Search

[Patient] A 65-year-old man. [History of present illness] An abnormal chest shadow was noted in March of 2011, and hoarseness was observed in November of 2017. Both times, AL amyloidosis was diagnosed by biopsy. The patient was admitted to our department for treatment in March 2018, and received 6 cycles of melphalan plus dexamethasone for systemic AL amyloidosis in May. His condition was good, but a blood test in August 2019 showed white blood cells 50,000/µl and 44.9% blasts in the peripheral blood, leading to a diagnosis of treatment-related acute leukemia (AML with inv (16)(p13.1q22);CBFB::MYH11). He achieved complete remission with standard treatment, but relapsed in May 2020, CNS relapsed in September 2020, CNS relapsed again in July 2021, and CNS relapsed a third time in May 2022. He underwent intensive chemotherapy, whole brain radiation therapy, 13 rounds of intrathecal injection, and five cycles of venetoclax plus azacitidine, but his general condition gradually worsened. He was transferred to best supportive care in November and died in June 2023. [Discussion] Although advances in treatment have extended survival in systemic AL amyloidosis, long-term follow-up for secondary cancer is important for patients with long-term exposure, as in this case.

Purpose: To investigate the accuracy of proton density fat fraction (PDFF) measurement using chemical shift-encoded MRI (CSE-MRI) with fast imaging techniques in a phantom., Methods: A 1.5T imaging system (Prodiva; Philips Healthcare) and PDFF phantom (Fat Fraction Phantom Model 300; Calimetrix) were used in this study. The acquisitions without fast imaging techniques (conventional acquisition), with parallel imaging in phase-encode direction (SENSE acquisition), with compressed sensing (CS-SENSE acquisition), and with parallel imaging in both phase-encode and slice-encode direction (Dual-SENSE acquisition) were performed. The following acceleration factors in SENSE and CS-SENSE acquisition were used: 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, and 8.0. For Dual-SENSE acquisition, the same acceleration factors (1.5, 2.0, 3.0, 4.0, 5.0) were set in each of the two directions. The relationships between reference PDFF values and PDFF measurements obtained using each acquisition were assessed using linear regression analysis and Bland-Altman analysis., Results: According to the linear regression analysis, the slopes and intercepts of regression lines were from 0.87 to 1.02 and from 0.06% to 3.55%, respectively. According to Bland-Altman analysis, there were fixed bias between reference PDFF values and PDFF measurements obtained using SENSE acquisition with reduction factor 8.0 and Dual-SENSE acquisition with reduction factor 5.0. For CS-SENSE acquisition with reduction factor from 7.0 to 8.0, SENSE acquisition with reduction factor from 3.0 to 8.0, and Dual-SENSE acquisition with reduction factor from 2.0 to 5.0, some vials had ±1.5% or more errors between the reference PDFF values and PDFF measurements in the range of 0% to 50% PDFF., Conclusion: In CS-SENSE acquisition, the accuracy of PDFF measurement was maintained within 1.5% up to a reduction factor 6.0. The accuracy of PDFF measurement was maintained within 1.5% up to a reduction factor 2.0 in SENSE acquisition and a reduction factor 1.5 in Dual-SENSE acquisition.

Purpose: It is very difficult for a radiologist to correctly detect small lesions and lesions hidden on dense breast tissue on a mammogram. Therefore, recently, computer-aided detection (CAD) systems have been widely used to assist radiologists in interpreting images. Thus, in this study, we aimed to segment mass on the mammogram with high accuracy by using focus images obtained from an eye-tracking device., Methods: We obtained focus images for two mammography expert radiologists and 19 mammography technologists on 8 abnormal and 8 normal mammograms published by the DDSM. Next, the auto-encoder, Pix2Pix, and UNIT learned the relationship between the actual mammogram and the focus image, and generated the focus image for the unknown mammogram. Finally, we segmented regions of mass on mammogram using the U-Net for each focus image generated by the auto-encoder, Pix2Pix, and UNIT., Results: The dice coefficient in the UNIT was 0.64±0.14. The dice coefficient in the UNIT was higher than that in the auto-encoder and Pix2Pix, and there was a statistically significant difference (p<0.05). The dice coefficient of the proposed method, which combines the focus images generated by the UNIT and the original mammogram, was 0.66±0.15, which is equivalent to the method using the original mammogram., Conclusion: In the future, it will be necessary to increase the number of cases and further improve the segmentation.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment option for multiple myeloma (MM), but few patients are eligible due to its high risk of treatment-related toxicity and relapse. Here, we report the feasibility and efficacy of allo-SCT after myeloablative conditioning with 8 Gy of total body irradiation (TBI) for reducing relapse of MM. We retrospectively analyzed data from 30 consecutive patients who received allo-SCT for MM after 8 Gy of TBI at Japanese Red Cross Medical Center between 2012 and 2021. Median age at allo-SCT was 47 (range 31-61) years. Stem-cell sources were peripheral blood from an HLA-matched related donor (MRD, n=5), bone marrow from an HLA-matched unrelated donor (MUD, n=5), bone marrow from an HLA-mismatched unrelated donor (MMUD, n=13), and cord blood (n=7). All patients received conditioning with 8 Gy of TBI combined with Flu/Mel (n=28) or others (n=2). Five-year PFS and 5-year OS were 36.7% and 46.2%, respectively. Sixteen patients died during the observation period (12 of primary disease and 4 of treatment-related toxicity). Patients with VGPR or better before allo-SCT had significantly better PFS (p=0.009) and OS (p=0.01) than others. Patients who received MMUD cells tended to have better PFS than those with other cell sources. Our report showed that allo-SCT for MM after 8 Gy of TBI is feasible, and the better PFS of MMUD suggests graft-versus-myeloma effects.

