Publications by authors named "Masaki Nakamura"

245 Publications

Comparison of a Hybrid IMRT/VMAT technique with non-coplanar VMAT and non-coplanar IMRT for unresectable olfactory neuroblastoma using the RayStation treatment planning system-EUD, NTCP and planning study.

J Radiat Res 2021 Apr 12. Epub 2021 Apr 12.

Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

The purpose of this study was to compare hybrid intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (Hybrid IMRT/VMAT), with non-coplanar (nc) IMRT and nc-VMAT treatment plans for unresectable olfactory neuroblastoma (ONB). Hybrid IMRT/VMAT, nc-IMRT and nc-VMAT plans were optimized for 12 patients with modified Kadish C stage ONB. Dose prescription was 65 Gy in 26 fractions. Dose-volume histogram parameters, conformation number (CN), homogeneity index (HI), integral dose and monitor units (MUs) delivered per fraction were assessed. Equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) based on the EUD model (NTCPLogit) and the Lyman-Kutcher-Burman model (NTCPLKB) were also evaluated. We found that the Hybrid IMRT/VMAT plan significantly improved the CN for clinical target volume (CTV) and planning treatment volume (PTV) compared with the nc-VMAT plan. In general, sparing of organs at risk (OARs) is similar with the three techniques, although the Hybrid IMRT/VMAT plan resulted in a significantly reduced Dmax to contralateral (C/L) optic nerve compared with the nc-IMRT plan. The Hybrid IMRT/VMAT plan significantly reduce EUD to the ipsilateral (I/L) and C/L optic nerve in comparison with the nc-IMRT plan and nc-VMAT plan, but the difference in NTCP between the three technique was <1%. We concluded that the Hybrid IMRT/VMAT technique can offer improvement in terms of target conformity and EUD for optic nerves, while achieving equal or better OAR sparing compared with nc-IMRT and nc-VMAT, and can be a viable radiation technique for treating unresectable ONB. However, the clinical benefit of these small differences in dosimetric data, EUD and NTCP of optic nerves may be minimal.
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http://dx.doi.org/10.1093/jrr/rrab010DOI Listing
April 2021

Natural factories that manufacture antimicrobial resistance genes: quadruple bla-carrying plasmids in Aeromonas and Pseudomonas species.

Int J Antimicrob Agents 2021 Mar 28:106327. Epub 2021 Mar 28.

Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.ijantimicag.2021.106327DOI Listing
March 2021

Novel operative technique of advancement urethral meatoplasty utilizing buccal mucosa for Vulvar Paget's disease with urethral invasion: two case reports.

J Med Case Rep 2021 Mar 28;15(1):136. Epub 2021 Mar 28.

Department of Urology, The Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Vulvar Paget's disease (VPD) is a rare malignant disorder originating in the external genitalia. It occasionally invades into urethral or vaginal mucosa of female, making surgical treatment more complicating. In case of urethral invasion of Paget's cells, systematic mapping biopsy of urethral mucosa is the standard of care to determine the range of surgical resection. Resection of urethral mucosa and simple skin grafting often result in urethral stricture after surgery, which severely deteriorates patient's quality of life.

Case Presentation: We applied a new technique of advancement urethral meatoplasty using buccal mucosa, in two Japanese cases of VPD with urethral invasion. After broad resection of vulvar skin together with the urethral mucosa, buccal mucosa was implanted between advanced urethral mucosa and skin graft. In both cases, we could prevent urethral stricture one year and two years after surgery, respectively.

Conclusion: This technique prevented urethral stricture after surgery and could be a useful technique as part of urethroplasty for VPD.
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http://dx.doi.org/10.1186/s13256-021-02729-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005229PMC
March 2021

Oncolytic virotherapy with SOCS3 enhances viral replicative potency and oncolysis for gastric cancer.

Oncotarget 2021 Feb 16;12(4):344-354. Epub 2021 Feb 16.

Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.

Oncolytic virotherapy is an encouraging treatment using herpes simplex virus (HSV) for gastric cancer patients. To treat gastric cancer, we generated and evaluated the efficacy of an attractive type of oncolytic HSV expressing the suppressor of cytokine signaling 3 (SOCS3). We constructed a third-generation type of oncolytic HSV (T-SOCS3) arming with SOCS3 by a bacterial artificial chromosome (BAC) system. We examined the viral replicative intensification and oncolysis of T-SOCS3 for human gastric cancer cell lines . T-SOCS3 enhanced its replication and potentiated its cell-killing effect for MKN1 human gastric cancer cell lines, which are resistant to a non-armed third-generation type of oncolytic HSV (T-01) . T-SOCS3 also induced the destruction within human gastric cancer specimens. Armed oncolytic HSVs expressing SOCS3 may be an efficacious therapeutic agent for gastric cancer treatment.
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http://dx.doi.org/10.18632/oncotarget.27873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899552PMC
February 2021

Development of a simple and cost-effective gel-based duplex PCR method to identify both encapsulated and unencapsulated Neisseria meningitidis applicable under resource-limited conditions.

J Infect Chemother 2021 May 3;27(5):773-777. Epub 2021 Feb 3.

Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.

