Publications by authors named "Yasuhito Tanaka"

834 Publications

Risk factors of fracture following curettage for bone giant cell tumors of the extremities.

BMC Musculoskelet Disord 2022 May 19;23(1):477. Epub 2022 May 19.

Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136, Bologna, Italy.

Background: Following curettage of giant cell tumor of bone (GCTB), it is common to fill the cavity with polymethylmethacrylate (PMMA) bone cement, bone allograft, or artificial bone to maintain bone strength; however, there is a 2-14% risk of postoperative fractures. We conducted this retrospective study to clarify the risk factors for fractures after curettage for GCTB of the extremities.

Methods: This study included 284 patients with GCTBs of the extremities who underwent curettage at our institutions between 1980 and 2018 after excluding patients whose cavities were not filled with anything or who had additional plate fixation. The tumor cavity was filled with PMMA bone cement alone (n = 124), PMMA bone cement and bone allograft (n = 81), bone allograft alone (n = 63), or hydroxyapatite graft alone (n = 16).

Results: Fractures after curettage occurred in 10 (3.5%) patients, and the median time from the curettage to fracture was 3.5 months (interquartile range [IQR], 1.8-8.3 months). The median postoperative follow-up period was 86.5 months (IQR, 50.3-118.8 months). On univariate analysis, patients who had GCTB of the proximal or distal femur (1-year fracture-free survival, 92.5%; 95% confidence interval [CI]: 85.8-96.2) presented a higher risk for postoperative fracture than those who had GCTB at another site (100%; p = 0.0005). Patients with a pathological fracture at presentation (1-year fracture-free survival, 88.2%; 95% CI: 63.2-97.0) presented a higher risk for postoperative fracture than those without a pathological fracture at presentation (97.8%; 95% CI: 95.1-99.0; p = 0.048). Patients who received bone grafting (1-year fracture-free survival, 99.4%; 95% CI: 95.7-99.9) had a lower risk of postoperative fracture than those who did not receive bone grafting (94.4%; 95% CI: 88.7-97.3; p = 0.003).

Conclusions: For GCTBs of the femur, especially those with pathological fracture at presentation, bone grafting after curettage is recommended to reduce the risk of postoperative fracture. Additional plate fixation should be considered when curettage and cement filling without bone grafting are performed in patients with GCTB of the femur. This should be specially performed for those patients with a pathological fracture at presentation.
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http://dx.doi.org/10.1186/s12891-022-05447-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118605PMC
May 2022

Oxidized high mobility group B-1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells.

Cancer Sci 2022 May 15. Epub 2022 May 15.

Department of Molecular Pathology, Nara Medical University, Nara, Japan.

High mobility group box-1 (HMGB1) is known to be a chemotactic factor for mesenchymal stem/stromal cells (MSCs), but the effect of post-translational modification on its function is not clear. In this study, we hypothesized that differences in the oxidation state of HMGB1 would lead to differences in the function of MSCs in cancer. In human colorectal cancer, MSCs infiltrating into the stroma were correlated with liver metastasis and serum HMGB1. In animal models, oxidized HMGB1 mobilized three-fold fewer MSCs to subcutaneous tumors compared with reduced HMGB1. Reduced HMGB1 inhibited the proliferation of mouse bone marrow MSCs (BM-MSCs) and induced differentiation into osteoblasts and vascular pericytes, whereas oxidized HMGB1 promoted proliferation and increased stemness, and no differentiation was observed. When BM-MSCs pretreated with oxidized HMGB1 were co-cultured with syngeneic cancer cells, cell proliferation and stemness of cancer cells were increased, and tumorigenesis and drug resistance were promoted. In contrast, co-culture with reduced HMGB1-pretreated BM-MSCs did not enhance stemness. In an animal orthotopic transplantation colorectal cancer model, oxidized HMGB1, but not reduced HMGB1, promoted liver metastasis with intratumoral MSC chemotaxis. Therefore, oxidized HMGB1 reprograms MSCs and promotes cancer malignancy. The oxidized HMGB1-MSC axis may be an important target for cancer therapy.
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http://dx.doi.org/10.1111/cas.15400DOI Listing
May 2022

Effect of adjuvant chemotherapy on periosteal osteosarcoma: a systematic review.

Jpn J Clin Oncol 2022 Apr 28. Epub 2022 Apr 28.

Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.

Background And Objective: The effects of adjuvant chemotherapy on periosteal osteosarcoma are controversial. Therefore, we conducted a systematic review of studies comparing mortality, local recurrence, distant metastasis and secondary malignancy incidence among patients who underwent surgery and (neo-) adjuvant chemotherapy or surgery alone for periosteal osteosarcoma without distant metastases at diagnosis.

Methods: Of the 210 studies identified in the search, 13 were included in this study, involving 291 patients with periosteal osteosarcoma in total.

Results: The mortality rates in the surgery and (neo-) adjuvant chemotherapy and surgery alone groups were 11.3% (8/71) and 16.3% (16/98), respectively. The overall pooled odds ratio was 0.89 (P = 0.800). The local recurrence rate in the surgery and (neo-) adjuvant chemotherapy group was 12.1% (8/66), while that in the surgery alone group was 17.6% (13/74). The overall pooled odds ratio was 1.31 (P = 0.601). The distant metastasis rate in the surgery and (neo-) adjuvant chemotherapy group was 15.2% (10/66) and that in the surgery alone group was 10.8% (8/74). The overall pooled odds ratio was 1.51 (P = 0.444). The incidence of secondary malignancy in the surgery and (neo-) adjuvant chemotherapy group was 7.6% (9/118) and that in the surgery alone group was 2.7% (2/74). The overall pooled odds ratio was 2.29 (P = 0.187).

Conclusions: Adjuvant chemotherapy did not appear to improve the prognosis of patients with periosteal osteosarcoma. No association was found between the use of adjuvant chemotherapy and development of secondary malignancies.
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http://dx.doi.org/10.1093/jjco/hyac059DOI Listing
April 2022

Clinical usefulness of a novel high-sensitivity hepatitis B core-related antigen assay to determine the initiation of treatment for HBV reactivation.

J Gastroenterol 2022 Apr 28. Epub 2022 Apr 28.

Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Backgrounds: A fully automated, novel, high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developing. The purpose of this study is to evaluate the efficacy of measuring HBcrAg, using that assay, to diagnose HBV reactivation in a multi-center setting, compared with ultra-high-sensitivity HBsAg (iTACT-HBsAg) and HBV DNA assays.