Recent studies have shown that proteins already possess supersulfides during the translation. However, the distribution and the role of supersulfides are not fully understood. In this review, we focus on supersulfides in biological fluids, especially in serum. Various methods for measuring supersulfides have been developed, and these methods have elucidated the presence of supersulfides in serum proteins including serum albumin. Since the levels of supersulfides in serum and serum albumin of patients with chronic kidney disease were lower than those in healthy subjects and recovered by hemodialysis, the levels of supersulfides in serum would be an indicator reflecting oxidative stress. In addition, it has long been known that serum albumin is responsible for sulfur transference. We have applied this phenomenon to the synthesis of sulfur-added albumin (S n -HSA) by the reaction of serum albumin with sodium polysulfide (Na 2 S n ). S n -HSA suppressed the melanin production via scavenging oxidative stress. As described above, studies on the characterization of supersulfides in serum albumin may contribute to the monitoring of redox balance and prevention of oxidative stress-related diseases.

Purpose: The aim of this study were to compare electron density (ED), obtained by dual energy computed tomography (DECT), between hepatocellular carcinoma (HCC) and hemangioma, and to assess the differential diagnostic performance of ED between HCC and hemangioma., Methods: A total of 46 patients (27 men and 19 women; mean age, 65.7±14.0 years) diagnosed with HCC or hemangioma who underwent upper abdominal DECT between October 2021 and December 2022 were included. ED of each lesion was measured. Relative ED (rED), which is normalized by the ED of background liver parenchyma, was calculated. ED and rED of HCC and hemangioma were statistically analyzed., Results: The HCC group showed significantly higher ED (48.1±5.2) and rED (80.0±7.3) than the hemangioma group (43.7±4.1, 69.7±7.2, respectively) (p<0.01). The area under the curve of rED was greater than that of ED, but no significant difference was found (p=0.153)., Conclusion: ED may help in the differential diagnosis between HCC and hemangioma.

Confirmation of patient information is required to ensure the safety of radiation therapy. The purpose of this study was to construct a system that facilitates radiation therapy operations by linking a radiation therapy information system to a smartphone. By linking a smartphone to a radiation therapy operation support system, without using a PC terminal, we were able to input information about the patient's position and fixation into images taken with a smartphone. In addition, patient information could be directly linked into the radiation therapy information system. In addition, patient information could be verified in the irradiation room by synchronizing the smartphone with the radiation therapy support system. The questionnaire was highly evaluated in terms of radio reception, usability, visibility and barcode reading. In this study, by linking a smartphone to a radiotherapy information system, it was possible to construct a system that facilitates radiotherapy operations by checking and registering patient information at hand.

A 28-year-old female was diagnosed with acute myeloid leukemia (AML) due to t (8;21) (q22;q22.1); RUNX1-RUNX1T1 at 21 weeks of gestation. Because no adverse prognostic genetic mutations were discovered, we decided to continue the pregnancy without chemotherapy for as long as possible. After careful monitoring with blood tests every two weeks, the disease did not progress until full-term, and a cesarean section was performed at 39 weeks of gestation. About two months after delivery, blasts in the peripheral blood increased to 46.5%, and myeloblasts in the bone marrow increased to 21.2%. The patient received idarubicin and cytarabine induction therapy, followed by three cycles of high-dose cytarabine consolidation therapy, and complete remission was maintained. Here we report a rare case who could avoid chemotherapy until full-term labor without progression of AML.

The IFM/DFCI group reported that VRD induction followed by up-front autologous peripheral blood stem cell transplantation (ASCT) and maintenance therapy led to median PFS of 50 months, which established up-front ASCT as the standard of care even in the era of novel agents. We conducted a retrospective analysis on outcomes of patients who received triplet induction therapy followed by up-front ASCT at our institution. A total of 124 patients received ASCT between November 2016 and December 2021 at Japanese Red Cross Medical Center. Patient characteristics, treatment response before and after ASCT, and PFS and OS were retrospectively analyzed. VRD-based induction therapy was used for 94%. Among 118 evaluable patients, 116 (98%) received either consolidation and/or maintenance therapy. Best responses were ≥CR 77% and ≥VGPR 94%, respectively. Sixty-eight out of 104 patients achieved MRD-negativity by multiparameter FCM (<10 -5 ). Five-year estimated PFS and OS were 54.7% and 80.2%, respectively. Age ≥65, high-risk cytogenetic abnormalities, and

Selenium is an essential trace element and its deficiency causes myositis, myocardial damage, and other symptoms. Patients receiving long-term intravenous nutrition or tube-feeding in particular are deficient in essential trace elements, including selenium, and require regular supplementation. In Japan, injectable selenium-containing products are listed on the National Health Insurance drug price list, and oral solutions are prepared and used in hospitals. However, these formulations have problems related to preservation and require complicated administration procedures. In this study, we developed a new fast-disintegrating tablet formulation of selenium, using SmartEx ® (D-mannitol·low substituted hydroxypropylcellulose (L-HPC)·fully hydrolyzed polyvinyl alcohol (PVA) mixture) as a coprocessing additive, that can be administered orally or by feeding tube. The tablet formulation had excellent disintegrable capability, sufficient hardness, and did not cause tube blockage when administered in the simple suspension method. In addition, the tablet formulation showed no changes in properties in an accelerated test without packaging for 42 d, indicating that it could be stored for a long period. Fast-disintegrating tablets prepared with SmartEx ® are expected to improve the adherence and quality of life of patients who require selenium supplementation.