Tens of thousands of cases of invasive meningococcal diseases (IMD) with thousands of deaths are reported annually worldwide; however, only approximately 40 cases occur each year in Japan. Therefore, the majority of medical technologists in Japan have never performed or prepared for analyses of the causative agent, Neisseria meningitidis. Since IMD outbreaks have been reported at mass gathering events, the risk of IMD will increase in Japan in 2021 because of the Olympics. In the present study, we developed a new simple gel-based duplex PCR method that may be employed by the majority Japanese clinical laboratories. It is simple to perform and time- and cost-effectively identifies encapsulated and unencapsulated N. meningitidis by detecting the encapsulated N. meningitidis-specific ctrB and N. meningitidis-specific ggt genes. We consider this simple and cost-effective identification method to compensate for the lack of experience and resource-poor conditions in most Japanese laboratories in which N. meningitidis has rarely been examined.
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http://dx.doi.org/10.1016/j.jiac.2021.01.013DOI Listing
May 2021

Safety and feasibility of laparoscopic gastrectomy for remnant gastric cancer compared with open gastrectomy: Single-center experience.

Medicine (Baltimore) 2021 Jan;100(4):e23932

Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama, Japan.

Abstract: The usefulness, safety and oncological validity of laparoscopic gastrectomy (LG) for remnant gastric cancer (RGC) have not been widely reported.A total of 38 patients who underwent gastrectomy for RGC were enrolled at Wakayama Medical University Hospital between April 2008 and December 2018. All consecutive patients were included in this retrospective study; the patients were divided into the open gastrectomy group and the laparoscopic group according to the sequential nature of their operation. Fifteen patients underwent open gastrectomy for RGC (OGR) between April 2008 and December 2013, and 23 patients underwent LG for RGC (LGR) after 2014.In the OGR group, all initial operations were performed by open surgery, whereas in the LGR group, 11 patients (47%) initially underwent laparoscopic surgery and 12 patients (53%) initially underwent open surgery (P = .002), 3 patients of which (25%) converted to open gastrectomy. There was no significant difference in the number of lymph node dissections or in operative time between the 2 groups, but blood loss was significantly lower in the LGR group than that in the OGR group (P = .002). Furthermore, although there was no difference between the 2 groups in C-reactive protein value on postoperative day 1, C-reactive protein value on postoperative day 3 was significantly lower in the LGR group than in the OGR group (P = .012). There were no differences in postoperative complications or long-term outcomes, including recurrence-free survival and overall survival.LGy is suitable in cases in which the initial surgery is performed by laparoscopic surgery. Even if the initial surgery is open surgery, it is oncologically equivalent to open gastrectomy and can be performed safely with less blood loss.
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http://dx.doi.org/10.1097/MD.0000000000023932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850663PMC
January 2021

Liquid Biopsy Cell-free DNA Biomarkers in Patients With Oligometastatic Colorectal Cancer Treated by Ablative Radiotherapy.

Anticancer Res 2021 Feb;41(2):829-834

Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Chiba, Japan.

Background/aim: To investigate the usefulness of cell-free DNA (cfDNA) in patients with oligometastasis.

Patients And Methods: This study included oligometastatic colorectal cancer (CRC) patients who underwent ablative irradiation using stereotactic body radiotherapy or proton beam therapy for metastatic lesions at a single institution. cfDNA was purified from the plasma of pretreated patients and gene mutations were analyzed by next-generation sequencing. Progression-free survival (PFS) was statistically compared according to gene mutation, clonality or allele frequency.

Results: A total of 20 patients were analyzed. Mutations were detected in the following genes; TP53 (45%), APC (40%), KRAS (15%), PIK3CA (15%), NF1 (5%), BRCA1 (5%), ERBB2 (5%), FBXW7 (5%), KIT (10%), and HRAS (10%). Patients with multi-clonality of gene mutation showed tendency for poor PFS (p=0.07). Among 7 patients whose metastatic site was the lung, those with no cfDNA detected had significantly better PFS than those with cfDNA (p=0.02).

Conclusion: cfDNA profiles could be predictive tools for early recurrence of oligometastatic CRC patients after ablative radiotherapy.
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http://dx.doi.org/10.21873/anticanres.14835DOI Listing
February 2021

Impact of Initial Computed Tomography Findings on Management of Atypical Urinary Cytology of the Upper Urinary Tract.

Urol Int 2021 Jan 28:1-5. Epub 2021 Jan 28.

Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Introduction: Management of patients with atypical urinary cytology (class III) of the upper urinary tract is often complicated because some patients develop upper urinary tract urothelial carcinoma (UTUC). Here, we aimed to help define the optimal management of these patients.

Methods: We investigated 31 patients who underwent retrograde ureteropyelography (RP) and were diagnosed with atypical findings of upper urinary tract cytology.

Results: UTUC was revealed in 17 of 31 patients during the follow-up period of 1 year or longer. Tumor-like lesions and wall thickening in the upper urinary tract on initial computed tomography (CT) were significant predictors of UTUC (p = 0.0002 and p = 0.012, respectively). All 11 patients with tumor-like lesions and 3 of 8 patients with wall thickening on initial CT underwent nephroureterectomy, and UTUC was confirmed histologically. Moreover, 3 of 12 patients with hydronephrosis only or with normal findings later went on to develop UTUC. Repeated RP performed within 6 months from the initial RP was able to distinguish patients with UTUC from those without, even in individuals with normal CT findings.

