Allogeneic stem cell transplantation for inherited metabolic disorders: 35 years' experience at a single institution.

Hematopoietic stem cell transplants for inherited metabolic disorders performed at Tokai University Hospital between June 5, 1986, and May 28, 2021, were analyzed and compared between the period before 2007 and the period from 2007 onward based on availability of medical resources. Transplants were performed for 38 patients with mucopolysaccharidosis, 33 with adrenoleukodystrophy, and 16 with another disorder. Before 2007, oral busulfan-based regimens were mainly used. From 2007 onward, intravenous busulfan-based regimens or 4 Gy of thoracoabdominal irradiation (TAI), fludarabine, and melphalan (Mel)/treosulfan were adopted. Between 2002 and 2010, adrenoleukodystrophy was treated with 12 Gy of TAI and Mel. HLA-identical sibling bone marrow was used in 43% of cases before 2007 and 15% from 2007 onward, while alternative donors were selected for other transplants. Overall survival and event-free survival (EFS) before 2007 and from 2007 onward were 76% and 62%, and 97% and 85%, respectively (P = 0.006 and 0.017). Transplant era predicted superior overall survival and EFS, while myeloablative conditioning also predicted EFS. The incidence of primary graft failure decreased from 2007 onward, especially in cord blood transplant when 4 Gy of TAI with 150 mg/m2 fludarabine and 180 mg/m2 Mel or 42 g/m2 treosulfan were used as conditioning.

Subcutaneous Panniculitis-like T Cell Lymphoma Diagnosed with a Slowly Progressive Course: A Case Report.

Panniculitis is an inflammation that occurs in subcutaneous adipose tissue. Panniculitis includes physical panniculitis (e.g., traumatic) and infectious panniculitis (e.g., bacterial, fungal, subcutaneous panniculitis-like T cell lymphoma [SPCTL], etc.). Accurate diagnosis is crucial due to similar clinical presentation of all types of panniculitis. Here, we report a case of SPCTL which was initially diagnosed with traumatic panniculitis. A 15-year-old male patient was admitted to a previous hospital due to a progressively enlarged right flank and inguinal mass after an abdominal bruise. He was initially diagnosed with traumatic panniculitis, but the mass expanded throughout the chest and abdomen accompanied by a fever of over 11 months. Computed tomography (CT) revealed a subcutaneous mass in the anterior chest and abdominal wall. Fludeoxyglucose F18 (FDG) uptake was observed at those lesions using FDG-positron emission tomography (PET). A biopsy of the mass lesion was performed, during which SPCTL was diagnosed based on pathological examination. He was initially treated with prednisolone and cyclosporine A for two weeks. His fever went down, but subcutaneous mass in the chest and abdominal wall persisted. Therefore, he received a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen. After 6 courses of CHOP, CT revealed no disease evidence. He remained in complete remission at 30 months of therapy.

Pure Orbital Floor Blow-In Fracture: An Extremely Rare Case.

A 57-year-old man presented with left diplopia on an upward gaze and ophthalmalgia after hitting the left side of his head. CT revealed a fracture on the left side of the orbital floor without orbital rim fractures and the protrusion of a small bone fragment into the orbit. Hess charts indicated markedly limited vertical movement of the left eye. Based on these findings, the patient was diagnosed with a pure orbital floor blow-in fracture (BIF). Symptoms persisted after a two-week monitoring period; therefore, the bone fragment was removed by a transcutaneous surgical approach with the assistance of a navigation system and an endoscope. Symptoms resolved after surgery, and CT and Hess examinations six months after surgery showed a good outcome. A pure BIF is rare, particularly on the orbital floor. Only a few similar case reports have been published to date, and we herein describe the surgical procedures performed and the treatment outcome of our case.

Assessment of eosinophilic rhinosinusitis cases that required secondary treatment (biologics or reoperation) during long-term postoperative courses.