A 74-year-old woman was taken to our hospital with a chief complaint of chest and back pain. She was diagnosed with Stanford type A acute aortic dissection and underwent ascending aortic replacement. Fifteen months after surgery, a giant anastomotic aneurysm was found at the proximal and distal anastomoses on chest computed tomography (CT), and reoperation was indicated. Following sternal re-entry, anastomotic dehiscence was found where BioGlue, albumin/glutaraldehyde sealant, had been applied during the previous surgery, and caused aneurysm. Severe postoperative adhesion precluded extensive surgery, and redo replacement of the ascending aorta was carried out. Histopathological examination revealed extensive necrosis of smooth muscle cells in the aortic wall at the anastomotic site and a marked inflammatory cell infiltration around the aortic wall and the artificial graft, and association of BioGlue use was suggested. The use of appropriate tissue adhesives to reinforce the dissected aortic wall is important, as well as careful long-term follow-up.

A 36-year-old man presented with painless swelling in the right side scrotum. Ultrasonography showed a hypoechoic tumor with mosaic pattern. Plain computed tomograghy (CT) revealed a 67 mm scrotal cystic lesion with low density area. We suspected an intrascrotal tumor and performed right side radical orchiectomy. The removed sample was yellow clear and elastic hard. A 7 cm multilocular cystic tumor was present on the head side of the normal testis. The cut-surface and the contents of the mass revealed a jelly-like viscous liquid. On the microscopic examination, the tumor was composed of mucinous stroma and spindle-shaped atypical cells with hyperchromatic oval nuclei and eosinophilic cytoplasm. There was a characteristic network of blood vessesls with hyperhyalinization in the myxoid zones. Immunohistochemically, CDK4, MDM2, AE1/AE3, S-100, Alpha-SMA and desmin were negative, but MUC4 showed focal cytoplasmic positivity in the neoplastic cells. In the reverse transcription polymerase chain reaction assay, no FUS-CREB3L2/FUS-CREB3L1 fusion transcripts were identified although the detectable messages of the housekeeping genes were noted. The tumour was finally diagnosed as a paratesticular low-grade fibromyxoid sarcoma. Postoperative course was uneventful and no recurrence or metastasis was seen four months after the operation.

We present a case of a 41-year-old woman who was diagnosed with autoimmune polyendocrine syndrome type 1 (APS-1) at the age of 2. She developed severe anemia and was diagnosed with pure red cell aplasia (PRCA) and T-cell large granular lymphocyte leukemia at the age of 34. The pathogenesis of APS-1 is based on the presence of an inactive mutation in the autoimmune regulator gene on thymic medullary epithelial cells. It is thought that the autoimmune T cells generated by impaired negative selection in the thymus induce PRCA. The patient was treated with immunosuppressive therapy (ciclosporin, antithymocyte globulin, prednisolone, and cyclophosphamide) for a long time by her previous doctor. After a long period of remission and exacerbation, she became dependent on blood transfusion approximately at the age of 40 and was transferred to our hospital. At our hospital, alemtuzumab treatment resulted in the disappearance of large granular lymphocytes and improvement of anemia. We report this case as a valuable demonstration of the efficacy of alemtuzumab for treating PRCA associated with APS-1.

A 44-year-old female was diagnosed with follicular lymphoma (FL), grade 3A stage III, by right cervical lymph node biopsy at the age of 43 years. The patient chose to not receive the treatment despite the high tumor burden. The patient came back after 18 months with respiratory distress and had systemic infiltration and pleural effusion. Positron emission tomography (PET)/computed tomography (CT) showed fluorine-18 deoxyglucose accumulation with maximum standardized uptake value ranging from 10 to 18 in bone marrow, liver, spleen, lung, and systemic lymph nodes (cervical, supraclavicular, infraclavicular, axillary, mediastinal, hilar, para-aortic, iliac, and inguinal). Left inguinal lymph node biopsy revealed mixed cellularity classical Hodgkin lymphoma (CHL), which was thought to be an FL transformation or a composite condition. The patient was treated with A + AVD and achieved lymph node shrinkage as well as improvement of tumor fever and pleural effusion. Interim PET/CT showed improvement in most parts after two courses; however, it revealed some new or progressive lesions in the bone marrow and left cervical lymph nodes. Left cervical lymph node biopsy revealed nodular sclerosis CHL. The patient was treated with ESHAP, which resulted in stable disease; following this, the patient was treated with nivolumab, which was highly effective. FL transformation to CHL is rare, and this is the first report of such transformation without treatment.

The spread of COVID-19 has re-affirmed the crucial importance of the pharmaceuticals industry in improving the level of citizens' health and medical care, as well as the industry's importance in terms of contribution to economic growth and tax revenues. Although some time has passed since the importance of industry-academia collaboration was first raised in relation to the creation of innovative new drugs and the continuation of global competitiveness, conflicts between academia and companies have also been highlighted as barriers that hinder efforts to promote the practical realization of academia-initiated seeds. The authors have hypothesized that conflicts between academia and companies can be attributed to the vulnerability of innovation creation environments, including drug discovery, on the academia side, insufficient awareness concerning human resources that will undertake industry-academia operations, and inadequate development of structures. Consequently, we implemented fact-finding investigations in relation to universities and public research institutions in Japan, with the objective of ascertaining the actual status of innovation creation environments, including drug discovery, on the academia side. From the results of these investigations, we will clarify the issues that may present barriers to innovation creation, and consider policies, etc. for the enhancement of innovation creation environments.