Methods: Forty-four patients with HBV reactivation from 2008 to 2020 were enrolled in four hospitals. Serial serum specimens from the patients were assessed retrospectively for their HBcrAg levels by iTACT-HBcrAg (lower limit of detection; 2.0 log U/mL) and HBsAg levels by iTACT-HBsAg (lower limit of detection; 0.0005 IU/mL); these were compared to the HBV DNA levels. HBV reactivation was defined as detection of serum HBV DNA, including unquantifiable detection.

Results: At HBV reactivation and/or thereafter, HBV DNA levels were quantified (≥ 1.3 log IU/mL) in the sera of 27 patients, and were below the level of quantification (< 1.3 log IU/mL) in the sera of 17 patients. Of the 27 patients with HBV reactivation and whose serum HBV DNA was quantified, the sera of 26 and 24 patients (96.3% and 88.9%) were positive by iTACT-HBcrAg and iTACT-HBsAg, respectively. HBcrAg was detectable by iTACT-HBcrAg before HBV DNA was quantifiable in 15 of the 27 patients. Of the 11 patients with HBV reactivation and undetectable HBcrAg by iTACT-HBcrAg at HBV reactivation and/or thereafter, 10 had unquantifiable HBV DNA and none developed HBV reactivation-related hepatitis.

Conclusions: The iTACT-HBcrAg assay is useful for monitoring HBV reactivation to determine the initiation of treatment with nucleos(t)ide analogues.
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http://dx.doi.org/10.1007/s00535-022-01872-wDOI Listing
April 2022

A pilot study with 3D T1ρ-mapping for quantitative evaluation of cartilage after open-wedge high tibial osteotomy.

Eur J Radiol 2022 Jun 9;151:110308. Epub 2022 Apr 9.

Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Japan.

Purpose: To evaluate the recently developed three-dimensional (3D) T1ρ-mapping technique for the quantitative evaluation of cartilage changes after open-wedge high tibial osteotomy (OWHTO).

Method: Eleven patients with medial knee osteoarthritis and spontaneous osteonecrosis of the medial femoral condyle underwent T1ρ magnetic resonance imaging. The full-thickness cartilage of the medial femoral condyle (MFC), lateral femoral condyle, medial tibial condyle, and lateral tibial condyle, and the trochlea and patella were set as regions of interest; mean T1ρ values were calculated using two-dimensional (2D) and 3D analyses. The state of cartilage injury was evaluated using the International Cartilage Repair Society grading system (ICRS grade). T1ρ values before OWHTO and after hardware removal were compared using the Wilcoxon signed-rank test. The correlation between T1ρ values and the ICRS grade was explored using the Spearman rank correlation coefficient.

Results: Cartilage repair at the MFC was observed in a high proportion of patients (82%), but 2D analysis did not reveal a significant difference after surgery at any site. In contrast, 3D analysis revealed a significant decrease in T1ρ values after surgery at the MFC (before surgery: 44.1 ms; after surgery: 38.9 ms; p = 0.016), but no significant difference at any other site. In the MFC, there was a positive correlation between 3D T1ρ values and arthroscopic findings before and after surgery (rs = 0.62, p < 0.01), which was absent from the 2D T1ρ values.

Conclusions: 3D T1ρ-mapping may be an effective tool for detecting changes in cartilage quality after OWHTO.
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http://dx.doi.org/10.1016/j.ejrad.2022.110308DOI Listing
June 2022

Ultrasound-Guided Cervical Intervertebral Disc Injection Without Fluoroscopy.

J Ultrasound Med 2022 Apr 14. Epub 2022 Apr 14.

Department of Orthopedics, Nara Medical University, Kashihara, Nara, Japan.

Cervical disc degeneration commonly results in referred neck pain, which is traditionally diagnosed via fluoroscopy-guided provocative discography. Herein, we discuss three cases of neck and shoulder pain treated with cervical intradiscal injections administered under ultrasound (US) guidance. The most painful intervertebral disc was identified using the sonopalpation technique, which involved palpation while visualizing anatomical structures using US. Injectant spread within the intervertebral disc was validated using superb microvascular imaging rather than fluoroscopy. Symptoms significantly improved following blocks at the identified sites, suggesting that US can be used to guide cervical intradiscal injections even in the examination room.
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http://dx.doi.org/10.1002/jum.15989DOI Listing
April 2022

Preliminary Screening Method for Low Bone Mineral Density Using a Self-Reported Questionnaire among Peri- and Postmenopausal Women.

Asian Spine J 2022 Apr 6. Epub 2022 Apr 6.

Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan.

Study Design: Retrospective cohort study.

Purpose: We propose a method for screening for low bone mineral density (BMD) among perimenopausal and postmenopausal women using a self-reported questionnaire.

Overview Of Literature: Osteoporosis is a major health problem worldwide. However, it is not cost-effective to evaluate BMD in all patients. Although several tools for predicting osteoporosis have been established, they do not focus much on low BMD prior to the development of osteoporosis.

Methods: We retrospectively reviewed the medical records of 198 women aged 40-70 years who underwent mass screening for osteoporosis at our hospital between 2016 and 2019. The BMD values and the following data were collected: age, body mass index, fracture history, lower back pain, height loss, kyphosis, history of fragility fracture, family history of vertebral or hip fracture, and menopause. The reliability of each data point for the young adult mean <80% was calculated using discriminant analysis. Variables with large weight coefficients were selected and scored. This scoring tool was examined, and a cutoff score for predicting the young adult mean <80% was determined.

Results: Sixty-four participants (32.3%) had a young adult mean <80%. According to the weight coefficients, the following five variables were scored as follows: age ≥60 years 3 points, body mass index <22 kg/m2 3 points, lower back pain 1 point, height loss (cm) 1 point, and menopause 1 point. The area under the receiver operating characteristic curve was 0.738 (95% confidence interval, 0.669-0.807). At cutoff scores of ≥5 and <5, the sensitivity was 82.8%, with specificity of 52.0%.

Conclusions: The scoring tool performed well for predicting young adult mean <80% among perimenopausal and postmenopausal women in Japan. This tool may be useful to screen for low BMD.
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http://dx.doi.org/10.31616/asj.2021.0356DOI Listing
April 2022

Transcranial electrical stimulation motor-evoked potentials rescue from postoperative neurological deficit due to inadequate neck position for the case of lumbar surgery with asymptomatic cervical stenosis.

Eur Spine J 2022 Mar 26. Epub 2022 Mar 26.

Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Nara, 6348522, Japan.

