Impact of Frailty and Sarcopenia on Short- and Long-Term Outcomes in Elderly Patients Undergoing Radical Gastrectomy for Gastric Cancer.

BACKGROUND: The impact of frailty and sarcopenia in patients with gastric cancer is unclear. This study aimed to comprehensively examine the impact of frailty and sarcopenia on the short- and long-term outcomes in elderly patients undergoing radical gastrectomy for gastric cancer. METHODS: We retrospectively assessed 246 patients aged ≥ 65 years who underwent radical gastrectomy. Frailty and sarcopenia were assessed using the modified frailty index (mFI) and psoas muscle mass index (PMI), respectively. RESULTS: There were 30 (12.2%) and 60 (24.4%) patients with High-mFI and Low-PMI, respectively. As the age increased, both sexes showed significant correlations with PMI and mFI (r = - 0.238, 0.322, P = 0.003 and 0.002, respectively). High-mFI and Low-PMI did not affect the short-term outcomes. However, High-mFI was an independent risk factor for non-home discharge (P = 0.004) and was a significant predictor of 3- and 5-year overall survival (OS) (HR = 2.76 and 2.26; P = 0.002 and 0.005, respectively) and 1-, 3- and 5-year non-cancer-specific survival (non-CSS) (HR = 4.88, 8.05, and 4.01; P = 0.017, < 0.001, < 0.001, respectively). Low-PMI was a significant predictor of only 5-year OS (HR = 2.03, P = 0.003) and non-CSS (HR = 2.10, P = 0.020). CONCLUSIONS: Frailty is significant predictor of non-home discharge and 1-, 3-, 5-year OS and 3- and 5-year non-CSS. Sarcopenia is a significant predictor of 5-year OS and non-CSS. Preoperative assessment of both frailty and sarcopenia can help surgeons to select adequate treatment strategies for the elderly population.

The Combination of Preoperative Skeletal Muscle Quantity and Quality is an Important Indicator of Survival in Elderly Patients Undergoing Curative Gastrectomy for Gastric Cancer.

BACKGROUND: The diagnosis of sarcopenia emphasizes both, the quantity and quality of skeletal muscle. However, the impact of the combination of muscle quantity and quality on long-term survival remains unclear. This study aimed to assess the impact of the combination of skeletal muscle quantity and quality on long-term outcomes in patients with gastric cancer who underwent curative resection. METHODS: We retrospectively assessed 242 patients aged ≥ 65 ears who underwent curative gastrectomy between 2006 and 2015. The psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) were measured on preoperative computed tomography as skeletal muscle quantity and quality, respectively. The sarcopenia stage was classified by the combination of preoperative skeletal muscle quantity and quality (non-sarcopenia, sarcopenia, and severe sarcopenia). Prognostic factors for the 5-year overall survival (OS), non-cancer-specific survival (non-CSS), and cancer-specific survival (CSS) were evaluated by multivariable Cox regression. RESULTS: The median follow-up period was 63.2 months. The non-sarcopenia, sarcopenia, and severe sarcopenia groups comprised 88, 121, and 33 patients (36.4%, 50.0%, and 13.6%), respectively. The severe sarcopenia group was older, and had a greater depth of invasion, than the non-sarcopenia group. Multivariable analysis revealed severe sarcopenia as an independent predictive indicator of OS (hazard ratio [HR] 4.01; 95% confidence interval [CI] 1.75 to 9.22) and non-CSS (HR 3.27; 95% CI 1.61 to 6.67), but not CSS. CONCLUSIONS: The combination of preoperative skeletal muscle quantity and quality was useful for predicting survival, especially death from other diseases, in elderly patients who underwent gastrectomy for gastric cancer.

Risk and incidence of perioperative deep vein thrombosis in patients undergoing gastric cancer surgery.

