Prognostic Value of the 18F-FDG PET/CT and Haematological Parameters in Head and Neck Cancer.

INTRODUCTION: Fluorine 18-fluoro-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) is commonly used for the staging of head and neck cancer. This study aimed to evaluate the correlation between 18F-FDG PET/CT, haematological parameters and prognosis in patients with advanced head and neck cancer. METHODS: This was a single-institutional retrospective study of 83 patients with advanced head and neck squamous cell carcinoma (HNSCC) who underwent 18F-FDG PET/CT imaging before initial treatment between 2014 and 2018. 18F-FDG PET/CT after treatment was performed in 57 patients. The prognostic parameters of the pre- and post-treatment maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), total lesion glycolysis (TLG) of primary tumours and haematological parameters were analysed to evaluate the association between overall survival (OS) and progression-free survival (PFS). RESULTS: Pre-MTV, pre-TLG and post-SUVmax were significantly associated with poor OS and PFS (p < 0.05). Haematological parameters, including pretreatment neutrophil/lymphocyte ratio and C-reactive protein/albumin ratio, were associated with 18F-FDG PET/CT parameters. In multivariate analysis, post-SUVmax was an independent prognostic factor for OS and PFS. CONCLUSION: A correlation between PET/CT metabolic and haematological parameters was observed. The volume and intensity of 18F-FDG uptake region, in addition to haematological parameters, are feasible markers for predicting the progression of HNSCC in daily practice. Further, post-SUVmax could be an independent parameter for predicting poor survival.

Glycative stress inhibits hypertrophy and impairs cell membrane integrity in overloaded mouse skeletal muscle.

BACKGROUND: Glycative stress, characterized by the formation and accumulation of advanced glycation end products (AGEs) associated with protein glycation reactions, has been implicated in inducing a decline of muscle function. Although the inverse correlation between glycative stress and muscle mass and strength has been demonstrated, the underlying molecular mechanisms are not fully understood. This study aimed to elucidate how glycative stress affects the skeletal muscle, particularly the adaptive muscle response to hypertrophic stimuli and its molecular mechanism. METHODS: Male C57BL/6NCr mice were randomly divided into the following two groups: the bovine serum albumin (BSA)-treated and AGE-treated groups. Mice in the AGE-treated group were intraperitoneally administered AGEs (0.5 mg/g) once daily, whereas those in the BSA-treated group received an equal amount of BSA (0.5 mg/g) as the vehicle control. After 7 days of continuous administration, the right leg plantaris muscle of mice in each group underwent functional overload treatment by synergist ablation for 7 days to induce muscle hypertrophy. In in vitro studies, cultured C2C12 myocytes were treated with AGEs (1 mg/mL) to examine cell adhesion and cell membrane permeability. RESULTS: Continuous AGE administration increased the levels of fluorescent AGEs, Nε-(carboxymethyl) lysine, and methylglyoxal-derived hydroimidazolone-1 in both plasma and skeletal muscle. Plantaris muscle weight, muscle fibre cross-sectional area, protein synthesis rate, and the number of myonuclei increased with functional overload in both groups; however, the increase was significantly reduced by AGE treatment. Some muscles of AGE-treated mice were destroyed by functional overload. Proteomic analysis was performed to explore the mechanisms of muscle hypertrophy suppression and myofibre destruction by AGEs. When principal component analysis was performed on 4659 data obtained by proteomic analysis, AGE treatment was observed to affect protein expression only in functionally overloaded muscles. Enrichment analysis of the 436 proteins extracted using the K-means method further identified a group of proteins involved in cell adhesion. Consistent with this finding, dystrophin-glycoprotein complex proteins and cell adhesion-related proteins were confirmed to increase with functional overload; however, this was attenuated by AGE treatment. Additionally, the treatment of C2C12 muscle cells with AGEs inhibited their ability to adhere and increased cell membrane permeability. CONCLUSIONS: This study indicates that glycative stress may be a novel pathogenic factor in skeletal muscle dysfunctions by causing loss of membrane integrity and preventing muscle mass gain.

Combined approach for predicting the efficacy of nivolumab in head and neck carcinoma by tissue and soluble expressions of PD-L1 and PD-L2.