Purpose: Transcranial electrical stimulation motor-evoked potentials (TES-MEPs) are an intraoperative neurophysiologic monitoring method that reduces adverse outcomes in various spine surgeries. Although spine surgeons rarely use TES-MEPs for simple lumbar decompression surgery, we herein firstly report the efficacy of TES-MEPs for lumbar spinal canal stenosis with asymptomatic coexisting cervical canal stenosis.

Methods: We report the case of a 71-year-old man who underwent lumbar decompression surgery for lumbar spinal canal stenosis. He had asymptomatic cervical spinal canal stenosis before surgery.

Results: TES-MEPs showed apparent derivation failure of wave amplitudes from the upper and lower limb muscles immediately after posture change from supine to prone for operative preparation. The cervical alignment was corrected. Subsequently, the TES-MEP wave amplitudes became derivable immediately.

Conclusions: While TES-MEPs can be used to prevent neurological deficits in lumbar spine surgery, it can also be used to indirectly monitor other spinal lesions. Based on our experience, we recommend using TES-MEPs even in lumbar spine surgery.
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http://dx.doi.org/10.1007/s00586-022-07172-4DOI Listing
March 2022

Mac-2-binding protein glycan isomer predicts all malignancies after sustained virological response in chronic hepatitis C.

Hepatol Commun 2022 Mar 28. Epub 2022 Mar 28.

Core Research Facilities, Research Center for Medical Science, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.

Despite reports of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection after achieving sustained virological response (SVR), only few studies have demonstrated the incidence of other (non-HCC) malignancies. This study aimed to clarify the incidence, survival probability, and factors associated with malignancy, especially non-HCC malignancies, in patients with chronic HCV infection after achieving SVR. In this retrospective study, records of 3580 patients with chronic HCV infection who achieved SVR following direct-acting antiviral (DAA) treatment were analyzed. The cumulative post-SVR incidence of non-HCC malignancies was 0.9%, 3.1%, and 6.8% at 1, 3, and 5 years, respectively. The survival probability for patients with non-HCC malignancies was 99.1%, 78.8%, and 60.2% at 1, 3, and 5 years, respectively, and the rate was significantly lower than that for patients with HCC. The Cox proportional hazards regression model identified Mac-2-binding protein glycan isomer (M2BPGi) cutoff index (COI) ≥ 1.90 at baseline and ≥ 1.50 at 12 weeks following DAA treatment as significant and independent factors associated with the post-SVR incidence of non-HCC malignancies. Furthermore, patients with either M2BPGi COI ≥ 1.90 at baseline or M2BPGi COI ≥ 1.50 at SVR12 had a significantly higher risk of post-SVR incidence of non-HCC malignancies than of HCC. Conclusion: M2BPGi measurements at baseline and SVR12 may help predict the post-SVR incidence of non-HCC malignancies in patients with chronic HCV infection who achieved SVR following DAA treatment. Early identification of these patients is critical to prolong patient survival.
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http://dx.doi.org/10.1002/hep4.1941DOI Listing
March 2022

Acromioclavicular joint instability on cross-body adduction view: the biomechanical effect of acromioclavicular and coracoclavicular ligaments sectioning.

BMC Musculoskelet Disord 2022 Mar 23;23(1):279. Epub 2022 Mar 23.

Department of Orthopedic Surgery, Nara Medical University, 840 Shijoutyou, Kashihara City, Nara, 634-5821, Japan.

Background: The acromioclavicular (AC) and coracoclavicular (CC) ligaments are important stabilizers of the AC joint. We hypothesized that AC and trapezoid ligament injuries induce AC joint instability and that the clavicle can override the acromion on cross-body adduction view even in the absence of conoid ligament injury. Accordingly, we investigated how sectioning the AC and CC ligaments contribute to AC joint instability in the cross-body adduction position.

Methods: Six fresh-frozen cadaveric shoulders were used in this study, comprising five male and one female specimen, with a mean age of 68.7 (range, 51-87) years. The left side of the trunk and upper limb, and the cervical and thoracic vertebrae and sternum were firmly fixed with an external fixator. The displacement of the distal end of the clavicle relative to the acromion was measured using an electromagnetic tracking device. We simulated AC joint dislocation by the sequential resection of the AC ligament, AC joint capsule, and CC ligaments in the following order of stages. Stage 0: Intact AC and CC ligaments and acromioclavicular joint capsule; stage 1: Completely sectioned AC ligament, capsule and joint disc; stage 2: Sectioned trapezoid ligament; and stage 3: Sectioned conoid ligament. The superior clavicle displacement related to the acromion was measured in the horizontal adduction position, and clavicle overriding on the acromion was assessed radiologically at each stage. Data were analyzed using a one-way analysis of variance and post-hoc tests.

Results: Superior displacement was 0.3 mm at stage 1, 6.5 mm at stage 2, and 10.7 mm at stage 3. On the cross-body adduction view, there was no distal clavicle overriding at stages 0 and 1, and distal clavicle overriding was observed in five cases (5/6: 83%) at stage 2 and in six cases (6/6: 100%) at stage 3.

Conclusion: We found that AC and trapezoid ligament sectioning induced AC joint instability and that the clavicle could override the acromion on cross-body adduction view regardless of conoid ligament sectioning. The traumatic sections of the AC and trapezoid ligament may lead to high grade AC joint instability, and the distal clavicle may subsequently override the acromion.
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http://dx.doi.org/10.1186/s12891-022-05245-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943985PMC
March 2022

Usefulness of ultrasound in diagnosing long head of the biceps tendon malposition in patients with rotator cuff tears.

J Med Ultrason (2001) 2022 Apr 23;49(2):289-295. Epub 2022 Mar 23.

Department of Orthopaedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.

Purpose: This study aimed to determine the role of preoperative shoulder ultrasonography (SUS) in detecting positional abnormalities of the long head of the biceps tendon (LHBT) and predicting subscapularis (SSC) tears in patients with rotator cuff injuries.

Methods: A total of 331 patients (365 shoulders) who had undergone arthroscopic shoulder surgery for the treatment of rotator cuff tears were included in the study. Their preoperative SUS and magnetic resonance imaging (MRI) findings were examined retrospectively to assess the presence of LHBT abnormalities at the bicipital groove. Using arthroscopic findings as the standard of reference, the sensitivity, specificity, and diagnostic accuracy of SUS and MRI were calculated for detection of LHBT malposition. Furthermore, the correlation between SSC rupture and preoperative LHBT condition was evaluated by MRI and SUS.