BACKGROUND AND PURPOSE: Venous thromboembolism (VTE) is a potentially fatal perioperative complication. Understanding the risk factors for deep vein thrombosis (DVT) and initiating appropriate prophylaxis is pivotal for reducing the risk of VTE. The purpose of this study was to clarify the perioperative risk factors for DVT in patients undergoing surgery for gastric cancer. METHODS: We reviewed the findings of lower limb ultrasonography performed in 160 patients who underwent gastrectomy for gastric cancer. RESULTS: The preoperative and postoperative incidence of DVT was 4.4% (7/160) and 7.2% (11/153), respectively. All postoperative DVTs were of the distal type, whereas preoperative DVTs were of the proximal (n = 3) and distal type (n = 4). None of the patients suffered symptomatic VTE. Multivariate analysis indicated that depth of invasion and D-dimer concentration were independent risk factors for preoperative DVT and that gender and performance status were risk factors for postoperative DVT. Receiver operating characteristic analysis revealed that the optimal cut-off D-dimer concentration was 1.4 µg/mL. CONCLUSIONS: The incidence of perioperative DVT was low for patients undergoing gastric cancer surgery. Therefore, the risk-stratified application of perioperative pharmacologic thromboprophylaxis is thought to be more appropriate than routine pharmacologic thromboprophylaxis for Japanese patients undergoing surgery for gastric cancer.

Prognostic relevance of miR-137 in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Cancer stem cells (CSCs) play a pivotal role in progression, metastasis and recurrence of cancer. Therefore, it is clinically useful to identify the relevant CSC marker that is associated with prognosis of hepatocellular carcinoma (HCC) and clarify its genetic and biological characteristics. METHODS: Expression of four CSC markers, CD13, EpCAM, CD44 and CD44v9, was examined in 99 HCC patients. Biological and cDNA/miRNA microarray data were compared among CD44-positive/-negative HCC cells and normal hepatic cells. The significance of the representative miRNAs was examined with regard to prognosis of additional 110 HCC patients. RESULTS: CD44-positive HuH7 cells proliferated faster and showed a greater sphere forming ability than CD44-negative HuH7 cells. CD44-positive HuH7 cells exhibited higher expression of specific genes involved in resistance to reactive oxygen species, anticancer drugs and tumour invasion than CD44-negative HCC cells. Higher expression of six miRNAs was observed in CD44-positive HuH7 cells, CD44-negative HuH7 cells, and human normal hepatic cells in that order. Of the six miRNAs, miR-137 was closely associated with overall and cancer-specific survivals, as well as with invasion of hepatic vein, hepatic artery, portal vein and bile duct, and alpha-foetoprotein in additional 110 HCC patients. CONCLUSIONS: miR-137 may serve as a prognostic marker in patients with HCC and may be a potential target for the elimination of liver CSCs.

Estimation of the symptoms for GERD by GerdQ in the patients with rheumatic diseases.

OBJECTIVE: Gastroesophageal reflux disease (GERD) is one of the most common comorbidity in many diseases, but the frequency in rheumatic disease has not been well understood. METHODS: We investigated the prevalence of GERD by GerdQ in 530 rheumatic patients [systematic lupus erythematosus (SLE; n = 120), rheumatoid arthritis (RA; n = 117), polymyalgia rheumatica (PMR; n = 40), dermatomyositis and polymyositis (PM/DM; n = 38), systemic scleroderma (SSc; n = 37), mixed connective tissue disease (MCTD; n = 18), Behçet disease (BD; n = 17), adult onset still disease (AOSD; n = 14), and other rheumatic diseases (n = 129)]. RESULTS: The mean GerdQ scores of patients was 6.2 ± 1.8, respectively, and no significant differences were observed between all patients. However, the GERD prevalence in SSc and BD was increased compared to that in SLE, RA, PMR, PM/DM, MCTD, and AOSD. In no medication of proton pump inhibitors (PPIs), a significant increase in the risk of GERD symptoms was 2.5 times compared with that in the medication of PPIs in all patients by multivariable regression analysis. On the other hand, there were no increased risks of GERD symptoms with corticosteroids. CONCLUSION: In rheumatic diseases, GerdQ would be the useful tool of diagnosis GERD, regardless whether the patients complain or not about gastrointestinal (GI) symptoms.