OBJECTIVE: Endoscopic sinus surgery (ESS) is selected as the primary treatment for eosinophilic chronic rhinosinusitis (ECRS). Biologics or reoperation are sometimes required as secondary treatment after ESS. The present study examined the long-term postoperative courses of ECRS cases treated according to the current treatment concept, the frequency of secondary treatment, and its predictive factors. METHODS: Ninety-four patients with ECRS who underwent ESS and received continuous management for 1-5 years were retrospectively investigated. Patient characteristics, long-term changes in endoscopic scores and the results of olfactory function tests, and secondary treatment were evaluated. RESULTS: Five patients underwent reoperation and 11 received dupilumab during the follow-up period (35.9±19.2 months). Sixteen patients (17%) required secondary treatment due to the deterioration of sinus conditions. These patients were significantly younger, had higher comorbidity rates of allergic rhinitis and bronchial asthma, and a higher preoperative CT score than those who did not require secondary treatment. Three months after surgery, CT scores, endoscopic scores (E-scores), and the self-administered odor questionnaire (SAOQ) were significantly worse in patients who required secondary treatment. A multivariate regression analysis identified age, preoperative CT scores, and 3-month E-scores as predictive factors for secondary treatment. Three-month E-scores showed higher sensitivity and specificity, and the odds ratio was 11.3 when the cut-off value was set at 10. CONCLUSION: The early identification of patients for whom ESS may fail is important and additional treatments need to be provided at the appropriate timing where needed. Patients with the following factors need to be carefully followed up: a young age, high preoperative CT score, and high early postoperative E-score.

Retrospective evaluation of the improvement in the urinary status-related quality of life after robot-assisted radical prostatectomy.

OBJECTIVES: This study aimed to investigate the characteristics of patients who report improvement in quality of life (QOL) related to urinary status after undergoing robot-assisted radical prostatectomy (RARP) for localized prostate cancer. METHODS: We retrospectively reviewed the patients who underwent RARP between May 2010 and May 2021 at our institution and were preoperatively unsatisfied with their urinary status. Patients were grouped as Group 1 (improved patients: "satisfied" with urinary status based on international prostate symptom score QOL [IPSS-QOL] = 0-2 at 12 months after RARP) and Group 2 (unimproved group: "unsatisfied"-IPSS-QOL 3-6). Additionally, the Expanded Prostate Cancer Index Composite (EPIC) urinary subdomains (urinary function, urinary bother [UB], urinary incontinence, and urinary irritation/obstruction [UIR]) and IPSS were evaluated preoperatively and till 12 months after RARP. RESULTS: Of the 237 patients, 72 (30.4%) were Group 1, and 165 (69.6%) were Group 2. Only UB and UIR improved at 12 months after RARP in Group 1, while other EPIC urinary subdomains remained unimproved at 12 months in both groups. On the other hand, IPSS improved at 12 months in both groups. Univariate and multivariate analysis revealed that the nerve-sparing, preoperative low IPSS (<11 vs. ≥11), and low IPSS-QOL (3 vs. 4-6) were associated with improvement in urinary status-related QOL (p < 0.05). CONCLUSIONS: Improvement in UB and UIR are important factors to ascertain improvement in urinary status-related QOL after RARP. Nerve-sparing and preoperative IPSS/IPSS-QOL values are useful predictors of this improvement.

Successful Emergency Decompressive Laminectomy for Burkitt Lymphoma with Metastatic Spinal Lesions: A Case Report.

Although Burkitt lymphoma (BL) usually arises in the abdomen or pelvis, it can also arise in the epidural space as a primary or secondary site and present with back pain or limb weakness. Emergency management is necessary to relieve spinal cord compression (SCC). Herein, we report a case of BL with metastatic spinal lesions in a 16-year-old female who presented with sudden-onset progressive walking difficulty. She was admitted to a previous hospital where she presented with abdominal pain and vomiting and was diagnosed with intussusception via a computed tomography scan. Laparoscopic small bowel resection was performed, during which a diagnosis of BL was made on the basis of pathological examination. Sudden numbness in the extremities and the complete inability to walk occurred ten days after surgery. Thoracolumbar MRI revealed a metastatic mass extending from C7 to T6 with evidence of SCC. Emergency decompressive laminectomies (from C7 to T6) and partial debulking of the tumor were performed 12 hours after the onset of her neurologic symptoms. She was subsequently treated with chemotherapy, and she made a complete neurologic recovery. Emergency decompressive laminectomies for BL with spinal lesions could effectively lead to the recovery of neurologic symptoms.