Results: LHBT malposition was preoperatively diagnosed with a sensitivity of 92%, specificity of 90%, and accuracy of 91% with SUS, and a sensitivity of 74%, specificity of 84%, and accuracy of 80% with MRI. Preoperative SUS was significantly superior to MRI in terms of sensitivity, specificity, and accuracy (p < 0.001 each). Further, the preoperative SUS LHBT findings could predict well the presence or absence of intraoperative SSC rupture (odds ratio: 1.73, p < 0.001).

Conclusion: SUS is a useful diagnostic modality for preoperative detection of LHBT malposition and prediction of SSC tears in patients with rotator cuff tears.
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http://dx.doi.org/10.1007/s10396-022-01200-yDOI Listing
April 2022

Anti-nuclear antibody and a granuloma could be biomarkers for iCIs-related hepatitis by anti-PD-1 treatment.

Sci Rep 2022 03 7;12(1):3669. Epub 2022 Mar 7.

Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

It has been reported that various kinds of immune checkpoint inhibitors (iCIs) could induce immune-related liver damage. We should focus on the programmed cell death-receptor-1 (PD-1) antibody and non-small cell lung cancer (NSCLC) to analyze the characteristics of hepatitis related to iCIs and find factors that could be useful biomarkers for the diagnosis. A single-center retrospective study of 252 NSCLC patients who received PD-1 antibody (nivolumab or pembrolizumab). Some of the biochemical markers and immunological markers were analyzed during PD-1-antibody treatment with or without ALT elevation. Histopathological features were reviewed by a single expert of hepatic pathology focusing on the following features: fibrosis, portal inflammation, lobular inflammation, lobular necrosis. The formation of macro- and micro-granulomas was also evaluated. The frequency of liver damage induced by nivolumab including grade 1 to 4 (ALT) was 41.9% (78/186 patients). The positive rate of anti-nuclear antibody in the nivolumab group with iCIs-related hepatitis was significantly higher than that in the nivolumab group without iCIs-related hepatitis (p = 0.00112). Granulomatous changes were significantly increased in patients with iCIs-related hepatitis compared with DILI and AIH patients (p < 0.05). The ratios of inflammatory cells CD4/CD8, and CD138/CD3 in ICIs-related hepatitis were significantly lower than those in AIH or DILI patients (p < 0.05). We demonstrated that the pre-existing ANA and characteristic liver histology including CD8 cells dominancy and granulomatous hepatitis could be biomarkers for the diagnosis of iCIs-related hepatitis in the NSCLC with anti-PD-1 therapy.
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http://dx.doi.org/10.1038/s41598-022-07770-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901662PMC
March 2022

Surgery Can Improve Locomotive Syndrome Due to Lumbar Spinal Canal Stenosis and Loco-Check Can Predict Best Timing of Surgery to Avoid Progress of Locomotive Syndrome.

Spine Surg Relat Res 2022 11;6(1):58-62. Epub 2021 Jun 11.

Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Japan.

Introduction: The loco-check is a simple tool for evaluating locomotive syndrome (LS), and a previous report suggested that it can be used to identify patients with stage 2 LS. The purpose of this study was to investigate the improvement in LS stage after surgery based on the loco-check in elderly patients with lumbar spinal stenosis (LSS) and to clarify the characteristics associated with improvement to non-stage 2 LS.

Methods: We reviewed 40 elderly patients with LSS who underwent surgery at our institution. We compared the pre- and postoperative Japanese Orthopaedic Association score, loco-check, Oswestry Disability Index, EuroQoL-5 dimension utility values, and the EuroQoL-visual analog scale. We divided patients according to the presence or absence of stage 2 LS after surgery and compared their preoperative clinical findings and assessment measures.

Results: Ninety percent of all patients had been preoperatively diagnosed with stage 2 LS according to the loco-check. After surgery, patients showed a decreased number of affirmative answers on the loco-check, according to which only 65% were postoperatively diagnosed with stage 2 LS. The receiver operating characteristic curve analysis identified less than four affirmative answers on the loco-check before LSS as predictive of improvement to non-stage 2 LS.

Conclusions: Surgical treatment for elderly patients with LSS could improve LS. In patients with less than four affirmative answers on the loco-check preoperatively, improvement to non-stage 2 LS status may be possible.
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http://dx.doi.org/10.22603/ssrr.2021-0046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842354PMC
June 2021

Management of hepatitis B virus (HBV) reactivation in patients with resolved HBV infection based on a highly sensitive HB core-related antigen assay.

Hepatol Res 2022 Feb 23. Epub 2022 Feb 23.

Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Aims: To prevent hepatitis B virus (HBV) reactivation-related hepatitis, we examined the clinical usefulness of a highly sensitive HB core-related antigen (iTACT-HBcrAg) assay in patients with resolved HBV infection after nucleos(t)ide analog (NA) treatment for HBV reactivation.

Methods: We retrospectively analyzed 27 patients with resolved HBV infection who experienced HBV reactivation (defined as HBV DNA levels of 1.3 log IU/ml or more), and who received systemic chemotherapies for hematological malignancies between 2008 and 2020. iTACT-HBcrAg, HBsAg-HQ, and antibodies against hepatitis B surface antigen (anti-HBs) were measured using samples stored after HBV reactivation. The lower limit of quantification for iTACT-HBcrAg was 2.0 log U/ml.

Results: HBV reactivation was diagnosed at a median HBV DNA level of 1.8 log IU/ml, and then all patients received NA treatment. No patient had HBV-related hepatitis with a median maximum HBV DNA level of 2.0 log IU/ml. The positivities of iTACT-HBcrAg and HBsAg-HQ were 96% and 52% after HBV reactivation, respectively. Of 25 patients with detectable iTACT-HBcrAg at the initiation of NA treatment, 17 (68%) achieved iTACT-HBcrAg loss. Median durations from NA treatment to HBV DNA loss and iTACT-HBcrAg loss or the last follow-up were 35 and 175 days, respectively. Recurrence of HBV reactivation after NA cessation was not observed in seven of eight patients who achieved iTACT-HBcrAg loss or seropositive for anti-HBs during follow-up, except for one without anti-HBs after allogeneic transplantation.

Conclusions: iTACT-HBcrAg could be a potential surrogate marker for diagnosing early-stage HBV reactivation as well as safe cessation of NA treatment in patients with resolved HBV infection after HBV reactivation.
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http://dx.doi.org/10.1111/hepr.13761DOI Listing
February 2022

The Long-Term Clinical Results of Total Talar Replacement at 10 Years or More After Surgery.

J Bone Joint Surg Am 2022 05 21;104(9):790-795. Epub 2022 Feb 21.