Discussion/conclusion: Repeated RP based on initial CT findings is recommended in patients with atypical urinary cytology of the upper urinary tract. Nephroureterectomy without repeated RP may be warranted in patients with tumor-like lesions on initial CT findings.
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http://dx.doi.org/10.1159/000512978DOI Listing
January 2021

Single nucleotide polymorphism leads to daptomycin resistance causing amino acid substitution-T345I in MprF of clinically isolated MRSA strains.

PLoS One 2021 22;16(1):e0245732. Epub 2021 Jan 22.

Department of Microbiology, Kitasato University School of Allied Health Sciences, Kanagawa, Japan.

Daptomycin (DAP) is one of the most potent antibiotics used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Due to an increase in its administration for combating MRSA infections, DAP non-susceptible (DAP-NS) MRSA strains have recently been reported in clinical settings. The presence of single nucleotide polymorphisms (SNPs) in the multiple peptide resistance factor (mprF) gene is the most frequently reported cause for the evolution of DAP-NS MRSA strains; however, there are some variations of SNPs that could lead to DAP-NS. In this study, we used two clinical MRSA strains, including DAP susceptible (DAP-S) and DAP-NS, isolated from the same patient at different time points. We introduced T345I SNP to mprF of the DAP-S MRSA strain using the gene exchange method with pIMAY vector. Further, we investigated the phenotype of the mutant strain, including drug susceptibility, cell surface positive charge, and growth speed. The mutant strain exhibited (i) resistance to DAP, (ii) up-regulation of positive surface charge, (iii) slower growth speed, and (iv) thickened cell walls. Hence, the SNP in mprF may have caused an up-regulation in MprF function, with a subsequent increase in positive surface charge. Cumulatively, these results demonstrated that the T345I amino acid substitution in mprF represents one of the primary causes of DAP-NS in MRSA strains.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245732PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822245PMC
January 2021

Trends in Diabetes Care during the COVID-19 Outbreak in Japan: an Observational Study.

J Gen Intern Med 2021 Jan 19. Epub 2021 Jan 19.

Department of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1007/s11606-020-06413-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814982PMC
January 2021

Single-incision laparoscopic antrectomy for type I gastric neuroendocrine tumor: a case report.

Surg Case Rep 2021 Jan 12;7(1):15. Epub 2021 Jan 12.

Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan.

Background: Type I gastric neuroendocrine tumors (GNETs) originate from hyperplasia of enterochromaffin-like (ECL) cells and are commonly detected in patients with chronic atrophic gastritis, including autoimmune gastritis. Typical treatment for type I GNETs comprises simple surveillance and/or endoscopic resection. For alleviation of hypergastrinemia resulting in ECL cell hypertrophy, antrectomy is a treatment option. Type I GNETs mostly have excellent prognosis, and if a surgical approach is chosen, the procedure must be minimally invasive. One such technique for multiple type I GNETs, minimally invasive single-incision laparoscopic antrectomy (SILA), is reported here for the first time.

Case Presentation: We performed SILA on a 46-year-old woman who developed type I GNETs caused by hypergastrinemia due to autoimmune gastritis. A Lap-Protector was inserted in a 3 cm incision at the umbilicus, and set an EZ Access equipped with two 5 mm trocars and one 12 mm trocar. Antrectomy without lymph node dissection was performed using a 5 mm forward-oblique viewing endoscope, a vessel sealing device, and linear staplers, while reconstruction was by Billroth I reconstruction. Side-to-side anastomosis was performed using a 45 mm linear stapler. The stapler entry hole was sutured intracorporeally using barbed suture material. The operation time was 140 min and blood loss was 5 ml. The patient was discharged ten days after surgery without complications. Serum gastrin level decreased to within the normal range on the day after the operation. One year after surgery, esophagogastroduodenoscopy showed pathological disappearance of all lesions of the remnant stomach.

Conclusions: SILA is a minimally-invasive and tolerable technique for treatment of multiple type I GNETs. In this reported case there was good cohesiveness and effectiveness in normalizing gastrin levels and in elimination of remnant gastric lesions.
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http://dx.doi.org/10.1186/s40792-021-01109-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803843PMC
January 2021

Impact of age, body mass index, and renal function for severe hypotension caused by oral 5-aminolevulinic acid administration in patients undergoing transurethral resection of bladder tumor.

Photodiagnosis Photodyn Ther 2021 Mar 8;33:102179. Epub 2021 Jan 8.

Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Severe hypotension is a notable adverse event caused by administration of 5-aminolevulinic acid (5-ALA) during photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT). Hypotension can be prolonged following induction of anesthesia and may require continuous administration of a vasopressor. Here, we investigated the risk factors for severe hypotension caused by oral administration of 5-ALA.

Methods: A total of 128 patients with bladder tumors who underwent PDD-TURBT using 5-ALA were included in this study. Clinicopathological data were collected retrospectively and the correlations between the incidence of severe hypotension and clinicopathological factors were analyzed.

Results: Severe hypotension developed in 8 cases (6.3 %). Age ≥ 80 years, body mass index (BMI) ≥ 25 (kg/m), and estimated glomerular filtration rate (eGFR) < 45 (mL/min/1.73 m) were significantly correlated with severe hypotension (P = 0.003, 0.017, and 0.027, respectively). Severe hypotension developed in 1 of 89 cases (1.1 %) which have 0 or 1 risk factor, and in 3 of 31 cases (9.7 %) which have 2 risk factors, whereas it developed in 4 of 8 cases (50 %) which have all risk factors. Patients with all risk factors developed severe hypotension significantly more frequently compared with patients with 1 or fewer risk factors (P < 0.001).

