The efficacy of surgical treatment on locomotive syndrome and physical function in patients with lumbar spinal canal stenosis

BackgroundLocomotive syndrome is a condition of reduced mobility due to problems with locomotive organs. Although lumbar spinal canal stenosis is one of the major diseases constituting locomotive syndrome, only few studies have focused on the association between the two pathologies. We aimed to investigate the effect of surgery on lumbar spinal canal stenosis with respect to locomotive syndrome using various physical function tests, including locomotive syndrome risk tests, before and after surgery.MethodsClinical data of 101 consecutive patients (male = 46; female = 55; mean age, 69.3 years) who underwent surgery for lumbar spinal canal stenosis at our institute were prospectively collected. Results of physical function tests, including stand-up test, two-step test, and 25-Question Geriatric Locomotive Function Scale, and the sagittal vertical axis were evaluated before and 1 year after surgery. The association between several parameters and improvement of risk level in locomotive syndrome was evaluated.ResultsIn the total assessment, 93.1% of cases were in stage 2 and 6.9% in stage 1 preoperatively, while 72.4% were in stage 2, 22.4% in stage 1, and 5.2% in stage 0 at 1 year postoperatively. Postoperative improvement in the total assessment was observed in 28.7% of cases. Several physical function tests and sagittal vertical axis showed significant improvement after surgery. On multiple logistic regression analysis, age >75 years (odds ratio = 10.9, confidence interval = 1.09–109) and postoperative sagittal vertical axis >40 mm (odds ratio = 17.8, confidence interval = 1.78–177) were significant risk factors associated with non-improvement in risk level of locomotive syndrome.ConclusionsSurgical treatment for lumbar spinal canal stenosis improved physical function, including locomotive syndrome. Risk factors associated with non-improvement of locomotive syndrome were later-stage elderly and postoperative sagittal balance impairment.     

Comparing bone resorption after anatomical shoulder arthroplasty between various surgical procedures using a single-stem model

BackgroundIn shoulder arthroplasty, bone resorption around the stem can lead to stem loosening and makes surgery difficult at the time of revision. Proximal bone resorption after reverse shoulder arthroplasty can cause instability because of a decrease of deltoid wrapping effect. As factors of the stem itself, such as stem coating, shape, length, and use of bone cement, may also affect bone resorption, a single-stem model should be used to compare bone resorptions between different pathologies and surgical procedures. However, to date, a few reports have compared these differences in detail using a single-stem model. Therefore, we investigated the prevalence and location of humeral bone resorption in a single-stem model.MethodsThe study included 100 shoulders that underwent anatomical total shoulder arthroplasty (TSA) or humeral head replacement (HHR) with a single uncemented humeral stem from 2008 to 2018. The patients were 31 men and 69 women. The mean age at surgery was 72.9 years (range, 41-86 years). The patients were divided into three groups: especially, 25, 61, and 14 shoulders received TSA for primary osteoarthritis without rotator cuff tears (TSA group), HHR using an anatomical head with rotator cuff repair for cuff tear arthropathy (CTA) (HHR group), and HHR using a CTA head without rotator cuff repair (CTA group), respectively. Patients were monitored for a mean of 56 months (range, 12-98 months). The location of bone resorption was divided into seven zones as follows: zone 1, greater tuberosity; zone 2, lateral diaphysis; zone 3, lateral diaphysis beyond the deltoid tuberosity; zone 4, tip of the stem; zone 5, medial diaphysis beyond the deltoid tuberosity; zone 6, medial diaphysis; and zone 7, calcar region. The degree of bone resorption was classified from grade 0 to 4.ResultsBone resorption of grade 3 or higher was significantly more frequent at the greater tuberosity in the HHR and CTA groups (P < .001 and P < .001, respectively) than that in the TSA group. Grade 4 bone resorption was significantly more frequent in the CTA than that in the TSA and HHR groups in zone 1 (P = .016 and P = .041, respectively).ConclusionThe state of attachment of the rotator cuff to the greater tuberosity might affect bone resorption at the greater tuberosity, such as the greater tuberosity after shoulder arthroplasty. In cases of shoulder arthroplasty for arthropathy with rotator cuff tear, performing rotator cuff repair might prevent bone resorption.Level of evidenceLevel IV; Prognosis Study     

Japanese version of The Cancer Genome Atlas,JCGA, established using fresh frozen tumors obtained from 5143 cancer patients

This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single‐center study called “High‐tech Omics‐based Patient Evaluation” or “Project HOPE” conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole‐exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed “Shizuoka Multi‐omics Analysis Protocol” developed in‐house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non–cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients.     