Department of Orthopedic Surgery, Nara Medical University, Kashihara, Japan.

Background: Total talar replacement has been reported to have favorable short-term and intermediate-term results for the treatment of osteonecrosis of the talus. The purpose of this study was to evaluate the long-term clinical results of total talar replacement for a minimum of 10 years after the surgical procedure.

Methods: From October 2005 to April 2011, 19 ankles in 18 patients (1 male and 17 female) were treated using a total talar prosthesis for osteonecrosis of the talus. The median follow-up period was 152 months (interquartile range [IQR], 138, 160 months). The Ankle Osteoarthritis Scale (AOS) score, the Japanese Society for Surgery of the Foot (JSSF) Ankle-Hindfoot Scale score, and the presence of osteophytes and degenerative changes in the adjacent joints were assessed preoperatively and at the final follow-up. Subsidence of the prosthesis was also assessed at the earliest opportunity for full weight-bearing and the final follow-up. The postoperative range of motion of the ankle was assessed at the final follow-up.

Results: The median scores for all subscales of the AOS significantly improved. The median JSSF Ankle-Hindfoot Scale score significantly improved from 58 (IQR, 55, 59.5) to 97 (IQR, 87, 99.5). In the subcategories of this scale, the median pain score improved from 20 (IQR, 20, 20) to 40 (IQR, 30, 40), and the median function score improved from 28 (IQR, 26, 30.5) to 47 (IQR, 47, 50). The median postoperative range of motion of the ankle was 45° (IQR, 42.5°, 55°). Subsidence of the implant was not recognized at the final follow-up (p = 0.083). Proliferation of osteophytes and degenerative changes in the adjacent joints did not affect the overall results.

Conclusions: The customized alumina ceramic total talar prosthesis produced stable clinical outcomes over 10 years, and the patients treated with total talar replacement showed favorable clinical results over this time frame.

Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.21.00922DOI Listing
May 2022

Serum miR-192-5p levels predict the efficacy of pegylated interferon therapy for chronic hepatitis B.

PLoS One 2022 14;17(2):e0263844. Epub 2022 Feb 14.

Departments of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.

We examined the association between serum miRNA (-192-5p, -122-3p, -320a and -6126-5p) levels and the efficacy of pegylated interferon (Peg-IFN) monotherapy for chronic hepatitis B (CHB) patients. We enrolled 61 CHB patients treated with Peg-IFNα-2a weekly for 48 weeks, of whom 12 had a virological response (VR) and 49 did not VR (non-VR). A VR was defined as HBV DNA < 2,000 IU/ml, hepatitis B e antigen (HBeAg)-negative, and nucleos(t)ide analogue free at 48 weeks after the end of treatment. The non-VR group showed a significantly higher HBeAg-positivity rate, ALT, HBV DNA, and serum miR-192-5p levels at baseline (P = 0.024, P = 0.020, P = 0.007, P = 0.021, respectively). Serum miR-192-5p levels at 24-weeks after the start of treatment were also significantly higher in the non-VR than the VR group (P = 0.011). Multivariate logistic regression analysis for predicting VR showed that miR-192-5p level at baseline was an independent factor (Odds 4.5, P = 0.041). Serum miR-192-5p levels were significantly correlated with the levels of HBV DNA, hepatitis B core-related antigen, and hepatitis B surface antigen (r = 0.484, 0.384 and 0.759, respectively). The serum miR-192-5p level was useful as a biomarker for the therapeutic efficacy of Peg-IFN in CHB treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0263844PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843190PMC
February 2022

Comparison of symptomatic unstable ankle with and without os subfibulare.

J Orthop Sci 2022 Feb 7. Epub 2022 Feb 7.

Nara Medical University, School of Medicine, Kashihara-shi, Nara, 6348522 Japan.

Background: This study aimed to compare the patients background, clinical scores, condition of the lateral ligament, mechanical instabilities, and chondral lesions in ankles with symptomatic os subfibulare compared to those in ankles with chronic lateral instability without os subfibulare.

Methods: Of the 212 ankles with a chronic lateral instability that were surgically treated, 72 ankles had an os subfibulare. All ankles were examined by arthroscopy during surgery. Age, sex, preoperative American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale scores, remnant condition of the lateral ligaments, and chondral lesions were compared between ankles with symptomatic os subfibulare and ankles with chronic lateral instability without os subfibulare.

Results: There were no statistically significant differences between the groups in terms of the sex ratio (males: females, 35:37 vs. 53:87, n.s.) and the AOFAS Ankle-Hindfoot Scale scores (median; 75 vs. 77, n.s.). There were statistically significant differences in patient age (median: 20 vs. 24.5 years, p < 0.01), talar tilt angle (median: 9.0° vs 12.0°, p < 0.01), anterior drawer distance (6.2 vs. 7.0 mm, p < 0.01), chondral lesions (G0:G1:G2:G3, 35:21:66:5 vs. 40:44:27:29, p < 0.01), condition of the anterior talofibular ligament (intact: repairable remnant: poor remnant, 0:70:2 vs. 1:112:27, p < 0.01), and condition of the calcaneofibular ligament (intact: repairable remnant: poor remnant, 44:26:2 vs. 77:35:28, p < 0.01) between the groups.

Conclusion: This study suggests that the condition of the lateral ligaments including mechanical instability and cartilage of the ankle were less severe in the ankles with symptomatic os subfibulare than in those with chronic lateral instability without os subfibulare. The patients' age was lower in the ankles with symptomatic os subfibulare than in those with chronic lateral instability without os subfibulare. The clinical scores and gender ratio were not statistically different between the group.
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http://dx.doi.org/10.1016/j.jos.2022.01.007DOI Listing
February 2022

Droplet digital PCR assay provides intrahepatic HBV cccDNA quantification tool for clinical application.

Sci Rep 2022 02 8;12(1):2133. Epub 2022 Feb 8.

Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

The persistence of covalently closed circular DNA (cccDNA) poses a major obstacle to curing chronic hepatitis B (CHB). Here, we used droplet digital PCR (ddPCR) for cccDNA quantitation. The cccDNA-specific ddPCR showed high accuracy with the dynamic range of cccDNA detection from 10 to 10 copies/assay. The ddPCR had higher sensitivity, specificity and precisely than qPCR. The results of ddPCR correlated closely with serum HB core-related antigen and HB surface antigen (HBsAg) in 24 HBV-infected human-liver-chimeric mice (PXB-mice). We demonstrated that in 2 PXB-mice after entecavir treatment, the total cccDNA content did not change during liver repopulation, although the cccDNA content per hepatocyte was reduced after the treatment. In the 6 patients with HBV-related hepatocellular carcinoma, ddPCR detected cccDNA in both tumor and non-tumor tissues. In 13 HBeAg-negative CHB patients with pegylated interferon alpha-2a, cccDNA contents from paired biopsies were more significantly reduced in virological response (VR) than in non-VR at week 48 (p = 0.0051). Interestingly, cccDNA levels were the lowest in VR with HBsAg clearance but remained detectable after the treatment. Collectively, ddPCR revealed that cccDNA content is stable during hepatocyte proliferation and persists at quantifiable levels, even after serum HBsAg clearance.
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http://dx.doi.org/10.1038/s41598-022-05882-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8826402PMC
February 2022

Implantation of autogenous meniscal fragments wrapped with a fascia sheath induces fibrocartilage regeneration in a large meniscal defect in sheep: A histological and biomechanical study.

Orthop Traumatol Surg Res 2022 May 31;108(3):103225. Epub 2022 Jan 31.

Sports Medicine and Arthroscopy Center, Yagi Orthopaedic Hospital, Sapporo, Hokkaido, Japan.

Introduction: Currently, various studies have been reported to regenerate the meniscus tissue in a large defect after partial meniscectomy using biological or synthetic scaffolds with or without fibrochondrocytes. However, the clinical utility of those treatments has not been established as of yet.

Hypothesis: Purposes of this study were to develop a sheep model to evaluate feasibility of this new surgical strategy to treat the irreparable meniscus injury, and to test the hypothesis that implantation of autogenous meniscal fragments wrapped with a fascia sheath may significantly induce fibrocartilage regeneration in a large meniscal defect in the sheep model.

Methods And Methods: Twenty Suffolk sheep were used. In each animal, an anterior 10-mm width of the right medial meniscus was resected. Then, the animals were divided into the following 2 groups. In Group I, the defect was enveloped with a fascia from the left thigh. In Group II, the resected meniscus fragmented into small pieces was grafted into the defect. Then the defect was enveloped with a fascia. In each group, 5 of 10 sheep were used for histological and biomechanical evaluations, respectively, at 12 weeks after surgery.

Results: In Group I, the defect was incompletely filled with thin fibrous tissues, while fibrocartilage tissues rarely regenerated in the tissue. In Group II, all defects were completely filled with thick fibrocartilage tissues, which were richly stained with the safranin O staining. Both the gross and histological observation score of Group II was significantly (p=0.0005, p=0.0005) greater than that of Group I. Concerning the cross-sectional area of the regenerated tissue, Group II was significantly (p=0.0002) greater than Group I. In the biomechanical evaluation, the maximal load and the linear stiffness of the meniscus-tibia complex were significantly (p=0.0015, p=0.0283) greater in Group II than in Group I.

Discussion: Implantation of autogenous meniscal fragments wrapped with a fascia sheath significantly induces fibrocartilage regeneration into a large meniscal defect in the sheep model.

Level Of Evidence: Not applicable; Controlled Laboratory Study, Experimental in vivo study.
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http://dx.doi.org/10.1016/j.otsr.2022.103225DOI Listing
May 2022

The Relationship Between the Distal Tibial Fibular Syndesmosis and the Varus Deformity in Patients With Varus Ankle Osteoarthritis.

Foot Ankle Orthop 2021 Oct 26;6(4):24730114211041111. Epub 2021 Oct 26.

Nara Medical University, Kashihara, Nara, Japan.

Background: The impact of varus ankle osteoarthritis (OA) on the distal tibial fibular syndesmosis is poorly described. This study aimed to investigate the possible relationship between the condition of the distal tibial fibular syndesmosis and the degree of the varus deformity using weightbearing simulated computed tomography (CT), in patients with varus ankle OA.

Methods: This retrospective comparative study included 155 varus ankles, divided into 4 Takakura-Tanaka groups (stage 2, 3a, 3b, and 4). A control group comprised 35 ankles without prior ankle disorders. The angles between the tibial shaft and the articular surface of the tibial plafond on the anteroposterior view (TAS), and articular surfaces of the tibial plafond and talar dome (TTW) were measured from weightbearing ankle radiographs. The varus angle of the ankle (VA) was defined as 90 - TAS + TTW. On the CT axial view, 1 cm proximal to the tibial plafond, the area of the syndesmosis ("CT-area") and the distance between the fibula and the tibia (CT-FCS) were measured.

Results: The CT area in stages 2, 3a, 3b, 4, and control group were 99, 79, 77, 103, and 97 mm, respectively. The CT-FCS were 3.5, 3.1, 2.9, 4.3, and 3.9 mm, respectively. In all 155 OA ankles, CT area and CT-FCS were negatively correlated with the VA (correlation coefficient = -0.38, < .01; and = 0.38, < .01, respectively). Both CT area and CT-FCS were significantly smaller in stages 3a and 3b than in the control group ( < .01).

Conclusion: There may be a relationship between the narrowing of the syndesmosis and the varus deformity in patients with varus ankle OA, especially in stages 3a and 3b.

Clinical Relevance: Clinicians should be aware of the impact of varus ankle arthritis on the distal tibial fibular syndesmosis when operatively treating varus ankle OA. For some patients, the isolated treatment for the tibiotalar joint may be insufficient, and treatment for the syndesmosis as well as tibiotalar joint may be needed.

Level Of Evidence: Level III, retrospective case control study.
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http://dx.doi.org/10.1177/24730114211041111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554566PMC
October 2021

Morphologic Analysis of Nonosseous Talocalcaneal Coalitions Using 3D Reconstruction.

Foot Ankle Orthop 2021 Oct 19;6(4):24730114211039487. Epub 2021 Oct 19.

Department of Orthopaedic Surgery, Nara Prefecture General Medical Center, Nara, Japan.

Background: Resection of talocalcaneal coalitions has generally involved osseous coalitions. We attempted to evaluate the morphology of nonosseous talocalcaneal coalitions. This study aimed to investigate if the calcaneal articular surface area of feet with talocalcaneal coalitions is different than that of normal feet.

Methods: Twenty nonosseous talocalcaneal coalition cases with analyzable computed tomography (CT) scans were compared to 20 control cases. Three-dimensional models of the talus and calcaneus were constructed, and the surface areas of the posterior facet (SPF), whole talocalcaneal joint of the calcaneus (SWJ), and coalition site (SCS) of each 3D-CT model were measured. "Calibrated" values of the 2 groups were created to adjust for relative size of the tali and then compared. The preoperative and postoperative AOFAS Ankle-Hindfoot scale was calculated for 9 cases that had undergone single coalition resection.