BACKGROUND: Predictive biomarkers for nivolumab in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) have not yet been established. METHODS: The tumor proportion score (TPS), combined positive score (CPS), and soluble forms of programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2) were retrospectively analyzed in patients with RMHNSCC treated with nivolumab. RESULTS: The positivity rates for TPS (PD-L1), CPS (PD-L1), TPS (PD-L2), and CPS (PD-L2) were 73.8%, 78.2%, 56.4%, and 78.2%, respectively. Patients with high TPS (PD-L1), CPS (PD-L1), or CPS (PD-L1 and PD-L2) showed significantly prolonged progression-free survival. Favorable overall survival was associated with high CPS (PD-L1 and PD-L2) and low soluble PD-L1 and PD-L2 levels. The expressions of tissue and soluble PD-L1/2 were not correlated. CONCLUSIONS: Our study revealed that compared to PD-L1 expression alone, dual expression of PD-L1 and PD-L2 in tissue or soluble form could be feasible biomarkers in patients with RMHNSCC who received nivolumab.

Immunotherapy targeting tumor-associated antigen in a mouse model of head and neck cancer.

BACKGROUND: The identification of epitope peptides from tumor-associated antigens (TAAs) is informative for developing tumor-specific immunotherapy. However, only a few epitopes have been detected in mouse TAAs of head and neck cancer (HNSCC). METHODS: Novel mouse c-Met-derived T-cell epitopes were predicted by computer-based algorithms. Mouse HNSCC cell line-bearing mice were treated with a c-Met peptide vaccine. The effects of CD8 and/or CD4 T-cell depletion, and vaccine combination with immune checkpoint inhibitors (ICIs) were evaluated. Tumor re-inoculation was performed to assess T-cell memory. RESULTS: We identified c-Met-derived short and long epitopes that elicited c-Met-reactive antitumor CD8 and/or CD4 T-cell responses. Vaccination using these peptides showed remarkable antitumor responses via T cells in which ICIs were not required. The c-Met peptide-vaccinated mice rejected the re-inoculated tumors. CONCLUSIONS: We demonstrated that novel c-Met peptide vaccines can induce antitumor T-cell response, and could be a potent immunotherapy in a syngeneic mouse HNSCC model.

Soluble CD27 as a predictive biomarker for intra-tumoral CD70/CD27 interaction in nasopharyngeal carcinoma.

In CD70-expressing tumors, the interaction of CD70 on tumor cells with its lymphocyte receptor, CD27, is thought to play a role in immunosuppression in the tumor microenvironment and elevated serum levels of soluble CD27 (sCD27). Previous studies showed that CD70 is expressed in nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-related malignancy. However, the association between intratumoral CD70/CD27 expression and serum levels of sCD27 in NPC remains unclear. In the present study, we show that CD70 is primarily expressed by tumor cells in NPC and that CD27-positive lymphocytes infiltrate around tumor cells. NPC patients with CD27-positive lymphocytes had significantly better prognosis than patients lacking these cells. In addition, high CD70 expression by tumor cells tended to be correlated with shorter survival in NPC patients with CD27-positive lymphocytes. Serum sCD27 levels were significantly increased in patients with NPC and provided good diagnostic accuracy for discriminating patients from healthy individuals. The concentration of serum sCD27 in patients with CD70-positive NPC with CD27-positive lymphocytes was significantly higher than in patients with tumors negative for CD70 and/or CD27, indicating that the intratumoral CD70/CD27 interaction boosts the release of sCD27. Furthermore, positive expression of CD70 by NPC cells was significantly correlated with EBV infection. Our results suggest that CD70/CD27-targeted immunotherapies may be promising treatment options and that sCD27 may become an essential tool for evaluating the applicability of these therapies by predicting the intratumoral CD70/CD27 interaction in NPC.

Two cases of colorectal liver metastasis with residual liver recurrence after a long recurrence-free survival period.

