Publications by authors named "Hajime Tanaka"

279 Publications

Nonmetastatic castration-resistant prostate cancer treated with salvage focal brachytherapy after external beam radiotherapy.

IJU Case Rep 2021 Jul 3;4(4):228-230. Epub 2021 May 3.

Department of Urology Tokyo Medical and Dental University Tokyo Japan.

Introduction: The efficacy of salvage local therapy after external beam radiotherapy has recently gained attention. However, a challenge with these therapies is the risk of significant genitourinary and gastrointestinal toxicity. Focal brachytherapy may be a treatment option because of its potential to reduce side effects.

Case Presentation: A patient with castration-resistant prostate cancer was found to be free of metastases on whole-body magnetic resonance imaging following external beam radiotherapy, and prostate biopsy revealed a localized recurrence in the ventral prostate. The patient underwent salvage focal brachytherapy and had a prostate-specific antigen progression-free survival of 23 months. No adverse effects were observed following salvage brachytherapy.

Conclusion: Our case suggests that salvage focal brachytherapy may be an effective local treatment option for nonmetastatic castration-resistant prostate cancer that has relapsed after external beam radiotherapy, wherein the lesion is confined to a small area within the prostate.
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http://dx.doi.org/10.1002/iju5.12294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255295PMC
July 2021

Nonuse of antimicrobial prophylaxis in clean surgeries for adrenal and renal tumors: Results of the risk-based strategy in 1362 consecutive patients.

Int J Urol 2021 Jul 10. Epub 2021 Jul 10.

Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan.

Objectives: To evaluate the incidence of perioperative infections without antimicrobial prophylaxis in patients undergoing clean surgeries for adrenal and renal tumors.

Methods: We prospectively enrolled 1362 consecutive patients who underwent minimally invasive adrenalectomy (n = 303), radical nephrectomy (n = 499), and partial nephrectomy (n = 560) using the gasless laparoendoscopic single-port surgery technique between 2005 and 2019. In 1059 patients, antimicrobial prophylaxis was not administered. The remaining 303 patients were considered at high risk for infection and received single-dose antimicrobial prophylaxis. The endpoint was the incidence of perioperative infections within 1 month from the surgery date. Perioperative infections were classified into surgical site infections, urinary tract infections, and remote infections.

Results: Seventy-four patients whose collecting systems were opened during partial nephrectomy were excluded, and the remaining 1013 patients with nonuse of antimicrobial prophylaxis and 275 patients with single-dose antimicrobial prophylaxis were retrospectively analyzed. The incidence of superficial surgical site infections, deep/organ-space surgical site infections, urinary tract infections, and remote infections was 1.6%, 0.7%, 2.8%, and 1.3%, respectively, in patients with nonuse of antimicrobial prophylaxis and 0.4%, 1.8%, 1.5%, and 1.5%, respectively, in patients with single-dose antimicrobial prophylaxis. All patients who developed perioperative infections were successfully treated. No clinical or surgical variables were significantly associated with the incidence of surgical site infections. One limitation of the present study was its nonrandomized and noncontrolled design.

Conclusions: In minimally invasive clean surgeries for adrenal and renal tumors, antimicrobial prophylaxis is not necessary when individual risk of infection is considered low.
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http://dx.doi.org/10.1111/iju.14642DOI Listing
July 2021

SARS-CoV-2 Infection and Significance of Oral Health Management in the Era of "the New Normal with COVID-19".

Int J Mol Sci 2021 Jun 18;22(12). Epub 2021 Jun 18.

Department of Microbiology, School of Dentistry, Nihon University, Chiyoda-ku, Tokyo 101-8310, Japan.

More than a year ago, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization, with the world approaching its fourth wave. During this period, vaccines were developed in a much shorter period than thought possible, with the initiation of the pertinent vaccination. However, oral cavities have come under renewed scrutiny worldwide because saliva, a mixture of salivary secretions, pharyngeal secretions, and gingival crevicular fluid, have not only been shown to contain infective viral loads, mediating the route of SARS-CoV-2 transmission via droplet, aerosol, or contagion, but also used as a sample for viral RNA testing with a usefulness comparable to the nasopharyngeal swab. The oral cavity is an important portal for ingress of SARS-CoV-2, being an entryway to the bronchi, alveoli, and rest of the lower respiratory tract, causing inflammation by viral infection. Moreover, angiotensin-converting enzyme 2, a host receptor for SARS-CoV-2, coupled with proteases responsible for viral entry have been found to be expressed on the tongue and other oral mucosae, suggesting that the oral cavity is the site of virus replication and propagation. Furthermore, there is a possibility that the aspiration of oral bacteria (such as periodontal pathogens) along with saliva into the lower respiratory tract may be a complicating factor for COVID-19 because chronic obstructive pulmonary disease and diabetes are known COVID-19 comorbidities with a greater risk of disease aggravation and higher death rate. These comorbidities have a strong connection to chronic periodontitis and periodontal pathogens, and an oral health management is an effective measure to prevent these comorbidities. In addition, oral bacteria, particularly periodontal pathogens, could be proinflammatory stimulants to respiratory epithelia upon its exposure to aspirated bacteria. Therefore, it may be expected that oral health management not only prevents comorbidities involved in aggravating COVID-19 but also has an effect against COVID-19 progression. This review discusses the significance of oral health management in SARS-CoV-2 infection in the era of "the new normal with COVID-19" and COVID-19 prevention with reference to the hypothetical mechanisms that the authors and the other researchers have proposed.
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http://dx.doi.org/10.3390/ijms22126527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235682PMC
June 2021

Revealing thermally-activated nucleation pathways of diffusionless solid-to-solid transition.