Results: The calibrated SPF and SWJ were significantly greater in the coalition group than in the control group (40% and 12%, respectively). No significant difference was detected between the calibrated (SWJ - SCS) value of the coalition group and the calibrated SWJ value of the control group. The AOFAS scale was improved postoperatively in all 9 cases analyzed.

Conclusion: The calcaneal articular surface of nonosseous talocalcaneal coalition feet in our series was larger than that of the normal feet. This study indicates that the total calcaneal articular surface after coalition resection may be comparable to the calcaneal articular surface of normal feet. We suggest that the indication for coalition resection be reconsidered for nonosseous coalition.

Level Of Evidence: Level III, retrospective comparative study.
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http://dx.doi.org/10.1177/24730114211039487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529318PMC
October 2021

Probability of HBsAg loss after nucleo(s)tide analogue withdrawal depends on HBV genotype and viral antigen levels.

J Hepatol 2022 May 29;76(5):1042-1050. Epub 2022 Jan 29.

Department of Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany.

Background & Aims: Nucleo(s)tide analogue (NUC) withdrawal may result in HBsAg clearance in a subset of patients. However, predictors of HBsAg loss after NUC withdrawal remain ill-defined.

Methods: We studied predictors of HBsAg loss in a global cohort of HBeAg-negative patients with undetectable HBV DNA who discontinued long-term NUC therapy. Patients requiring retreatment after treatment cessation were considered non-responders.

Results: We enrolled 1,216 patients (991 with genotype data); 98 (8.1%) achieved HBsAg loss. The probability of HBsAg loss was higher in non-Asian patients (adjusted hazard ratio [aHR] 8.26, p <0.001), and in patients with lower HBsAg (aHR 0.243, p <0.001) and HBV core-related antigen (HBcrAg) (aHR 0.718, p = 0.001) levels. Combining HBsAg (<10, 10-100 or >100 IU/ml) and HBcrAg (<2log vs. ≥2 log) levels improved prediction of HBsAg loss, with extremely low rates observed in patients with HBsAg >100 IU/ml with detectable HBcrAg. HBsAg loss rates also varied with HBV genotype; the highest rates were observed for genotypes A and D, and none of the patients with HBV genotype E experienced HBsAg loss (p <0.001 for the overall comparison across genotypes; p <0.001 for genotypes A/D vs. genotypes B/C). HBV genotype C was independently associated with a higher probability of HBsAg loss when compared to genotype B among Asian patients (aHR 2.494; 95% CI 1.490-4.174, p = 0.001).

Conclusions: The probability of HBsAg loss after NUC cessation varies according to patient ethnicity, HBV genotype and end-of-treatment viral antigen levels. Patients with low HBsAg (<100 IU/ml) and/or undetectable HBcrAg levels, particularly if non-Asian or infected with HBV genotype C, appear to be the best candidates for treatment withdrawal.

Lay Summary: A subset of patients may achieve clearance of hepatitis B surface antigen (HBsAg) - so-called functional cure - after withdrawal of nucleo(s)tide analogue therapy. In this multicentre study of 1,216 patients who discontinued antiviral therapy, we identified non-Asian ethnicity, HBV genotype C, and low hepatitis B surface antigen and hepatitis B core-related antigen levels as factors associated with an increased chance of HBsAg loss.
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http://dx.doi.org/10.1016/j.jhep.2022.01.007DOI Listing
May 2022

Trends in hepatocellular carcinoma incident cases in Japan between 1996 and 2019.

Sci Rep 2022 01 27;12(1):1517. Epub 2022 Jan 27.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.

We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996-2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients < 60 years, 60-69 years, 70-79 years, and ≥ 80 years were 3711 (18.1%), 6652 (32.4%), 7448 (36.2%), and 2736 (13.3%), respectively. The average age of newly-diagnosed patients increased in each quarter. HCC was associated with HBV, HBV + HCV, and HCV infections and non-BC in 2997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased. HCC incident cases tend to increase in the elderly and in non-BC patients; in contrast, HCC incident cases due to HCV tend to decrease.
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http://dx.doi.org/10.1038/s41598-022-05444-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795252PMC
January 2022

Severe complication subsequent to surgical site infection after cervical laminoplasty: a case report.

Spinal Cord Ser Cases 2022 01 14;8(1). Epub 2022 Jan 14.

Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan.

Introduction: Surgical site infections (SSI) following spinal surgery can result in serious complications. Although early detection and intensive care are essential to minimize possible sequelae, more than one surgical intervention is required to alleviate the infection in some cases.

Case Presentation: A 66-year-old man with long-standing Parkinson's disease (PD) developed SSIs after cervical laminoplasty. Despite surgical debridement and irrigation, his neurological status worsened severely and anterior infectious involvement at the C4-5 level was identified by magnetic resonance imaging. He underwent another urgent surgery for anterior debridement and iliac bone grafting. His laboratory results gradually normalized with antibiotic therapy, and his neurological status improved. One year after surgery, he was ambulatory with walker assistance. However, his right hand remained difficult to control with significant sensory loss and numbness.

Discussion: To our knowledge, this is the first case of SSI that extended rapidly to the anterior side despite immediate and intensive treatment in a patient with PD after laminoplasty. During SSI treatment, meticulous observation should be performed to check for exacerbations.
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http://dx.doi.org/10.1038/s41394-021-00472-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758777PMC
January 2022

Long-term outcomes after endoscopic resection for late-elderly patients with early gastric cancer.

Gastrointest Endosc 2022 05 31;95(5):873-883. Epub 2021 Dec 31.

Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan.

Background And Aims: With the population aging, the incidence of early gastric cancer (EGC) is increasing. We aimed to clarify the indications for endoscopic resection (ER) in late-elderly patients with EGC in terms of life expectancy.

Methods: Patients aged ≥75 years who underwent ER for EGC at our institution from January 2007 to December 2012 were enrolled. Clinical data, including Eastern Cooperative Oncology Group performance status (ECOG-PS), Charlson comorbidity index, and Prognostic Nutritional Index (PNI), were collected at the time of ER. Overall survival (OS) was the main outcome measure.