Conclusion: Age ≥ 80 years, BMI ≥ 25, and eGFR < 45 are risk factors for severe hypotension in PDD-TURBT using 5-ALA. The risk of developing severe hypotension is extremely high in patients who have all factors. Adjustment of the 5-ALA dose may be desirable in those patients.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102179DOI Listing
March 2021

Relationship between the frequency of electrocautery of Hunner lesions and changes in bladder capacity in patients with Hunner type interstitial cystitis.

Sci Rep 2021 Jan 8;11(1):105. Epub 2021 Jan 8.

Japanese Red Cross Medical Center, Tokyo, Japan.

Electrocautery is a promising treatment option for patients with Hunner type interstitial cystitis (HIC), but frequently requires multiple sessions due to recurrence of the lesions. In the present study, we assessed the relationship between the frequency of electrocautery of Hunner lesions and changes in maximum bladder capacity (MBC) at hydrodistension in a large cohort of 118 HIC patients. Three mixed-effect linear regression analyses were conducted for MBC against (1) the number of sessions; (2) the number of sessions and the time between each session and the first session; and (3) other relevant clinical parameters in addition to the Model (2). The mean number of sessions was 2.8 times. MBC decreased approximately 50 mL for each additional electrocautery session, but this loss was offset by 10 mL for each year the subsequent session was postponed. MBC of < 400 mL at the first session was a significant risk factor for MBC loss with further sessions. No other clinical parameters were associated with MBC over time. This study demonstrates a significant relationship between the frequency of electrocautery of Hunner lesions and MBC changes in HIC patients. Low MBC at the first session is a poor prognostic marker for MBC loss over multiple sessions.
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http://dx.doi.org/10.1038/s41598-020-80589-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794499PMC
January 2021

Dermatomyositis associated with prostate adenocarcinoma with neuroendocrine differentiation.

BMC Urol 2021 Jan 7;21(1). Epub 2021 Jan 7.

Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 1138655, Japan.

Background: Although it is known that malignancies can be associated with dermatomyositis, there are few reports on dermatomyositis associated with prostate cancer with neuroendocrine differentiation.

Case Presentation: A 63-year-old man visited our hospital due to pollakiuria. High levels of PSA and NSE were observed, and prostate biopsy revealed an adenocarcinoma with neuroendocrine differentiation. Multiple metastases to the lymph nodes, bones, and liver were identified, and androgen deprivation therapy (ADT) was started immediately. Following 2 weeks of treatment, erythema on the skin, and muscle weakness with severe dysphagia appeared. The patient was diagnosed with dermatomyositis, and high-dose glucocorticoid therapy was initiated. ADT and subsequent chemotherapy with etoposide and cisplatin (EP) were performed for prostate cancer, which resulted in decreased PSA and NSE and reduction of all metastases. After the initiation of EP therapy, dermatomyositis improved, and the patient regained oral intake function. Although EP therapy was replaced by docetaxel, abiraterone, and enzalutamide because of adverse events, no cancer progression was consistently observed. Dermatomyositis worsened temporarily during the administration of abiraterone, but it improved upon switching from abiraterone to enzalutamide and dose escalation of glucocorticoid.

Conclusions: We successfully treated a rare case of dermatomyositis associated with prostate adenocarcinoma with neuroendocrine differentiation.
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http://dx.doi.org/10.1186/s12894-020-00779-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791876PMC
January 2021

Complete genome sequencing and comparative plasmid analysis of KPC-2-producing Klebsiella pneumoniae isolated from hospital sewage water in Japan.

J Glob Antimicrob Resist 2021 Mar 26;24:180-182. Epub 2020 Dec 26.

Department of Environmental Microbiology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan; Department of Microbiology, School of Allied Health Sciences, Kitasato University, Kanagawa, Japan; Regenerative Medicine and Cell Design Research Facility, Kanagawa, Japan. Electronic address:

Objectives: The Klebsiella pneumoniae carbapenemase (bla) gene is one of the most widespread carbapenemase genes in the world. However, there are few reports on KPC-producing bacteria in Japan. The aim of this study was therefore to investigate KPC-producing K. pneumoniae in Japan.

Methods: A KPC-2-producingK. pneumoniae strain (KAM260) was isolated from hospital sewage water in Japan in 2018. The complete genome was determined by whole-genome sequencing. Subsequent comparative sequence analysis of the bla-carrying plasmid was performed.

Results: Klebsiella pneumoniae KAM260, belonging to sequence type 3026 (ST3026), harboured the bla gene in 114.6-kbp plasmid pKAM260_2 with IncFIB(pQIL) and IncFII(K) replicons. pKAM260_2 was highly identical to pKpQIL-like plasmids, which carry bla genes and have spread worldwide. pKAM260_2 had functional conjugation-associated genes and was transferable to Escherichia coli.

Conclusion: pKAM260_2, the self-transmissible plasmid carrying thebla gene, was detected from hospital sewage water in Japan and was characterised as a pKpQIL-like plasmid. This plasmid needs to be monitored in Japan in the future owing to its high diffusivity.
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http://dx.doi.org/10.1016/j.jgar.2020.12.007DOI Listing
March 2021

Trends in intensive neonatal care during the COVID-19 outbreak in Japan.