Multiple myeloma (MM) is still one of the most difficult hematological diseases. It is distinguished by recurrent relapses despite successful treatment. Proteasome inhibitors, immunomodulatory imide drugs, and monoclonal antibodies have all been developed in the last 10 years as treatment options for MM. However, obtaining a long-term treatment-free period for relapsed and refractory multiple myeloma (RRMM) remains difficult. The most recent and intriguing research is on new BCMA-targeting therapies. CAR-T cell therapy, in particular, has shown promising results in the treatment for triple class refractory MM patients. BCMA CAR-T cell therapy is gaining attention as a potentially game-changing treatment for multiple myeloma. Fortunately, CAR-T cell therapy will be available in Japan in January 2022. However, numerous issues must be addressed. Many RRMM patients receive CAR-T cell therapy, for example, relapse, and progression-free survival are short. This section provides an overview of clinical study results for CAR-T cell therapy targeting BCMA, and the antibody-drug conjugate, bispecific antibodies, selinexor, and venetoclax.

We report a 66-year-old man with primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD). He had received a living-donor kidney transplantation at the age of 64 years. Although he had a good postoperative course by continuing to take oral immunosuppressive agents, he was admitted to our hospital for subacute cognitive impairment and urinary retention two years after the transplantation. Brain MRI revealed high-intensity lesions on FLAIR and T 2 -weighted images in the left parietal operculum, deep white matter around the anterior horn of the lateral ventricle, and the genu and splenium of the corpus callosum. A part of these lesions showed ring enhancement. The cerebrospinal fluid examination revealed lymphocytic pleocytosis, elevation of protein level, and mild hypoglycorrhachia. Blood tests showed no abnormalities except for positive serum VCA-IgG antibody of Epstein-Barr virus. A brain biopsy was performed and diagnosis of PCNS-PTLD was made. There was no evidence of systemic PTLD. We reduced the dose of immunosuppressive agents and started the initial treatment with methylprednisolone pulse therapy. The patient showed a partial response to the treatment and transferred to another hospital for subsequent chemotherapy. PTLD is an important post-transplant complication that can affect the patient's prognosis. The incidence of PTLD is increasing with the growing numbers of transplantations and older age of donors and recipients. Although CNS involvement is known to be rare, PCNS-PTLD is an important differential diagnosis when symptoms of CNS origin develop in post-transplant patients.

A 56-year-old man visited a clinic with the chief complaint of frequent micturition and residual sensation of urine. He was referred to our hospital for close examination. Cystoscopy showed a tumor protruding toward the bladder neck from the prostate with stones and debris on the surface. Magnetic resonance imaging showed an encapsulated tumor of iso-intensity in the prostate in T2-weighed images. Prostate specific antigen was 0.88 mg/dl. Transurethral resection of prostate was performed under the diagnosis of benign prostate hyperplasia. During the operation, a solid tumor with mucus deposit was observed. Intraoperative rapid pathological diagnosis was mucinous adenocarcinoma. A radical cystectomy was performed. Pathologically, mucinous adenocarcinoma was distributed in the bladder neck, the prostate and surrounding tissue, but the prostatic urethra was intact. The surgery was assessed to be curative. Neither neoadjuvant nor adjuvant chemotherapy was performed, since the effectiveness of chemotherapy for mucinous adenocarcinoma arising from urothelial epithelium has not been established.

Japanese pharmaceutical products continue to experience a trade deficit, since import values exceed export values. In drug discovery development, given the pace of technological innovations, there has been a major shift from low-molecular-weight compounds to biomedicine. It is anticipated that industry, academia and government will work more closely together in support of the pharmaceutical industry. Drug discovery requires much time and vast resources before the results can be put to practical use, and evidence suggests that many newly approved drugs derive from university-sourced technology. Pharmaceutical companies keep a close eye on technology evolving in universities. However, some reports state that there is a substantial difference compared to the development costs of the major Japanese pharmaceutical companies. Therefore, the authors hypothesized that there may be some issues hindering industrial-academic partnerships in drug discovery. In order to understand the actual situation and barriers to promoting industrial-academic collaboration, the Japan Pharmaceutical Manufacturers Association (JPMA), Japan Agency for Medical Research and Development (AMED), and the Medical Industry-Academia Collaboration Network (medU-net) Council will work together in issuing questionnaires and conducting an awareness survey. This survey sought the personal opinions of individuals belonging to JPMA and medU-net. Based on the results of this survey, we will introduce the issues related to industrial-academic collaboration and partnerships, and any gaps between industry and academia. Furthermore, we suggest solutions to promoting drug discovery innovation in Japan.

Fluorescence imaging is a very useful method for visualizing molecules and cells, but when tissues are measured", decrease in resolution due to increased scattering and absorption of light in proportion to tissue thickness (problem 1)" and "decrease in signal to noise(S/N)ratio of positive signal due to tissue autofluorescence(problem 2)"are problems to be solved. In this paper, to develop a technology to improve the analysis accuracy of drug efficacy mechanisms in preclinical trial of drug discovery, we performed development of a supporting technology for drug discovery of antibody drug conjugates by imaging living tumor tissues, while solving problem 1. This technology is expected to lead to an improvement in the success rate of clinical trials. Next, to develop a diagnostic method to predict the response to neoadjuvant chemotherapy with antibody drugs for breast cancer, we performed development of fluorescence imaging of pathological tissues using fluorescent nanoparticles with ultra-high brightness, while solving problem 2. This diagnostic technology makes it possible to evaluate the expression level of the target protein of antibody drug with high quantitative and wide range sensitivity. This improved the accuracy of drug efficacy prediction. Therefore, patients who are expected to have a low drug efficacy will be able to select anticancer drugs with different mechanisms of action. These results of this study showed the reduction of drug discovery costs and improvement of individualized medicine. Thus, this study will greatly contribute to the development of precision medicine.