Nat Commun 2021 Jun 30;12(1):4042. Epub 2021 Jun 30.

State Key Laboratory of Surface Physics and Department of Physics, Fudan University, Shanghai, China.

Solid-to-solid transitions usually occur via athermal nucleation pathways on pre-existing defects due to immense strain energy. However, the extent to which athermal nucleation persists under low strain energy comparable to the interface energy, and whether thermally-activated nucleation is still possible are mostly unknown. To address these questions, the microscopic observation of the transformation dynamics is a prerequisite. Using a charged colloidal system that allows the triggering of an fcc-to-bcc transition while enabling in-situ single-particle-level observation, we experimentally find both athermal and thermally-activated pathways controlled by the softness of the parent crystal. In particular, we reveal three new transition pathways: ingrain homogeneous nucleation driven by spontaneous dislocation generation, heterogeneous nucleation assisted by premelting grain boundaries, and wall-assisted growth. Our findings reveal the physical principles behind the system-dependent pathway selection and shed light on the control of solid-to-solid transitions through the parent phase's softness and defect landscape.
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http://dx.doi.org/10.1038/s41467-021-24256-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245452PMC
June 2021

Usefulness of texture features of apparent diffusion coefficient maps in predicting chemoradiotherapy response in muscle-invasive bladder cancer.

Eur Radiol 2021 Jun 13. Epub 2021 Jun 13.

Department of Urology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan.

Objectives: To examine the usefulness of the texture analysis (TA) of apparent diffusion coefficient (ADC) maps in predicting the chemoradiotherapy (CRT) response of muscle-invasive bladder cancer (MIBC).

Methods: We reviewed 45 MIBC patients who underwent cystectomy after CRT. CRT response was assessed through histologic evaluation of cystectomy specimens. Two radiologists determined the volume of interest for the index lesions on ADC maps of pretherapeutic 1.5-T MRI and performed TA using the LIFEx software. Forty-six texture features (TFs) were selected based on their contribution to the prediction of CRT sensitivity. To evaluate diagnostic performance, diagnostic models from the selected TFs were created using random forest (RF) and support vector machine (SVM), respectively.

Results: Twenty-three patients achieved pathologic complete response (pCR) to CRT. The feature selection identified first quartile ADC (Q1 ADC), gray-level co-occurrence matrix (GLCM) correlation, and GLCM homogeneity as important in predicting CRT response. Patients who achieved pCR showed significantly lower Q1 ADC and GLCM correlation values (0.66 × 10 mm/s and 0.53, respectively) than those who did not (0.81 × 10 mm/s and 0.70, respectively; p < 0.05 for both). The AUCs of the RF and SVM models incorporating the selected TFs were 0.82 (95% confidence interval [CI]: 0.67-0.97) and 0.96 (95% CI: 0.91-1.00), respectively, and the AUC of the SVM model was better than that of the mean ADC value (0.76, 95% CI: 0.61-0.90; p = 0.0037).

Conclusion: TFs can serve as imaging biomarkers in MIBC patients for predicting CRT sensitivity. TAs of ADC maps can potentially optimize patient selection for CRT.

Key Points: • Texture analysis of ADC maps and feature selection identified important texture features for classifying pathologic tumor response in patients with muscle-invasive bladder cancer. • The machine learning model incorporating the texture features set, which included first quartile ADC, GLCM correlation, and GLCM homogeneity, showed high performance in predicting chemoradiotherapy response. • Texture features could serve as imaging biomarkers that optimize eligible patient selection for chemoradiotherapy in muscle-invasive bladder cancer.
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http://dx.doi.org/10.1007/s00330-021-08110-6DOI Listing
June 2021

First-line combination chemotherapy with etoposide, ifosfamide and cisplatin for the treatment of disseminated germ cell cancer: Efficacy and feasibility in current clinical practice.

Int J Urol 2021 May 24. Epub 2021 May 24.

Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Objectives: To evaluate the efficacy and safety profiles of first-line etoposide, ifosfamide and cisplatin and primary prophylaxis with pegfilgrastim as first-line chemotherapy for disseminated germ cell cancer.