Arch Dis Child Fetal Neonatal Ed 2021 May 23;106(3):327-329. Epub 2020 Nov 23.

Department of Public Health, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan

The reduction in the use of neonatal intensive care units (NICUs) during the COVID-19 outbreak has been reported, but whether this phenomenon is widespread across countries is unclear. Using a large-scale inpatient database in Japan, we analysed the intensive neonatal care volume and the number of preterm births for weeks 10-17 vs weeks 2-9 (during and before the outbreak) of 2020 with adjustment for the trends during the same period of 2019. We found statistically significant reductions in the numbers of NICU admissions (adjusted incidence rate ratio (aIRR), 0.76; 95% CI, 0.65 to 0.89) and neonatal resuscitations (aIRR, 0.37; 95% CI, 0.25 to 0.55) during the COVID-19 outbreak. Along with the decrease in the intensive neonatal care volume, preterm births before 34 gestational weeks (aIRR, 0.71) and between 34 0/7 and 36 6/7 gestational weeks (aIRR, 0.85) also showed a significant reduction. Further studies about the mechanism of this phenomenon are warranted.
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http://dx.doi.org/10.1136/archdischild-2020-320521DOI Listing
May 2021

Dose-Volume and Radiobiological Model-Based Comparative Evaluation of the Gastrointestinal Toxicity Risk of Photon and Proton Irradiation Plans in Localized Pancreatic Cancer Without Distant Metastasis.

Front Oncol 2020 23;10:517061. Epub 2020 Oct 23.

Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan.

Radiobiological model-based studies of photon-modulated radiotherapy for pancreatic cancer have reported reduced gastrointestinal (GI) toxicity, although the risk is still high. The purpose of this study was to investigate the potential of 3D-passive scattering proton beam therapy (3D-PSPBT) in limiting GI organ at risk (OAR) toxicity in localized pancreatic cancer based on dosimetric data and the normal tissue complication probability (NTCP) model. The data of 24 pancreatic cancer patients were retrospectively analyzed, and these patients were planned with intensity-modulated radiotherapy (IMRT), volume-modulated arc therapy (VMAT), and 3D-PSPBT. The tumor was targeted without elective nodal coverage. All generated plans consisted of a 50.4-GyE (Gray equivalent) dose in 28 fractions with equivalent OAR constraints, and they were normalized to cover 50% of the planning treatment volume (PTV) with 100% of the prescription dose. Physical dose distributions were evaluated. GI-OAR toxicity risk for different endpoints was estimated by using published NTCP Lyman-Kutcher-Burman (LKB) models. Analysis of variance (ANOVA) was performed to compare the dosimetric data, and ΔNTCP and ΔNTCP were also computed. Similar homogeneity and conformity for the clinical target volume (CTV) and PTV were exhibited by all three planning techniques ( > 0.05). 3D-PSPBT resulted in a significant dose reduction for GI-OARs in both the low-intermediate dose range (below 30 GyE) and the highest dose region ( and ) in comparison with IMRT and VMAT ( < 0.05). Based on the NTCP evaluation, the NTCP reduction for GI-OARs by 3D-PSPBT was minimal in comparison with IMRT and VMAT. 3D-PSPBT results in minimal NTCP reduction and has less potential to substantially reduce the toxicity risk of upper GI bleeding, ulceration, obstruction, and perforation endpoints compared to IMRT and VMAT. 3D-PSPBT may have the potential to reduce acute dose-limiting toxicity in the form of nausea, vomiting, and diarrhea by reducing the GI-OAR treated volume in the low-to-intermediate dose range. However, this result needs to be further evaluated in future clinical studies.
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http://dx.doi.org/10.3389/fonc.2020.517061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645056PMC
October 2020

Diaphyseal femoral fracture due to severe vitamin D deficiency and low parathyroid hormone levels on long-term hemodialysis: a case report.

Arch Osteoporos 2020 11 12;15(1):179. Epub 2020 Nov 12.

Department of Nephrology Center, Toranomon Hospital, 1-3-1, Takatsu, Kawasaki, Kanagawa, 212-0015, Japan.

Introduction: Currently, there are no reports of diaphyseal femoral fracture equivalent to atypical femoral fractures (AFFs) in patients receiving long-term hemodialysis (HD).

Case Report: A 56-year-old Japanese man receiving long-term HD for 34 years was admitted to our hospital due to a delay in postoperative healing. The patient began maintenance hemodialysis at 22 years of age. The patient then underwent surgical parathyroidectomy (PTX) for secondary hyperparathyroidism at 43 years of age, which resulted in decreased levels of parathyroid hormone (PTH). Thereafter, this patient's serum 1,25(OH) D level was very low because active vitamin D derivative was not administered. At 54 years of age, a transverse fracture of the femoral shaft equivalent to AFF occurred. Surgery with open reduction and internal fixation using intramedullary nailing was performed; however, the delay of postoperative healing continued for 16 months. A left iliac crest bone biopsy was performed and showed osteoid-like lesion and an increase of woven bone. The patient received active vitamin D derivative and recombinant human PTH (1-34) derivative. Twenty-nine months after the first surgery, a reoperation was performed. Simultaneously, a right iliac crest bone biopsy was performed. Bone morphometrical improvement was confirmed. Six months after resurgery, the bone union was achieved. Severe vitamin D deficiency and decreased levels of PTH may induce a higher osteoid state and an increase of woven bone, which may then attribute to the development of diaphyseal femoral fracture and impairment of postoperative bone healing. It is hypothesized that treatment with active vitamin D and teriparatide acetate may be a therapeutic option via the accelerated formation of lamellar bone for refractory diaphyseal femoral fracture of long-term dialysis.
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http://dx.doi.org/10.1007/s11657-020-00849-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661412PMC
November 2020

Identification of the mutation signature of the cancer genome caused by irradiation.

