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Introduction: Central post-stroke pain (CPSP) is a common type of central neuropathic pain (CNeP) that can occur following the onset of stroke. The oral gabapentinoid mirogabalin besylate (mirogabalin) is a selective α 2 δ ligand that is effective for the treatment of CNeP, including CPSP. However, it is unknown whether the analgesic effect of mirogabalin on CPSP varies in patients with different background factors., Methods: This was a post hoc subgroup analysis of a multinational, open-label, long-term phase 3 study of mirogabalin for the treatment of CNeP conducted between March 2019 and December 2020. Data from patients with CPSP were stratified by type of stroke (ischemic or hemorrhagic), stroke location (thalamus, putamen, brainstem, or other), presence/absence of motor weakness, median time since stroke (≥ 59 or < 59 months), and median duration of CPSP (≥ 55.5 or < 55.5 months). Efficacy was assessed with the short-form McGill Pain Questionnaire (SF-MPQ), and treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were recorded., Results: This subanalysis included all 94 patients with CPSP from the phase 3 study; all were Japanese, and the mean age was 65.3 years. The least squares mean change [95% confidence interval] in SF-MPQ visual analog scale (VAS) score from baseline at week 52 (last observation carried forward) was - 17.0 [- 22.1, - 11.9] mm. Among the subgroups, least squares mean changes in SF-MPQ VAS scores were not different. Most TEAEs were mild or moderate; severe TEAEs occurred in six patients (6.4%). Somnolence (25.5%), peripheral edema (13.8%), dizziness (11.7%), and weight gain (6.4%) were the most common ADRs, and the types and frequencies of ADRs were similar among subgroups., Conclusion: Mirogabalin was generally effective and well tolerated in patients with CPSP, regardless of background factors such as stroke type or location, presence/absence of motor weakness, time since stroke, and duration of CPSP., Trial Registration: Trial registration number NCT03901352., (© 2024. The Author(s).)

Introduction: There is no approved effective drug for diabetic peripheral neuropathic pain (DPNP) in China. Gabapentinoids including mirogabalin have shown promise, although data in Chinese patients are scarce., Methods: This phase 3, multicenter, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of mirogabalin for treating DPNP in China. Mirogabalin was administered at 5 mg twice daily for the first week and uptitrated to 15 mg twice daily for a total duration of 14 weeks. The primary efficacy endpoint was the change from baseline in weekly average daily pain score (ADPS) at week 14; secondary endpoints included the ADPS responder rate, Short-Form McGill Pain Questionnaire visual analogue scale score, patient global impression of change (PGIC), average daily sleep interference score (ADSIS), EuroQol 5-dimensions 5-levels (EQ-5D-5L), and incidence of treatment-emergent adverse events (TEAEs)., Results: Of 393 patients (mirogabalin, n = 196; placebo n = 197), the mean age was 58.2 years (mirogabalin, 58.7 years; placebo, 57.7 years) and 54.2% were male (mirogabalin, 56.1%; placebo, 52.3%). Mirogabalin elicited a greater change from baseline in the weekly ADPS vs. placebo at week 14: least-squares mean difference (95% confidence interval) vs. placebo - 0.39 (- 0.74, - 0.04), p = 0.0301. PGIC, ADSIS, and EQ-5D-5L data reflected significantly better improvements for patients receiving mirogabalin vs. placebo. The incidence of TEAEs was 75.0% and 75.1% in the mirogabalin and placebo groups, respectively. Most TEAEs were mild or moderate, and the incidence of TEAEs leading to treatment discontinuation was 2.6% in the mirogabalin group and 1.5% in the placebo group., Conclusions: Although the effect size of mirogabalin was reduced due to the placebo effect, mirogabalin is a safe and effective treatment option for Chinese patients with DPNP., Trial Registration: ClinicalTrials.gov identifier, NCT04094662., (© 2024. The Author(s).)

