In 2006, we established a scar/keloid-specialized unit in the Department of Plastic, Reconstructive, and Aesthetic Surgery at Nippon Medical School (NMS) in Tokyo, Japan. In the ensuing 15 years, we treated approximately 2,000 new scar/keloid patients annually. This extensive experience has greatly improved the efficacy of the treatments we offer. Therefore, we discuss here the latest NMS protocol for preventing and treating keloids and hypertrophic scars. While this protocol was optimized for Japanese patients, our experience with a growing body of non-Japanese patients suggests that it is also effective in other ethnicities. The extensive evidence-based experience underlying the NMS protocol suggests that it may be suitable as the foundation of a standard international prevention/treatment algorithm for pathological scars.

The effectiveness and safety of antipsychotics have not been fully established in children and adolescents. Many antipsychotics approved for use in adults are prescribed off-label to children and adolescents. We investigated the effectiveness and tolerability of antipsychotics for children and adolescents with schizophrenia and bipolar disorder. A literature review of the empirical evidence regarding the use of antipsychotics, particularly second-generation antipsychotics, in children and adolescents showed that these drugs were safe and effective for this population. Antipsychotics were similarly effective for treatment of schizophrenia and bipolar disorder in children and adolescents. When prescribing antipsychotics to this population, clinicians should consider adverse events and the discontinuation rate in treated patients. However, the current evidence shows a lack of consensus regarding the use of antipsychotics in children and adolescents.

With advancements in the development of flexible endoscopes and endoscopic devices and the increased demand for minimally invasive treatments, the indications of therapeutic endoscopy have been expanded. Methods of endoscopic treatment used for tissue removal, hemostasis, and dilatation are as follows. Endoscopic submucosal dissection (ESD) is considered the gold standard curative method for removal of gastrointestinal node-negative neoplasms, regardless of their size or the presence of ulcer formation. Laparoscopic endoscopic cooperative surgery (LECS), which incorporates ESD, was introduced for removal of lesions in deeper layers. Another technique is endoscopic full-thickness resection, which is challenging without the assistance of laparoscopy. In terms of hemostasis, management of iatrogenic bleeding after endoscopic treatment is an important issue. Shielding methods and suturing techniques have been introduced for large mucosal defects after ESD, and their efficacy has been investigated clinically. Peroral endoscopic myotomy (POEM) is a new alternative surgical approach for minimally invasive treatment of esophageal achalasia. Furthermore, endoscopic fundoplication after POEM was devised to prevent post-POEM gastroesophageal reflux disease. Many endoscopic treatments, including ESD, LECS, and POEM, have been introduced in Japan. With the aging of the population, more attention will be directed toward therapeutic endoscopy for elderly patients, because it is less invasive. Development of endoscopic treatments with expanded indications is expected.

Background: Because of population aging in Japan, the number of cancer diagnoses is increasing rapidly. The pedicle sign is a valuable radiographic indicator of metastases, as the pedicle is the most commonly affected vertebral structure in radiographic assessment. However, few studies have carefully examined the morphological features of pedicle signs. To improve the capacity of medical professionals to diagnose symptomatic spinal metastases, we retrospectively examined the morphological characteristics of pedicle signs and their associations with clinical and radiological features. Methods: 186 patients with symptomatic spinal metastases who visited our department during the period from January 1, 2011 through December 31, 2017 were enrolled. The pedicle sign was defined as a missing or obscured pedicle on an anteroposterior radiograph. Radiographs were evaluated for pedicles and other vertebrae structures. Clinical and other radiological features were compared in relation to the type of pedicle sign identified. Results: Pedicle signs were classified as completely disappeared (complete, 26 patients), partially disappeared (partial, 40 patients), or obscured by the osteoblastic background (blastic, 28 patients). Disappearance of both the bone cortex and pedicle was observed in almost half of the patients with complete or partial pedicle signs. The complete pedicle sign was associated with significantly longer survival. Conclusion: Diagnosis of bone metastases requires understanding of pedicle sign types.