BACKGROUND: The rate of residual liver recurrence after the resection of colorectal liver metastases is high, and most cases recur within 5 years of the initial hepatectomy. Here, we report two cases of residual liver recurrence after radical resection of colorectal liver metastases after a long recurrence-free survival period. CASE PRESENTATION: Case 1 involved a 62-year-old woman treated for ascending colon cancer in April 2011 who underwent right hepatectomy for synchronous colorectal liver metastasis in April 2012. However, in September 2021, computed tomography revealed residual recurrence in the lateral segment of the liver, and a lateral segmentectomy of the liver was performed. In Case 2, a 52-year-old man treated for cecal cancer in July 2002 underwent lateral segmentectomy of the liver for metachronous colorectal liver metastasis in October 2006. Subsequently, there was no recurrence; however, computed tomography showed residual liver recurrence in the right lobe of the liver in October 2021, and an expanded posterior hepatic segmentectomy was performed. Histopathological findings in both cases were consistent with colorectal liver metastases. CONCLUSIONS: We encountered two cases in which residual liver recurrence was observed after a long period of recurrence-free survival. Although rare, there have been a few cases of late recurrence of liver metastases after radical resection of cancer liver metastases.

A case of acquired hemophilia A after pancreaticoduodenectomy for distal cholangiocarcinoma.

Acquired hemophilia A (AHA) is a rare disease that results from factor VIII inhibitors causing abnormal coagulation, and certain cases may develop after highly invasive surgery. The present case study reports on a 68-year-old male patient who developed AHA after undergoing a subtotal stomach-preserving pancreatoduodenectomy for distal cholangiocarcinoma. The patient experienced complications after surgery, requiring reoperation on postoperative day (PD) 5 due to rupture of the Braun's enterostomy. On PD 6, angiography was performed after bleeding was detected in the jejunal limb, but hemostasis occurred spontaneously during the examination. Bleeding was observed again on PD 8 and direct surgical ligation was performed. On PD 14, bleeding recurred in the jejunal limb and angiography was performed to embolize the periphery of the second jejunal artery. During the procedure, the prothrombin time was normal, but only the activated partial thromboplastin time was prolonged. A close examination of the coagulation system revealed a decrease in factor VIII levels and the presence of factor VIII inhibitors, resulting in the diagnosis of AHA. Administration of steroids was initiated on PD 15 and, in addition to daily blood transfusions, activated prothrombin complex concentrate was administered to achieve hemostasis. The patient was discharged from the intensive care unit on PD 36 but later developed an intractable labial fistula due to suture failure at the gastrojejunostomy site. As the use of factor VIII inhibitors continued despite the administration of steroids, cyclophosphamide (CPA) pulse therapy was added at PD 58. However, CPA was ineffective and the administration of rituximab was initiated on PD 98. After 12 courses of rituximab, the patient tested negative for factor VIII inhibitors on PD 219. On PD 289, labial fistula closure was performed with continuous replacement of factor VIII and the patient was discharged on PD 342.

Treatment outcomes of alternating chemoradiotherapy for nasopharyngeal carcinoma: a single-center safety and efficacy study

Abstract Objective To evaluate the efficacy and safety of Alternating Chemoradiotherapy (ACRT) using cisplatin and 5-Fluorouracil (5-FU) in patients with nasopharyngeal carcinoma. Methods This was a retrospective study in which patients' clinical records were reviewed to identify patients with a new diagnosis of nasopharyngeal carcinoma at our institution between January 2005 and January 2019. Thirty-seven eligible patients were identified; of these, the clinical details of 27 patients treated with ACRT were evaluated. Patient outcomes, including overall survival and progression-free survival, and adverse events were assessed. Results Of these initial 37 patients, 1, 10, 13, 10, and 3 were staged as I, II, III, IVA, and IVB, respectively, as defined by the 8th edition of the TNM classification system. Twenty-seven patients received ACRT comprising sequential administration of chemotherapy, radiotherapy (wide field), chemotherapy, radiotherapy (shrinking field), and chemotherapy. The 5-year overall survival and progression-free survival rates were 83.7% and 88.9%, respectively. Treatment compliance was 93%, which is comparable to that of previous reports. Conclusion ACRT using cisplating and 5-fluorouracil was well tolerated with acceptable efficacy. Level of Evidence IVa

Brachyury-targeted immunotherapy combined with gemcitabine against head and neck cancer.