Signaling Rho-kinase mediates inflammation and apoptosis in T cells and renal tubules in cisplatin nephrotoxicity.

Nephrotoxicity is a frequent complication of cisplatin-induced chemotherapy, in which T cells are known to promote acute kidney injury (AKI). Apoptosis and necrosis of tubules and inflammatory events also contribute to the nephrotoxicity. A delineation of the mechanisms that underlie the inappropriate renal and tubular inflammation can thus provide important insights into potential therapies for cisplatin-induced AKI. Rho-kinases are known to act as molecular switches controlling several critical cellular functions, including cell migration, cytokine production, and apoptosis. Here, we show that the Rho-kinase inhibitor fasudil attenuated cisplatin nephrotoxicity, resulting in less histological damage, improved renal function, and the infiltration of fewer leukocytes into the kidney. Renal nuclear factor-κB activation and apoptosis were reduced, and the expressions of proinflammatory renal cytokine and chemokine mRNA were decreased. Urinary and renal kidney injury molecule-1 (Kim-1) expression was also reduced, a finding that is consistent with diminished kidney injury. In the current study, we also showed that fasudil could be protective of the impaired tubules. In vitro, fasudil reduced the apoptosis (annexin-V+PI cells) and cytokine production (tumor necrosis factor+ cells) in T cells and the apoptosis (annexin-V+PI cells) and tubular damage (Kim-1+ cells) in proximal tubular cells by flow cytometric analysis. As Rho-kinase plays an important role in promoting cisplatin nephrotoxicity, inhibiting Rho-kinase may be a therapeutic strategy for preventing cisplatin-induced AKI.

The pathological role of IL-18Rα in renal ischemia/reperfusion injury.

Interleukin (IL)-18 is a proinflammatory cytokine produced by leukocytes and parenchymal cells (eg, tubular epithelial cells (TECs), mesangial cells, and podocytes). IL-18 receptor (IL-18R) is expressed on these cells in the kidney during ischemia/reperfusion injury (IRI), but its role in this injury is unknown. Fas/Fas ligand (FasL) is also involved in the pathogenesis of renal IRI via tubular apoptosis. In addition, IL-18 enhances the expression of FasL on TECs, but the mechanism underlying this enhancement is not known. Here we used IL-18Rα-deficient mice to explore the pathological role of IL-18Rα in renal IRI. We found that compared to wild-type (WT) mice with renal IRI as an acute kidney injury (AKI), the IL-18Rα-deficient mice demonstrated decreased renal function (as represented by blood urea nitrogen), tubular damage, an increased accumulation of leukocytes (CD4+ T cells, neutrophils, and macrophages), upregulated early AKI biomarkers (ie, urinary kidney injury molecule-1 levels), and increased mRNA expressions of proinflammatory cytokines (IL-1ß, IL-12p40, and IL-18) and chemokines (intercellular adhesion molecule-1 and CCL2/monocyte chemoattractant protein-1). The mRNA expression of FasL in the kidney was increased in the IL-18Rα-deficient mice compared to the WT mice. The adoptive transfer of splenocytes by WT mice led to decreased renal IRI compared to the IL-18Rα-deficient mice. In vitro, the mRNA expression of FasL on TECs was promoted in the presence of recombinant IL-18. These data reveal that IL-18Rα has an anti-inflammatory effect in IRI-induced AKI. Above all, IL-18 enhanced the inflammatory mechanisms and the apoptosis of TECs through the Fas/FasL pathway by blocking IL-18Rα.

Biological and clinical implications of retinoic acid-responsive genes in human hepatocellular carcinoma cells.