Background: The reliability of methods for identifying the circumferential position of small lower esophageal lesions is unknown. We prospectively investigated a new method that presents lesion positions as times on a clock face. Methods: Eighty-seven patients were consecutively examined by endoscopy. After observing the esophagus, an endoscope was inserted into the stomach and fixed, and the greater curvature folds at the upper gastric corpus were set as horizontal on the endoscope monitor display. The scope was retrogressed into the lower esophagus. At this point, the right wall at the hiatus is at the 3 o'clock position (R-line). The scope was then retrogressed from the gastric angle to the cardia along the center of the lesser curvature in the retroflexed view to obtain the LC-line (the center of the lesser curvature at the cardia). The LC-line in the esophageal hiatus in the frontal view was then identified, and the angle between the R- and LC-lines (R-LC) was measured. Results: After excluding 7 patients with hernias >2 cm and 3 with esophageal stenosis, data from 77 patients were analyzed. The R-LC angle ranged from −38° to +35°. The mean R-LC angle was −0.3°± 15.9°, and its 95% confidence interval was [−4.0°, 3.3°] within [−15°, + 15°]. When indicating lesion locations as times on a clock face, there was an error of ±30 min (±15°); therefore, R- and LC-lines were shown to be identical on an equivalence test. Conclusions: This new method allows the circumferential position of small lower esophageal lesions to be reliably represented as a clock face.

Background: Since 2002, the Department of Pediatrics of Nippon Medical School Chiba Hokusoh Hospital has offered educational activities for children with short stature. We analyzed outcomes of growth hormone (GH) treatment for children with short stature treated at our hospital, particularly outcomes after the growth spurt. Methods: We analyzed data from children aged 0 to 17 years who were treated with recombinant GH during the period from 2000 through 2016 and were followed for at least 2 years after the start of treatment. Results: Among children with short stature, 85 had GH deficiency, 5 had Turner syndrome, 9 were small for gestational age, and 1 had Noonan syndrome. The outcomes of GH treatment was similar to those previously reported in Japan. Children with GH deficiency who started GH treatment before the growth spurt exhibited marked height catch-up until the second year, but the effect decreased after 3 years. The effect of treatment for GH deficiency that was started after the growth spurt continued for 4 to 5 years after the start of treatment. Conclusions: Improvement in height standard deviation score was similar when treatment was started before and after the growth spurt.

Background: Because peripheral blood stem cell (PBSC) collection places a burden on the patient and should ideally be completed in a single procedure, a convenient clinical predictive factor is needed. Methods: This retrospective study included 72 patients who underwent autologous PBSC collection. A median volume of 3.9 × 10⁶ CD34-positive cells/kg (range: 0.3-47.4 × 10⁶ cells/kg) was collected on the first day. We defined failure as inability to collect 2.0 × 10⁶ cells/kg on the first day. PBSC collection was classified as failed (n = 25, 34.7%) and successful (n = 47, 65.3%), and patient clinical characteristics were analyzed. Results: The success group had significantly more cases in which a differential white blood cell count in peripheral blood on the day of PBSC collection detected promyelocytes (n = 34 [72.3%] vs. n = 11 [44.0%] in the failure group; P = 0.008). Sixty-two patients underwent autologous PBSC transplantation (median number of transplanted cells, 5.6 × 10⁶/μL; range: 1.60-47.4 × 10⁶ cells/μL). Among transplanted patients, the success and failure groups did not significantly differ in relation to the interval until neutrophil, platelet, or red blood cell engraftment. Conclusion: The presence of promyelocytes in peripheral blood may be a useful indicator of the optimal timing for single-step PBSC collection.

Background: The nuclear receptor genes, including estrogen receptor β (ERβ), contain non-conventional internal and terminal exons, and alternative choice of the exons yields multiple mRNA and protein variants with unique structures and functions. However, the genomic structure of the intronic and 3'-downstream regions of the human ERβ gene and the presence of novel ERβ variants with non-conventional sequences have not been re-examined in about 20 years. Therefore, we attempted to re-characterize the structure of the human ERβ gene and identify novel non-conventional exons and distinct splice variants. Methods: Rapid amplification of cDNA 3'-end and RT-PCR cloning were used to isolate human ERβ mRNA variants from the testis. The identified cDNA sequences were mapped on the human genome assembly. Expression profiles of the variants were assessed by RT-PCR analysis. Results: We cloned multiple ERβ mRNA variants with novel nucleotide sequences from the testis and identified several alternative splice sites, 3'-elongation of conventional coding exons, and novel terminal exons in the human ERβ gene. The variants encode C-terminally truncated ERβ proteins termed ERβ6, ERβ7, ERβEx. 4_L, and ERβEx. 6_L. Furthermore, we identified exon 7-defective forms of ERβ2/βcx, ERβ4, ERβ6, and ERβ7. Subsequently, we noted distinct expression patterns of the variants in human peripheral organs and brain subregions. Conclusion: This study clarified complicated genomic organization and splicing patterns of the human ERβ gene that contribute to the distinct heterogeneity of human ERβ mRNAs and proteins.