Radiother Oncol 2021 02 17;155:10-16. Epub 2020 Oct 17.

Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Japan; Department of Radiation Oncology, National Cancer Center Hospital East, , Japan.

Background And Purpose: Ionising radiation causes mutations in the genomes of tumour cells and serves as a potent treatment for cancer. However, the mutation signatures in the cancer genome following ionising radiation have not been documented.

Materials And Methods: We established an in vitro experimental system to analyse the presence of de novo mutations in the cancer genome of irradiated (60 Gy/20 fr/4 weeks) oesophageal cancer cell lines. Subsequently, we performed whole-genome, chromatin immunoprecipitation, and RNA sequencing using untreated and irradiated samples to assess the damage to the genome caused by radiation and understand the underlying mechanism.

Results: The irradiated cancer cells exhibited hotspots for the de novo 8502-12966 single nucleotide variants and 954-1,331 indels on the chromosome. These single nucleotide variants primarily originated from double-stranded break repair errors, as determined using mutation signature analysis. The hotspots partially overlapped with the sites of H3K9 trimethylation, which are regions characterised by a weak capacity for double-stranded break repair.

Conclusion: This study highlights the signature and underlying mechanism of radiation on the cancer genome.
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http://dx.doi.org/10.1016/j.radonc.2020.10.020DOI Listing
February 2021

Trends in hospitalizations for asthma during the COVID-19 outbreak in Japan.

J Allergy Clin Immunol Pract 2021 01 14;9(1):494-496.e1. Epub 2020 Oct 14.

Department of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.jaip.2020.09.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553873PMC
January 2021

Full robotic Roux-en-Y reconstruction after gastrectomy for gastric cancer: a loop reconstruction technique.

Updates Surg 2020 Dec 15;72(4):1279-1281. Epub 2020 Sep 15.

Second Department of Surgery, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan.

A robotic approach with radical lymph node dissection for gastric cancers is a safe and effective surgical procedure. However, there are still only a few studies in the reconstruction procedure after gastrectomy and many aspects of the use of the robotic surgical system remain controversial. In Roux-en-Y reconstruction, most institutions are adapted for reconstruction using small laparotomy due to the complicated procedure. We, therefore, developed a new and easy procedure for full robotic Roux-en-Y reconstruction after robotic gastrectomy. We named this procedure "loop reconstruction technique". This article including video shows our loop reconstruction technique with an intracorporeal robot-sewn anastomosis after robotic gastrectomy.
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http://dx.doi.org/10.1007/s13304-020-00889-1DOI Listing
December 2020

A Fatal Case of Myocarditis Following Myositis Induced by Pembrolizumab Treatment for Metastatic Upper Urinary Tract Urothelial Carcinoma.

Int Heart J 2020 Sep 12;61(5):1070-1074. Epub 2020 Sep 12.

Department of Urology, Graduate School of Medicine, The University of Tokyo.

We report a case of lethal myocarditis and myositis after pembrolizumab treatment for advanced upper urinary tract urothelial carcinoma. A 69-year-old man underwent pembrolizumab therapy as a second-line treatment. He had myalgia and a slightly elevated creatinine kinase (CK) on the day of the second administration of pembrolizumab. Five days later, the patient was admitted with severe fatigue and an abnormal gait. Physical examination revealed reduced muscle reflexes and proximal muscle weakness. An electrocardiogram (ECG) demonstrated a wide QRS complex ventricular rhythm. A marked elevation of cardiac enzymes, including CK, myoglobin, and cardiac troponin I, was detected. Myocardial biopsy revealed inflammatory cell infiltration and the partial impairment of myocardial tissue. The electromyogram was normal, but inflammation in myofibers was noted in a muscle biopsy. Myocarditis and myositis as immune-related adverse events (irAEs) were suspected, and the patient began intravenous steroid therapy and plasma exchange. However, the patient underwent cardiac arrest three days after admission and began extracorporeal membrane oxygenation and intra-aortic balloon pumping therapy. Despite steroid pulse therapy, the patient demonstrated no sign of improvement and subsequently died 17 days after admission. Immune-mediated myocarditis is a rare but fatal irAE of an immune checkpoint inhibitor (ICI). The present case suggests that myositis precedes myocarditis. Therefore, if myositis is suspected, subsequent myocarditis may need attention. In conclusion, we found that myositis and myocarditis developed in a patient with advanced urothelial carcinoma after pembrolizumab treatment. A routine follow-up of CK and cardiac troponin I, as well as an ECG, should be performed to identify any possible ICI-induced myocarditis and myositis quickly.
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http://dx.doi.org/10.1536/ihj.20-162DOI Listing
September 2020

Rare gastrointestinal stromal tumor in an ileal conduit detected by recurrent massive bleeding from the stoma.

IJU Case Rep 2020 Sep 4;3(5):207-210. Epub 2020 Aug 4.