Methods: This study reviewed 154 consecutive patients with previously untreated disseminated germ cell cancer who received first-line etoposide, ifosfamide and cisplatin between 1995 and 2020. Of these, 54 patients were managed with primary prophylaxis using pegfilgrastim (primary prophylaxis group), and 100 were managed with the therapeutic use of short-acting granulocyte colony-stimulating factor (non-primary prophylaxis group).

Results: The International Germ Cell Cancer Collaborative Group classification identified 90 (58%)/40 (26%)/24 (16%) patients with good/intermediate/poor prognosis, respectively. Overall, 139 patients (90%) were disease free after etoposide, ifosfamide and cisplatin with/without post-chemotherapy surgery. The median relative dose intensity of etoposide, ifosfamide and cisplatin was 96%, and there was a significant difference between the primary prophylaxis and non-primary prophylaxis groups (100% vs 90%, P < 0.01). The 5-year salvage treatment-free and overall survival rates were 83% and 94%, respectively. In total, 138 patients (90%) developed grade 4 hematological toxicities, and there were no treatment-related deaths due to myelosuppression. Grade 4 neutropenia was less commonly observed in the primary prophylaxis group compared with the non-primary prophylaxis group (80% vs 95%, P < 0.01).

Conclusions: This is the largest study of first-line etoposide, ifosfamide and cisplatin, and its sufficient efficacy and safety profiles are confirmed in current clinical practice. Primary prophylaxis using pegfilgrastim might further improve the feasibility of etoposide, ifosfamide and cisplatin.
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http://dx.doi.org/10.1111/iju.14604DOI Listing
May 2021

Fast crystal growth at ultra-low temperatures.

Nat Mater 2021 May 6. Epub 2021 May 6.

State Key Laboratory of Surface Physics and Department of Physics, Fudan University, Shanghai, China.

It is believed that the slow liquid diffusion and geometric frustration brought by a rapid, deep quench inhibit fast crystallization and promote vitrification. Here we report fast crystal growth in charged colloidal systems under deep supercooling, where liquid diffusion is extremely low. By combining experiments and simulations, we show that this process occurs via wall-induced barrierless ordering consisting of two coupled steps: the step-like advancement of the rough interface that disintegrates frustration, followed by defect repairing inside the newly formed solid phase. The former is a diffusionless collective process, whereas the latter controls crystal quality. We further show that the intrinsic mechanical instability of a disordered glassy state subject to the crystal growth front allows for domino-like fast crystal growth even at ultra-low temperatures. These findings contribute to a deeper understanding of fast crystal growth and may be useful for applications related to vitrification prevention and crystal-quality control.
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http://dx.doi.org/10.1038/s41563-021-00993-6DOI Listing
May 2021

Porphyromonas gingivalis enhances pneumococcal adhesion to human alveolar epithelial cells by increasing expression of host platelet-activating factor receptor.

FEBS Lett 2021 06 8;595(11):1604-1612. Epub 2021 Apr 8.

Department of Microbiology, Nihon University School of Dentistry, Tokyo, Japan.

Streptococcus pneumoniae causes pneumonia by infecting the alveolar epithelium via binding to host receptors, such as the platelet-activating factor receptor (PAFR). Although chronic periodontitis has been identified as a pneumonia risk factor, how periodontopathic bacteria cause pneumonia is not known. We found that S. pneumoniae adhered to PAFR expressed on A549 human alveolar epithelial cells stimulated by Porphyromonas gingivalis culture supernatant, and this was abrogated by a PAFR-specific inhibitor. Among the major virulence factors of P. gingivalis [lipopolysaccharide (LPS), fimbriae and gingipains (Rgps and Kgp)], PAFR expression and pneumococcal adhesion were executed in an Rgp-dependent manner. LPS and fimbriae did not induce PAFR expression. Hence, our findings suggest that P. gingivalis enhances pneumococcal adhesion to human alveoli by inducing PAFR expression and that gingipains are responsible for this.
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http://dx.doi.org/10.1002/1873-3468.14084DOI Listing
June 2021

Metastatic Diffusion Volume Based on Apparent Diffusion Coefficient as a Prognostic Factor in Castration-Resistant Prostate Cancer.

J Magn Reson Imaging 2021 08 11;54(2):401-408. Epub 2021 Mar 11.

Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan.

Background: Whole-body diffusion-weighted MRI (WB-DWI) is useful for assessing disease activity in castration-resistant prostate cancer (CRPC). MET-RADS-P is a subjective assessment-based reporting system proposed to standardize the interpretation of WB-DWI. However, a quantitative evaluation of WB-DWI has not been fully investigated.

Purpose: To investigate the validity, and analyze the prognostic value, of quantitative evaluation of WB-DWI based on apparent diffusion coefficient (ADC) values for CRPC.

Study Type: Retrospective.

Population: Sixty-six patients with CRPC. The median age was 75 years. During the median follow-up period of 25.2 months, 23 of 66 patients (34.8%) died of prostate cancer.

Field Strength/sequence: A 1.5 T WB-DWI was used with two b-values (0 s/mm -1000 s/mm ). A single-shot echo-planar imaging sequence was used.