[LOWER RESPIRATORY TRACT SCREENING USING FRACTIONAL EXHALED NITRIC OXIDE IN PATIENTS WITH EOSINOPHILIC CHRONIC RHINOSINUSITIS].

BACKGROUND: It is known that eosinophilic chronic rhinosinusitis is often associated with adult-onset bronchial asthma, and undiagnosed bronchial asthma is also known to be included. The purpose of this study is to screen patients with eosinophilic chronic rhinosinusitis using fractional exhaled nitric oxide, and to examine its usefulness in detecting undiagnosed bronchial asthma. METHODS: We retrospectively examined the data of patients with eosinophilic chrnoic rhinosinusitis who underwent surgical treatment at Kagawa University from April 2015 to July 2022. Patients were included if they received examinations of fractional exhaled nitric oxide and spirometry before surgical treatment. RESULTS: Of the 127 subjects, 52 had no history of treatment or diagnosis of bronchial asthma at the initial consultation. Among them, 15 patients who had high fractional exhaled nitric oxide value were diagnosed with bronchial asthma by the respiratory medicine department. Comorbid of bronchial asthma was eventually increased to 70.9% even though it was 59.1% at initial consultation. CONCLUSION: A certain number of patients with eosinophilic chronic rhinosinusitis have undiagnosed bronchial asthma, which can be difficult to detect with basic examination alone therefore fractional exhaled nitric oxide is useful as an additional screening examination.

Early postoperative endoscopic score can predict the long-term endoscopic outcomes in eosinophilic chronic rhinosinusitis (ECRS) patients.

OBJECTIVE: Eosinophilic Chronic Rhinosinusitis (ECRS) is refractory and recurrent, requiring long-term follow-up after Endoscopic Sinus Surgery (ESS). Endoscopic evaluation is common during postoperative assessment, but how the findings vary over time in postoperative ECRS patients who were treated by the recent standardized management is unclear. We assessed the long-term change in postoperative endoscopic score in ECRS patients using a novel endoscopic scoring system (Escore). METHODS: This retrospective study included 80 ECRS patients who underwent full-house ESS and were followed for longer than 1-year. Endoscopic procedures were repeated at every follow-up visit and postoperative Escores were assessed from 3-months up to 5-years (median follow-up period was 3-years). RESULTS: The Escore did not significantly change from that at 3-months (3m-Escore). The Escore at the final observation point (f-Escore) among 80 patients was 9.2 ± 5.6 and there was no significant difference from the 3m-Escore (8.5 ± 4.1, p = 0.363). Twenty-one patients (21/80, 26.3%) were considered to have endoscopically uncontrolled ECRS at their final observation points and the 3m-Escore was identified as an independent predictive factor by multivariate logistic regression analysis. The 3m-Escore cut-off value that was able to predict endoscopically uncontrolled ECRS after long-term follow-up was ≥12. CONCLUSION: We demonstrated the long-term endoscopic outcomes after full-house ESS and continuous outpatient treatment. Early endoscopic findings (3m-Escore) were a potential predictive factor for the later endoscopic outcome, and a 3m-Escore of 12 or higher may be an indicator of the poor long-term prognosis of sinus mucosa.

A highly specific recurrent pleomorphic adenoma of the nasal septum.

A 90-year-old woman presented with the sudden onset of visual loss. She previously underwent surgery to treat a right septal pleomorphic adenoma (PA) at 77 years old. She initially presented to our hospital with severe nasal obstruction at 83 years old. A large tumor occupied the bilateral nasal cavities and, thus, surgery was performed using midfacial degloving and an endoscopic endonasal combined approach. A 60×45×43 mm tumor was completely removed; however, a small area of the tumor capsule was damaged. Six years after surgery, PA recurred in the posterior midline portion of the nasal cavity. Imaging examinations revealed a 48×42×45 mm mass, which compressed the bilateral optic canal, thereby causing severe visual loss. The recurrent tumor was endoscopically removed, and vision recovered after surgery. The lack of malignant transformation was pathologically confirmed throughout this period. The present case had several highly specific features: she was very elderly, the tumor was very large, and visual dysfunction was caused by nasal PA. We described surgical procedures in detail and considered the specific findings of the present case. En bloc resection with a sufficient margin was considered to be important in the present case because recurrence may be caused by incomplete excision.