Background: In patients undergoing mastectomy for locally advanced breast cancer (LABC), surgical skin flap reconstruction is sometimes required in order to cover large skin defects. This study assessed the efficacy of local, cutaneous (rhomboid) flap reconstruction after mastectomy by comparing data from patients with LABC requiring local flap reconstruction after mastectomy and those that underwent mastectomy alone. Methods: Data from 68 patients with LABC who underwent mastectomy were reviewed retrospectively; 14 underwent local (rhomboid) flap reconstruction after mastectomy (local flap group) and 54 underwent direct closure after mastectomy (direct closure group). A pinch test was performed to determine the closure method. Data on the operation, postoperative complications, and postoperative quality of life (QOL) were compared between groups. Results: It was possible to close defects in the local flap group that were significantly larger than those in the direct closure group (p=0.0002). There was no significant difference in postoperative complications between groups. Although operative duration was significantly longer in the local flap group than in the direct closure group (p=0.016), the average difference was only 25 minutes. There was no significant difference in variables related to postoperative QOL. Conclusions: Rhomboid flap reconstruction was effective for covering large defects after mastectomy in patients with LABC.

Background: Combination therapy with an alpha-glucosidase inhibitor or glinide plus a dipeptidyl peptidase-4 inhibitor is thought to be effective for glycemic control because of its effects on postprandial hyperglycemia. However, no studies have directly compared these two combination therapies in relation to efficacy and safety. Methods: Eighteen patients with type 2 diabetes were studied. All had diabetes not adequately controlled with diet and exercise therapy, an HbA1c level of ≥7.5%, and were not receiving any medication for diabetes. The patients were randomized to either miglitol- or repaglinide-based combination therapy with alogliptin. Patients received miglitol or repaglinide monotherapy for 3 months (the miglitol and repaglinide groups, respectively), after which alogliptin was added to each group as combination therapy for 3 months. A meal tolerance test (MTT) was performed before the start of treatment and at the end of monotherapy and combination therapy. Results: During the study period, decreases in HbA1c and glycated albumin were significantly greater in the repaglinide group than in the miglitol group; however, there was no significant difference between treatment groups at the end of the study. At the end of monotherapy, insulin secretion relative to glucose elevation (ISG_0-30: area under the curve of insulin from 0 to 30 min during MTT [AUC_0-30 of IRI]/AUC_0-30 of plasma glucose) was significantly higher only in the repaglinide group; ISG_0-30 did not significantly increase in either group after the addition of alogliptin. Conclusions: The addition of alogliptin to repaglinide monotherapy did not cause glucose-independent inappropriate insulin secretion and did not appear to increase the incidence of hypoglycemia.

Background: Coronavirus disease 2019 (COVID-19) and heat-related illness are systemic febrile diseases. These illnesses must be differentiated during a COVID-19 pandemic in summer. However, no studies have compared and distinguished heat-related illness and COVID-19. We compared data from patients with early heat-related illness and those with COVID-19. Methods: This retrospective observational study included 90 patients with early heat-related illness selected from the Heatstroke STUDY 2017-2019 (nationwide registries of heat-related illness in Japan) and 86 patients with laboratory-confirmed COVID-19 who had fever or fatigue and were admitted to one of two hospitals in Tokyo, Japan. Results: Among vital signs, systolic blood pressure (119 vs. 125 mm Hg, p = 0.02), oxygen saturation (98% vs. 97%, p < 0.001), and body temperature (36.6°C vs. 37.6°C, p<0.001) showed significant between-group differences in the heatstroke and COVID-19 groups, respectively. The numerous intergroup differences in laboratory findings included disparities in white blood cell count (10.8 × 10³/μL vs. 5.2 × 10³/μL, p<0.001), creatinine (2.2 vs. 0.85 mg/dL, p<0.001), and C-reactive protein (0.2 vs. 2.8 mg/dL, p<0.001), although a logistic regression model achieved an area under the curve (AUC) of 0.966 using these three factors. A Random Forest machine learning model achieved an accuracy, precision, recall, and AUC of 0.908, 0.976, 0.842, and 0.978, respectively. Creatinine was the most important feature of this model. Conclusions: Acute kidney injury was associated with heat-related illness, which could be essential in distinguishing or evaluating patients with fever in the summer during a COVID-19 pandemic.