BACKGROUND & AIMS: Accumulating data from epidemiological and experimental studies have suggested that retinoids, which are vitamin A derivatives, exert antitumor activity in various organs. We performed a gene screening based on in silico analysis of retinoic acid response elements (RAREs) to identify the genes facilitating the antitumor activity of retinoic acid (RA) and investigated their clinical significance in hepatocellular carcinoma (HCC). METHODS: In silico analysis of RAREs was performed in the 5-kb upstream region of EST clusters. Chromatin immunoprecipitation analysis of the retinoic acid receptors and gene expression analysis were performed in HuH7, HepG2, and MCF7 cells treated with all-trans RA (ATRA). mRNA expression of RA-responsive genes was investigated using tumor and non-tumor tissues of clinical HCC samples from 171 patients. The association between gene expression and survival of patients was examined by Cox regression analysis. RESULTS: We identified 201 candidate genes with promoter regions containing consensus RARE and finally selected 26 RA-responsive genes. Of these, downregulation of OTU domain-containing 7B (OTUD7B) gene, which was upregulated by ATRA, in tumor tissue was associated with a low cancer-specific survival of HCC patients. Functional analyses revealed that OTUD7B negatively regulates nuclear factor κB (NF-κB) signaling and decreases the survival of HCC cells. CONCLUSIONS: We identified RA-responsive genes which are regulated by retinoid signal and found that low-OTUD7B mRNA expression is associated with a poor prognosis for HCC patients. OTUD7B-mediated inhibition of NF-κB signaling may be an effective target for antitumor therapy for HCC.

[Present situation and future prospects of the certification system for medical technologists--from the viewpoint of the Japanese Society of Clinical Cytology].

The circumstances surrounding the certification examination for cytotechnologists in Japan are closely related with the history of the Japanese Society of Clinical Cytology. The examination for cytotechnologists is open only to medical technologists. The examination has two parts: primary and secondary. Qualification for candidacy for the secondary examination requires candidates to have passed the primary examination. The rate of successful applicants in the past 10 years was approximately 25-40%. Certified cytotechnologists are required to renew their qualifications every 4 years for their study and job history. I will present the purpose of the qualification update system, future themes, the reporting system for cytodiagnosis, and the possibility that the certification examination for cytotechnologists will become a national examination.

Case Report: A Rare Case of Elderly-Onset Adult-Onset Still's Disease in a Patient With Systemic Lupus Erythematosus.

The rare systemic inflammatory disorder 'adult-onset Still's disease (AOSD)' is characterized by recurrent fever, evanescent rash, arthralgia, and leukocytosis with neutrophilia. The Yamaguchi criteria are widely used to diagnose AOSD; these criteria can be used for diagnosis after a wide range of infectious, rheumatic, and neoplastic diseases have been excluded. AOSD generally does not overlap with other rheumatic diseases. We present the rare case of an 80-year-old Japanese woman who presented with arthralgia, fever, and skin rash during treatment for systemic lupus erythematosus (SLE), which was finally diagnosed as an overlap of AOSD. Blood tests revealed leukocytosis with neutrophilia, high C-reactive protein (CRP), and liver dysfunction. Her anti-ds-DNA antibody titer and serum complement titer were at the same level as before and remained stable. We suspected AOSD based on the high serum ferritin level but hesitated to diagnose AOSD because of the patient's SLE history. We measured serum interleukin (IL)-18; it was extremely high at 161,221 pg/mL, which was strongly suggestive of AOSD. We thus diagnosed AOSD complicated during the course of treatment for SLE. The patient's arthralgia and high CRP level persisted after we increased her oral prednisolone dose and added oral methotrexate, but her symptoms eventually improved with the addition of intravenous tocilizumab. We note that the presence of autoantibodies or other rheumatic diseases cannot be absolutely ruled out in the diagnosis of AOSD. Although high serum IL-18 levels are not specific for AOSD, the measurement of serum IL-18 may aid in the diagnosis of AOSD in similar rare cases.