Introduction: Central neuropathic pain (CNeP) is difficult to treat and has diverse etiology, including spinal cord injury (CNePSCI), Parkinson's disease (CNePPD), and central post-stroke pain (CPSP). The safety and efficacy of mirogabalin have been demonstrated in short-term trials, including patients with CNePSCI. The objective of our study was to confirm the safety/efficacy of mirogabalin in patients with CNePPD and CPSP, and obtain long-term data for CNePSCI., Methods: This 52-week, open-label extension of a previous randomized controlled study was conducted across Japan, Korea, and Taiwan. Patients with CNePSCI, CNePPD, or CPSP received twice daily (BID) 5-10 mg mirogabalin for a 4-week titration period, after which the dosage was maintained for 47 weeks at a maximum of 15 mg BID, followed by a 1-week taper period receiving the same dose but only administered once daily. The primary endpoint was safety, assessed primarily by incidence and severity of treatment-emergent adverse events (TEAEs). Efficacy was assessed in a post hoc analysis of data obtained by the short-form McGill Pain Questionnaire (SF-MPQ)., Results: Of the 210 patients enrolled, 106, 94, and 10 had CNePSCI, CPSP, and CNePPD, respectively. The mean overall age of patients was 62.9 years, and most patients were male and of Japanese ethnicity. TEAEs occurred in 84.8% of patients, the most common being somnolence (16.7%), peripheral edema (12.4%), edema (11.4%), nasopharyngitis (11.0%), and dizziness (7.6%). Most TEAEs were mild. Severe and serious TEAEs occurred in 6.2% and 13.3% of patients, respectively. All patient groups experienced reductions in SF-MPQ visual analog scores for pain: mean ± standard deviation changes from baseline at week 52 were -2.3 ± 21.13 mm (CNePSCI), -17.0 ± 24.99 mm (CPSP), and -17.1 ± 35.32 mm (CNePPD)., Conclusion: Mirogabalin was generally safe, well tolerated, and effective for treatment of CNeP in this long-term study., Trial Registration: ClinicalTrials.gov identifier, NCT03901352., (© 2023. The Author(s).)

Background and Objectives: Patients with spinal cord injury (SCI) commonly experience central neuropathic pain (CNeP), which is challenging to treat. Mirogabalin is effective for peripheral neuropathic pain, but evidence for CNeP is lacking., Methods: This randomized, double-blind, placebo-controlled, phase 3 study investigated mirogabalin efficacy and safety for the treatment of CNeP in patients with traumatic SCI. Adult patients from 120 sites throughout Japan, Korea, and Taiwan were randomized (1:1) to receive placebo or mirogabalin (5 mg twice daily [BID] for 1 week, 10 mg BID for 1 week, and 10 or 15 mg BID for 12 weeks). Patients with moderate renal impairment received half the dosage. The primary efficacy endpoint was change from baseline in the weekly average daily pain score (ADPS) at week 14. The secondary endpoints included ADPS responder rates, the Short-Form McGill Pain Questionnaire (SF-MPQ), average daily sleep interference score (ADSIS), and Neuropathic Pain Symptom Inventory (NPSI). Adverse events were monitored for safety., Results: Each treatment group comprised 150 patients. Mirogabalin elicited a statistical and clinically relevant improvement in change from baseline in the weekly ADPS at week 14 (least-squares mean difference [95% CI] vs placebo -0.71 [-1.08 to -0.34], p = 0.0001). Responder rates at week 14 were higher for mirogabalin than those for placebo (odds ratio [95% CI] 1.91 [1.11-3.27] for the ≥30% responder rate; 2.52 [1.11-5.71] for the ≥50% responder rate). Statistical improvements (i.e., least-squares mean difference [95% CI] vs placebo) were also observed in the SF-MPQ (-2.4 [-3.8 to -1.1]), ADSIS -0.71 (-1.04 to -0.38), and NPSI -7.7 (-11.1 to -4.4) scores. Most treatment-emergent adverse events were mild; no serious adverse drug reactions were reported., Discussion: Mirogabalin elicited clinically relevant decreases in pain and was well tolerated, suggesting that mirogabalin is a promising treatment for patients with CNeP due to SCI., Trial Registration Information: ClinicalTrials.gov (NCT03901352); first submitted April 3, 2019; first patient enrolled March 14, 2019; available at clinicaltrials.gov/ct2/show/NCT03901352., Classification of Evidence: This study provides Class I evidence that in adult patients with CNeP due to traumatic SCI, mirogabalin, 10 or 15 mg BID, effectively improves weekly ADPS at week 14., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