Brachyury is a transcription factor belonging to the T-box gene family and is involved in the posterior formation of the mesoderm and differentiation of chordates. As the overexpression of Brachyury is a poor prognostic factor in a variety of cancers, the establishment of Brachyury-targeted therapy would be beneficial for the treatment of aggressive tumors. Because transcription factors are difficult to treat with a therapeutic antibody, peptide vaccines are a feasible approach for targeting Brachyury. In this study, we identified Brachyury-derived epitopes that elicit antigen-specific and tumor-reactive CD4+ T cells that directly kill tumors. T cells recognizing Brachyury epitopes were present in patients with head and neck squamous cell carcinoma. Next, we focused on gemcitabine (GEM) as an immunoadjuvant to augment the efficacy of antitumor responses by T cells. Interestingly, GEM upregulated HLA class I and HLA-DR expression in tumor, followed by the upregulation of anti-tumor T cell responses. As tumoral PD-L1 expression was also augmented by GEM, PD-1/PD-L1 blockade and GEM synergistically enhanced the tumor-reactivity of Brachyury-reactive T cells. The synergy between the PD-1/PD-L1 blockade and GEM was also confirmed in a mouse model of head and neck squamous cell carcinoma. These results suggest that the combined treatment of Brachyury peptide with GEM and immune checkpoint blockade could be a promising immunotherapy against head and neck cancer.

Treatment outcomes of sialendoscopy for submandibular gland sialolithiasis.

OBJECTIVE: Sialendoscopy is a procedure used to remove salivary stones intraorally using a sialendoscope. In this study, we identified treatment outcomes of sialendoscopic surgery and identified predictive factors for successful stone removal by sialendoscopy alone. METHODS: We assembled the medical records of 144 patients who underwent sialendoscopic surgery for submandibular gland sialolithiasis at the Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, from October 2010 to November 2021, and collected patient backgrounds, medical condition, perioperative factors including operation method and complications, postoperative course, and stone constituents from a clinical laboratory testing company. RESULTS: Submandibular gland stones were successfully removed using sialendoscopy in 58 patients (40%). In multivariate analysis, location, major axis, and mobility of the stones were independent factors for successful removal. In receiver operating characteristic analysis, <7.5 mm of a major axis may be used as a measuring standard for successful removal. Removal of parenchymal stones is prone to involve prolonged operation times, increased postoperative complications, and development of retained stones. The stones mainly consisted of calcium phosphate and protein, with content percentages ranging from 0 to 98% (median 37%) and from 0 to 100% (median 63%), respectively. The percentage of calcium phosphate was negatively correlated with the number of floating stones and successful stone removal. CONCLUSION: Sialendoscopy is an aesthetically attractive treatment for sialolithiasis that avoids cervical incisions. The present results showed not only known but also new predictive factors for the successful removal of stones (<7.5 mm) and percentage of calcium phosphate. Moreover, our results suggest that careful consideration is required regarding the indication of sialendoscopic surgery in patients with parenchymal stones.

Expression of soluble CD27 in extranodal natural killer/T-cell lymphoma, nasal type: potential as a biomarker for diagnosis and CD27/CD70-targeted therapy.

The engagement of CD27 on lymphocytes with its ligand, CD70, on tumors is believed to mediate tumor immune evasion and the elevation of serum soluble CD27 (sCD27) levels in patients with CD70-positive malignancies. We previously showed that CD70 is expressed in extranodal natural killer/T-cell lymphoma, nasal type (ENKL), an Epstein-Barr virus (EBV)-related malignancy. However, little is known about serum sCD27 expression and its association with the clinical characteristics of, and the CD27/CD70 interaction in, ENKL. In the present study, we show that serum sCD27 is significantly elevated in the sera of patients with ENKL. The levels of serum sCD27 provided excellent diagnostic accuracy for discriminating patients with ENKL from healthy subjects, correlated positively with the levels of other diagnostic markers (lactate dehydrogenase, soluble interleukin-2 receptor, and EBV-DNA), and decreased significantly following treatment. Elevated serum sCD27 levels also correlated significantly with advanced clinical stage and tended to correspond with shorter survival, in patients with ENKL. Immunohistochemistry indicated that CD27-positive tumor-infiltrating immune cells exist adjacent to CD70-positive lymphoma cells. In addition, serum sCD27 levels in patients with CD70-positive ENKL were significantly higher than those in patients with CD70-negative ENKL, suggesting that the intra-tumoral CD27/CD70 interaction boosts the release of sCD27 in serum. Furthermore, the EBV-encoded oncoprotein latent membrane protein 1 upregulated CD70 expression in ENKL cells. Our results suggest that sCD27 may serve as a novel diagnostic biomarker and also may serve as a tool for evaluating the applicability of CD27/CD70-targeted therapies by predicting intra-tumoral CD70 expression and CD27/CD70 interaction in ENKL.