A 69-year-old woman admitted to our hospital with the lump in the left breast. Further examination was performed for the lesion, and it was diagnosed as invasive ductal carcinoma. Partial resection and sentinel lymph node biopsy were performed. Pathological diagnosis was metaplastic carcinoma with squamous metaplasia. As the adjuvant treatment, docetaxel and cyclophosphamide(TC)therapy and radiotherapy was performed. Following the treatment of those, tegafur-uracil was administered for 2 years. Three years after the surgery, an isolated lung metastasis was revealed by CT. Capecitabine and cyclophosphamide(XC)therapy was administered, but not effective. Stereotactic body radiation therapy(SBRT)was performed for the lesion. As a result, the metastatic lesion was obscured. Drug therapy was stopped due to adverse events, and she is observed by no medication. Thirty-six months after SBRT and 78 months after the surgery, the patient is alive without recurrence. SBRT could be an effective treatment strategy for the oligometastais of the lung.

A 50-year-old man was diagnosed with right staghorn calculus. Urine cytology showed atypical cells, and he was followed for suspicion of urothelial carcinoma. However, there was no evidence of tumor six months later, and percutaneous nephrolithotripsy (PNL) was performed for right staghorn calculus. Eight months later, renal pelvic squamous cell carcinoma extending to the abdominal wall through the nephrostomy tract was identified. After neoadjuvant chemotherapy, radical nephroureterectomy and enbloc resection of the nephrostomy tract tumor was performed. The renal pelvic squamous cell carcinoma did not recur. However he died of small cell lung cancer 3 years postoperatively. Planning of treatment strategy was difficult in the present case. Even though PNL was performed after sufficient follow up and examination, renal pelvic cancer could not be diagnosed and extended to the PNL tract. Fortunately, radical en-bloc resection was possible. We herein, report a case of renal pelvic squamous cell carcinoma after PNL.

Acute leukemia (AL) during pregnancy poses a substantial risk to both mothers and fetuses. Treatment for leukemia should be initiated promptly; however, the management of AL in pregnant women and fetuses is usually challenging, especially during the second trimester. Here, we report two cases of AL that developed during the second trimester of pregnancy. In one case, chemotherapy was initiated while continuing the pregnancy; in the second case, a cesarean section was performed prior to chemotherapy initiation. As per current medical records, both infants are thriving without any medical problems. The optimal strategy for the treatment of AL during pregnancy typically includes chemotherapy after delivery. However, if fetal development is not sufficient for ex utero survival, the only alternatives available are the initiation of treatment while continuing the pregnancy or treatment after therapeutic abortion (if it is legally allowed). According to previous studies and as per the results from our first case, the initiation of chemotherapy while sustaining the pregnancy may be an acceptable option if it is conducted with appropriate informed consent. The treatment of AL in the second trimester of pregnancy should be carefully decided, while taking into account the medical, legal, and social aspects, such as gestational weeks, maternal and fetal status, and wishes of the patients and their families.

Modification of proteins with polyethylene glycol (PEG) (PEGylation) is a gold standard technique that improves the solubility, pharmacokinetics, and immunogenicity of modified proteins. To date more than 10 PEGylated protein formulations have been approved, and more than 20 PEGylated drugs are entering clinical trials. PEG has been considered non-immunogenic and non-toxic, but several studies have shown that PEG acquires immunogenicity following attachment to nanoparticles. The administration of PEGylated liposomes, micelles and proteins induces the production of antibodies against PEG (anti-PEG antibodies) in animals and human subjects. Indeed, approximately 20% of healthy human subjects possess pre-existing anti-PEG antibodies prior to treatment with PEGylated therapeutics. The induced and pre-existing anti-PEG antibodies cause not only the elimination of PEGylated proteins from blood circulation, but also allergic responses via the release of anaphylatoxins. Consequently, therapeutic outcomes for PEGylated proteins are impaired. The utility of PEGylated proteins could be improved by attenuating the PEG-related immune response. On the other hand, anti-PEG immune responses might be exploited for vaccine applications. Our recent studies demonstrated that anti-PEG antibodies mediate the delivery of antigens encapsulated in PEGylated liposomes, and enhance antigen-specific immune responses. In this review, we summarize anti-PEG antibody induction by PEGylated proteins and alterations in anti-PEG IgM-mediated pharmacokinetics and pharmacodynamics. These findings extend our knowledge of PEG-related immune responses.

Although multiple myeloma has been defined as incurable, and the treatment outcome has recently improved rapidly. Antibodies against multiple myeloma, elotuzumab, and daratumumab can safely enhance their effects even when added to the combination therapy of proteasome inhibitors and immunomodulators that have been used till date. Initially, triplet therapy combining antibody therapy with doublet therapy was approved in Japan for relapsed or refractory multiple myeloma. In 2019, daratumumab combination therapies were approved for newly diagnosed multiple myeloma patients, and these therapies are the new standard of care. Recently, the results of clinical trials that added daratumumab to the triplet therapies of proteasome inhibitors, immunomodulators, and dexamethasone have been reported. These trials report greater therapeutic effects, with a significant improvement in the MRD negative rate. We hope that quadruplet therapy including these antibodies will be available in clinical practice, leading to further improvements in the treatment outcomes.