Post-colostomy internal hernia of the stomach treated with laparoscopic gastropexy: a case report.

BACKGROUND: Internal hernias are formed by the protrusion of internal organs through an aperture formed congenitally or postoperatively. Internal hernias are most commonly associated with the small intestine. Only two cases of a post-sigmoid colostomy internal hernia of the stomach have been reported. This hernia arises from the space between the lifted sigmoid colon and the left abdominal wall. In the two aforementioned cases, treatment comprised suturing of the sigmoid colon to the lateral abdominal wall and changing of the intraperitoneal route to an extraperitoneal one. Herein, we present a very rare case who underwent laparoscopic gastropexy for a post-sigmoid colostomy internal hernia of the stomach. CASE PRESENTATION: Our patient, a 67-year-old woman, was undergoing chemoradiation for rectal cancer and planned to undergo abdominoperineal resection. However, tumor perforation resulted in a high fever and a right gluteal abscess; therefore, a sigmoid colostomy was performed through the intraperitoneal route in the left lower abdomen. One month after the surgery, the patient presented to our emergency room with vomiting, abdominal pain, and abdominal distension. Computed tomography revealed a markedly distended stomach caused by the obstruction of the pylorus secondary to the colostomy; laparoscopic gastropexy was performed subsequently and the postoperative course was uneventful. CONCLUSIONS: This is the first report on the laparoscopic gastropexy treatment of a post-sigmoid colostomy internal hernia of the stomach; our findings may help physicians manage such hernias.

What is necessary to shorten the operative time in initial introduction of robotic gastrectomy for gastric cancer?

INTRODUCTION: Robotic gastrectomy (RG) is a good alternative to laparoscopic gastrectomy, as it improves treatment outcomes and reduces the burden of technical difficulties; however, prolonged operative time may be a disadvantage. This study aimed to identify measures to shorten the operative time during the initial introduction of RG at an institution. METHODS: We assessed 33 patients with gastric cancer who underwent radical distal gastrectomy with Billroth-I reconstruction and divided them into three groups: laparoscopic distal gastrectomy (LDG), robotic distal gastrectomy in the early phase (RDG-E), and in the late phase (RDG-L). Operative time, six technical steps, and junk time, including the roll-in/roll-out, docking/undocking, and instrument exchange times, were compared among the groups. RESULTS: The median (range) overall operative times of LDG, RDG-E, and RDG-L were 248 (179-323), 304 (249-383), and 263 (220-367) min, respectively, but no significant differences were observed. For each surgical step of RG, RDG-L in suprapancreatic lymph node dissection was significantly shorter than that in RDG-E. The median (range) junk times of LDG, RDG-E, and RDG-L were 16.7 (12.7-26.4), 48.3 (38.6-67.7), and 42.0 (35.4-49.2) min, respectively. Junk time was significantly longer in RDG-L than in LDG (p = 0.003), but not significant between RDG-E and RDG-L. The learning curve effect of overall, console, and junk times were achieved in four cases of RDG. CONCLUSION: Junk time is a major factor in prolonging RDG operative time. However, to reduce the time after initial introduction, measures to promote robot-specific standardization and more effective use of robotic instruments are essential.

Interleukin-18 in Inflammatory Kidney Disease.

Interleukin (IL)-18, a member of the IL-1 superfamily, is a pro-inflammatory cytokine that is structurally similar to IL-1ß. IL-18 promotes the production of interferon gamma (IFN-γ) and strongly induces a Th1 response. IL-18 drives the same myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway as IL-1ß. In physiological conditions, IL-18 is regulated by the endogenous inhibitor IL-18 binding protein (IL-18BP), and the activity of IL-18 is balanced. It is reported that in several inflammatory diseases, the IL-18 activity is unbalanced, and IL-18 neutralization by IL-18BP is insufficient. IL-18 acts synergistically with IL-12 to induce the production of IFN-γ as a Th1 cytokine, and IL-18 acts alone to induce the production of Th2 cytokines such as IL-4 and IL-13. In addition, IL-18 alone enhances natural killer (NK) cell activity and FAS ligand expression. The biological and pathological roles of IL-18 have been studied in many diseases. Here we review the knowledge regarding IL-18 signaling and the role of IL-18 in inflammatory kidney diseases. Findings on renal injury in coronavirus disease 2019 (COVID-19) and its association with IL-18 will also be presented.