Department of Urology Graduate School of Medicine The University of Tokyo Tokyo Japan.

Introduction: The development of secondary tumors is a well-known late adverse event after urinary diversion. However, the frequency of secondary tumors after an ileal conduit is the lowest compared to other methods used for urinary diversion. We observed a rare case of a gastrointestinal stromal tumor in an ileal conduit detected by recurrent massive bleeding from the stoma.

Case Presentation: An 87-year-old female was hospitalized at our hospital due to recurrent bleeding from a stoma 22 years after radical cystectomy. Contrast-enhanced computed tomography revealed a 5-cm mass in her ileal conduit. She underwent a complete resection of the tumor, a histological examination of which revealed it to be a gastrointestinal stromal tumor. The condition of the patient has been good showing no recurrence or metastases 4 years after surgery.

Conclusion: We report a rare secondary tumor, a gastrointestinal stromal tumor, arising from an ileal conduit.
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http://dx.doi.org/10.1002/iju5.12190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469789PMC
September 2020

Phase 1 Study of Combined Chemotherapy of Nab-Paclitaxel, S-1, and Oxaliplatin for Gastric Cancer with Peritoneal Metastasis (NSOX Study).

Oncology 2021 2;99(1):57-61. Epub 2020 Sep 2.

Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.

Objectives: A regimen of S-1 combined with oxaliplatin (SOX) has been widely used as the first-line regimen for advanced gastric cancer. To further improve the antitumor efficacy for gastric cancer patients with peritoneal metastasis, we added nab-paclitaxel to the established SOX regimen (NSOX). Nab-paclitaxel (nanoparticle albumin-bound paclitaxel) has effective transferability to tumor tissues and strong antitumor effects for peritoneal metastasis. We performed a phase 1 study of this regimen to determine the maximum tolerated dose (MTD) and the recommended dose (RD) in patients with gastric cancer with peritoneal metastasis.

Methods: The NSOX regimen involved 21-day cycles with escalated doses of nab-paclitaxel (50 [level 1] to 80 [level 4] mg/m2 on days 1 and 8) and fixed doses of oxaliplatin (100 mg/m2 on day 1) and S-1 (80 mg/m2/day for 2 weeks).

Results: Six patients with gastric cancer with peritoneal metastasis were enrolled. The MTD was determined to be dose level 2, as 2 of 3 patients experienced dose-limiting toxicities (DLTs), grade 4 non-hematological toxicities. One patient experienced acute myocardial infarction, and the other patient developed jejunal perforation. There were no treatment-related deaths. No patients experienced DLTs, so the RD was determined to be dose level 1.

Conclusions: The NSOX regimen was shown to be a tolerable regimen and may be a promising triplet therapy for patients with gastric cancer with peritoneal metastasis.
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http://dx.doi.org/10.1159/000509396DOI Listing
January 2021

Latent prostate cancer among Japanese males: a bibliometric study of autopsy reports from 1980-2016.

Jpn J Clin Oncol 2021 Jan;51(1):156-159

Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo.

Prostate cancer is one of the most common malignancies, but a substantial portion remains latent throughout the patients' lifetime. Analysis of temporal change in the latent prostate cancer pool would be beneficial for clinical decision-making, but longitudinal autopsy studies are rare. We conducted a hand-search of the Annual of Pathological Autopsy Cases in Japan from 1980 to 2016 for cases of latent prostate cancer. Of 570 997 males aged 30 or older, latent prostate cancer was detected in 12 562 patients (2.2%). Proportion of detected cases correlated strongly with 'aging rate', the percentage of population aged 65 or older (squared Pearson's correlation coefficient r2 = 0.972, P value <0.0001). Temporal increase in proportion was also seen in each age group as well. This continuous growth reinforces evidence from past Japanese reports on latent prostate cancer. The rapidly rising ageing rate of Japan may forecast further increase in the latent prostate cancer pool moving forward.
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http://dx.doi.org/10.1093/jjco/hyaa161DOI Listing
January 2021

Clinical characterization of interstitial cystitis/bladder pain syndrome in women based on the presence or absence of Hunner lesions and glomerulations.

Low Urin Tract Symptoms 2021 Jan 23;13(1):139-143. Epub 2020 Aug 23.

Japanese Red Cross Medical Center, Tokyo, Japan.

Objectives: To compare the clinical characteristics of three groups of female patients with interstitial cystitis/bladder pain syndrome (IC/BPS) classified according to the presence or absence of Hunner lesions (HL) and glomerulations.

Methods: The clinical records of 100 female patients with IC/BPS who underwent their first bladder hydrodistension at our institution were retrospectively reviewed. They were divided into patients having (HL-IC; n = 57) or lacking (BPS; n = 43) HL. BPS patients were further classified as those with (29) and without (14) glomerulations. Among these three subtypes, demographics, comorbidities, symptom parameters including a visual analog scale for pain scores, O'Leary and Sant Symptom and Problem (OSSI/OSPI) Indices, frequency volume chart variables, and bladder capacity at hydrodistension were compared.

Results: HL-IC patients were older and had higher OSSI/OSPI scores, greater daytime frequency and nocturia, reduced maximum and average voided volumes, and smaller bladder capacity at hydrodistension compared with BPS patients. Pain intensity and illness duration were comparable among the three groups. HL-IC patients had autoimmune disorders as comorbidities more often, but had psychiatric disorders and irritable bowel syndrome less often compared with BPS patients. No discernible differences in clinical characteristics of symptom severity and comorbid disorders were evident between BPS patients with and without glomerulations.