A 39-year-old man was referred to us for further examination of a right inguinal mass. He had noticed the mass several months prior and had undergone positron emission tomography/computed tomography, which revealed a mass with an SUVmax of 1.48 at the right inguinal subcutis. Magnetic resonance imaging (MRI) showed a well-circumscribed, heterogeneously enhanced adipose tumor 7cm in length, adjacent to the right spermatic cord and corpora cavernosa with clear boundaries. The tumor was a suspected atypical lipomatous tumor (well-differentiated liposarcoma), and he underwent tumor extirpation surgery. At surgery, the right inguinal canal was not opened, and the right spermatic cord and corpora cavernosa were safely spared. The excised specimen was composed of lipomatous tissue macroscopically. Histopathological diagnosis was of a spindle cell lipoma. Spindle cell lipomas are relatively rare, benign tumors, comprising only 1.5% of all lipomatous tumors. They arise most commonly in the shoulder and posterior region of the neck, and rarely develop in the groin. Differential diagnosis includes atypical lipomatous tumors, but radiological diagnosis is often difficult because of similar findings on MRI. Spindle cell lipomas typically present as a subcutaneous tumor, while atypical lipomatous tumors arise in the deep layers of connective tissue. This difference in the site of the tumor may contribute to their differential diagnosis before surgery.

Purpose: The International Commission on Radiological Protection recommended that interventional radiologies (IRs) have high radiation doses and that staff may also be exposed to high doses. In the present study, we measured the radiation exposure dose [3 mm dose equivalent, Hp (3) ] in the eye using an appropriate dosimeter placed next to the physician' s eye during neurovascular intervention procedure (Neuro-IR) and interventional cardiac electrophysiology procedure (EP-IR)., Method: Physicians wore a direct eye dosemeter just lateral to the left eye and an additional direct eye dosemeter outside the radiation protective glasses close to their left eye. Additionally, a neck badge [0.07 mm dose equivalent, Hp (0.07) ] was worn outside the protective apron to the left of the neck, to compare the direct eye dosimeter estimated doses. The occupational eye lens dose was evaluated over a period of 6-month., Results: The maximum Hp (3) of the Neuro-IR physician was estimated 5.1 mSv without the radiation protective glasses and 1.6 mSv with the radiation protective glasses. On the other hand, the maximum Hp (3) of the EP-IR physician was estimated 29 mSv without the radiation protective glasses and 15 mSv with the radiation protective glasses., Conclusion: Physicians eye lens dose [Hp (3) ] tended to be overestimated by the neck badge measurements [Hp (0.07)]. A correct evaluation of the lens dose [Hp (3) ] using the direct eye dosimeter is recommended. Although we found a positive correlation between Hp (0.07) and Hp (3), the value of R 2 in the regression equation is low, we recommended that the eye lens dose estimated carefully from Hp (0.07).

Plerixafor is increasingly used in combination with granulocyte-colony-stimulating factor (G-CSF) for peripheral blood stem cell collection. Although it is an expensive drug, its cost-benefit performance is not well investigated. Thus, we analyzed its cost-effectiveness in our hospital. A retrospective observational analysis was performed in patients who underwent stem cell collection between December 2013 and November 2018. A total of 203 patients were investigated and classified into three groups according to their pre-mobilization regimen: G-CSF alone, G-CSF and cyclophosphamide (G+CY), and G-CSF and plerixafor (G+plerixafor). The cost-effectiveness of apheresis of the collected cluster of differentiation (CD) 34+ cells was assessed based on two viewpoints: cost of drugs and cost of equipment. Due to the high cost of plerixafor, the cost of apheresis was higher in patients who received G+plerixafor. However, the difference narrowed when we calculated the cost to collect 2.0×10 6 CD34+ cells/kg body weight required for a single transplant. The number of stem cells collected from patients who received G+plerixafor was higher than those who received other regimens (median CD34+ cells harvested/day were 2.90 for G-CSF, 2.13 for G+CY, and 4.63 for G+plerixafor, ×10 6 /kg body weight, P<0.01). Our results show that plerixafor enables efficient apheresis.

Parkinson's disease is a neurodegenerative disorder characterized by the degenerative loss of dopaminergic neurons in the substantia nigra. Dopamine deficiency is thought to disrupt motor control of the basal ganglia and cause characteristic motor symptoms in Parkinson's disease such as bradykinesia, akinesia, and tremor. Therefore, dopamine replacement therapy is widely used in the clinical setting. Safinamide is a novel, selective, and reversible inhibitor of monoamine oxidase B expected to increase dopamine levels in the brain and improve the symptoms of Parkinson's disease. In addition, safinamide shows non-dopaminergic actions such as sodium channel blockade and inhibition of glutamate release. Preclinical studies have demonstrated that safinamide ameliorates "wearing off" symptoms after administration in rat and monkey models with selectively destroyed dopaminergic neurons. In the monkeys, safinamide concurrently inhibited levodopa-induced dyskinesia. These findings suggest that safinamide not only increases the dopaminergic effect of levodopa, but also reduces levodopa-induced adverse events via its non-dopaminergic effects. In clinical trials of patients with Parkinson's disease with the "wearing off" phenomenon, safinamide has been found to prolong the "on time" and improve motor function as assessed by Unified Parkinson's Disease Rating Scale Part III. In Japan, safinamide was approved in September 2019 as a levodopa combination drug for Parkinson's disease with "wearing off" phenomenon. Safinamide is therefore expected to be a new treatment option for patients with Parkinson's disease.

A 65-year-old male was diagnosed with rectal cancer invading the urinary bladder, swollen para-aorticlymph nodes, and multiple liver metastases in abdominal CT. After 8 courses of mFOLFOX6 plus panitumumab, the rectal cancer, para-aortic lymph nodes metastasis, and liver metastases decreased significantly in size. Rectal cancer and liver metastases were considered resectable, hence low anterior resection of the rectum was performed. Intraoperative frozen section analysis showed negative metastaticinvolvement of the para-aorticlymph nodes and surgical margins of the urinary bladder; therefore, the urinary bladder was completely preserved. Partial resection of the liver was performed 2 months later. In conclusion, the patient showed good surgical and quality of life results. Thus, the bladder-sparing strategy with preoperative chemotherapy could be considered for appropriately selected rectal cancer patients with urinary bladder involvement.