Internal carotid artery dissection caused by elongated styloid process.

A 69-year-old man with impaired consciousness, right hemiplegia, and aphasia was admitted to our emergency room for thorough examination. Magnetic resonance imaging (MRI) and 3-dimensional computed tomography (3D CT) scan of the head revealed a cerebral infarction due to dissection of the left internal carotid artery. Contrast-enhanced CT prior to internal carotid artery stenting showed that the left elongated styloid process ran in close proximity to the left internal carotid artery, with a minimum distance of 2 mm. The patient underwent stenting at the internal carotid artery 16 days after disease onset. The patient was referred to our department for left elongated styloid process resection to reduce the risk of further internal carotid artery injury. Resection of the left styloid process through a cervical incision was performed. Six months after surgery, there was no recurrence of the internal carotid artery dissection.

Treatment outcomes of alternating chemoradiotherapy for nasopharyngeal carcinoma: a single-center safety and efficacy study.

OBJECTIVE: To evaluate the efficacy and safety of Alternating Chemoradiotherapy (ACRT) using cisplatin and 5-Fluorouracil (5-FU) in patients with nasopharyngeal carcinoma. METHODS: This was a retrospective study in which patients' clinical records were reviewed to identify patients with a new diagnosis of nasopharyngeal carcinoma at our institution between January 2005 and January 2019. Thirty-seven eligible patients were identified; of these, the clinical details of 27 patients treated with ACRT were evaluated. Patient outcomes, including overall survival and progression-free survival, and adverse events were assessed. RESULTS: Of these initial 37 patients, 1, 10, 13, 10, and 3 were staged as I, II, III, IVA, and IVB, respectively, as defined by the 8th edition of the TNM classification system. Twenty-seven patients received ACRT comprising sequential administration of chemotherapy, radiotherapy (wide field), chemotherapy, radiotherapy (shrinking field), and chemotherapy. The 5-year overall survival and progression-free survival rates were 83.7% and 88.9%, respectively. Treatment compliance was 93%, which is comparable to that of previous reports. CONCLUSION: ACRT using cisplating and 5-fluorouracil was well tolerated with acceptable efficacy. LEVEL OF EVIDENCE: IVa.

Central-part laryngectomy after laryngotracheal separation to manage pharyngocutaneous fistula: A case report and retrospective analysis of 12 cases.

A 15-year-old girl presented with a 3-year-history of continuous outflow of saliva from a pharyngocutaneous fistula, located at 5 mm superior to her tracheal stoma. She was diagnosed with Miller-Dieker syndrome at birth. At 2 years of age, pediatric surgeons at our institution carried out laryngotracheal separation to prevent aspiration pneumonia. At the age of 12 years, she developed continuous saliva discharge from the fistula. We performed central-part laryngectomy and resection of the pharyngocutaneous fistula, which relieved her from the continuous saliva discharge. Central-part laryngectomy is less invasive and easier to perform than total laryngectomy. We hereby present a case and retrospective analysis of 12 patients, who underwent central-part laryngectomy.

Impact of arm position on vertebral bone marrow proton density fat fraction in chemical-shift-encoded magnetic resonance imaging: a preliminary study.