Conclusions: The presence of HL is associated with distinctive clinical characteristics, while glomerulations are not in female patients with IC/BPS. The presence of HL, but not glomerulations, is a robust phenotypic feature of IC/BPS in women.
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http://dx.doi.org/10.1111/luts.12344DOI Listing
January 2021

Robotic D2 total gastrectomy with en-mass removal of the spleen and body and tail of the pancreas for locally advanced gastric cancer.

Surg Oncol 2020 Dec 6;35:22-23. Epub 2020 Aug 6.

Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.

Background: Safety and efficacy of robotic surgery in advanced gastric cancers (AGC) have not been proven by randomized control trials (Ojima et al., 2018) [1], and therefore, standard procedure for AGC is still open surgery. Robotic surgery, however, plays an essential role in ergonomics and offers advantages, such as motion scaling, tremor filtering, seven degrees of wrist-like motion, and three-dimensional vision. Here, we initially report successful robotic gastric cancer surgery on a 49-year-old male with proximal gastric cancer adherent to tail of pancreas and mesentery of the colon.

Methods: The patient underwent a diagnostic laparoscopy 10 days before surgery, confirming negative peritoneal dissemination and washing cytology. The patient was placed in a supine position and we inserted five ports. We performed robotic D2 total gastrectomy with en-mass removal of the spleen and body and tail of the pancreas using the da Vinci Xi Surgical System (Intuitive, Sunnyvale, CA) (Japanese Gastric Cancer Association, 2017) [2]. After gastrectomy, to evaluate the blood supply of transverse colon, we employed Indocyanine Green fluorescence using the da Vinci Firefly system and performed a partial resection of the transverse colon and a colostomy. In order to avoid anastomotic leakage of colocolostomy due to pancreatic fistula, we chose to have end colostomy. Roux-en-Y esophago-jejunostomy and jejuno-jejunostomy reconstruction were performed robotically (Ojima et al., 2019) [3]. After the operation, a nasal feeding tube was inserted.

Results: The operation took 472 min with no intraoperative complications and blood loss of 105 ml. Final pathological examination showed poorly-differentiated adenocarcinoma (T4BN1M0, TNM stage IIIC). The patient was discharged uneventfully on postoperative day 25. He is receiving adjuvant chemotherapy. At six months, there was no evidence of complications or recurrence.

Conclusions: Robotic D2 total gastrectomy with en-mass distal pancreatectomy and splenectomy are feasible and safe in advanced gastric cancer, however, its oncological value has yet to be determined.
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http://dx.doi.org/10.1016/j.suronc.2020.07.007DOI Listing
December 2020

Robotic Double Tract Reconstruction After Proximal Gastrectomy for Gastric Cancer.

Ann Surg Oncol 2021 Mar 13;28(3):1445-1446. Epub 2020 Aug 13.

Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan.

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http://dx.doi.org/10.1245/s10434-020-09015-2DOI Listing
March 2021

Clinical and radiological features of immune checkpoint inhibitor-related pneumonitis in lung cancer and non-lung cancers.

Br J Radiol 2020 Nov 12;93(1115):20200409. Epub 2020 Aug 12.

Department of Radiology, Tenri Hospital, Nara, Japan.

Objective: To investigate the clinical and radiological features of immune checkpoint inhibitor-related pneumonitis (ICI-P), a rare but serious pulmonary complication of cancer immunotherapy and to evaluate key differences between lung cancer (LC) and non-LC patients.

Methods: 247 patients (LC, = 151) treated with ICI for malignancies were retrospectively screened in a single institute. The number of patients, history of other immune-related adverse events (irAE), the onset, serum KL-6 levels, and chest CT features (types of pneumonitis, symmetry, laterality, location) were recorded for the ICI-P population and compared for LC and non-LC groups.

Results: ICI-P was identified in 26 patients in total (LC, = 19; non-LC, = 7). The incidence of other irAE was significantly higher in ICI-P group (63%) compared with patients without ICI-P (34%) ( = 0.0056). An earlier onset of ICI-P was recorded in LC (78 days) compared to non-LC patients (186 days) ( = 0.0034). Serum KL-6 was significantly elevated only in the non-LC group when ICI-P was noticed ( = 0.029). Major CT findings of ICI-P, irrespective of primary disease, were organizing pneumonia pattern and ground glass opacities. LC patients commonly exhibited consolidation and traction bronchiectasis and were prone to asymmetrical shadows ( < 0.001). Non-LC patients were more likely to exhibit symmetrical infiltrations. A small fraction of both groups experienced relapse or moving patterns of ICI-P.

Conclusion: ICI-P patients more often experienced other irAE prior to the development of ICI-P. The characteristics of ICI-P can differ in terms of the onset, KL-6 reliability, and chest CT findings between LC and non-LC patients.

Advances In Knowledge: In ICI-P patients, a history of other irAE can be more frequently observed. Differences in disease onset and radiological patterns between LC and non-LC patients might be helpful to make a diagnosis of ICI-P; however, longitudinal observation of chest CT scans is advised to observe the pneumonitis activity irrespective of cancer types.
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http://dx.doi.org/10.1259/bjr.20200409DOI Listing
November 2020