos were transferred as single blastocysts. The clinical pregnancy rate per transfer was 60.6%. We obtained 41 healthy live births with 3 incidences of miscarriage (7.0%). The average cumulative live birth rate was 76.9% during 4.6 OR cycles using a mild ovarian stimulation strategy. The outcomes were classified into four groups based on carrier gender and maternal age (young (<38 years) or advanced). PGD was performed for 52 couples of which the average number of OR cycles was 4.1, 2.1, 6.7 and 4.5 in young female and male carriers and female and male carriers of advanced age; the live birth rate for a primiparity was 77.8, 72.7, 66.7 and 50.0% in those groups. These results suggest that the final live birth rate might be influenced by maternal age regardless of the gender of the carrier.

Malignant transformation of breast ductal adenoma: a diagnostic pitfall.

We present what is believed to be the first report of heterogeneous carcinoma arising from breast ductal adenoma. A 57-year-old woman presented with a nodule in her right breast. Histological examination of a vacuum-assisted biopsy specimen revealed epithelial tubular proliferation and papillary apocrine epithelium. The myoepithelial cells lining the tubules were confirmed by immunohistochemistry. The nodule had increased in size 18 months later and tumorectomy was performed. The surgical specimen revealed proliferating apocrine epithelium with sheet-like and cribriform architecture within a mammary duct. Some myoepithelial cells showed irregular proliferation around the tubular epithelium. All three components, including apocrine, myoepithelial and glandular cells, showed prominent nuclear atypia and significant mitotic activity. The patient was diagnosed with malignant transformation of ductal adenoma. The malignant potential of ductal adenoma has not previously been discussed, but this heterogeneous carcinoma could represent a serious pitfall in the diagnosis of ductal adenomas.

Evaluation of Steroid-Induced Osteoporosis Prevention Using Tracing Reports in Collaboration between Hospitals and Community Pharmacists.

Glucocorticoid-induced osteoporosis (GIOP) is a side effect of glucocorticoid (GC) treatment; however, despite established prevention guidelines in various countries, a gap persists between these guidelines and clinical practice. To address this gap, we implemented a collaborative intervention between hospitals and community pharmacists, aiming to assess its effectiveness. Pharmacists recommended to the prescribing doctor osteoporosis treatment for patients who did not undergo osteoporosis treatment with a fracture risk score of ≥3 via tracing reports (TRs), between 15 December 2021, and 21 January 2022. Data were extracted from electronic medical records, including prescriptions, concomitant medications, reasons for not pursuing osteoporosis treatment, and TR contents. Of 391 evaluated patients, 45 were eligible for TRs, with 34 (75.6%) being males. Prednisolone was the most common GCs administered, and urology was the predominant treatment department. Among the 45 patients who received TRs, prescription suggestions were accepted for 19 (42.2%). After undertaking the intervention, guideline adherence significantly increased from 87% to 92.5%. This improvement indicates that TRs effectively bridged the evidence-practice gap in GIOP prevention among GC patients, suggesting their potential utility. Expansion of this initiative is warranted to further prevent GIOP.

A novel ex vivo lung cancer model based on bioengineered rat lungs.

Introduction: Two-dimensional cell cultures have contributed substantially to lung cancer research, but 3D cultures are gaining attention as a new, more efficient, and effective research model. A model reproducing the 3D characteristics and tumor microenvironment of the lungs in vivo, including the co-existence of healthy alveolar cells with lung cancer cells, is ideal. Here, we describe the creation of a successful ex vivo lung cancer model based on bioengineered lungs formed by decellularization and recellularization. Methods: Human cancer cells were directly implanted into a bioengineered rat lung, which was created with a decellularized rat lung scaffold reseeded with epithelial cells, endothelial cells and adipose-derived stem cells. Four human lung cancer cell lines (A549, PC-9, H1299, and PC-6) were applied to demonstrate forming cancer nodules on recellularized lungs and histopathological assessment were made among these models. MUC-1 expression analysis, RNA-seq analysis and drug response test were performed to demonstrate the superiority of this cancer model. Results: The morphology and MUC-1 expression of the model were like those of lung cancer in vivo. RNA sequencing revealed an elevated expression of genes related to epithelial-mesenchymal transition, hypoxia, and TNF-α signaling via NF-κB; but suppression of cell cycle-related genes including E2F. Drug response assays showed that gefitinib suppressed PC-9 cell proliferation equally well in the 3D lung cancer model as in 2D culture dishes, albeit over a smaller volume of cells, suggesting that fluctuations in gefitinib resistance genes such as JUN may affect drug sensitivity. Conclusions: A novel ex vivo lung cancer model was closely reproduced the 3D structure and microenvironment of the actual lungs, highlighting its possible use as a platform for lung cancer research and pathophysiological studies.

Association of quantitative analysis of intratumoral reduced E-cadherin expression with lymph node metastasis and prognosis in patients with breast cancer.