The patient was a 48-year-old woman. At the time of consultation, a hard mass of 30 mm in size was palpated in area A of the right breast, and a firm mass of about 10 mm was seen in the umbilical region. Histological diagnosis of the breast mass was invasive ductal carcinoma. PET-CT scan showed accumulation in the right breast, as well as suspicion of umbilical metastasis and peritoneal dissemination, uterine mass, and left ovarian cancer. Since this is an atypical metastatic site for invasive ductal carcinoma of the breast, and the possibility of peritoneal dissemination due to gynecological cancer complications cannot be ruled out, resection of the umbilical mass and laparoscopy was performed. The review laparoscopy revealed no evidence of primary cancer in the uterine body or left ovary, and a white nodular lesion of suspected seeding in the peritoneum around the left ovary. The histology and immunostaining results of the umbilical mass and left peri-ovarian nodule both showed glandular luminal structures similar to those of the primary breast cancer, and the left peri-ovarian nodule was ER positive, GATA3 positive, and PAX8 negative, leading to the diagnosis of umbilical metastasis and peritoneal seeding derived from breast cancer. Umbilical metastasis is often referred to as Sister Mary Joseph's nodule in the case of visceral malignancies and is often associated with peritoneal dissemination and is often caused by invasive metastasis of peritoneal dissemination lesions on the dorsal side of the umbilical region. In this case, histological examination of the umbilical specimen showed no disseminated lesion on the peritoneal side, so it was not considered to be an invasive metastasis due to peritoneal dissemination.

HER2-targeted anticancer therapies may be associated with cardiovascular adverse events. This study evaluated effects of the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd, DS-8201a) on QT/QTc interval and its pharmacokinetics. Patients with heavily pretreated, metastatic HER2-expressing breast cancer were enrolled at seven study sites in Japan. T-DXd was administered intravenously at 6.4 mg/kg on day 1 of each 21-day cycle. Primary end points were baseline-adjusted QTcF interval and pharmacokinetics parameters. Key secondary end points included safety events, serum concentration of T-DXd and DXd at the time of electrocardiographic measurements, and antitumor activity parameters. Among 51 total patients, 47 (92.2%) had HER2-low breast cancer (immunohistochemistry 1+ or 2+ and in situ hybridization-negative/equivocal/missing). Pharmacokinetic parameters after a single dose of T-DXd were consistent with previous studies. After multiple doses, T-DXd showed moderate accumulation (accumulation ratio (cycle 3/cycle 1), 1.35), but DXd showed minimal accumulation (1.09). The upper bound of the 90% confidence interval for mean ΔQTcF interval was < 10 ms at all timepoints, and at mean maximum serum concentration was also < 10 ms. Based on concentration-QT analysis, ΔQTcF increased with increasing concentrations of T-DXd and DXd. No clinically meaningful QTcF prolongation was observed. T-DXd had a manageable safety profile and showed antitumor activity in HER2-low breast cancer. In this study, a T-DXd dose of 6.4 mg/kg, higher than the 5.4-mg/kg dose currently approved for breast cancer, was not associated with clinically relevant QTcF prolongation in heavily pretreated patients with HER2-expressing metastatic breast cancer. This study adds to our understanding of T-DXd for treatment of HER2-low breast cancer., (© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The patient is a 67-year-old female. She was diagnosed with left breast cancer cT2N1M0, Stage ⅡB, Luminal B-like, and was desided dose-dense AC therapy(ddAC)plus dose-dense paclitaxel therapy(ddPTX)as preoperative chemotherapy. After completing 4 courses of ddAC and visiting to start the first course of ddPTX, she presented with symptoms of fatigue and shortness of breath on exertion. Chest X-ray showed no abnormality and echocardiography showed decreased left ventricular wall motion, leading to a diagnosis of doxorubicin-induced cardiac dysfunction. Preoperative chemotherapy was discontinued and surgery was decided. Two weeks later, CT imaging was performed for preoperative evaluation, which showed the appearance of diffuse pale ground-glass opacity in the bilateral lung fields, and a diagnosis of drug-induced interstitial pneumonia was made. After 3 weeks of steroid treatment, the symptoms improved and the ground-glass opacity disappeared on CT imaging. We were keenly aware that interstitial pneumonia can develop with pale ground-glass opacity that is difficult to diagnose without CT imaging, and that the need for CT should always be considered.

A 28-year-old woman realized a left breast tumor. Mammography and ultrasonography revealed focal asymmetric density on the MI area(category 3)and a low-echoic 10 mm tumor with unclear boundaries. We performed an US-guided breast biopsy to confirm the diagnosis. The histopathological examination result suspected nodular fasciitis; however, borderline phyllodes tumor cannot be denied. Tumorectomy was performed under general anesthesia. The final histopathological examination revealed nodular fasciitis due to amplifying fibroblasts with irregular directions. Nodular fasciitis is a benign lesion and sometimes disappears spontaneously. Tumorectomy is often needed to confirm the diagnosis that cannot be identified by needle biopsy. We report a case of breast nodular fasciitis needed to differentiate from borderline phyllodes tumor.