Assessment: WB-DWI were evaluated by three readers according to MET-RADS-P scoring system. Using imaging software, Attractive BDScore, tumor diffusion volume (mDV) and ADC value of metastatic lesion (mADC) was calculated by two readers. The mDV was calculated with ADC values (×10  mm /sec) of 0.4-0.9 (mDV ), 0.9-1.4 (mDV ), and 1.4-1.8 (mDV ), respectively.

Statistical Tests: Spearman's rank correlation coefficient was used to assess the correlation. The relationships between the variables with cancer-specific survival (CSS) were evaluated. Multivariate analysis was performed using the Cox proportional hazards model.

Results: mDVs showed a strong positive correlation with MET-RADS-P scores (r = 0.90/0.87, P < 0.05 for both). mDV showed a statistically significant association with CSS (hazard ratio [HR]: 1.01, P < 0.05). When the mDVs calculated based on the ADC values were included, mDV (HR: 1.02, P < 0.05) and the number of therapeutic lines (HR: 1.35, P < 0.05) were significant independent indicators of CSS shortening.

Conclusion: Assessment of metastatic tumor volume based on ADC values can be used in the prognostic evaluation of patients with CRPC. WB-DWI might be a potential prognostic imaging biomarker for CRPC.

Evidence Level: 4 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27596DOI Listing
August 2021

Editorial Comment.

J Urol 2021 05 24;205(5):1319-1320. Epub 2021 Feb 24.

Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan.

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http://dx.doi.org/10.1097/JU.0000000000001549.02DOI Listing
May 2021

Power-law coarsening in network-forming phase separation governed by mechanical relaxation.

Nat Commun 2021 Feb 10;12(1):912. Epub 2021 Feb 10.

Department of Fundamental Engineering, Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8505, Japan.

A space-spanning network structure is a basic morphology in phase separation of soft and biomatter, alongside a droplet one. Despite its fundamental and industrial importance, the physical principle underlying such network-forming phase separation remains elusive. Here, we study the network coarsening during gas-liquid-type phase separation of colloidal suspensions and pure fluids, by hydrodynamic and molecular dynamics simulations, respectively. For both, the detailed analyses of the pore sizes and strain field reveal the self-similar network coarsening and the unconventional power-law growth more than a decade according to ℓ ∝ t, where ℓ is the characteristic pore size and t is the elapsed time. We find that phase-separation dynamics is controlled by mechanical relaxation of the network-forming dense phase, whose limiting process is permeation flow of the solvent for colloidal suspensions and heat transport for pure fluids. This universal coarsening law would contribute to the fundamental physical understanding of network-forming phase separation.
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http://dx.doi.org/10.1038/s41467-020-20734-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875975PMC
February 2021

Long-term survival after radical cystectomy and mesenteric lymph node dissection for squamous cell carcinoma arising from augmented bladder with lymph node metastasis: a case report.

Int Cancer Conf J 2021 Jan 1;10(1):20-23. Epub 2020 Sep 1.

Department of Urology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan.

Surgical resection is commonly performed for augmented bladder cancer, yet an optimal treatment strategy for augmented bladder cancer with lymph node metastasis has not been established. Here, we report a case that achieved 7 years of survival after radical cystectomy and mesenteric lymph node dissection for squamous cell carcinoma arising from augmented bladder with lymph node metastasis. Extended surgery could be a useful treatment option for locally advanced augmented bladder cancer including mesenteric lymph node metastasis.
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http://dx.doi.org/10.1007/s13691-020-00442-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797405PMC
January 2021

Genuine- and induced-oligometastatic castration-resistant prostate cancer: clinical features and clinical outcomes after progressive site-directed therapy.

Int Urol Nephrol 2021 Jun 16;53(6):1119-1125. Epub 2021 Jan 16.

Department of Urology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan.

Purpose: To evaluate the clinical characteristics of genuine- and induced-oligometastatic castration-resistant prostate cancer (OM-CRPC) and assess the therapeutic effect of progressive-site directed therapy (PSDT).

Methods: We performed a retrospective analysis of 45 patients with OM-CRPC. Whole-body diffusion-weighted MRI (WB-DWI) was used to diagnose oligo-progressive disease. Based on the clinical and radiological findings, the OM-CRPCs were classified as genuine or induced. PSDT was performed with the intent to ablate all the progressive sites detected on WB-DWI with radiotherapy. Systemic therapy remained unchanged during and after PSDT.

Results: A total of 31 (69%) and 14 (31%) patients were diagnosed with genuine- and induced-OM-CRPC, respectively. The genuine-OM-CRPC group had significantly fewer patients treated with taxane-based chemotherapy and new hormonal drugs than the induced-OM-CRPC group. Of these, 26 OM-CRPC patients were treated with PSDT, and a 50% PSA decline was observed in 14 (93%) of 15 patients with genuine-OM-CRPC and 4 (36%) of 11 patients with induced-OM-CRPC (P = 0.033). Further, the duration of PSA-progression-free survival was significantly longer in the genuine-OM-CRPC group than in the induced-OM-CRPC group (8.7 vs. 5.8 months, P = 0.040).