Early postoperative endoscopic score can predict the long-term endoscopic outcomes in eosinophilic chronic rhinosinusitis (ECRS) patients

Abstract Objective: Eosinophilic Chronic Rhinosinusitis (ECRS) is refractory and recurrent, requiring long-term follow-up after Endoscopic Sinus Surgery (ESS). Endoscopic evaluation is common during postoperative assessment, but how the findings vary over time in postoperative ECRS patients who were treated by the recent standardized management is unclear. We assessed the long-term change in postoperative endoscopic score in ECRS patients using a novel endoscopic scoring system (Escore). Methods: This retrospective study included 80 ECRS patients who underwent full-house ESS and were followed for longer than 1-year. Endoscopic procedures were repeated at every follow-up visit and postoperative Escores were assessed from 3-months up to 5-years (median follow-up period was 3-years). Results: The Escore did not significantly change from that at 3-months (3m-Escore). The Escore at the final observation point (f-Escore) among 80 patients was 9.2 ± 5.6 and there was no significant difference from the 3m-Escore (8.5 ± 4.1, p = 0.363). Twenty-one patients (21/80, 26.3%) were considered to have endoscopically uncontrolled ECRS at their final observation points and the 3m-Escore was identified as an independent predictive factor by multivariate logistic regression analysis. The 3m-Escore cut-off value that was able to predict endoscopically uncontrolled ECRS after long-term follow-up was ≥12. Conclusion: We demonstrated the long-term endoscopic outcomes after full-house ESS and continuous outpatient treatment. Early endoscopic findings (3m-Escore) were a potential predictive factor for the later endoscopic outcome, and a 3m-Escore of 12 or higher may be an indicator of the poor long-term prognosis of sinus mucosa. Level of evidence: 4.

A Boy Presenting with a Fever and Pancytopenia Diagnosed with Systemic Lupus Erythematosus without a Positive Anti-ds-DNA Antibody Result or Hypocomplementemia: A Case Report.

BACKGROUND: Hematological involvement, including anemia, leukopenia, lymphopenia, and thrombocytopenia, is one of the most common manifestations of childhood-onset systemic lupus erythematosus (cSLE). Specifically, relatively severe forms of hematological involvement, such as macrophage activation syndrome (MAS) and thrombotic microangiopathy, occur in the course of the disease. Positivity for anti-double stranded-DNA (ds-DNA) antibody and hypocomplementemia are important as not only criteria of diagnosing cSLE but also in the determination of the disease activity. CASE REPORT: A 13-year-old boy without pre-existing disease was referred to our hospital chiefly complaining of a fever for > 7 days, long-lasting malaise, nausea, and non-malar face rash. His blood examination showed pancytopenia and hyperferritinemia, but positive results for anti-ds-DNA antibody and hypocomplementemia were not recognized. Bone marrow aspiration revealed no evidence of malignant diseases, hemophagocytic lymphohistiocytosis, or MAS. A renal biopsy for the differential diagnosis of proteinuria and hematuria revealed class IIIa +V lupus nephritis, leading to the diagnosis of cSLE. CONCLUSIONS: It is important for cSLE to be considered in patients with pancytopenia, even those without positive anti-ds-DNA antibody findings or hypocomplementemia, and for aggressive approaches to be adopted for the differential diagnosis, including a renal biopsy.

Invasive Pulmonary Aspergillosis Successfully Treated with Granulocyte Transfusions Followed by Hematopoietic Stem Cell Transplantation in a Patient with Severe Childhood Aplastic Anemia.

Granulocyte transfusions (GTX) have been used in patients with neutropenia or neutropenia associated with invasive fungal infection. An 11-year-old girl with severe aplastic anemia (SAA) received immunosuppressive therapy (IST) with rabbit antithymocyte globulin, cyclosporine, and granulocyte colony-stimulating factor. However, IST was not effective and her condition became complicated with life-threatening invasive pulmonary aspergillosis. Owing to the necessity for early neutrophil recovery to resolve the infection, GTX were performed, followed by bone marrow transplantation (BMT) from her mother with human leukocyte antigen-B locus mismatch. Her dyspnea improved and she eventually became afebrile after the initiation of GTX. Despite engraftment failure following BMT, successful engraftment was achieved by salvage therapy with peripheral blood stem cell transplantation. Chest computed tomography scan obtained 4 months after BMT revealed marked improvement in pneumonia. The current case illustrates that GTX may be useful in controlling invasive fungal infections before hematopoietic stem cell transplantation in patients with SAA.