Propylthiouracil-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis after COVID-19 Vaccination.

We report the case of a patient who developed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) after receiving the coronavirus disease 2019 (COVID-19) vaccine BNT162b (Pfizer-BioNTech). A 37-year-old Japanese woman had been taking propylthiouracil for Graves' disease. She had erythema on her forearm on the 12th day after receiving the first dose of the vaccine, fever on the 13th day, and redness and swelling of her left auricle on the 25th day. Her serum myeloperoxidase-ANCA and proteinase 3-ANCA levels, which were negative before the Graves' disease treatment, were elevated. She had unilateral auricular symptoms but no other typical relapsing polychondritis findings. She was diagnosed with propylthiouracil-induced AAV. She was treated with oral glucocorticoids, and her symptoms improved. Propylthiouracil is considered to be the main cause of the onset of AAV in this case, but it cannot be ruled out that BNT162b may have had some effect on the onset of the disease. Although the development of propylthiouracil-induced AAV in this case may have been incidental and unrelated to the vaccination, this report provides important data for evaluating the safety of the vaccine.

Four-Year Teriparatide Followed by Denosumab vs. Continuous Denosumab in Glucocorticoid-Induced Osteoporosis Patients With Prior Bisphosphonate Treatment.

Objectives: In our previous 24-month study, we observed that teriparatide had some advantages over denosumab for bone mineral density (BMD) in glucocorticoid-induced osteoporosis (GIO) patients with prior bisphosphonate treatment. We conducted this extension study to investigate whether the advantage of teriparatide obtained in the first 2 years would be maintained after the switch to denosumab. Materials and Methods: We switched patients who had completed 24-month daily teriparatide treatment to denosumab (switch group, n=18) and compared their BMD every 6 months up to 48 months with the group who continued to receive denosumab (denosumab group, n=16). Results: At 48 months, the lumbar spine BMD was significantly increased from baseline in both groups (denosumab: 10.4 ± 8.7%, p<0.001; switch: 14.2 ± 6.8%, p<0.001). However, a significant increase in femoral neck BMD from baseline occurred only in the switch group (11.2 ± 14.6%, p<0.05); denosumab (4.1 ± 10.8%). The total hip BMD increased significantly from baseline in both groups (denosumab: 4.60 ± 7.4%, p<0.05; switch: 7.2 ± 6.9%, p<0.01). Femoral neck BMD was significantly increased in the switch versus the denosumab group (p<0.05). Conclusion: In GIO patients with prior bisphosphonate treatment, the advantage of teriparatide may be maintained after the treatment period. A continuous increase in BMD can be expected with teriparatide followed by denosumab.

Usefulness of Interleukin-18 as a Diagnostic Biomarker to Differentiate Adult-Onset Still's Disease With/Without Macrophage Activation Syndrome From Other Secondary Hemophagocytic Lymphohistiocytosis in Adults.