Loss of E-cadherin expression is a poor prognostic factor in patients with breast cancer. Breast cancer cells co-cultured with adipocytes reportedly promote E-cadherin attenuation and tumor progression. The current study aimed to investigate the association of reduced E-cadherin expression with adipose tissue invasion (ATI) and prognosis in breast cancer. Surgical specimens were collected from 188 women with invasive ductal carcinoma of the breast who had undergone surgery without neoadjuvant treatment. We compared E-cadherin expression in ATI and invasive front (IF) using immunohistochemistry with ImageJ. Reduced E-cadherin expression was detected not only in the ATI area but also in the IF, and the degree of reduced E-cadherin expression was positively correlated with both areas. In patients with lymph node metastasis compared to those without, E-cadherin expression was reduced and this reduction was associated with poor recurrence-free survival. We concluded that E-cadherin expression is reduced not only at the ATI area but also at the IF of the tumor. Reduced E-cadherin expression is a clear prognostic factor for breast cancer. Hence, future research is warranted for establishing an objective and quantitative E-cadherin staining assay that will allow clinical use of E-cadherin as a prognostic factor.

Perinatal outcomes and congenital anomalies associated with letrozole and natural cycles in single fresh cleaved embryo transfers: A single-center, 10-year cohort study.

Objective: To investigate and compare the safety of letrozole and natural cycles in fresh early embryo transfers. Design: A retrospective cohort study. Setting: A large fertility treatment center. Patients: Women who underwent natural and letrozole cycles during fresh early embryo transfer at Kato Ladies Clinic between January 2008 and December 2017. Interventions: None. Main Outcome measures: Perinatal complications and congenital anomalies. Results: No significant differences were observed in pregnancy complications, gestational age, birth weight, small for gestational age, large for gestational age, and congenital anomalies between the the women who underwent natural and letrozole cycles. Conclusions: The perinatal outcomes and congenital anomaly rates associated with letrozole and natural cycles in fresh early embryo transfers were comparable. Therefore, our data support the safe use of letrozole in fresh early embryo transfers in assisted reproductive technology.

Endometrial preparation and maternal and obstetrical outcomes after frozen blastocyst transfer.

BACKGROUND: Two types of endometrial preparation protocols are used for frozen embryo transfers in current practice: hormone replacement and the natural cycle. Endometrial preparation in the natural cycle reportedly increases the chances of live birth and decreases early pregnancy loss compared with that in the hormone replacement cycle. However, the influence of endometrial preparation on maternal and neonatal health remains unclear. OBJECTIVE: This study aimed to investigate whether the differences between hormone replacement cycle and natural cycle influence perinatal outcomes and risk of congenital anomalies in frozen-thawed blastocyst transfer fetuses or births. STUDY DESIGN: Perinatal outcomes and congenital abnormalities were compared between the natural and hormone replacement cycles. According to the timing of ovulation, frozen-thawed blastocyst transfers in the natural cycle were classified into 2 patterns: on day 4.5 (ovulation 4.5) or day 5 (ovulation 5.0) after ovulation. When the serum luteinizing hormone level was not increased on the day of the trigger, a single vitrified-warmed blastocyst transfer was performed on day 7 after the trigger (ovulation 5.0). When the luteinizing hormone level was slightly increased on the day of trigger, single vitrified-warmed blastocyst transfer was performed on day 6 after the trigger (ovulation 5.0). In total, 67,018 cycles (ovulation 4.5, 29,705 cycles; ovulation 5.0, 31,995 cycles; hormone replacement, 5318 cycles) of frozen-thawed blastocyst transfer between January 2008 and December 2017 at Kato Ladies Clinic were retrospectively analyzed. During the study period, embryo cryopreservation was performed using a vitrification method in all cycles. RESULTS: Hormone replacement cycles were associated with a higher occurrence of hypertensive disorders of pregnancy (adjusted odds ratio, 2.16; 95% confidence interval, 1.66-2.81) and placenta accreta (adjusted odds ratio, 4.14; 95% confidence interval, 1.64-10.44) compared with the natural cycle. The risks of cesarean delivery (adjusted odds ratio, 1.93; 95% confidence interval, 1.78-2.18), preterm birth (adjusted odds ratio, 1.55; 95% confidence interval, 1.25-1.93), and low birthweight (adjusted odds ratio, 1.42; 95% confidence interval, 1.18-1.73) were also higher for hormone replacement cycles. No significant difference in the risk of congenital anomalies was observed between the 2 cycles. CONCLUSION: The risk of hypertensive disorders of pregnancy, placenta accreta, cesarean delivery, preterm delivery, and low birthweight was higher in hormone replacement cycles than in natural cycles, whereas the risk of congenital anomalies was similar between both cycles. Further follow-up is needed to investigate these risks and to explore alternative endometrial preparation methods.

Maternal and obstetric outcomes are influenced by developmental stage and cryopreservation of transferred embryos after clomiphene citrate-based minimal stimulation IVF.