Conclusions: PSDT can be a promising treatment option for genuine-OM-CRPC. The procedure might also be considered effective for induced-OM-CRPC, although there was less therapeutic benefit of PSDT in patients with induced-OM-CRPC than in patients with genuine-OM-CRPC.
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http://dx.doi.org/10.1007/s11255-020-02762-xDOI Listing
June 2021

Infiltrative Renal Malignancies: Imaging Features, Prognostic Implications, and Mimics.

Radiographics 2021 Mar-Apr;41(2):487-508. Epub 2021 Jan 15.

From the Imaging Institute (D.E.S., R.D.W., E.M.R.) and Glickman Urological and Kidney Institute (Y.W., H.T., S.C.C., E.M.R.), Cleveland Clinic, 9500 Euclid Ave, L10, Cleveland, OH 44195; Department of Urology, First Hospital of Jilin University, Changchun, China (Y.W.); and Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan (H.T.).

Infiltrative renal malignancies are a subset of renal masses that are morphologically characterized by a poorly defined interface with the renal parenchyma. Infiltrative renal malignancies are less common but more aggressive than more typical renal malignancies and carry an overall worse prognosis. Although an infiltrative renal process often represents a malignant neoplasm, infiltrative masses include a wide spectrum of diseases including primary renal cortical, medullary, and pelvic tumors; lymphoproliferative processes; metastases; and various infectious, inflammatory, immune-mediated, and vascular mimics. The imaging features of these masses are often nonspecific, but with the appropriate history, laboratory results, and clinical context, the radiologist can help narrow the diagnosis and guide further treatment. RSNA, 2021.
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http://dx.doi.org/10.1148/rg.2021200123DOI Listing
January 2021

Combination of Cisplatin and Irradiation Induces Immunogenic Cell Death and Potentiates Postirradiation Anti-PD-1 Treatment Efficacy in Urothelial Carcinoma.

Int J Mol Sci 2021 Jan 7;22(2). Epub 2021 Jan 7.

Department of Urology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

The therapeutic benefit of immune checkpoint inhibitor monotherapy is limited to a subset of patients in urothelial carcinoma (UC). Previous studies showed the immunogenicity of cisplatin and irradiation. Here, we investigated whether chemoradiotherapy (CRT), a combination of cisplatin and irradiation, could improve the efficacy of postirradiation anti-programmed cell death 1 (PD-1) treatment in UC. In our advanced UC patient cohort, patients with CRT showed a significantly better objective response rate (75%/22%) and overall survival (88%/30% at 12 months) following later pembrolizumab therapy compared to those without. Then, we created syngeneic UC mouse models by inoculating MB49 cells s.c. in C57BL/6J mice to examine the potential of CRT to enhance antitumor immunity in conjunction with postirradiation anti-PD-1 treatment. Nonirradiated tumors of the mice treated with CRT/postirradiation anti-PD-1 treatment had a significantly slower growth rate and a significantly higher expression of cytotoxic T cells compared to those of the mice treated with anti-PD-1 treatment alone. The mice treated with CRT/postirradiation anti-PD-1 treatment showed the best survival. Mechanistically, CRT provoked strong direct cytotoxicity and increased expressions of immunogenic cell death markers in MB49 cells. Therefore, the combination of cisplatin and irradiation induces immunogenic cell death and potentiates postirradiation anti-PD-1 treatment efficacy in UC.
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http://dx.doi.org/10.3390/ijms22020535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825793PMC
January 2021

Physical origin of glass formation from multicomponent systems.

Sci Adv 2020 Dec 11;6(50). Epub 2020 Dec 11.

Department of Fundamental Engineering, Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.

The origin of glass formation is one of the most fundamental issues in glass science. The glass-forming ability (GFA) of multicomponent systems, such as metallic glasses and phase-change materials, can be enormously changed by slight modifications of the constituted elements and compositions. However, its physical origin remains mostly unknown. Here, by molecular dynamics simulations, we study three model metallic systems with distinct GFA. We find that they have a similar driving force of crystallization, but a different liquid-crystal interface tension, indicating that the latter dominates the GFA. Furthermore, we show that the interface tension is determined by nontrivial coupling between structural and compositional orderings and affects crystal growth. These facts indicate that the classical theories of crystallization need critical modifications by considering local ordering effects. Our findings provide fresh insight into the physical control of GFA of metallic alloys and the switching speed of phase-change materials without relying on experience.
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http://dx.doi.org/10.1126/sciadv.abd2928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732196PMC
December 2020

Outcomes of gasless laparoendoscopic single-port partial nephrectomy in 356 consecutive patients: Feasibility of a clampless and sutureless technique.

Int J Urol 2021 03 9;28(3):302-307. Epub 2020 Dec 9.

Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan.