Background: Interleukin (IL)-18 is markedly elevated in systemic inflammatory diseases that cause the 'cytokine storm' such as adult-onset Still's disease (AOSD) and hemophagocytic lymphohistiocytosis (HLH). The differences in IL-18 between AOSD and HLH, especially in adults, is uncertain. Macrophage activation syndrome (MAS), a form of secondary HLH, is often difficult to differentiate cases of AOSD that include MAS from other secondary HLH. In this case-control study, we investigated whether serum IL-18 levels could be a useful biomarker for the differential diagnosis of AOSD with or without MAS (AOSD group) and other secondary HLH in adults (adult HLH group). Patients and Methods: We enrolled 46 patients diagnosed with AOSD including 9 patients with MAS and 31 patients in the adult HLH group, which excluded AOSD-associated MAS. The clinical features and laboratory data were compared between the AOSD and adult HLH groups. In addition, we subdivided the AOSD group (with or without MAS) and the adult HLH group (whether lymphoma-associated or not) and compared the four groups. A logistic regression analysis was used to identify factors with high efficacy in differentiating the two groups, followed by a receiver operating characteristic (ROC) curve analysis to evaluate the differential diagnostic ability of IL-18. We analyzed the correlation between IL-18 and various laboratory parameters in the AOSD group. Results: Serum IL-18 levels of patients in the AOSD groups were significantly higher than those of the adult HLH groups, and were closely correlated with ferritin, soluble interleukin-2 receptor (sIL-2R), and other laboratory data. Univariate and multivariate logistic regression analyses revealed that IL-18, sIL-2R, and 'arthralgia or arthritis' are independent factors useful in the differential diagnosis of AOSD from adult HLH. In the differential diagnosis of both groups, the area under the curve obtained from the ROC curve of IL-18 with a cutoff value of 18,550 pg/mL was 0.91 (95% confidence interval 0.83-1.00; sensitivity 90.3%, specificity 93.5%), and the differential diagnosis ability of IL-18 was superior to that of other laboratory data. Conclusions: IL-18 could be a useful biomarker for the differential diagnosis of AOSD and adult HLH.

FDG-PET/CT and Auricular Cartilage Biopsy Are Useful for Diagnosing with Relapsing Polychondritis in Patients without Auricular Symptoms.

Relapsing polychondritis (RP) is a rare autoimmune inflammatory disease characterized by recurrent inflammation and destruction of cartilage. Although auricular chondritis is a characteristic finding in RP, it can be difficult to diagnose in the absence of auricular symptoms. A 64-year-old Japanese male was referred to our hospital with fever and respiratory distress. Contrast-enhanced computed tomography (CT) revealed bronchial wall thickening and we suspected RP; however, he had no auricular symptoms and did not meet the diagnostic McAdam criteria for RP, so we used 18F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) to search for other cartilage lesions. This analysis revealed FDG accumulation not only in the bronchial walls, but also in the left auricle. Instead of a bronchial biopsy using a bronchoscope, we performed a biopsy of the left auricular cartilage, which is considered a relatively less invasive site. Even though the auricle was asymptomatic, the pathology results revealed chondritis. He was diagnosed with RP, and his symptoms rapidly improved with corticosteroid therapy. A biopsy of asymptomatic auricular cartilage may be useful in the diagnosis of RP. FDG-PET/CT is a powerful tool for the early diagnosis of RP, identifying inflammatory areas even in the absence of symptoms, and guiding the selection of appropriate biopsy sites.

A novel biomarker TERTmRNA is applicable for early detection of hepatoma.

BACKGROUNDS: We previously reported a highly sensitive method for serum human telomerase reverse transcriptase (hTERT) mRNA for hepatocellular carcinoma (HCC). alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) are good markers for HCC. In this study, we verified the significance of hTERTmRNA in a large scale multi-centered trial, collating quantified values with clinical course. METHODS: In 638 subjects including 303 patients with HCC, 89 with chronic hepatitis (CH), 45 with liver cirrhosis (LC) and 201 healthy individuals, we quantified serum hTERTmRNA using the real-time RT-PCR. We examined its sensitivity and specificity in HCC diagnosis, clinical significance, ROC curve analysis in comparison with other tumor markers, and its correlations with the clinical parameters using Pearson relative test and multivariate analyses. Furthermore, we performed a prospective and comparative study to observe the change of biomarkers, including hTERTmRNA in HCC patients receiving anti-cancer therapies. RESULTS: hTERTmRNA was demonstrated to be independently correlated with clinical parameters; tumor size and tumor differentiation (P < 0.001, each). The sensitivity/specificity of hTERTmRNA in HCC diagnosis showed 90.2%/85.4% for hTERT. hTERTmRNA proved to be superior to AFP, AFP-L3, and DCP in the diagnosis and underwent an indisputable change in response to therapy. The detection rate of small HCC by hTERTmRNA was superior to the other markers. CONCLUSIONS: hTERTmRNA is superior to conventional tumor markers in the diagnosis and recurrence of HCC at an early stage.