Breath sound analyses of infants with respiratory syncytial virus acute bronchiolitis.

INTRODUCTION: The reliability of a breath sound analysis using an objective method in infants has been reported. OBJECTIVE: Breath sounds of infants with respiratory syncytial virus (RSV) acute bronchiolitis were analyzed via a breath sound spectrogram to evaluate their characteristics and examine their relationship with the severity. SUBJECTS AND METHODS: We evaluated the inspiratory and expiratory breath sound parameters of 33 infants diagnosed with RSV acute bronchiolitis. The sound powers of inspiration and expiration were evaluated at the acute phase and recovery phase of infection. Furthermore, the relationship between the breath sound parameters and the clinical severity of acute bronchiolitis was examined. RESULTS: Analyses of the breath sound spectrogram showed that the power of expiration as well as the expiration-to-inspiration sound ratio in the mid-frequency (E/I MF) was increased in the acute phase and decreased during the recovery phase. The E/I MF was inversely correlated with the SpO2 and positively correlated with the severity score. CONCLUSION: In infants with RSV acute bronchiolitis, the sound power of respiration was large at the acute phase, significantly decreasing in the recovery phase. In 61% of participants, nonuniform, granular bands were shown in the low-pitched region of the expiratory spectrogram.

Novel antiangiogenic therapy targeting biglycan using tumor endothelial cell-specific liposomal siRNA delivery system.

Tumor blood vessels play important roles in tumor progression and metastasis. Targeting tumor endothelial cells (TECs) is one of the strategies for cancer therapy. We previously reported that biglycan, a small leucine-rich proteoglycan, is highly expressed in TECs. TECs utilize biglycan in an autocrine manner for migration and angiogenesis. Furthermore, TEC-derived biglycan stimulates tumor cell migration in a paracrine manner leading to tumor cell intravasation and metastasis. In this study, we explored the therapeutic effect of biglycan inhibition in the TECs of renal cell carcinoma using an in vivo siRNA delivery system known as a multifunctional envelope-type nanodevice (MEND), which contains a unique pH-sensitive cationic lipid. To specifically deliver MEND into TECs, we incorporated cyclo(Arg-Gly-Asp-D-Phe-Lys) (cRGD) into MEND because αV ß3 integrin, a receptor for cRGD, is selective and highly expressed in TECs. We developed RGD-MEND-encapsulating siRNA against biglycan. First, we confirmed that MEND was delivered into OS-RC-2 tumor-derived TECs and induced in vitro RNAi-mediated gene silencing. MEND was then injected intravenously into OS-RC-2 tumor-bearing mice. Flow cytometry analysis demonstrated that MEND was specifically delivered into TECs. Quantitative RT-PCR indicated that biglycan was knocked down by biglycan siRNA-containing MEND. Finally, we analyzed the therapeutic effect of biglycan silencing by MEND in TECs. Tumor growth was inhibited by biglycan siRNA-containing MEND. Tumor microenvironmental factors such as fibrosis were also normalized using biglycan inhibition in TECs. Biglycan in TECs can be a novel target for cancer treatment.

Gradually progressive cholangiolocellular carcinoma: a case report.