Objectives: To investigate the outcomes and feasibilities of gasless laparoendoscopic single-port clampless sutureless partial nephrectomy.

Methods: We reviewed 356 consecutive patients with primary unilateral non-metastatic renal masses who underwent gasless laparoendoscopic single-port partial nephrectomy (2011-2018), which was performed retroperitoneally using a three-dimensional flexible endoscope, without vascular clamping or renorrhaphy in principle.

Results: The median tumor size was 2.5 cm, and 213 (60%), 105 (29%), and 38 (11%) patients had peripheral, central, and hilar tumors, respectively. Clampless and sutureless partial nephrectomy was accomplished in 337 patients (95%), while eight (2%) and 16 (4%) patients required vascular clamping and renorrhaphy, respectively. The median operative time and blood loss were 220 min and 266 mL, respectively; eight patients (2%) received blood transfusion. Clavien-Dindo grade 3a complications occurred in 27 patients (8%); all these patients had urinary leakage treated with ureteral stent placement, one of whom also developed a postoperative pseudoaneurysm. Among 324 patients diagnosed with renal cell carcinoma, six (2%) had positive surgical margins, and one (0.3%) and seven (2%) developed metastatic and local recurrences, respectively. During a median follow-up of 54 months, no patient died from kidney cancer. The median percent decrease in estimated glomerular filtration rate at 3 months after surgery was 5.7%. No patient experienced postoperative acute renal failure, while one patient with preexisting renal impairment started dialysis at 70 months after surgery.

Conclusions: Clampless and sutureless partial nephrectomy can be safely accomplished in most patients undergoing gasless laparoendoscopic single-port surgery, yielding favorable oncological and functional outcomes.
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http://dx.doi.org/10.1111/iju.14452DOI Listing
March 2021

Editorial Comment to Lymph node dissection for bladder cancer: Current standards and the latest evidence.

Int J Urol 2021 01 3;28(1):16. Epub 2020 Nov 3.

Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan.

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http://dx.doi.org/10.1111/iju.14419DOI Listing
January 2021

The anomalies and criticality of liquid water.

Proc Natl Acad Sci U S A 2020 10 15;117(43):26591-26599. Epub 2020 Oct 15.

Department of Fundamental Engineering, Institute of Industrial Science, University of Tokyo, Tokyo 153-8505, Japan

The origin of water's anomalies has been a matter of long-standing debate. A two-state model, dating back to Röntgen, relies on the dynamical coexistence of two types of local structures-locally favored tetrahedral structure (LFTS) and disordered normal-liquid structure (DNLS)-in liquid water. Phenomenologically, this model not only explains water's thermodynamic anomalies but also can rationalize the existence of a liquid-liquid critical point (LLCP) if there is a cooperative formation of LFTS. We recently found direct evidence for the coexistence of LFTS and DNLS in the experimental structure factor of liquid water. However, the existence of the LLCP and its impact on water's properties has remained elusive, leaving the origin of water's anomalies unclear. Here we propose a unique strategy to locate the LLCP of liquid water. First, we make a comprehensive analysis of a large set of experimental structural, thermodynamic, and dynamic data based on our hierarchical two-state model. This model predicts that the two thermodynamic and dynamical fluctuation maxima lines should cross at the LLCP if it exists, which we confirm by hundred-microsecond simulations for model waters. Based on recent experimental results of the compressibility and diffusivity measurements in the no man's land, we reveal that the two lines cross around 184 K and 173 MPa for real water, suggesting the presence of the LLCP around there. Nevertheless, we find that the criticality is almost negligible in the experimentally accessible region of liquid water because it is too far from the LLCP. Our findings would provide a clue to settle the long-standing debate.
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http://dx.doi.org/10.1073/pnas.2008426117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959589PMC
October 2020

Liquid-liquid transition and polyamorphism.

Authors:
Hajime Tanaka

J Chem Phys 2020 Oct;153(13):130901

Department of Fundamental Engineering, Institute of Industrial Science, University of Tokyo, Meguro-ku, Tokyo 153-8505, Japan.

Two or more liquid states may exist even for single-component substances, which is known as liquid polymorphism, and the transition between them is called liquid-liquid transition (LLT). On the other hand, the existence of two or more amorphous states is called polyamorphism, and the transition between them is called amorphous-amorphous transition (AAT). Recently, we have accumulated a lot of experimental and numerical evidence for LLT and AAT. These intriguing phenomena provide crucial information on the fundamental nature of liquid and amorphous states. Here, we review the recent progress in this field and discuss how we can physically rationalize the existence of two or more liquids (glasses) for a single-component substance. We also discuss the relationship between liquid-, amorphous-, and crystal-polymorphisms, putting a particular focus on the roles of thermodynamics, mechanics, and kinetics.
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http://dx.doi.org/10.1063/5.0021045DOI Listing
October 2020

A unique route of colloidal phase separation yields stress-free gels.

Sci Adv 2020 Oct 7;6(41). Epub 2020 Oct 7.

Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.

Phase separation often leads to gelation in soft and biomatter. For colloidal suspensions, we have a consensus that gels form by the dynamical arrest of phase separation. In this gelation, percolation of the phase-separated structure occurs before the dynamical arrest, leading to the generation of mechanical stress in the gel network. Here, we find a previously unrecognized type of gelation in dilute colloidal suspensions, in which percolation occurs after the local dynamical arrest, i.e., the formation of mechanically stable, rigid clusters. Thus, topological percolation generates little mechanical stress, and the resulting gel is almost stress-free when formed. We also show that the selection of these two types of gelation (stressed and stress-free) is determined solely by the volume fraction as long as the interaction is short-ranged. This universal classification of gelation of particulate systems may have a substantial impact on material and biological science.
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http://dx.doi.org/10.1126/sciadv.abb8107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541077PMC
October 2020

Infiltrative Renal Masses: Clinical Challenges.

Urology 2020 Nov 30;145:3-8. Epub 2020 Sep 30.

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH. Electronic address:

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http://dx.doi.org/10.1016/j.urology.2020.06.038DOI Listing
November 2020

Emergent solidity of amorphous materials as a consequence of mechanical self-organisation.

Nat Commun 2020 Sep 25;11(1):4863. Epub 2020 Sep 25.

Department of Fundamental Engineering, Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8505, Japan.

Amorphous solids have peculiar properties distinct from crystals. One of the most fundamental mysteries is the emergence of solidity in such nonequilibrium, disordered state without the protection by long-range translational order. A jammed system at zero temperature, although marginally stable, has solidity stemming from the space-spanning force network, which gives rise to the long-range stress correlation. Here, we show that such nonlocal correlation already appears at the nonequilibrium glass transition upon cooling. This is surprising since we also find that the system suffers from giant anharmonic fluctuations originated from the fractal-like potential energy landscape. We reveal that it is the percolation of the force-bearing network that allows long-range stress transmission even under such circumstance. Thus, the emergent solidity of amorphous materials is a consequence of nontrivial self-organisation of the disordered mechanical architecture. Our findings point to the significance of understanding amorphous solids and nonequilibrium glass transition from a mechanical perspective.
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http://dx.doi.org/10.1038/s41467-020-18663-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519136PMC
September 2020

Editorial Comment to Retroperitoneal tumors: Review of diagnosis and management.

Authors:
Hajime Tanaka

Int J Urol 2020 12 18;27(12):1071. Epub 2020 Sep 18.

Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan.

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http://dx.doi.org/10.1111/iju.14374DOI Listing
December 2020

Effects of oral bovine lactoferrin on a mouse model of inflammation associated colon cancer.

Biochem Cell Biol 2021 02 9;99(1):159-165. Epub 2020 Sep 9.

Nanotoxicology Project, Nagoya City University, Nagoya, Japan.

Patients with ulcerative colitis or colonic Crohn's disease have a significantly increased risk of developing colorectal cancer. Bovine lactoferrin (bLF) reportedly inhibited the development of colon cancer in rats and mice, and in a placebo controlled trial, ingestion of bLF inhibited the growth of intestinal polyps. In addition, in a case study, a patient with Crohn's disease was reported to have remained in remission for over 7 years while ingesting 1 g of bLF daily. Thus, bLF has an inhibitory effect on colon carcinogenesis, and it may also promote remission of Crohn's disease. The purpose of this study was to investigate the effects of bLF in a mouse model of colorectal cancer related to irritable bowel disease (IBD). The mice were divided into 4 groups: () no treatment; () treated with bLF only; () treated with azoxymethane plus dextran sulfate sodium (AOM + DSS); and () treated with AOM + DSS + bLF. AOM was used to initiate intestinal cancer, and DSS was used to induce IBD-like inflammation in the intestine of the C57BL/6 mice. At the end of the study, the mice treated with AOM + DSS + bLF had a better fecal score, fewer lesions in the colon, and less weight loss than the mice treated with AOM + DSS without bLF. However, there were no statistically significant differences between the two groups with respect to tumor burden.
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http://dx.doi.org/10.1139/bcb-2020-0087DOI Listing
February 2021

Severe gastrointestinal symptoms caused by a novel DDX3X variant.

Eur J Med Genet 2020 Dec 5;63(12):104058. Epub 2020 Sep 5.

Department of Genome Medicine, National Center for Child Health and Development, Tokyo, Japan.

Mutations in DDX3X have recently been identified as a common cause of intellectual disability and congenital anomalies. DDX3X (Xp11.4) encodes the DEAD box RNA helicase that plays an important role in gene regulation, apoptosis, and oncogenesis. Here, we report a case of 6-year-old Japanese girl with a novel variant (NM_001193416.3: c.1574A > G; p.(Tyr525Cys), who exhibited psychomotor retardation, severe constipation, and a recurrent paralytic ileus. This is the second report of severe gastrointestinal symptoms being associated with this disease. This report expands the phenotype caused by DDX3X variants and reveals an important clinical aspect for patients and medical staff.
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http://dx.doi.org/10.1016/j.ejmg.2020.104058DOI Listing
December 2020

Impact of radiotherapy to the primary tumor on the efficacy of pembrolizumab for patients with advanced urothelial cancer: A preliminary study.