Arm positions employed during magnetic resonance imaging (MRI) can affect magnetic field distribution, which may result in variability in proton density fat fraction (PDFF) measurements. This study evaluated the effect of arm position on lumbar PDFF measured using chemical-shift-encoded MRI (CSE-MRI). Fifteen healthy volunteers from a single-center underwent lumbar CSE-MRI at two different arm positions (side and elevated) using a single 3T scanner. Scans were performed twice in each position. PDFFs of the L1-L5 vertebrae were independently measured by two readers, and reader measurements were compared by calculating intraclass correlation coefficients (ICC). We compared PDFF measurements from two arm positions and from two consecutive scans using the Wilcoxon test and Bland-Altman analysis. Measurements from the two readers were in high agreement [ICC =0.999; 95% confidence interval (CI), 0.998-0.999]. No significant difference was observed between PDFFs from the first and second scans of all vertebrae for each reader (all P>0.05); however, PDFF for the elevated arm position was significantly higher than that for the side arm position (37.9-44.8% vs. 37.0-43.8%; all P<0.05), except at the L2 level by reader 2. The mean differences in PDFF measurements from the first and second scans [0.1%; 95% limits of agreement (LoA), -1.8% to 1.9%] and from the side arm and elevated arm positions (0.8%; 95% LoA, -1.6% to 3.2%) were small. In conclusion, these preliminary data suggest that different arm positions during CSE-MRI can slightly affect lumbar PDFF; however, the mean absolute differences were very small.

Variability in contrast and apparent diffusion coefficient of kiwifruit used as prostate MRI phantom: 1-week validation.

Kiwifruit has been proposed as a phantom for prostate magnetic resonance imaging (MRI) to adjust multiparametric MRI factors. This study evaluated the variability in contrasts and apparent diffusion coefficients (ADCs) via repeated scans of kiwifruits for 1 week. All scans were performed using a 3T MRI system. Six kiwifruits were prepared as phantoms. Each kiwifruit was scanned consecutively for 1 week, and T2-weighted and diffusion-weighted images were acquired. Contrasts between the peripheral placenta (PP) and central placenta (CP), and between the outer pericarp (OP) and CP were calculated. The ADCs of the PP, OP, and CP were also determined. The Friedman test with Scheffé's post hoc comparison was used to assess contrast and ADC variability over 1 week; no significant differences between the contrasts or ADCs were found. Thus, each kiwifruit phantom exhibited low variability when used as a prostate MRI phantom.

Covering reinforced staples with polyethylene glycolic acid felt-covered fibrin sealant to prevent pancreatic fistula after distal pancreatomy: a retrospective comparative study.

BACKGROUND: In accordance with previous reports on the utility of polyethylene glycolic acid (PGA) felt and fibrin glue for postoperative pancreatic fistula (POPF), we usually perform distal pancreatectomy (DP) with a PGA felt reinforcement stapler when dissecting the pancreas and cover the stump with PGA felt and fibrin glue (the PPF method). In this study, we retrospectively analyzed our DP cases to compare the risk factors for POPF and the postoperative course of patients receiving the PPF method of treatment versus that of those receiving conventional treatment. METHODS: A total of 127 DP procedures performed in our department between January 2008 and June 2021 were retrospectively analysed. RESULTS: In the PPF method, grade B/C POPF rate tended to decrease, and POPF rate showed a significant decrease. The duration of drainage and the length of postoperative hospitalisation were also significantly shorter with the PPF method. The risk of grade B/C POPF significantly decreased with the PPF method if the pancreas was thick (> 13.5 mm) or the patients were obese. CONCLUSIONS: The PPF method is useful for POPF in DP and is particularly effective when a thick pancreas or obese patient is involved. Removing the drainage tube early in the PPF method may lead to early discharge.

Fasting potentiates insulin-mediated glucose uptake in rested and prior-contracted rat skeletal muscle.