Results: Four hundred consecutive patients were enrolled. Mean patient age was 79.3 years (range, 75-93). The 5-year follow-up rate was 89.0% (median follow-up period, 5.6 years). Five-year OS was 80.8% (95% confidence interval [CI], 76.4-84.4), and 5-year net survival standardized for age, sex, and calendar year was 1.09 (95% CI, 1.03-1.15). With a multivariate analysis, ECOG-PS 2 to 4 (hazard ratio, 8.84; 95% CI, 3.07-25.4), PNI <49.1 (hazard ratio, 2.49; 95% CI, 1.53-4.06), and eCura C-2 (hazard ratio, 1.79; 95% CI, 1.11-2.88) were independent prognostic factors. When none of these factors was met, the 5-year OS rate was 90.4% (95% CI, 84.0-94.3).

Conclusions: ER for EGC in late-elderly patients may improve life expectancy. ER is recommended in patients with a good ECOG-PS and PNI and in whom ER is expected to be non-eCura C-2.
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http://dx.doi.org/10.1016/j.gie.2021.12.028DOI Listing
May 2022

Endosialin/CD248 may be a potential therapeutic target to prevent the invasion and metastasis in osteosarcoma.

Oncol Lett 2022 Feb 6;23(2):42. Epub 2021 Dec 6.

Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara 634-8521, Japan.

Endosialin/CD248/tumor endothelial marker 1 is classified as a C-type lectin-like transmembrane receptor, found on the plasma membrane of activated mesenchymal cells, which binds to fibronectin. Although endosialin is expressed at high levels in stem-like cells of sarcomas, its role has not been fully uncovered. The present study aimed to determine whether endosialin expression is associated with tumor progression and metastasis, and whether endosialin has the potential to act as a novel therapeutic target in osteosarcoma (OS) using MORAb-004/ontuxizumab, a humanized monoclonal antibody, which targets the type C lectin domain of endosialin. The results demonstrated that endosialin was highly expressed in OSs with metastatic disease. Furthermore, MORAb-004 had no cytostatic effect on OS cells and did not change the expression of stem cells and differentiation markers; however, it inhibited migration of OS cells. Taken together, these results suggest that endosialin may play a role in migration, and may be involved in the metastatic process of OSs. Furthermore, MORAb-004 reduces the motility of OS cells, and suppresses invasion and the development of metastatic lesions.
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http://dx.doi.org/10.3892/ol.2021.13160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674875PMC
February 2022

Improved visibility of early gastric cancer by using a combination of chromoendoscopy and texture and color enhancement imaging.

Gastrointest Endosc 2022 Apr 28;95(4):800-801. Epub 2021 Dec 28.

Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

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http://dx.doi.org/10.1016/j.gie.2021.12.016DOI Listing
April 2022

Development of hepatocellular carcinoma from various phases of chronic hepatitis B virus infection.

PLoS One 2021 28;16(12):e0261878. Epub 2021 Dec 28.

Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Background & Aims: There is insufficient data on the clinical course of chronic hepatitis B (CHB) patients in the immune-tolerant (IT) and immune-clearance, inactive (IC) phases over a long follow-up period.

Design: We enrolled 466 CHB patients from our historical cohort, including 56 IT+MA  (mildly active), 134 IC, 230 with chronic active hepatitis (CH) and 46 with liver cirrhosis (LC), who were categorized to each phase by at least one year of follow-up period from the first visit to our hospital. We investigated long-term risks, and their factors, of developing hepatocellular carcinoma (HCC), and the transition between the clinical phases, especially in the IT+MA and IC groups.

Results: Of the 56 patients in the IT+MA group, 27 remained the IT+MA phase, but 29 transitioned to the CH phase and started nucleot(s)ide analogue (NA) treatment during the follow-up period. Meanwhile, of the 134 patients in the IC group, only 5 started NA treatment after progressing to the CH phase. The development of HCC from the IT+MA, IC, CH, and LC groups was observed in 2, 2, 9, and 20 cases, respectively. The cumulative incidence rates of developing HCC in the IT+MA, IC, CH, and LC groups were 9.9, 1.8, 3.0, and 53.1% at 10 years. In the CH and LC group, patients who developed HCC were older, had higher levels of FIB-4 index, M2BPGi, HBcrAg and AFP, and had lower levels of albumin and platelet counts. In CH patients, FIB-4 index levels were elevated at the diagnosis of HCC compared to baseline, whereas these decreased during the follow-up period in non-HCC patients.

Conclusions: HCC occurred at a certain rate among patients in the IT+MA and IC groups. Careful follow-up is required for CH patients with higher levels of FIB-4 index and/or M2BPGi because of the high incidence of HCC development. (299 words).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261878PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714106PMC
January 2022

Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study.

BMC Gastroenterol 2021 Dec 20;21(1):489. Epub 2021 Dec 20.

Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, 105-8470, Japan.

Background: Tenofovir disoproxil fumarate (TDF) is widely used and recommended as first-line treatment for patients infected with the hepatitis B virus (HBV). However, current data are limited regarding the efficacy and safety of switching to TDF for the treatment of chronic hepatitis B in hepatitis B e-antigen (HBeAg)-positive patients who are virologically suppressed with another nucleos(t)ide analogue. The primary objective of this study was to evaluate the hepatitis B surface antigen (HBsAg) reduction potential of switching from entecavir (ETV) to TDF at week 48 in HBeAg-positive chronic hepatitis B patients with undetectable serum HBV-DNA.

Methods: In this multicenter, single-arm, open-label, phase 4 clinical study, 75 participants currently treated with ETV 0.5 mg once daily were switched to TDF 300 mg once daily for 96 weeks.

Results: At week 48, 3/74 participants (4%) achieved 0.25 log reduction of HBsAg levels from baseline (the primary endpoint). Mean HBsAg reduction was -0.14 log IU/mL and 12% (9/74) achieved 0.25 log reduction by 96 weeks. No participants achieved HBsAg seroclearance. HBsAg reduction at weeks 48 and 96 was numerically greater in participants with higher alanine aminotransferase levels (≥ 60 U/L). Seventeen participants (25%) achieved HBeAg seroclearance up to week 96. No participants experienced viral breakthrough. All drug-related adverse events (18 participants [24%]) were mild in intensity, including an increase in urine beta-2-microglobulin (15 participants [20%]).

Conclusions: In conclusion, HBsAg reduction was limited after switching from ETV to TDF in this study population. Further investigation is warranted to better understand the clinical impact of switching from ETV to TDF. ClinicalTrials.gov: NCT03258710 registered August 21, 2017. https://clinicaltrials.gov/ct2/show/NCT03258710?term=NCT03258710&draw=2&rank=1.
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http://dx.doi.org/10.1186/s12876-021-02008-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686386PMC
December 2021
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