BACKGROUND: Cholangiolocellular carcinoma (CoCC) is a relatively rare primary liver tumor. We present a literature review and case report of a patient who presented with a slow-growing CoCC that was completely resected after a 5-year follow-up period. CASE PRESENTATION: The patient was a 66-year-old man with a history of inflammatory thoracic and intra-abdominal pseudo-tumors. He was regularly followed up at our hospital for partial dilation of the pancreatic duct branch located in the body of the pancreas. Five years earlier, computed tomography (CT) demonstrated a small tumor in liver segment 4. Radiological findings were suggestive of hemangioma. Tumor size gradually increased during the 5-year follow-up period. CT scans showed that the tumor had progressed in size from 10 to 20 mm. Positron emission tomography CT revealed an accumulation of fluorodeoxyglucose (standardized uptake value max 5.3) at the tumor site. The tumor exhibited high intensity on T2-weighted and diffusion-weighted images of ethoxybenzyl magnetic resonance imaging. The tumor showed high intensity during the early phase but low intensity during the hepatobiliary phase. Tumor markers were within their respective normal ranges. Suspecting intrahepatic cholangiocarcinoma, left hepatectomy was performed. The tumor was diagnosed as CoCC based on pathological findings. The patient's post-operative course was uneventful. The patient survived for a year, without any recurrence. CONCLUSIONS: In cases dealing with small tumor sizes, it is difficult to distinguish between CoCC and hemangioma due to their similar radiological findings. Thus, it is important to consider the diagnosis of CoCC in small benign hepatic tumors. As such, follow-up radiological examination is recommended.

miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells.

Tumor endothelial cells (TECs) reportedly exhibit altered phenotypes. We have demonstrated that TECs acquire drug resistance with the upregulation of P-glycoprotein (P-gp, ABCB1), contrary to traditional assumptions. Furthermore, P-gp expression was higher in TECs of highly metastatic tumors than in those of low metastatic tumors. However, the detailed mechanism of differential P-gp expression in TECs remains unclear. miRNA was identified in highly metastatic tumor extracellular vesicles (EVs) and the roles of miRNA in endothelial cell resistance were analyzed in vitro and in vivo. In the present study, we found that treatment of highly metastatic tumor-conditioned medium induced resistance to 5-fluorouracil (5-FU) with interleukin-6 (IL-6) upregulation in endothelial cells (ECs). Among the soluble factors secreted from highly metastatic tumors, we focused on EVs and determined that miR-1246 was contained at a higher level in highly metastatic tumor EVs than in low metastatic tumor EVs. Furthermore, miR-1246 was transported via the EVs into ECs and induced IL-6 expression. Upregulated IL-6 induced resistance to 5-FU with STAT3 and Akt activation in ECs in an autocrine manner. These results suggested that highly metastatic tumors induce drug resistance in ECs by transporting miR-1246 through EVs.

Successful combination chemotherapy involving clofarabine, cyclophosphamide, and etoposide for pediatric relapsed acute myeloid leukemia: A case report.

Limited salvage chemotherapies are available for relapsed/refractory acute myeloid leukemia. Herein, we described successful reinduction chemotherapy, involving a combination of clofarabine, cyclophosphamide, and etoposide, in a 12-year-old male with relapsed acute myeloid leukemia prior to allogeneic bone marrow transplantation from his father. Although treatment with a combination of fludarabine, cytarabine, granulocyte colony-stimulating factor, idarubicin, and gemtuzumab ozogamicin had no positive effects, the aforementioned clofarabine-based chemotherapy induced complete remission and allowed the transplantation to go ahead. The abovementioned regimen may be useful for induction chemotherapy prior to hematopoietic stem cell transplantation for refractory/relapsed acute myeloid leukemia.

Anticoagulation treatment and prophylactic edoxaban for cerebral sinus venous thrombosis in an adolescent with acute lymphoblastic leukemia.

Pediatric acute lymphoblastic leukemia regimens include large L-asparaginase dosages and steroids, which are associated with an increased risk of venous thromboemboli in adolescents and young adults. Herein, we report the case of an 18-year-old male with acute lymphoblastic leukemia, who was treated with the pediatric regimen, in which edoxaban was employed as a prophylaxis against cerebral sinus venous thrombosis. The event happened on day 20 of induction therapy, when brain magnetic resonance imaging demonstrated a cerebral sinus venous thrombosis in the superior sagittal sinus. Anticoagulation therapy was initiated, and the patient's symptoms disappeared 3 days later. The induction therapy was restarted after an interruption of 16 days, and the consolidation therapies, which included L-asparaginase and steroids, were completed. Edoxaban was administered as a prophylaxis during the consolidation therapy. There were no further adverse events. Edoxaban could be an effective prophylaxis for coagulation complications in adolescents and young adults with acute lymphoblastic leukemia.