[Real-time tissue elastography in chronic liver disease].

BACKGROUND/AIM: In patients with chronic liver diseases, the histological classification of liver fibrosis is essential for predicting prognosis and selecting appropriate antiviral therapy. This study aimed to determine the usefulness of a new noninvasive method for the assessment of liver fibrosis by using real-time tissue elastography, which can be performed with conventional ultrasound probes. METHODS: Thirty-nine patients who had liver fibrosis and had undergone liver resection or liver biopsy were included in this study. The surgical specimens obtained were examined to determine the histological stage of liver fibrosis. The strain ratio of subcutaneous fat tissue to liver tissue was calculated. We examined the correlation between the strain ratio and the histological liver fibrosis stage, and compared the utility with various surrogate liver fibrosis markers. RESULTS: The strain ratio significantly differed with the stage of liver fibrosis, and they had significant correlation (Kruskal-Wallis test: p<0.0001; Spearman's rank correlation, p<0.0001, r=0.797). We identified 5.8 and 3.7 as the cutoff values of strain ratio for the diagnosis of cirrhosis and significant fibrosis. The sensitivity at these values was 92.9% and 81.9% respectively; the specificity, 96.0% and 88.9%; and the areas under the receiver operating characteristic curve (AUROCs), 0.977 and 0.913, respectively. The AUROC was superior to the other surrogate liver fibrosis markers tested. CONCLUSIONS: Real-time tissue elastography is a useful method for the diagnosis of significant fibrosis and cirrhosis in patients with chronic liver diseases.

Olfactory function deteriorates in patients with Parkinson's disease complicated with REM sleep behavior disorder.

INTRODUCTION: It is not concluded whether the association between olfactory dysfunction and REM sleep behavior disorder (RBD) were worsen cognitive function in patients with Parkinson's disease (PD). We sought to evaluate the impact of these symptoms in PD. METHODS: We examined 62 patients with PD using an olfactory test (Odor Stick Identification Test for Japanese: OSIT-J) and polysomnography (PSG). We divided the patients into 3 groups: PD with clinical RBD (n = 32), PD with subclinical RBD (n = 11), and PD with normal REM sleep (n = 19). We compared their clinical backgrounds, results of OSIT-J, autonomic functions, and cognitive functions such as Montreal cognitive assessment Japanese version (MoCA-J). Some factors associated with RBD were analyzed by multiple regression. RESULTS: There were significant differences in the results of OSIT-J, and autonomic and cognitive functions between the 3 groups. There were significant differences in the total OSIT-J score between the 3 groups (PD with clinical RBD: 3.3 ± 2.2, PD with subclinical RBD: 4.0 ± 2.6, PD with normal REM sleep: 6.7 ± 3.0, p < 0.001). Patients in the group with PD with clinical RBD had a significantly lower score than those with normal REM sleep (p < 0.001). Logistic regression analysis showed that OSIT-J score was significantly associated with RBD. The PD group with clinical RBD had more patients with mild cognitive impairment than the group with normal REM sleep. Multiple regression analysis revealed that olfactory dysfunction was correlated with MoCA-J. CONCLUSIONS: Olfactory dysfunction is associated with RBD. Especially, it is important to screen olfactory function in RBD complicated patients with PD in view of cognitive impairment.