Clinicopathological analysis of immunohistochemical expression of CD47 and SIRPα in adult T-cell leukemia/lymphoma

The interaction of CD47 and signal-regulatory protein alpha (SIRPα) induces “don't eat me signal”, leading suppression of phagocytosis. This signal can affect the clinical course of malignant disease. Although CD47 and SIRPα expression are associated with clinicopathological features in several neoplasms, the investigation for adult T-cell leukemia/lymphoma (ATLL) has not been well-documented. This study aimed to declare the association between CD47 and SIRPα expression and clinicopathological features in ATLL. We performed immunostaining on 73 biopsy samples and found that CD47 is primarily expressed in tumor cells, while SIRPα is expressed in non-neoplastic stromal cells. CD47 positive cases showed significantly higher FoxP3 (P = .0232) and lower CCR4 (P = .0214). SIRPα positive cases presented significantly better overall survival than SIRPα negative cases (P = .0132). SIRPα positive cases showed significantly HLA class I (P = .0062), HLA class II (P = .0133), microenvironment PD-L1 (miPD-L1) (P = .0032), and FoxP3 (P = .0229) positivity. In univariate analysis, SIRPα expression was significantly related to prognosis (Hazard ratio [HR] 0.470; 95% confidence interval [CI] 0.253-0.870; P = .0167], although multivariate analysis did not show SIPRα as an independent prognostic factor. The expression of SIRPα on stromal cells reflects activated immune surveillance mechanism in tumor microenvironment and induce good prognosis in ATLL. More detailed studies for gene expression or genomic abnormalities will disclose clinical and biological significance of the CD47 and SIRPα in ATLL.     

Cytokine-related genes play critical roles in extrafollicular growth of follicular lymphoma cells

Follicular lymphoma (FL) is a germinal center-derived B-cell lymphoma that is known to proliferate in the intrafollicular region. However, lymphoma cells can be identified in the extrafollicular regions, which are related to disease dissemination. We purified the intrafollicular and extrafollicular regions of FL cells by laser microdissection and conducted microarray analysis in order to characterize the gene expression profiles of FL cells from both regions. BCL2 and genes of germinal B-cell markers clearly separated intrafollicular and extrafollicular regions of reactive follicular hyperplasia, suggesting the adequacy of the current analysis. In FL cases, cytokine-related genes were significantly enriched in extrafollicular regions compared with those in the intrafollicular regions. In intrafollicular regions of FL, cell-cycle–related genes were enriched. We found that the FL cells in the extrafollicular region more strongly expressed IL3RA and CXCL12 than those of intrafollicular regions. The cytokines might be also derived from stroma cells in the extrafollicular regions, which may initiate activation and migration of the tumor cells to this region. Our results suggest that FL cell interaction with surrounding stroma cells plays an important role in the pathophysiology of FL and that such interactions should be a good target for therapy.     

Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012‐2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2‐3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type‐specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type‐specific RCs between CIN1 and CIN2‐3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type‐specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2‐3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2‐3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01‐4.98), followed by HPV31 (2.51, 1.54‐5.24), HPV18 (2.43, 1.59‐4.32), HPV35 (1.56, 0.43‐8.36), HPV33 (1.01, 0.49‐3.31), HPV52 (0.99, 0.76‐1.33), and HPV58 (0.97, 0.75‐1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71‐2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14‐0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9‐valent vaccine contributed to 89.7% (95% CI, 88.7‐90.7) of CIN2‐3/AIS and 93.8% (95% CI, 92.4‐95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9‐valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.     

Risk factors for pneumothorax associated with isolated congenital diaphragmatic hernia: results of a Japanese multicenter study

This study aimed to elucidate the clinical characteristics of neonates with congenital diaphragmatic hernia (CDH) associated with pneumothorax and evaluate the risk factors for the development of pneumothorax. A retrospective cohort study was conducted in the 15 institutions participating in the Japanese CDH Study Group. A total of 495 neonates with isolated CDH who were born between 2011 and 2018 were analyzed in this study. Among the 495 neonates with isolated CDH, 52 (10.5%) developed pneumothorax. Eighteen (34.6%) patients developed pneumothorax before surgery, while 34 (65.4%) developed pneumothorax after surgery. The log-rank test showed that the cumulative survival rate was significantly lower in patients with pneumothorax than in those without pneumothorax. Univariate analysis revealed significant differences between patients with pneumothorax and those without pneumothorax with regard to the best oxygenation index within 24 h after birth, mean airway pressure (MAP) higher than 16 cmH2O, diaphragmatic defect size, and need for patch closure. Multiple logistic regression analysis indicated that only the MAP was associated with an increased risk of pneumothorax. The cumulative survival rate was significantly lower in isolated CDH patients with pneumothorax than in those without pneumothorax. A higher MAP was a risk factor for pneumothorax in CDH patients.     

Cytomegalovirus-Associated Gastroduodenal Ulcers in a Patient With Functional Hypercortisolism: A Case Report

Cytomegalovirus (CMV)-associated gastroduodenal ulcers (GDU) are a rare digestive disease, which principally affect immunocompromised patients. We recently experienced CMV-associated GDU occurring in a seemingly immunocompetent patient. The rarity of such a condition was inimical to a correct clinical diagnosis.A 77-year-old woman with Alzheimer''s disease was admitted to our hospital because of vomiting and anorexia. Her general condition was extremely poor due to severe dehydration. Any invasive procedures including gastroduodenal endoscopy could not be performed. Laboratory test results showed electrolyte imbalance, hyperglycemia, and hypercortisolemia. The plasma adrenocorticotropic hormone level was rather low. On her 11th day in hospital, she suddenly fell into shock status. Despite intensive care, the patient could not be rescued. An autopsy was performed and revealed that she had suffered from CMV-associated GDU and died of candidemia that invaded through the ulcer. Her adrenal glands showed neither neoplasm nor hyperplasia, suggesting that her hypercortisolism was a purely functional disorder. We concluded that the severe opportunistic infections were developed in association with functional hypercortisolism.This case suggests that functional hypercortisolism, even though transient, can cause a patient to be immunocompromised.