Cancer Med 2020 11 4;9(22):8355-8363. Epub 2020 Sep 4.

Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan.

Radiotherapy plus immune checkpoint inhibitors can potentially induce synergistic antitumor immune responses. However, little clinical evidence is established regarding their combination therapy. Here, we aimed to assess whether radiotherapy to the primary tumor impacts on the efficacy of pembrolizumab in advanced urothelial cancer. We retrospectively reviewed 98 advanced urothelial cancer patients receiving pembrolizumab in a second- or later-line setting using our multicenter cohort. Patients were categorized according to a history of radiotherapy to the primary tumor: patients previously exposed to radiotherapy to the primary tumor (Radiotherapy group, 17 patients [17%]) and those not (Nonradiotherapy group, 81 patients [83%]). The associations of radiotherapy to the primary tumor with objective response and survival were evaluated. The Radiotherapy group showed a significantly higher objective response ratio than did the Non-radiotherapy group (65% vs 19%; P < .001). The Radiotherapy group had a higher progression-free survival rate compared with the Nonradiotherapy group (52% vs 28% at 12 months; P = .078), but statistical significance was not reached. The Radiotherapy group had a significantly higher overall survival rate compared with the Non-radiotherapy group (77% vs 50% at 12 months; P = .025). From multivariate analysis, radiotherapy to the primary tumor was an independent predictor for longer overall survival (hazard ratio, 0.31; P = .032) along with Eastern Cooperative Oncology Group performance status ≤1 and the absence of visceral metastasis. Therefore, radiotherapy to the primary tumor may enhance the efficacy of pembrolizumab for patients with advanced urothelial cancer.
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http://dx.doi.org/10.1002/cam4.3445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666746PMC
November 2020

Heat-Killed Triggers Varying Heme-Related Inflammatory and Stress Responses Depending on Primary Human Respiratory Epithelial Cell Type.

Molecules 2020 Aug 24;25(17). Epub 2020 Aug 24.

Department of Microbiology, Nihon University School of Dentistry, Tokyo 101-8310, Japan.

(Fn) is generally an opportunistic oral pathogen that adheres to mammalian mucosal sites, triggering a host inflammatory response. In general, Fn is normally found within the human oral cavity; however, it was previously reported that Fn is a risk factor for certain respiratory diseases. Surprisingly, this was never fully elucidated. Here, we investigated the virulence potential of heat-killed Fn on primary human tracheal, bronchial, and alveolar epithelial cells. In this study, we measured the secretion of inflammatory- (IL-8 and IL-6), stress- (total heme and hydrogen peroxide), and cell death-related (caspase-1 and caspase-3) signals. We established that the inflammatory response mechanism varies in each epithelial cell type: (1) along tracheal cells, possible Fn adherence would trigger increased heme secretion and regulated inflammatory response; (2) along bronchial cells, potential Fn adherence would simultaneously initiate an increase in secreted HO and inflammatory response (ascribable to decreased secreted heme amounts); and (3) along alveolar cells, putative Fn adherence would instigate the increased secretion of inflammatory responses attributable to a decrease in secreted heme levels. Moreover, regardless of the epithelial cell-specific inflammatory mechanism, we believe these are putative, not harmful. Taken together, we propose that any potential Fn-driven inflammation along the respiratory tract would be initiated by differing epithelial cell-specific inflammatory mechanisms that are collectively dependent on secreted heme.
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http://dx.doi.org/10.3390/molecules25173839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504371PMC
August 2020

[A Case of Primary Amelanotic Malignant Melanoma of the Esophagus, Wherein Pseudoprogression Was Suspected during Immune Checkpoint Inhibitor Treatment].

Gan To Kagaku Ryoho 2020 Aug;47(8):1251-1253

Dept. of Surgery, Funabashi Municipal Medical Center.

A 78-year-old man was admitted to our hospital with a diagnosis of esophageal cancer and gastric cancer. Gastroscopy showed a type 2 tumor located in the cardia from the lower esophagus, and a pathological examination showed malignant melanoma. Based on the physical examination and other imaging tests, the patient was diagnosed with primary amelanotic malignant melanoma of the esophagus, but the tumor was unresectable due to extensive lymph node metastasis. According to the guideline, immune checkpoint inhibitor(nivolumab)was used for treatment, but because the tumor progressed after 2 courses and the performance status of the patient worsened, aggressive treatment was ended. Six weeks after finishing treatment, computed tomography showed that the tumor had shrunk to some extent. The patient ultimately died from aspiration pneumonia 4 months after the first consultation. The patient was thought to have had an immune-related adverse event, with the tumor showing pseudoprogression.
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August 2020
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