A 60s man was diagnosed with rectal cancer and underwent low anterior resection of the rectum. The pathological diagnosis was mucinous adenocarcinoma, pT3(SS), pN0, pM0, pStage Ⅱ. Two years after the primary surgery, contrast-enhanced CT showed local recurrence on the oral side of the anastomosis. As the tumor had invaded the left seminal vesicle and coccygeus muscle, neoadjuvant chemoradiotherapy(NACRT)(S-1 80mg/m / 2 plus 45 Gy/25 Fr)was performed. After NACRT, abdominoperineal resection, including the left seminal vesicle, coccygeus muscle, and coccygeal bone, was performed. Pathological examination showed a histological response of Grade 2 and that R0 resection was achieved. Although the only radical treatment of locally recurrent rectal cancer is R0 resection, we performed R0 resection with Grade 2 histological response to NACRT.

A 45-year-old woman was referred to our hospital complaining of diarrhea. Colonoscopy showed a rectal tumor. Histological examination showed moderately differentiated adenocarcinoma. A CT scan revealed a tumor extending from the lower rectum to the anal canal with a lateral pelvic lymph node(LPLN)swelling. We administered neoadjuvant chemoradiotherapy (45 Gy/25 Fr, S-1 80mg/m / 2/day)and the tumor and LPLN shrank remarkably, with a clinically complete response by CT and PET-CT. We then performed abdominoperineal resection with D3 lymph node and bilateral LPLN dissection. Pathological examination revealed complete disappearance of the cancer cells in the primary site, while lymph node metastasis was detected in one LPLN. We report here a rare case in which LPLN metastasis remained despite the pathological complete response of the primary tumor.

Second transurethral resection of bladder tumor (TUR-Bt) is a standard treatment for high grade T1 initial, non-muscle invasive bladder cancer. In our hospital from October 2008 to April 2017, 2nd TUR-Bt was performed in 51 cases of initial T1 bladder cancer. The risk factors of residual tumors on 2nd TUR-Bt and the clinical outcome were examined retrospectively. Twenty two of the 51 cases (43.1%) had residual tumors on 2nd TUR-Bt, and upstaging was not admitted. To determine the risk factor for residual tumors in 2nd TUR-Bt, we examined gender, tumor morphology (papillary/non-papillary, pedunculated/ nonpedunculated), number of tumors (single/frequent), and tumor size (≧20 mm/＜20 mm), but none of these were significant risk factors for tumor residue. The recurrence free survival (RFS) of the 51 cases was 86.0% after 1 year, and 77.0% after 3 years. There tended to be a higher RFS in the pedunculated tumor group, pT0 group on 2nd TUR-Bt, intravesical BCG therapy group, but no statistically significant difference was observed. The progression free survival (PFS) was 90.6% after 3 years, and 87.3% after 5 years. These values were similar to those reported previously.

This report describes the case of a 67-year-old male with inflammatory breast cancer. He had noticed a left breast mass about seven years previously, but he had ignored it. He then visited our hospital 4 months previously when multiple small masses occurred in the left front chest wall. The tumor was diagnosed as skin metastasis of breast cancer by skin biopsy and he was referred to our department. The tumor cells were positive for estrogen receptor and progesterone receptor, and negative for HER2/neu, and the Ki67 expression was 10-15%. The subtype of his breast cancer was luminal A type. It had secondary inflammatory breast cancer and preceded chemotherapy. Also, as the veins in the lower extremity were filled with thrombus, we gave him an anticoagulant (Edoxaban), but due to the malignant hyper coagulable state (Trousseau syndrome) a CV port could not be implanted. 3 courses of docetaxel every 3 weeks failed to control the disease. Since an obstruction of the right iliac artery was newly observed, the anticoagulant was changed to cilostazol and rivaroxaban, but left second finger and fourth finger necrosis occurred due to peripheral circulatory failure. The condition of the disease was stabilized by FEC (5-FU, epirubicin, cyclophosphamide) therapy, but it became difficult to secure the blood vessel. Without constructing a CV port because of the thrombus, chemotherapy was changed to S-1 oral administration, and strength to the chest wall Modulated radiotherapy intensity modulated radiation therapy (IMRT) was performed. Although the tumor was reduced, the condition of the whole body gradually weakened and the patient died a year and a half after the start of the treatment. This case of inflammatory luminal in male breast cancer that caused thrombus was difficult to treat. Thrombosis in advanced cancer patients is often pointed out, but since male breast cancer patients tend to take a long time to visit the hospital after becoming aware of the mass and arrive at an advanced state, it is necessary to notify the public of the existence of male breast cancer.

Failure of autologous peripheral blood stem cell collection (PBSCH) can affect the treatment modality for patients with hematological malignancies. The clinical efficacy of plerixafor in PBSCH was analyzed in our institution. The medical records of 61 patients were retrospectively reviewed. The use of plerixafor was determined according to the CD34 + cell count in the peripheral blood (PB CD34 + ) on day 4 of G-CSF administration and patients' backgrounds. A total of 47 patients received G-CSF plus plerixafor: 31 with multiple myeloma, 8 with AL amyloidosis or POEMS syndrome, and 8 with non-Hodgkin lymphoma. The median fold increase in PB CD34 + following the first dose of plerixafor was 7.18 times. The median number of collected CD34 + cells on day 5 was 4.1×10 6 /kg and 5.3×10 6 /kg in total. Among the 47 patients, 44 (93.6%) yielded the minimum required cell collection of 2.0×10 6 /kg within an average of 1.3 days. Plerixafor enables rapid and efficient mobilization, and sufficient numbers of CD34 + cells were successfully collected.