A single bout of exercise can potentiate the effect of insulin on skeletal muscle glucose uptake via activation of the AMPK-TBC1 domain family member 4 (TBC1D4) pathway, which suggests a positive correlation between AMPK activation and insulin sensitization. In addition, prolonged fasting in rodents is known to upregulate and thereby synergistically enhance the effect of exercise on muscle AMPK activation. Therefore, fasting may potentiate the insulin-sensitizing effect of exercise. In the present study, we mimicked exercise by in situ muscle contraction and evaluated the effect of a 36-h fast on muscle contraction-induced insulin sensitization. Male Wistar rats weighing 150-170 g were allocated to either a 36-h fasting or feeding group. The extensor digitorum longus (EDL) muscles were electrically contracted via the common peroneal nerve for 10 min followed by a 3-h recovery period. EDL muscles were dissected and incubated in the presence or absence of submaximal insulin. Our results demonstrated that acute muscle contraction and 36 h of fasting additively upregulated AMPK pathway activation. Insulin-stimulated muscle glucose uptake and site-specific TBC1D4 phosphorylation were enhanced by prior muscle contraction in 36-h-fasted rats, but not in fed rats. Moreover, enhanced insulin-induced muscle glucose uptake and Akt phosphorylation due to 36 h of fasting were associated with a decrease in tribbles homolog 3 (TRB3), a negative regulator of Akt activation. In conclusion, fasting and prior muscle contraction synergistically enhance insulin-stimulated TBC1D4 phosphorylation and glucose uptake, which is associated with augmented AMPK pathway activation in rodents.NEW & NOTEWORTHY In this study, we revealed that 36 h of fasting additively upregulated acute muscle contraction-induced AMPK pathway activation in rats. Besides, fasting and muscle contraction synergistically enhanced insulin-stimulated site-specific TBC1D4 phosphorylation and glucose uptake, which was associated with augmented AMPK pathway activation. These results contribute to understanding the regulation of muscle insulin sensitivity.

Association of Glycative Stress With Motor and Muscle Function.

Glycative stress is a type of biological stress caused by non-enzymatic glycation reactions, which include advanced glycation end product (AGE) formation, AGE accumulation, glycation-driven dysfunction of proteins and cellular signaling, inflammation, oxidation, and tissue damage. Increased glycative stress derived from hyperglycemia and lifestyle disorders is a risk factor in metabolic and age-related diseases, such as type 2 diabetes, cardiovascular disease, cancer, Alzheimer's disease, osteoporosis, and dementia. Studies have shown that AGE accumulation is correlated with the age-related loss of muscle mass and power output, also called sarcopenia. Mechanistically, dysfunctions of contractile proteins, myogenic capacity, and protein turnover can cause glycative stress-induced skeletal muscle dysfunction. Because the skeletal muscle is the largest metabolic organ in the body, maintaining skeletal muscle health is essential for whole-body health. Increasing awareness and understanding of glycative stress in the skeletal muscle in this review will contribute to the maintenance of better skeletal muscle function.

Efficacy of 6-mm diameter fully covered self-expandable metallic stents in preoperative biliary drainage for pancreatic ductal adenocarcinoma.

Objectives: Plastic stents (PS) used for preoperative biliary drainage (PBD) of pancreatic ductal adenocarcinomas (PDAC) tend to be associated with a high incidence of recurrent biliary obstruction (RBO). Although 10-mm diameter fully covered self-expanding metallic stents (FCSEMS) have come into use, vigilance is still required to prevent complications, such as cholecystitis and surgical site infection. The present study examined the efficacy and safety of the 6-mm diameter FCSEMS for PBD. Methods: The present retrospective study compared the incidence of complications associated with the use of 6-mm FCSEMS and PS. The inclusion criteria were a diagnosis of PDAC and preoperative endoscopic biliary tract drainage performed at our institution between April 2012 and June 2019. Results: Of the 51 patients enrolled, 25 and 26 patients received a PS and a 6-mm FCSEMS, respectively. The RBO incidence was significantly lower in the 6-mm FCSEMS group (7.7%) than in the PS group (40.0%) (p = 0.009), and time to RBO was significantly longer in the 6-mm FCSEMS group (HR = 6.008, p = 0.021). The patency rate at three months after stent placement was significantly higher in the latter group (83.5% vs. 45.3%, p = 0.009, Log-rank test). The groups did not differ significantly in terms of complications associated with PBD, such as cholecystitis and surgical site infection. Conclusion: The present findings suggested that the 6-mm FCSEMS may be an effective drainage device for use in PBD in PDAC treatment.