The patient was a 58-year-old woman. She was diagnosed with cT4b, cN3c, cM1, cStage Ⅳ, Her2 positive breast cancer with liver, lung and bone metastases. Seven days after the first visit, she came to our hospital for dyspnea. Chest X-ray, chest CT, and echocardiography showed a decrease in EF to 50.6% due to a large amount of pericardial effusion, and she was diagnosed with cardiac tamponade. On the same day, pericardial drainage was performed urgently. The cytopathology of pericardial fluid was malignant, that is to say, she was diagnosed with cancerous pericarditis. Pericardial drainage relieved respiratory distress, and echocardiography showed disappearance of pericardial fluid and improvement of EF up to 80.4%. Docetaxel plus trastuzumab plus pertuzumab therapy was started 10 days after pericardial drainage as first-line treatment. After starting chemotherapy, the response has continued for 6 months without re-accumulation of pericardial fluid.

The patient is a 69-year-old female. She was aware of a right breast mass about a year ago, but left it alone. In March 2021, she visited our hospital with a 11 cm mass occupying the right breast and self-destruction due to skin invasion. The diagnosis of invasive ductal carcinoma of the breast(ER-positive, PgR-positive, HER2-negative), cT4bN1M0, Stage ⅢB was made, and preoperative chemotherapy was decided. We expected a high response rate for bevacizumab(Bv)because it was predicted that the skin defect would increase at surgical resection if a response to chemotherapy was not achieved, and in April 2021, paclitaxel(PTX)plus Bv therapy was initiated. After 4 courses, the mass had shrunk to 5 cm and a marked response had been achieved. However, she was unable to continue the treatment due to peripheral neuropathy. Therefore, considering the period of delayed wound healing due to Bv, we decided on AC therapy followed by surgery. In December 2021, Bt plus Ax was performed and the wound could be closed without skin grafting. Since PTX plus Bv therapy is expected to have a high response rate, we considered it to be one of the effective treatment options for locally advanced breast cancer.

We report a case of sphenoid bone metastasis from breast cancer detected with diplopia, as first site of recurrence. Forty- year-old woman with left breast cancer underwent breast-conserving surgery and sentinel lymph node biopsy. The diagnosis was papillotubular carcinoma, pT1pN0, ER(+), PgR(+), HER2(-). Tweleb years later, the examination of diplopia revealed left abducens nerve palsy for sphenoid bone metastasis from breast cancer. Radiation therapy(a total dose of 36 Gy with VMAT)was administrated as topical treatment, but diplopia did not improve. After that, systemic treatment was performed, and 2 years and 6 months have passed since the recurrence was found, she is still alive. We need to be careful of orbital metastasis as a symptom of metastasis from breast cancer.

The patient was a 56-year-old woman. who was aware of a tumor in her left axilla and consulted a nearby doctor. She was referred to our hospital for a detailed examination. No abnormalities were found in the breast by visual inspection, mammography, or breast ultrasound examination. One 29 mm swollen lymph node was found in the axilla. Fine needle aspiration cytology revealed malignant lymphoma; thus, so axillary lymph node excision biopsy was performed, and a diagnosis of axillary lymph node metastasis of breast cancer was made. However, no abnormalities were found. Based on the information presented above, the patient was diagnosed with occult breast cancer cT0N1M0, Stage ⅡA, and breast preservation plus axillary lymph node dissection up to level Ⅱ was performed. No metastases were found in the dissected lymph nodes. The treatment policy for occult breast cancer has not yet been established. We report this case with a review of the literature.

The patient is an 85-year-old female who had previously undergone a mastectomy for right breast cancer at the age of 42 years. In September 2020, she visited our hospital with a chief complaint of a chest wall tumor. Physical examination revealed a 3×3 cm ulcerative lesion on the right side of the center chest wall. She underwent a skin biopsy of the tumor under local anesthesia and was diagnosed with a recurrence of right breast cancer(ER positive, PR positive, HER2 negative). PET-CT revealed localized skin thickening on the right side of the sternum and FDG accumulation in the same area, with no other findings suggestive of distant metastasis. Treatment was started with anastrozole and is still ongoing. In this article, we report a very rare case of recurrence 43 years after surgery.