Because multiple myeloma is rare in young people, there are fewer reports on the same. Thus, its clinical aspects and prognosis remain unelucidated. We retrospectively evaluated 30 patients with multiple myeloma aged ≤ 45 years at diagnosis. We divided them into three groups based on their cytogenetic risks: standard risk (SR), high risk (HR), and unknown risk. The frequency of HR patients was 36.6%, the highest of the three groups, unlike the previous report. The median progression-free survival (PFS) was 35 months (SR vs. HR, 46 vs. 29 months), and the median overall survival (OS) was not reached (NR) (SR vs. HR, NR vs. 82 months). The OS was significantly worse, and the PFS also appeared inferior in HR patients. The International Staging System score was not associated with OS. Thus, young patients with myeloma appeared to have a higher frequency of HR features, suggesting that instead of age, the cytogenetic risk was a significant prognostic factor.

Although elotuzumab (ELO) is associated with improved outcomes in patients with relapsed/refractory multiple myeloma (MM), no data are available for the usage of ELO following allogeneic stem cell transplantation (allo-SCT). Here, we report two cases of relapsed MM treated with ELO in combination with lenalidomide (LEN) and dexamethasone (ELd) following allo-SCT. Case 1 had been treated with 11 lines of therapy followed by cord blood transplantation resulting in partial response. ELd was introduced 140 days post-transplantation and continued for eight cycles until disease progression. No worsening in graft-versus-host disease (GvHD) was observed under ELd treatment. Case 2 had received unrelated bone marrow transplantation due to primary refractory disease after undergoing six regimens. Carfilzomib-based maintenance therapy had to be discontinued owing to severe myelosuppression. Subsequently, ELd treatment was initiated 544 days following the allo-SCT, which led to an improvement in serum paraprotein level and amelioration in GvHD. In both cases, immunosuppressants were tapered off. Several studies have shown exacerbation of GvHD under LEN monotherapy following allo-SCT. However, an ELd regimen may be one of the safer options for treating post-allo-SCT relapse.

A 33-year-old woman became aware of a right breast mass at her 28th week of pregnancy. From the biopsy results, we diagnosed her with right breast cancer. At her 33rd week of pregnancy, she underwent modified radical mastectomy (pT2N3aM0, Stage III C, ER-negative, PR-negative, HER2-positive), and she elected to receive adjuvant therapy after the surgery during her pregnancy. She received the first course of EC (epirubicin plus cyclophosphamide) therapy on the 13th postoperative day (35 weeks of gestation) and gave a natural, vaginal delivery at 36 weeks and 5 days of gestation. On the 4th day after birth, the patient noticed a contralateral left breast mass and was diagnosed with left breast cancer, after core needle biopsy. She received 4 courses of EC therapy and is currently undergoing PTX plus HER (paclitaxel plus trastuzumab) therapy. Regarding chemotherapy during pregnancy, we recommend that there is no need to perform artificial preterm birth, because chemotherapy has little influence on children after their second-trimester. After the second-trimester, chemotherapy can be safely performed.

Twenty-nine patients with multiple myeloma were treated with carfilzomib, lenalidomide, and dexamethasone (KLd) therapy. A response better than partial response (PR) was observed in 72.4% patients with relapsed and/or refractory myeloma. Although 13.8% patients developed hypertension, none of them discontinued therapy as they could be managed by appropriate medication. A patient who had an elevated level of BNP prior to initiating KLd therapy developed heart failure. Results from this study demonstrate that KLd therapy is efficacious for treating patients with multiple myeloma; however, they should be carefully monitored for cardiotoxicity.

A 40-year-old female presented with a skin rash, hepatosplenomegaly, hypothyroidism, IgG-λ monoclonal gammopathy, slightly elevated serum VEGF levels, and >1-year history of weakness in the posterior cervical muscles. Based on these symptoms and her clinical course, she was suspected of having POEMS syndrome. However, because there was no sign of peripheral neuropathy (PN), the criteria for the diagnosis of POEMS syndrome were not met. Consequently, she continued follow-up and was under close observation as an outpatient. She complained of slowly progressive dyspnea that was identified as type 2 respiratory failure requiring non-invasive positive pressure ventilation. She received systemic chemotherapy, including thalidomide and dexamethasone, as the respiratory failure was predominantly a result of POEMS-associated PN. Although the skin eruptions improved upon treatment, respiratory failure gradually worsened, and she required mechanical ventilation. The patient was suspected of having sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance (SLONM-MGUS), because of resistant to chemotherapy and second opinion suggestion. A thigh muscle biopsy revealed the presence of nemaline rods and led to the definitive diagnosis of SLONM-MGUS. Unfortunately, she was unable to receive autologous stem cell transplantation, and finally died because of progressive respiratory failure. SLONM-MGUS is an extremely rare disease but should be considered as a critical, monoclonal-protein related condition.

Patients with adult T-cell leukemia/lymphoma (ATL), which is caused by human T-cell lymphotropic virus type 1, exhibit an extremely poor prognosis. ATL was first reported in 1977 in Japan as a distinct T-cell neoplasm, and its basic and clinical research have been led by Japanese investigators. This study aims to review the scenario since the discovery of ATL/HTLV-1 to the current status of ATL research and medicine and to consider its future directions.