STUDY QUESTION: Is the embryo transfer (ET) method associated with maternal and perinatal outcomes after minimal stimulation IVF using clomiphene citrate (CC)? SUMMARY ANSWER: The incidence of pregnancy complications and adverse perinatal outcomes was influenced by the developmental stage (cleavage versus blastocyst stages) and cryopreservation (fresh versus vitrified) of the transferred embryos. WHAT IS KNOWN ALREADY: Pregnancies resulting from IVF are associated with higher risks of adverse perinatal outcomes compared to natural conceptions; therefore, the next focus in reproductive medicine should be to assess whether these increased risks are attributable to IVF. Pregnancy complications and perinatal outcomes should be considered in addition to pregnancy outcomes when selecting the ET method, however, studies that describe the influence of transfer methods on perinatal and maternal outcomes are limited. STUDY DESIGN SIZE DURATION: This study retrospectively analysed a large single-centre cohort. The clinical records of 36 827 women who underwent oocyte retrieval (during a CC-based minimal stimulation cycle) followed by their first ET at the fertility treatment centre between January 2008 and December 2017 were retrospectively analysed. The patients underwent a single fresh cleavage-stage ET (SFCT), single vitrified-warmed cleavage-stage ET (SVCT) or single vitrified-warmed blastocyst transfer (SVBT). This study only included one cycle per patient. PARTICIPANTS/MATERIALS SETTING METHODS: Oocyte retrieval was performed following CC-based minimal ovarian stimulation. The embryos were transferred 2-3 days after retrieval or vitrified at the cleavage or blastocyst stage. The vitrified embryos were then warmed and transferred within the natural cycles. Pregnancy complications and perinatal outcomes were stratified according to the transfer methods used. Multivariate logistic regression analysis was performed to evaluate the effect of ET methods on the prevalence of pregnancy complications and congenital anomalies. MAIN RESULTS AND THE ROLE OF CHANCE: The rates of clinical pregnancy and delivery were significantly different among the groups. We analysed pregnancy complications in 7502 singleton births (SFCT, 3395 cycles; SVCT, 586 cycles; and SVBT, 3521 cycles). Multivariate logistic regression analysis revealed that the adjusted odds ratio (AOR) for hypertensive disorders in pregnancy was significantly lower in the SVBT group than in the SFCT group [AOR, 0.72; 95% CI, 0.56-0.92]. The AOR for low-lying placenta was lower in the SVBT group than in the SFCT group (AOR, 0.34; 95% CI, 0.19-0.60). The AOR for placenta previa was lower in the SVCT and SVBT groups than in the SFCT group (AOR, 0.21; 95% CI, 0.07-0.58 versus AOR, 0.53; 95% CI, 0.38-0.75, respectively). A total of 7460 follow-up data on neonatal outcomes was analysed. The AOR for preterm delivery was lower in the SVBT group than in the SFCT group (AOR, 0.78; 95% CI, 0.64-0.94). The AOR for low birthweight was significantly lower after SVCT and SVBT than after SFCT (AOR, 0.68; 95% CI, 0.46-0.98 versus AOR, 0.57; 95% CI, 0.48-0.66, respectively). The AOR for small for gestational age was lower in the SVCT and SVBT groups than in the SFCT group (AOR, 0.68; 95% CI, 0.46-0.98 versus AOR, 0.44; 95% CI, 0.36-0.55, respectively). The AOR for large for gestational age babies was higher in the SVBT group than in the SFCT group (AOR, 1.88; 95% CI, 1.62-2.18). The incidence of each congenital anomaly was similar among the groups. LIMITATIONS REASONS FOR CAUTION: The study data were collected through self-reported parental questionnaires on maternal and neonatal outcomes. Our findings were not compared with the incidence of pregnancy complications and congenital anomalies in natural pregnancies. Furthermore, this study was retrospective in nature; therefore, further studies are required to ascertain the generalizability of these findings to other clinics with different protocols and/or different patient demographics. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrated reassuring outcomes for SVBT (in terms of a lower incidence of pregnancy complications) compared to SFCT. Our findings provide valuable knowledge that will help improve perinatal and maternal outcomes in CC-based stimulation and inform couples of the possible benefits and risks of each type of ET method. STUDY FUNDING/COMPETING INTERESTS: This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Bilateral Inflammatory Breast Cancer That Developed Two Years after Treatment for Triple-negative Breast Cancer.

A 66-year-old woman underwent partial mastectomy and a sentinel lymph node biopsy for left breast cancer; the pathological diagnosis was invasive ductal carcinoma (pT1aN0, pStage I, triple-negative subtype). Postoperative radiotherapy was performed. Two years later, she developed redness and induration at both breasts. The diagnosis was bilateral inflammatory breast cancer. After four cycles of dose-dense epirubicin and cyclophosphamide followed by 12 weekly paclitaxel cycles, bilateral total mastectomy and axillary lymph node dissection were performed. At the one-year follow-up after undergoing operation and radiotherapy, she remained alive without recurrence. Dose-dense treatment regimens may help patients achieve complete resection without short-term recurrence.